Database: MEDLINE <: biomedical, nursing & dental literature, 1966 - Nov 2000.> Search Strategy (You Saved Citations 1-300 From Set 61): ----------------------------------------------------------------------------- 1 exp Tooth demineralization/ 22684 2 demineralization.mp. 1629 3 caries.mp. 15334 4 caires.mp. 1 5 craies.mp. 0 6 careis.mp. 4 7 carise.mp. 0 8 (teeth adj3 cavit:).mp. 422 9 (tooth adj3 cavit:).mp. 217 10 (dental adj3 cavit:).mp. 276 11 (dentin adj3 cavit:).mp. 256 12 (enamel adj3 cavit:).mp. 183 13 (teeth adj3 decay:).mp. 379 14 (tooth adj3 decay:).mp. 325 15 (dental adj3 decay:).mp. 251 16 (dentin adj3 decay:).mp. 12 17 (enamel adj3 decay:).mp. 20 18 (active adj decay).mp. 9 19 (rampant adj3 decay:).mp. 14 20 (recurrent adj3 decay:).mp. 30 21 (white adj spot:).mp. 513 22 carious.mp. 2083 23 cariology.ti,ab. 56 24 (non-cavitated adj3 lesion:).mp. 15 25 (noncavitated adj3 lesion:).mp. 2 26 Tooth remineralization/ 479 27 (dental adj3 fissure:).mp. 99 28 (tooth adj3 fissure:).mp. 50 29 (teeth adj3 fissure:).mp. 98 30 caries-free.mp. 606 31 cariesfree.mp. 17 32 Cariogenic agents/ 729 33 precavit:.mp. 8 34 (filled adj3 teeth).mp. 513 35 (filled adj3 tooth).mp. 117 36 (oral adj fissure:).mp. 6 37 (tooth adj3 remineraliz:).mp. 28 38 (teeth adj3 remineraliz:).mp. 24 39 dft.mp. 415 40 dfs.mp. 1266 41 dmf:.mp. 6412 42 cariogeni:.mp. 1789 43 or/1-42 32343 44 exp Genetics/ 1206180 45 (cn or ge).fs. 901090 46 gene$1.mp. 443661 47 genetic:.mp. 259943 48 genom:.mp. 99495 49 genotyp:.mp. 48882 50 chromosom:.mp. 199850 51 congenit:.mp. 84285 52 familial.mp. 37802 53 heritab:.mp. 5915 54 inherit:.mp. 33803 55 twin$1.mp. 19323 56 Diseases in twins/ 8030 57 exp Multiple birth offspring/ 12476 58 consanguin:.mp. 6420 59 or/44-58 1589028 60 43 and 59 1434 61 limit 60 to english language 1251 62 from 61 keep 1-300 300 63 from 61 keep 301-600 300 64 from 61 keep 601-900 300 *************************** <1> UI - 94003729 AU - Neimark J AU - Briand JP IN - Laboratoire de synthese de peptides, UPR 9021 Immunochimie des Peptides et des Virus, IBMC du CNRS, Strasbourg, France. TI - Development of a fully automated multichannel peptide synthesizer with integrated TFA cleavage capability. SO - Peptide Research 1993 Jul-Aug;6(4):219-28 AB - A fully automated multichannel peptide synthesizer has been constructed which performs simultaneous and rapid assembly of peptides on a 20-200 mumol scale. In situ activation of amino acids using BOP or PyBOP was chosen to give an optimized coupling chemistry. Specially designed blocks of valves, with a zero dead volume combined with an original circuitry, permit the distribution of amino acids derivatives and reagents pre-dissolved in DMF. Either Boc or Fmoc chemistry can be adapted on the synthesizer. In Boc synthesis a very rapid protocol involving Boc group deprotection in neat TFA, followed by the concomitant steps of neutralization and coupling, allows the addition of three amino acids per hour on each channel. In Fmoc chemistry we have integrated into the synthesizer an automatic TFA cleavage system that allows the peptides to be cleaved from the resin directly within the reactors used for synthesis. The stability of the Fmoc amino acid derivatives in solution in DMF was investigated, and decomposition was found to be insignificant during the time-span of a synthesis. The satisfactory performance of the instrument was demonstrated by routine synthesis of 15-20 mer peptides. <2> UI - 94008989 AU - Shearman MS AU - Herbst R AU - Schlessinger J AU - Ullrich A IN - Department of Molecular Biology, Max-Planck-Institut fur Biochemie, Martinsried, Germany. TI - Phosphatidylinositol 3'-kinase associates with p145c-kit as part of a cell type characteristic multimeric signalling complex. SO - EMBO Journal 1993 Oct;12(10):3817-26 AB - p145c-kit is expressed in cell lineages of diverse origin and appears to regulate distinct cell type characteristic functions. Independent mutations at the murine Dominant White Spotting (W) locus result in the alteration of p145c-kit tyrosine kinase activity and signalling potential, which differentially affects melanocyte migration, germ cell regeneration and hematopoietic cell differentiation. Molecules that may be involved in mediation and definition of p145c-kit signalling pathways were investigated in cell lines of hematopoietic, melanogenic and central nervous system origin. High-affinity association of endogenous cellular proteins with activated p145c-kit was limited to a characteristic set of molecules that correlated with the presence of phosphatidylinositol (PtdIns) 3'-kinase activity. The observed association pattern of proteins was cell type characteristic, and all of the proteins were displaced from the receptor by competition with excess receptor binding subunit of PtdIns 3'-kinase. Our data indicate that PtdIns 3'-kinase associates with p145c-kit as part of a multimeric signalling complex, and suggest that the cell type characteristic composition of this complex influences the signalling potential of p145c-kit in the diverse cell types in which it is expressed and thereby defines its cell type-specific functions. <3> UI - 94015213 AU - Seshadri R AU - Firgaira FA AU - Horsfall DJ AU - McCaul K AU - Setlur V AU - Kitchen P IN - Department of Haematology, Flinders Medical Centre, Bedford Park, South Australia. TI - Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. SO - Journal of Clinical Oncology 1993 Oct;11(10):1936-42 AB - PURPOSE: To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients. METHODS: HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained. RESULTS: HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size. CONCLUSION: Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients. <4> UI - 93367076 AU - van Loveren C AU - Buijs JF AU - ten Cate JM IN - Department of Cariology and Endodontology, Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. TI - Protective effect of topically applied fluoride in relation to fluoride sensitivity of mutans streptococci. SO - Journal of Dental Research 1993 Aug;72(8):1184-90 AB - The aim of the present in vitro experiments was to determine whether the protection of enamel by topically applied fluoride against demineralization by bacterial acids would depend on the fluoride sensitivity of the bacteria. Glucose-agarose gel suspensions of fluoride-sensitive and fluoride-resistant mutans streptococci were placed on bovine enamel specimens with different amounts of fluoride. One group of specimens was untreated, a second group had been pretreated with a F-lacquer, and a third group had been pretreated with the F-lacquer and rinsed subsequently with a KOH-solution, to remove deposited CaF2. After 22-hour incubations at 37 degrees C, the amounts of calcium and lactate and the pH of the agarose gels were determined. This procedure was repeated on three consecutive days. Two parent S. mutans strains, one parent S. sobrinus strain, and five fluoride-resistant derivatives were tested. Both pretreatments gave a significant protection to the enamel specimens. For the S. mutans strains, the degree of protection did not depend on the fluoride sensitivity of the strains. For the S. sobrinus strains, the results suggested a reduced protection against demineralization by the fluoride-resistant derivatives. Only from the second group of enamel specimens was enough fluoride released for inhibition of bacterial metabolism. Presumably, it was released by the dissolution of CaF2. It is concluded that a possible adaptation of mutans streptococci in dental plaque to frequent exposures to fluoride will not necessarily decrease the caries-preventive effects caused by topically applied fluoride agents. <5> UI - 93385379 AU - Lamkin MS AU - Oppenheim FG IN - Department of Periodontology and Oral Biology, Boston University Goldman School of Graduate Dentistry, MA 02118. TI - Structural features of salivary function. [Review] [58 refs] SO - Critical Reviews in Oral Biology & Medicine 1993;4(3-4):251-9 AB - Saliva plays an important role in the maintenance of oral health by exhibiting multiple host defense functions. These include homeostatic processes, lubrication, antimicrobial activity, and the control of demineralization/remineralization of teeth. Biochemical studies of saliva and salivary secretions established that specific salivary proteins are responsible for these defense functions. Because some of these salivary proteins have been characterized extensively, including their primary structures, it has become feasible to explore their structure/function relationships. Acidic proline-rich proteins (PRPs), for example, exhibit high affinity to hydroxyapatite, inhibit crystal growth of calcium phosphate salts from solutions supersaturated with respect to hydroxyapatite, bind calcium ions, and interact with several oral bacteria on adsorption to hydroxyapatite. Statherins, histatins, and cystatins also exhibit affinities to mineral surfaces, inhibit calcium phosphate precipitation, and play a role in maintaining the integrity of teeth. Furthermore, histatins exhibit both antibacterial and antifungal activities. Approaches to identifying the functional domains of these salivary proteins include functional assays of enzymatically digested proteins and peptides, synthetic peptides and peptide analogues, and chemically modified proteins as well as biophysical studies of native proteins or peptides. Such studies have demonstrated that the fungicidal activities of histatins reside in the middle portion of the polypeptide chain, whereas the hydroxyapatite binding domains of PRPs and statherin reside in the phosphorylated amino-terminal regions. Identification of functional domains is vital in understanding the mechanisms of action and this information can be exploited in the development of therapeutic agents. [References: 58] <6> UI - 93392235 AU - Fleischman RA IN - Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas 75235-8852. TI - From white spots to stem cells: the role of the Kit receptor in mammalian development. [Review] [17 refs] SO - Trends in Genetics 1993 Aug;9(8):285-90 AB - The Kit tyrosine kinase membrane receptor is essential for melanogenesis, gametogenesis and hematopoiesis during embryonic development and postnatal life. This review summarizes the genetic evidence implicating Kit and its ligand, Steel factor, in the control of stem cell proliferation, migration and survival, with emphasis on mutations in the human and mouse genes. [References: 17] <7> UI - 93373235 AU - Merkel DE AU - Winchester DJ AU - Goldschmidt RA AU - August CZ AU - Wruck DM AU - Rademaker AW IN - Section of Medical Oncology, Evanston Hospital, IL 60201. TI - DNA flow cytometry and pathologic grading as prognostic guides in axillary lymph node-negative breast cancer. SO - Cancer 1993 Sep 15;72(6):1926-32 AB - BACKGROUND. The recurrence or mortality rate of axillary lymph node-negative invasive breast cancer has been associated with the tumor S-phase fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using frozen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. METHODS. Histologic, nuclear, and mitotic grades, DNA ploidy, and S-phase fraction (SPF) were determined from paraffin-embedded tumors obtained from 280 women with node-negative invasive ductal carcinomas using standard grading schemes and flow cytometric techniques. These variables were compared with disease-free and cancer-specific survival (CSS) in univariate and multivariate analyses of these patients. RESULTS. Tumor diameter, SPF, histologic grade, and nuclear grade were significant predictors of disease-free survival (DFS); diameter and SPF had significant associations with CSS. Cox analysis showed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% risk of recurrence at 5 years. In contrast, 36% of patients in this series with medium-grade or high-grade high SPF tumors had a 30% risk of recurrence over the same interval. CONCLUSIONS. Histopathologic grading and flow cytometric determination of SPF appear to provide additive prognostic information for patients with early invasive ductal carcinomas of the breast. <8> UI - 93367074 AU - Bowden G AU - Johnson J AU - Schachtele C IN - Department of Oral Sciences and Clinical Research Center for Periodontal Diseases, School of Dentistry, University of Minnesota, Minneapolis 55455. TI - Characterization of Actinomyces with genomic DNA fingerprints and rRNA gene probes. SO - Journal of Dental Research 1993 Aug;72(8):1171-79 AB - Cellular DNA from 25 Actinomyces naeslundii and Actinomyces viscosus strains belonging to the 7 taxonomic clusters of Fillery et al. (1978) and several unclustered strains was obtained by enzymatic and N-lauroylsarcosine/guanidine isothiocyanate treatment of whole cells, followed by extraction of the nucleic acid. The DNA samples were digested with restriction endonucleases BamHI or PvuII, and agarose gel electrophoresis was used to obtain DNA fingerprints. The DNA fragments were subjected to Southern blot hybridization with a digoxigenin-labeled cDNA probe transcribed from Escherichia coli 16S and 23S rRNA. The patterns of bands from genomic (DNA fingerprints) and rDNA fingerprints (ribotypes) were used for comparison between the taxonomic cluster strains and strains within clusters. Representative strains from each taxonomic cluster provided different BamHI DNA fingerprints and ribotype patterns with 3 to 9 distinct bands. Some strains within a cluster showed identical ribotype patterns with both endonucleases (A. naeslundii B120 and A. naeslundii B102 from cluster 3), while others showed the same pattern with BamHI but a different pattern with PvuII (A. naeslundii ATCC 12104 and 398A from cluster 5). A viscosus ATCC 15987 (cluster 7) and its parent strain T6 yielded identical fingerprint and ribotype patterns. The genomic diversity revealed by DNA fingerprinting and ribotyping demonstrates that these techniques, which do not require phenotypic expression, are suited for study of the oral ecology of the Actinomyces, and for epidemiological tracking of specific Actinomyces strains associated with caries lesions and sites of periodontal destruction. <9> UI - 93366441 AU - Yamashita Y AU - Bowen WH AU - Burne RA AU - Kuramitsu HK IN - Department of Pediatric Dentistry, University of Texas Health Science Center, San Antonio 78284. TI - Role of the Streptococcus mutans gtf genes in caries induction in the specific-pathogen-free rat model. SO - Infection & Immunity 1993 Sep;61(9):3811-7 AB - The role of each of the Streptococcus mutans gtf genes coding for glucan synthesis in cariogenesis was evaluated by using strain UA130 in the specific-pathogen-free (SPF) rat model system. Mutants defective in either or both of the genes required for insoluble glucan synthesis, the gtfB and gtfC genes, exhibited markedly reduced levels of smooth-surface carious lesions relative to that of the parental organism. Likewise, the mutant defective in the gtfD gene coding for the glucosyltransferase-S enzyme synthesizing water-soluble glucans also produced significantly fewer smooth-surface lesions than strain UA130. None of these mutations markedly altered the rate of sulcal caries induction relative to that of the parental organism. In addition, a mutant of strain UA130 defective in the gtfA gene was reexamined in the SPF rat model. In contrast to previous results from a gnotobiotic rat system, these mutants also induced significantly fewer smooth-surface carious lesions compared with that by strain UA130. These results suggest that all four genes are important for smooth-surface caries formation. Furthermore, these results are discussed relative to the differences in the diets utilized in the SPF and gnotobiotic rat model systems for assessing the virulence factors of S. mutans. <10> UI - 93346487 AU - Grunt TW AU - Oeller H AU - Somay C AU - Dittrich E AU - Fazeny B AU - Mannhalter C AU - Dittrich C IN - Department of Internal Medicine, University of Vienna, Austria. TI - Modulation of the immunophenotype of ovarian cancer cells by N,N-dimethylformamide and transforming growth factor-beta 1. SO - Journal of Cellular Physiology 1993 Aug;156(2):358-66 AB - Exposure of HOC-7 ovarian adenocarcinoma cells to regulators of cell differentiation caused inducer-dependent alterations of the antigenic pattern of the cells. Immunocytochemistry revealed that N,N-dimethylformamide (DMF) elevated the membrane staining for epidermal growth factor (EGF)-receptor and for desmoplakins I and II. DMF also stimulated cytoplasmic and surface labeling for CA 125 and the deposition of fibronectin into the extracellular matrix. Stimulation of fibronectin was also seen after addition of transforming growth factor (TGF)-beta 1. These responses were quantified using a fixed-cell, enzyme-linked immunosorbent assay (ELISA) and revealed that DMF dose-dependently induced expression of EGF-receptor, CA 125, fibronectin, and desmoplakins I and II. TGF-beta 1 stimulated fibronectin and desmoplakins I and II only. Production of EGF and TGF-alpha was not affected by these inducers. Immunocytochemistry, ELISA and Western blotting showed that both inducers caused down-regulation of myc oncoproteins. DMF was more effective in changing the immunophenotype of HOC-7 cells than TGF-beta 1. Desmoplakins I and II demonstrated elevated epithelial differentiation, whereas fibronectin indicated stimulation of extracellular matrix formation. Elevated EGF-receptor could not compensate for the growth inhibition induced by DMF. The expression of myc oncoproteins was inversely related to cell proliferation. CA 125, however, seems to be unrelated to cell growth. <11> UI - 93345721 AU - Slomiany BL AU - Piotrowski J AU - Czajkowski A AU - Shovlin FE AU - Slomiany A IN - Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400. TI - Differential expression of salivary mucin bacterial aggregating activity with caries status. SO - International Journal of Biochemistry 1993 Jun;25(6):935-40 AB - 1. The low and high mol. wt mucin forms were isolated from saliva of caries-resistant (CR) and caries-susceptible (CS) individuals, and assessed for their bacterial aggregating potential towards S. mutans and S. sanguis, the common cariogenic microorganisms encountered in the oral cavity. 2. The high mol. wt mucin from both groups of subjects exhibited similar protein and carbohydrate content, but the level of covalently bound fatty acids was significantly lower in the CR group. The mucin from CR group showed only a weak inhibitory potential, and no inhibitory activity was observed with the mucin of CS group. 3. The low mol. wt mucins from both groups, while displaying compositional similarities, showed a marked variation in the bacterial aggregating activity. With both bacteria, the activity of the mucin from CR group was at least 128-fold greater than that of CS group. 4. The conversion of the high mol. wt mucin to a low mol. wt form through the action of salivary protease produced in both groups enhancement in mucin's bacterial aggregating capacity. This enhancement was, however, considerably less pronounced in the case of mucin from CS group. 5. The results for the first time demonstrate that the bacterial aggregating epitope of salivary mucins is expressed to a greater extent in CR individuals, and that this epitope is apparently more accessible to bacteria in the low mol. wt mucin form. <12> UI - 93318657 AU - Colombo G AU - Fanti P AU - Yao C AU - Malluche HH IN - Department of Biochemistry, Albert B. Chandler Medical Center, University of Kentucky, Lexington. TI - Isolation and complete amino acid sequence of osteocalcin from canine bone. SO - Journal of Bone & Mineral Research 1993 Jun;8(6):733-43 AB - Osteocalcin was purified in high yield and to homogeneity from the diaphysis of dog femora by the following steps: (1) acid demineralization of bone powder, (2) solid-phase extraction of acid-soluble proteins on Sep-Pak C18 cartridges, (3) gel filtration on Sephadex G-50, and (4) fast protein liquid chromatography on an Accell-QMA anion-exchange column. Starting from 30 g washed bone powder, approximately 7-10 mg pure protein was obtained in 2 days. The key step is the initial solid-phase extraction of osteocalcin from a large volume of a demineralized bone solution. The primary structure was established by automated sequence analyses of two tryptic peptides, of two endoproteinase Glu-C carboxy-terminal peptides, and of the first 30 amino acid residues of the intact protein. Dog osteocalcin contains 49 amino acids, has a molecular mass of 5654 daltons, contains no Thr, Met, Hyp, or Trp, has a disulfide bond between Cys 23 and 29, and is fully gamma-carboxylated at residues 17, 21, and 24. Dog osteocalcin does not contain a pair of basic amino acids found at positions 43-44 in most other osteocalcins from mammals and birds. A computer search for homology indicated 88, 90, 84, 88, 66, and 57% sequence identity of dog osteocalcin with human, bovine, cat, monkey, chicken, and swordfish osteocalcin, respectively, and weaker homologies with the gamma-carboxylated domains of blood-clotting proteins and the Pro-rich N-terminal extensions of myosin light-chain A1 and beta-crystalline B1. The possible relevance of these homologies to the structure and potential functions of osteocalcin is discussed. <13> UI - 93330656 AU - Serwint JR AU - Mungo R AU - Negrete VF AU - Duggan AK AU - Korsch BM IN - Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD. TI - Child-rearing practices and nursing caries. SO - Pediatrics 1993 Aug;92(2):233-7 AB - OBJECTIVE. To determine which child-rearing practices are associated with nursing caries. DESIGN. Cross-sectional study. SETTING. Hospital-based general pediatric clinic. PARTICIPANTS. Sequential sample of 110 healthy children aged 18 to 36 months. OUTCOME MEASURES. Feeding practices of children, limit-setting issues, and familial dental health were determined by maternal interview. Nursing caries were diagnosed by dental examination. RESULTS. Nursing caries were found in 22 (20%) of the children. Ninety percent of children with and without caries were bottle-feeding at 12 and 18 months of age. Ninety-one percent of children with caries and 84% without were still drinking a nighttime bottle at 18 months (P = .33). The mothers of children with caries were found to have fewer years of education, 8.9 vs 10.8 years (P = .02), and were more likely to have eight or more cavities, 55% vs 19% (P = .002). More infants in the caries group had been breast-fed, 72% vs 46% (P = .02), although length of breast-feeding was similar, 5.4 vs 6.7 months. Fewer children with caries drank fluoridated tap water, 27% vs 54% (P = .05), but there were no differences in topical fluoride use, dental hygiene practices, or visits to the dentist. CONCLUSIONS. These findings fail to substantiate a straightforward relationship between child-rearing practices and nursing caries and suggest that well-designed prospective studies are needed to clarify the etiology of early caries. <14> UI - 93306698 AU - Ooshima T AU - Minami T AU - Aono W AU - Izumitani A AU - Sobue S AU - Fujiwara T AU - Kawabata S AU - Hamada S IN - Department of Pedodontics, Osaka University, Faculty of Dentistry, Japan. TI - Oolong tea polyphenols inhibit experimental dental caries in SPF rats infected with mutans streptococci. SO - Caries Research 1993;27(2):124-9 AB - An extract of oolong tea (semifermented tea leaves of Camellia sinensis) and its chromatographically isolated polyphenolic compound was examined for in vitro inhibitory effects on glucosyltransferases (GTases) of mutans streptococci and on caries development in Sprague-Dawley rats infected with mutans streptococci. The samples showed no detectable effect on the growth of mutans streptococci. However, insoluble glucan synthesis from sucrose by the GTases of Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 was markedly inhibited, as was sucrose-dependent cell adherence of these mutans streptococci. The administration of the oolong tea extract and the isolated polyphenol compound into diet 2000 and drinking water resulted in significant reductions in caries development and plaque accumulation in the rats infected with mutans streptococci. The active components in the oolong tea extract were presumptively identified as polymeric polyphenols which were specific for oolong tea leaves. These results indicate that the oolong tea polyphenolic compounds could be useful for controlling dental caries. <15> UI - 93329361 AU - Willcox MD AU - Fitzgerald RJ AU - Adams BO AU - Patrikakis M AU - Knox KW IN - Institute of Dental Research, Surry Hills, NSW, Australia. TI - Biochemical properties of Streptococcus sobrinus reisolates from the gastrointestinal tract of a gnotobiotic rat. SO - Journal of General Microbiology 1993 May;139 ( Pt 5):929-35 AB - Streptococcus sobrinus strain 6715-13-201 was inoculated into the oral cavity of a gnotobiotic rat and then reisolated from different portions of the gastrointestinal tract. Fourteen isolates, selected on the basis of their colonial morphology, were then screened for their ability to adhere to saliva-coated hydroxyapatite (SHA) in vitro, and their ability to produce extracellular polysaccharide from sucrose, and low pH in glucose broth. Certain isolates were also tested for their cariogenic potential as monoinfectants in gnotobiotic rats. All isolates differed in their abilities to adhere to SHA, with most showing an increased level of adhesion in the presence of sucrose, but this did not correlate with their ability to be aggregated by dextran. Most isolates were capable of producing glucosyltransferases (with only one exception) and dextranases (also one exception). There was more variability in the production of dextranase inhibitor. No isolate was capable of producing dextranase inhibitor in the absence of dextranase production. There were no correlations between the ability of isolates to adhere in vitro or produce/utilize polysaccharides and their ability to produce caries in vivo. Due to the differences between strains in their abilities to adhere, produce polysaccharides, utilize polysaccharides or produce a low pH and the lack of correlation between any of these parameters and cariogenicity, the results suggest that the ability of strains to colonize and produce caries depends on a number of different characteristics, no one of which is essential. <16> UI - 93305436 AU - Larsson E AU - Luning B AU - Heinegard D IN - Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Sweden. TI - Synthesis and function of an O-phosphorylated peptide corresponding to the cell adhesion sequence of bone sialoprotein (BSP). SO - Acta Chemica Scandinavica 1993 Jun;47(6):565-9 AB - Bone sialoprotein contains a cell-binding RGD sequence followed by a threonine residue. Since the protein is extensively phosphorylated, this threonine may also be modified. To study whether such a phosphorylation may alter cell-binding properties, the hexapeptide Pro-Arg-Gly-Asp-Thr(O-phosphoryl)-Tyr has been synthesized by the Fmoc technique using benzyl protective groups for Tyr and phosphate, tert-butyl ester for Asp and Pmc for Arg. Removal of Fmoc groups was effected by treatment with 20% morpholine in DMF. The phospho-peptide inhibited binding of R1 cells to BSP-coated surfaces 10 times less efficiently compared with the non-phosphorylated peptide, as did, surprisingly, also the fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro. <17> UI - 93319980 AU - Raadal M AU - Elhassan FE AU - Rasmussen P IN - Department of Pedodontics, School of Dentistry, University of Bergen, Norway. TI - The prevalence of caries in groups of children aged 4-5 and 7-8 years in Khartoum, Sudan. SO - International Journal of Paediatric Dentistry 1993 Mar;3(1):9-15 AB - A total of 544 children, 275 pre-school children (aged 4-5 years) and 269 school children (aged 7-8 years), were examined for dental caries using WHO criteria with some modifications. The children were resident in Khartoum, Sudan. The mean dmft was 1.68 in the 4-5-year group, and 58% of them were caries-free. In the 7-8-year group the mean dmft (molars and canines) was 2.77, and 33% of the children were caries-free. Most of the caries in both groups was untreated. In decayed teeth which were not beyond repair, occlusal caries was most prevalent in the pre-school group and approximal caries most prevalent in the school group. The mean DMFT in the 7-8-year group was 0.15, and only occlusal surfaces in first molars were affected. Ninety-four percent in the 7-year group and 88% in the 8-year group were caries-free in the permanent dentition. When the children were grouped according to their socio-economic level, there were no statistically significant differences in caries prevalence between the groups. Since this is the first comprehensive caries prevalence study of these age groups in Sudan, it is impossible to conclude whether caries is increasing or not. The prevalence of caries-free preschool children is above the global goal of FDI/WHO for the year 2000, but below the goal for developing countries. <18> UI - 93293309 AU - Smith DJ AU - Taubman MA AU - Holmberg CF AU - Eastcott J AU - King WF AU - Ali-Salaam P IN - Department of Immunology, Forsyth Dental Center, Boston, Massachusetts 02115. TI - Antigenicity and immunogenicity of a synthetic peptide derived from a glucan-binding domain of mutans streptococcal glucosyltransferase. SO - Infection & Immunity 1993 Jul;61(7):2899-905 AB - The immunogenicity and antigenicity of a multiply antigenic peptide construct containing four copies of the synthetic peptide TGAQTIKGQKLYFKANGQQVKG were measured in rodents and humans, respectively. The composition of this peptide construct (termed GLU) was derived from a major repeating sequence in the C-terminal region of mutans streptococcal glucosyltransferases that synthesize water-insoluble glucan (GTF-I). The GLU peptide elicited high levels of serum immunoglobulin G antibody to GLU after subcutaneous injection into Sprague-Dawley rats. These antisera also reacted with intact GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (by enzyme-linked immunosorbent assay [ELISA] and Western blot [immunoblot] analyses) and with an 87-kDa glucan-binding protein from S. sobrinus (by Western blot). The synthesis of filter-retained glucan by GTF-Sd of S. sobrinus could be inhibited (30%) by preincubation with anti-GLU rat serum. Splenic and lymph node lymphocytes from rats injected once with S. sobrinus GTF isozymes demonstrated significant proliferation after 5 days of culture with GLU. The GLU peptide reacted with 4 of 29 human parotid saliva samples and 5 of 29 human serum samples (by ELISA). These results suggest that the GLU peptide contains B- and T-cell epitopes that are similar to those of intact mutans streptococcal GTFs and possibly certain other glucan-binding proteins as well. Furthermore, since antibody to this epitope(s) appears to inhibit GTF function, sequences within this peptide construct may have value for inclusion in a synthetic dental caries vaccine. <19> UI - 93284506 AU - Veronese SM AU - Gambacorta M AU - Gottardi O AU - Scanzi F AU - Ferrari M AU - Lampertico P IN - Department of Pathology, Niguarda-Ca Granda Hospital, Milan, Italy. TI - Proliferation index as a prognostic marker in breast cancer. SO - Cancer 1993 Jun 15;71(12):3926-31 AB - BACKGROUND. The proliferative activity of tumors has been extensively investigated with different approaches, among which the use of the monoclonal antibody Ki-67 represents an easy and reliable means of assessing cell proliferation. In this study, the proliferative activity of 129 primary breast cancers was investigated, and the results were related to prognosis. METHODS. Tumor samples, obtained from 129 patients who underwent surgery between January 1987 and December 1988, were processed for staining by an immunohistochemical procedure (avidin-biotin complex). The median time of observation was 42 months (range, 31-55 months). Life-table analysis (Mantel-Cox) was used to assess the probability of disease-free survival (DFS) and overall survival (OS). RESULTS. Tumors with high Ki-67 proliferation indices (> 20%) were associated with a higher 4-year probability of relapse of disease (55.3% versus 79.1%; P = 0.003) and death (71% versus 95.6%; P = 0.00005) when compared with tumors with low Ki-67 values. In addition, this proliferative parameter maintained its prognostic significance when the patients were stratified according to lymph node involvement, menopausal status, and nuclear estrogen receptor content. CONCLUSIONS. Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS. <20> UI - 93300811 AU - Yee NS AU - Langen H AU - Besmer P IN - Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021. TI - Mechanism of kit ligand, phorbol ester, and calcium-induced down-regulation of c-kit receptors in mast cells. SO - Journal of Biological Chemistry 1993 Jul 5;268(19):14189-201 AB - The proto-oncogene c-kit is allelic with the white spotting locus (W) on mouse chromosome 5 and it encodes a transmembrane protein tyrosine kinase which belongs to the platelet-derived growth factor and macrophage-colony stimulating factor (CSF-1) receptor subfamily. In an effort to study the function of the c-kit receptor, specifically the physiological mechanism of controlling the signal induced by the ligand, the effect and mechanism of down-regulation of the c-kit receptor by the kit ligand (KL) was investigated in mast cells. Following preincubation with KL, the capacity of mast cells to bind kit antibody was reduced and binding of radiolabeled KL to mast cells decreased with similar kinetics, suggesting that KL stimulates the loss of c-kit receptor from the cell surface. After binding to the c-kit receptor, KL was rapidly internalized, and degradation of the receptor was accelerated. The c-kit receptor was transmodulated by the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) and by the calcium ionophore ionomycin. TPA- and ionomycin-induced down-regulation of the c-kit receptor was accompanied by release of the extracellular domain of the receptor, presumably by proteolytic cleavage near the transmembrane domain. Release of the extracellular domain of the c-kit receptor occurred also in untreated cells but at a slow rate. In addition, ionomycin induced shedding of the intact c-kit receptor. In mast cells depleted of protein kinase C, the c-kit receptor remained sensitive to down-regulation induced by KL and ionomycin, but not by treatment with TPA. Therefore, the down-regulation of the c-kit receptor induced by KL, activated protein kinase C, and an increased level of intracellular calcium is mediated through independent mechanisms. <21> UI - 93300626 AU - Claros P AU - Guirado C AU - Claros A AU - Claros A Jr AU - Claveria A AU - Wienberg P IN - Clinica Claros, Los Vergos, Barcelona, Spain. TI - Association of spontaneous anterior fossa CSF rhinorrhea and congenital perilymphatic fistula in a patient with recurrent meningitis. SO - International Journal of Pediatric Otorhinolaryngology 1993 May;27(1):65-71 AB - A case of recurrent meningitis associated with spontaneous cerebrospinal fluid (CSF) rhinorrhea and left sensorineural hearing loss in a 4-year-old boy was found to be due to simultaneous congenital defects. High resolution CT examination clearly showed an anterior fossa defect and an inner ear malformation, including demineralization in the region of the footplate of the stapes, and thus provided clear guidance for the surgeon. <22> UI - 93257669 AU - Kasugai T AU - Okada M AU - Morimoto M AU - Arizono N AU - Maeyama K AU - Yamada M AU - Tei H AU - Dohmae K AU - Onoue H AU - Newlands GF AU - et al IN - Department of Pathology, Medical School, Osaka University, Japan. TI - Infection of Nippostrongylus brasiliensis induces normal increase of basophils in mast cell-deficient Ws/Ws rats with a small deletion at the kinase domain of c-kit. SO - Blood 1993 May 15;81(10):2521-9 AB - All basophils, mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC) are derived from the multipotential hematopoietic stem cell. Mutations at the c-kit locus resulted in deficiency of MMC and CTMC in both mice and rats. To investigate the role of the c-kit receptor tyrosine kinase for production of basophils, we used white spotting/white spotting (Ws/Ws) mutant rats that have a small deletion at the tyrosine kinase domain of the c-kit gene. When Ws/Ws, nude athymic, and normal (+/+) rats were infected with Nippostrongylus brasiliensis (NB), the number of basophils increased greater than 50-fold in the peripheral blood of Ws/Ws and +/+ rats but did not increase in that of nude rats. Blood histamine concentration increased significantly in Ws/Ws and +/+ rats but did not increase in nude rats. Immature basophils increased greater than 10-fold in the bone marrow of Ws/Ws and +/+ rats but did not increase in that of nude rats. Mature and immature basophils that developed after the NB infection were identified by electron microscopy. The present result confirms that T-cell-derived cytokines are indispensable for the augmented production of basophils and suggests that stimulation via the c-kit receptor may not be necessary for the augmented production. <23> UI - 93266351 AU - Mihara H AU - Xu M AU - Nishino N AU - Fujimoto T IN - Department of Applied Chemistry, Faculty of Engineering, Kyushu Institute of Technology, Kitakyushu, Japan. TI - Application of tryptic condensation strategy for the synthesis of alpha-melanocyte stimulating hormone. SO - International Journal of Peptide & Protein Research 1993 Apr;41(4):405-10 AB - The use of trypsin in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) paired with N,N-dimethylformamide (DMF) has been proposed for the enzymatic condensation of peptides. The tryptic condensation strategy was applied to the synthesis of the 13-peptide, alpha-melanocyte stimulating hormone (alpha-MSH), which contains two susceptible points to trypsin, in a low-water-containing solvent system, 4% H2O in HFIP/DMF (1/1, v/v). The N-terminal 8-peptide segment (S1) ending with Arg and C-terminal 5-peptide with the side-chain protections at Lys and Trp (S2) were prepared by the stepwise coupling on p-nitrobenzophenone oxime resin and by a conventional method, respectively. Both segments were condensed by the aid of trypsin. The acid component was converted into the partially protected alpha-MSH at as high as 95% conversion determined by reversed-phase HPLC. When the side-chain of Lys at the 11-position was not protected, alpha-MSH was obtained only in 35% yield, and was contaminated with products of secondary hydrolysis. Although the Lys11-Pro12 sequence was very poorly susceptible to trypsin, the side-chain of Lys had to be protected in order to be inert to trypsin under the synthetic conditions. HFIP is demonstrated as a good solvent with DMF to allow the efficient tryptic condensation of peptides. The strategy increased the value of the enzymatic condensation as practical method by avoidance of secondary hydrolysis, high dissolution of peptides and retention of activity of enzyme. <24> UI - 93253425 AU - Gamis AS AU - Haake R AU - McGlave P AU - Ramsay NK IN - Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis. TI - Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children. SO - Journal of Clinical Oncology 1993 May;11(5):834-8 AB - PURPOSE: Bone marrow transplantation (BMT) for Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) results in a 55% to 64% disease-free survival (DFS) rate in 20% to 30% of cases with a matched-sibling donor (MSD). Studies that include primarily adults with CML, using unrelated-donor (URD) BMT, have expanded this option to those without an MSD. We review and compare the efficacy of URD and MSD BMT in children with Ph1 CML. PATIENTS AND METHODS: Eleven children with URD BMTs were reviewed and compared with 11 children with MSD BMTs for Ph1 CML. Among the URD BMT recipients, there were three with fully matched marrows and 10 with advanced CML. The median time from diagnosis to transplant was 2.6 years. Among the MSD BMT recipients, 11 had fully matched marrows and five had advanced CML. The median time from diagnosis to BMT was 0.7 years. All received non-T-depleted marrows after cyclophosphamide and fractionated total-body irradiation. RESULTS: Both groups had similar engraftment times. Late graft failure occurred in two URD patients. Graft-versus-host disease (GVHD), > or = grade II, was similar in both groups (77% for URD BMT, 45% for MSD BMT), although more severe acute disease and more persistent chronic disease was seen in the URD group. The Kaplan-Meier estimate of DFS was 45% +/- 15% (SE) and 78% +/- 14% (SE) in the URD and MSD groups, respectively, at 3 years. All had Karnofsky scores of more than 70%, except one URD patient debilitated from GVHD. CONCLUSION: CML is eventually fatal to all patients without BMT. The high survival rate seen among children who receive a URD BMT, despite several adverse factors, opens this important therapeutic option to those without an MSD. <25> UI - 93264252 AU - Bircher AJ AU - Lang-Muritano M AU - Pfaltz M AU - Bruckner-Tuderman L IN - Department of Dermatology, University of Basle, Switzerland. TI - Epidermolysis bullosa junctionalis progressiva in three siblings. [Review] [12 refs] SO - British Journal of Dermatology 1993 Apr;128(4):429-35 AB - Three siblings of Swiss origin with epidermolysis bullosa junctionalis progressiva are described. The following clinical features were present from school age: dystrophy of the nails, non-scarring blistering of the skin, mild skin atrophy, hypodontia and dental caries. Light microscopy showed subepidermal blistering. Direct immunofluorescence was negative. On indirect immunofluorescence staining of a fresh spontaneous blister, bullous pemphigoid antigen and laminin were localized to the blister roof, and collagen IV and collagen VII to the blister base, indicating junctional splitting. Electron microscopy revealed a normal dermo-epidermal junction zone, including normal hemidesmosomes. There were no deposits of electron-dense amorphous material. [References: 12] <26> UI - 93241192 AU - Held KD AU - Hopcia KL IN - Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114. TI - Role of protein thiols in intrinsic radiation protection of DNA and cells. SO - Mutation Research 1993 May;299(3-4):261-9 AB - Previous data have been consistent with the hypothesis that the thiol depleter dimethyl fumarate (DMF) increases radiation sensitivity of hypoxic mammalian cells by a combination of two actions: depletion of glutathione (GSH) which interferes with the chemical competition between damage fixation and repair and depletion of protein thiol (PSH) which causes inhibition of enzymatic repair processes. However, one cannot rule out the possibility that PSH also acts in the chemical competition to restitute damaged DNA. The studies presented here have addressed this question by studying the effects of ionizing radiation on isolated nuclei which contain very low levels of GSH, but substantial amounts of PSH, compared to intact cells. The results show that DNA damage, measured using the non-denaturing filter elution assay, is increased about 1.6-fold in isolated nuclei irradiated in air, compared to whole cells, and about 4.3-fold in nuclei irradiated in N2. Thus, the OER for DNA damage decreases from about 3 in whole cells to 1 in isolated nuclei. Also, although DMF increases radiation-induced DNA damage in whole cells irradiated in hypoxia about 2-fold, it does not increase DNA damage in isolated nuclei irradiated in hypoxia. These data do not support the idea that PSH can act in the chemical competition reaction to chemically repair radiation-induced DNA radicals. The data are discussed in relation to the effect that various procedures for nuclei isolation can have on radiation sensitivity of DNA and on the OER. We also address the question of whether radiation-induced DNA damage measured by non-denaturing elution correlates with cell killing. <27> UI - 93235958 AU - Galli SJ AU - Tsai M AU - Wershil BK IN - Department of Pathology, Beth Israel Hospital, Boston, Massachusetts. TI - The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. [Review] [81 refs] SO - American Journal of Pathology 1993 Apr;142(4):965-74 AB - Many years ago, alert observers noticed among thousands of laboratory mice a few individuals that, unlike their littermates, exhibited areas of white spotting on their fur. No one could have predicted then that an effort to understand the basis for these abnormalities would ultimately contribute to the characterization of a receptor (c-kit) and a corresponding ligand (stem cell factor, SCF) that are critical not only to the migration and development of melanocytes, but also to hematopoiesis, gametogenesis, mast cell development, and, perhaps, development of the central nervous system. Nor could anyone have foretold then that this receptor and ligand would be shown to regulate the development of multiple distinct cellular lineages not only in mice, but also in humans and other primates, or that c-kit and its ligand would be found to influence the secretory function of cells bearing this receptor, as well as their development. Investigation of the effects of SCF on a single cell type, the mast cell, has produced the most complete picture of the spectrum of biological processes that can be regulated by interactions between c-kit and its ligand. This work shows that SCF critically regulates the migration and survival of mast cell precursors, promotes the proliferation of both immature and mature mast cells, enhances mast cell maturation, directly induces secretion of mast cell mediators, and can regulate the extent of mediator release in mast cells activated by IgE-dependent mechanisms. Indeed, SCF may well prove to be one of the most important of the factors influencing mast cell numbers, phenotype, and function in both health and disease. It now seems virtually certain that further studies of c-kit and SCF will produce important new insights into problems as diverse as the regulation of lineage commitment during normal hematopoiesis or the development and function of the central nervous system. And even though an effect on mast cell development was one of the last phenotypic abnormalities to be recognized in mice with mutations affecting the genes encoding c-kit or SCF, mast cells will continue to represent an important model system for analyzing the biology of c-kit and its ligand. [References: 81] <28> UI - 93219372 AU - Colagiovanni DB AU - Stillman WS AU - Irons RD IN - Molecular Toxicology and Environmental Health Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262. TI - Chemical suppression of a subpopulation of primitive hematopoietic progenitor cells: 1,3-butadiene produces a hematopoietic defect similar to steel or white spotted mutations in mice [published erratum appears in Proc Natl Acad Sci U S A 1993 Jul;90(13):6377]. SO - Proceedings of the National Academy of Sciences of the United States of America 1993 Apr 1;90(7):2803-6 AB - Chronic exposure of mice to 1,3-butadiene produces a macrocytic-megaloblastic anemia, thymic hypoplasia, and an increased incidence of T-cell lymphoma/leukemia. This is reminiscent of pathologies observed in mice bearing mutations at the W and Sl loci, which are deficient in c-kit and c-kit ligand (CKL), respectively. The influence of 3,4-epoxybutene (EB), the primary metabolite of 1,3-butadiene, on the colony-forming response of hematopoietic progenitor cells (HPCs) from C57BL/6, Sl, and W mice was investigated in order to elucidate the role of altered HPC regulation in the pathogenesis of 1,3-butadiene toxicity. EB pretreatment suppressed interleukin 3 colony formation and abrogated CKL synergism of the granulocyte-macrophage/colony-stimulating factor (GM-CSF) response in C57BL/6 cells, had no effect on colony formation induced by GM-CSF or granulocyte/colony-stimulating factor (G-CSF) alone, and failed to suppress CKL-induced synergism of the G-CSF response. Experiments conducted with cells from Sl and W mice revealed that they lack the same primitive HPC targeted by EB. EB pretreatment in vitro and butadiene exposure in vivo mimic hematopoietic defects seen in W and Sl mice, suggesting that the pleotypic pathologies encountered in these murine models may be largely due to a common defect in primitive HPCs. Susceptibility to EB appears to define a functional subpopulation of primitive HPCs and illustrates that differences observed in the susceptibility of specific cytokine responses to chemical/drug exposure may provide a valuable tool for characterizing functional subpopulations of HPCs. <29> UI - 93229763 AU - Ratanatharathorn V AU - Karanes C AU - Uberti J AU - Lum LG AU - de Planque MM AU - Schultz KR AU - Cronin S AU - Dan ME AU - Mohamed A AU - Hussein M AU - et al IN - Department of Medicine, Harper Hospital, Detroit, MI 48201. TI - Busulfan-based regimens and allogeneic bone marrow transplantation in patients with myelodysplastic syndromes. SO - Blood 1993 Apr 15;81(8):2194-9 AB - Preparative regimens containing busulfan (BU) followed by allogeneic bone marrow transplantation (BMT) were used in 27 consecutive patients with myelodysplastic syndromes (MDS). The median age was 33 years (range, 4 to 54). Ten were female and 17 male. Sixteen patients had primary MDS, 11 other patients had antecedent hematologic diseases or developed MDS after cytotoxic and/or radiation therapy. Six patients had leukemic transformation and received antileukemic therapy before BMT. Pre-BMT cytogenetic studies showed complex chromosomal abnormalities in 13 patients, a simple abnormality in 5 patients, and normal chromosome in 8 patients. Three BU-based preparative regimens were used: 1 patient received BU 4 mg/kg orally (PO) daily for 4 days and cyclophosphamide (CY) 50 mg/kg intravenously (IV) daily for 4 days (BUCY-4); 24 patients received BU 4 mg/kg PO daily for 4 days, cytosine arabinoside (ara-C) 2 g/m2 IV every 12 hours for 4 doses, and CY 60 mg/kg IV daily for 2 days (BAC); and 2 patients with preceding Fanconi anemia received BU 2 mg/kg PO daily for 4 days followed by total lymphoid irradiation of 5 Gy. Seventeen of 27 patients are alive with no evidence of disease. Ten patients have died: 2 from hepatic veno-occlusive disease, 3 from sepsis, 1 from a cerebral bleed, 1 from a massive gastrointestinal (GI) bleed associated with acute graft-versus-host disease, 1 from hemolytic uremic syndrome with adult respiratory distress syndrome, 1 from bronchiolitis obliterans, and the only patient who did not engraft died from acute myeloid leukemia. Regimen-related toxicities (RRT) include GI tract (diarrhea, 14; stomatitis, 11), liver (9), cardiac (1), and skin (5). Patients who received a genotypically matched marrow graft had a significantly better disease-free survival (DFS) than patients who received a nongenotypic marrow graft (P = .02). The Kaplan-Meier analysis projects an overall DFS of 56% +/- 13% and 78% +/- 10% for patients who received a genotypically matched marrow graft. With the exception of a child who did not engraft, there was no relapse of MDS or leukemia. Excellent DFS, acceptable RRT, and the ease of administration are advantages of this regimen. <30> UI - 93239289 AU - Doggett TA AU - Jagusztyn-Krynicka EK AU - Curtiss R 3d IN - Department of Biology, Washington University, St. Louis, Missouri 63130. TI - Immune responses to Streptococcus sobrinus surface protein antigen A expressed by recombinant Salmonella typhimurium. SO - Infection & Immunity 1993 May;61(5):1859-66 AB - In this study, we used a vaccine strain of Salmonella typhimurium to express antigenic determinants of the SpaA antigen of Streptococcus sobrinus, which is involved in the caries-forming process. We cloned either a single repeat (pYA2901) or three tandem repeats (pYA2905) of the 0.48-kb fragment of the spaA gene, which codes for an important component of the SpaA protein, plus a 1.2-kb minor antigenic determinant and measured the resulting immune responses to SpaA in orally immunized BALB/c mice. The single or triple repeat of the spaA gene fragment was inserted into the Asd+ vector pYA292 and was transformed into the S. typhimurium delta cya delta crp vaccine strain chi 4072 containing delta asd in the chromosome. Female BALB/c mice were then orally immunized with two doses of the S. typhimurium containing either of the two SpaA constructs, and the immune responses to the expressed SpaA protein were assessed. Significant serum immunoglobulin G (IgG) anti-SpaA titers were detected in mice immunized with chi 4072(pYA2905) but not chi 4072(pYA2901). Salivary anti-SpaA IgA titers were minimal and were only detected in mice immunized with S. typhimurium expressing the SpaA encoded by pYA2905. Intestinal anti-SpaA IgA titers, however, were detected in both groups of mice, particularly in mice immunized with chi 4072(pYA2905). An oral booster 26 weeks after the initial series of immunizations resulted in increased serum IgG titers in both chi 4072(pYA2901)- and chi 4072(pYA2905)-immunized animals, particularly in the chi 4072(pYA2905)-immunized animals. No anamnestic IgA response was detected in the saliva following the booster immunization. <31> UI - 93177027 AU - Russell BW AU - Mills D IN - Department of Botany and Plant Pathology, Oregon State University, Corvallis 97331-2902. TI - Electrophoretic karyotypes of Tilletia caries, T. controversa, and their F1 progeny: further evidence for conspecific status. SO - Molecular Plant-Microbe Interactions 1993 Jan-Feb;6(1):66-74 AB - Electrophoretic karyotypes were obtained from intact sporidia and mycelia of Tilletia controversa and T. caries, and hybrid progeny were obtained by crossing these pathogens. The chromosomes typically ranged from approximately 850 to 4,490 kilobases (kb) for all strains, and they were variable in number with 19 or 20 for strains of T. controversa, 14-20 for T. caries, and from 19 to 22 for the hybrid progeny. The estimated genome size varied from 28 to 42 megabases (Mb) for these strains. Radiolabeled probes made of single copy DNA fragments and a heterologous actin gene identified four linkage groups among all strains that exhibited maximum chromosome length polymorphisms of 14% or less. The chromosomes carrying the rDNA genes, representing a fifth linkage group, exhibited length polymorphisms of approximately 40%. The actin gene and a rDNA probe hybridized with one or more bands in these strains, suggesting that some of the variability in chromosome number may result from aneuploidy. The karyotypes of the hybrid progeny revealed chromosome numbers and genome sizes essentially identical to each parental strain, clearly indicating that the reduction division stage of meiosis had occurred. These data and other corroborative genetic data provide substantial evidence that T. controversa and T. caries are not different species, but variants of a single species. <32> UI - 93194748 AU - Frankel SR IN - Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York. TI - Acute promyelocytic leukemia. New insights into diagnosis and therapy. [Review] [139 refs] SO - Hematology - Oncology Clinics of North America 1993 Feb;7(1):109-38 AB - The clinical and laboratory features of APL are distinct. APL has been effectively treated with anthracyclines. Postremission therapy and the addition of other cytotoxic agents in induction may be beneficial. Early deaths remain a problem despite improved management of coagulopathy. The cytogenetic marker, t(15;17), reflects a molecular defect that splices two transcription factors, PML and RARA, to produce chimeric mRNA and proteins. RA, the natural ligand for RARA, is able to induce CR by stimulating differentiation and maturation of the malignant cells. The addition of RA to the therapeutic armamentarium of the hematologic oncologist will allow further refinement of the management of these patients. Diagnosis is unambiguous because the molecular defect can be readily detected. Our understanding of the biology downstream of the affected genes is incomplete. Other retinoids may be more effective than all-trans RA and may avoid the fall in plasma levels seen in patients chronically treated with RA. Combination of retinoids with other cytokines or cytotoxic agents may decrease the immediate mortality and improve long-term DFS in APL. [References: 139] <33> UI - 93168823 AU - Kuramitsu HK IN - Department of Pediatric Dentistry and Microbiology, University of Texas Health Science Center, San Antonio. TI - Virulence factors of mutans streptococci: role of molecular genetics. [Review] [109 refs] SO - Critical Reviews in Oral Biology & Medicine 1993;4(2):159-76 AB - Biochemical approaches were utilized initially to identify the virulence factors of the mutans streptococci (primarily Streptococcus mutans and S. sobrinu). Traditional mutant analysis of these organisms further suggested the important role of several of these factors in cariogenicity. However, because these mutations were not clearly defined, the utilization of cloned genes was necessary to verify their significance. The introduction of molecular genetic approaches for characterizing these factors has led not only to a clearer understanding of the role of these virulence factors in cariogenicity but has also suggested some novel approaches for reducing further the incidence of dental caries. [References: 109] <34> UI - 93163623 AU - Halaban R AU - Moellmann G IN - Yale University School of Medicine, Department of Dermatology, New Haven, Connecticut 06510-8059. TI - White mutants in mice shedding light on humans. [Review] [137 refs] SO - Journal of Investigative Dermatology 1993 Feb;100(2 Suppl):176S-185S AB - In this article we describe the rapid advances made in the molecular genetics of three inherited pigmentation disorders: albinism, piebaldism, and vitiligo, all of which throw light on normal pigment cell function. The focus is on studies in mice, with comparison of data in humans. The critical role of tyrosinase (c-locus or human tyrosinase protein) in normal pigmentation and albinism has been reinforced by the cloning and identification of mutations in tyrosinase and two other melanocyte-specific oxidoreductases structurally related to but functionally different from tyrosinase: the (b) brown-locus protein/gp75/catalase B and dopachrome tautomerase. Each possesses a distinct enzyme activity and yet the three share homology in strategic regions. Most of the point mutations that reduce or abrogate the respective enzyme activities are located in those regions. Tyrosinase-negative albinism is caused only by defects in tyrosinase. A locus for human tyrosinase-positive albinism has been recently mapped to chromosome 15q11.2-->q12, at a gene identified in mice as pink-eyed dilution. On the other hand, several genes encoding proteins critical for the proliferation of melanocytes are known to control the piebald phenotype. So far identified are two membrane-receptor tyrosine kinases, c-Kit and PDGF-R/alpha, and the ligand for c-kit, MGF (mast-cell growth factor, also known as stem-cell factor, c-Kit-ligand, or steel factor). Mutations in W/c-kit (white spotting), Ph/Pdgfr/a (patch), and Sl/MGF (steel), lead to a reduction in receptor kinase activity and failure of melanocytes to thrive and reach the skin during embryogenesis. Finally, mouse mutant models suggest at least two possible causes for vitiligo, a progressive loss of pigmentation that occurs after birth. In one mutant, the Blt (light) mouse, the cyclic death of hair melanocytes may be due to the toxicity of intermediates and byproducts of melanogenesis in the presence of a dysfunctional b-locus protein. In the other model, the "vitiligo mouse," in which the allele vit has been assigned to the microphthalmia (mi) locus, the loss of melanocytes may be caused by defective signal transduction, because in addition to vitiligo mivit/mivit mice have extensive piebaldism. [References: 137] <35> UI - 93161701 AU - Evans RW AU - Lo EC AU - Darvell BW IN - School of Dental Science, University of Melbourne, Victoria, Australia. TI - Determinants of variation in dental caries experience in primary teeth of Hong Kong children aged 6-8 years. SO - Community Dentistry & Oral Epidemiology 1993 Feb;21(1):1-3 AB - A representative sample of Hong Kong children aged 6-8 yr was examined for dental caries, and data on possible explanatory variables for dmft were obtained from questionnaires. Variation in dmft was partially accounted for by the effect of some demographic variables and other variables having a socioeconomic base. Girls had a lower dmft index than boys, and being born in Hong Kong rather than elsewhere (that is, China) was also associated with a lower dmft index. Better dental status was strongly associated with increasing educational level of the mother, monthly household income, and with an increasingly positive perception of the questionnaire respondent's own dental status. Preschool dental visits and enrollment in the School Dental Care Service were associated with higher dmft indices. Altogether, 22.5% of the variance in dmft was explained. It was concluded that: 1) demographic and socioeconomic factors significantly affect dmft variation in Hong Kong. 2) the mother's role in determining the dental status of her child is probably important, and 3) further elucidation of the variation in dmft will depend on the analysis of data pertaining to dietary and oral hygiene practices during the preschool years and to an analysis of tooth morphology, fluoride exposure, and microbiologic, salivary, and genetic factors. <36> UI - 93159784 AU - Edwards MJ AU - Taylor MF IN - Department of Entomology, University of Arizona, Tucson 85721. TI - Substitution of DMSO for DMF as a solvent for X-gal. SO - Biotechniques 1993 Feb;14(2):234 <37> UI - 93141276 AU - Reith AD AU - Ellis C AU - Maroc N AU - Pawson T AU - Bernstein A AU - Dubreuil P IN - Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada. TI - 'W' mutant forms of the Fms receptor tyrosine kinase act in a dominant manner to suppress CSF-1 dependent cellular transformation. SO - Oncogene 1993 Jan;8(1):45-53 AB - Point mutations in highly conserved amino acid residues in the catalytic domain of the Kit receptor tyrosine kinase (RTK) are responsible for the coat color, fertility and hematopoietic defects of mice bearing mutant alleles at the dominant white-spotting (W) locus. The dominant nature of structural Kit mutations suggests that expression of other kinase-defective RTKs might also specifically interfere with signal transduction by normal receptors. To test this possibility, we have investigated the functional consequences of introducing analogous mutations into the RTK encoded by the c-fms proto-oncogene. Both Fms37 (glu582-->lys) and Fms42 (asp776-->asn) mutant proteins, corresponding to the strongly dominant-negative W37 and W42 mutant c-kit alleles, had undetectable in vitro kinase activity and were unable to transform Rat-2 fibroblasts in the presence of exogenous CSF-1. Moreover, expression of Fms37 or Fms42 proteins in Rat-2 cells specifically inhibited anchorage-independent growth mediated by the normal Fms receptor in the presence of exogenous CSF-1 and conferred a dominant loss of Fms-associated PI3-kinase activity on CSF-1 stimulation. Mutant RTKs, bearing point substitutions identical to those present in mild or severe W mutants, may provide a generally applicable strategy for inducing dominant loss of function defects in RTK-mediated signalling pathways. <38> UI - 93115780 AU - Gilbert L AU - Elwood LJ AU - Merino M AU - Masood S AU - Barnes R AU - Steinberg SM AU - Lazarous DF AU - Pierce L AU - d'Angelo T AU - Moscow JA AU - et al IN - Medicine Branch, National Cancer Institute, Bethesda, MD 20892. TI - A pilot study of pi-class glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer. SO - Journal of Clinical Oncology 1993 Jan;11(1):49-58 AB - PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation. <39> UI - 93137225 AU - Levine AE AU - Lewis LR IN - University of Texas Health Science Center, Dental Branch, Houston 77225. TI - Transforming growth factor-beta 2 is an autocrine growth inhibitory factor for the MOSER human colon carcinoma cell line. SO - Cancer Letters 1993 Jan 15;68(1):33-41 AB - The MOSER human colon carcinoma cell line is significantly growth inhibited by exogenous transforming growth factor-beta (TGF-beta). The secretion of TGF-beta by these cells was examined to determine if endogenous TGF-beta might also regulate MOSER cell growth. MOSER cells secreted 11 ng TGF-beta/10(6) cells, 24% of which was in the active form. Blocking antibodies specific for TGF-beta 2 stimulated growth 1.4-fold, while TGF-beta 1 specific antibodies were without effect. Treatment of MOSER cells with the differentiation agent, N,N-dimethylformamide (DMF), inhibited cell growth and resulted in an 8-fold increase in secreted TGF-beta (20% active). Only antibodies specific for TGF-beta 2 were able to reverse the growth inhibitory effect of DMF on these cells. Therefore, TGF-beta 2 acted as a negative autocrine inhibitory factor for MOSER cells and the growth inhibitory effects of DMF were mediated by the increased secretion of active TGF-beta 2. <40> UI - 93101481 AU - Powell BR AU - Blank E AU - Benda G AU - Buist NR IN - Dept of Pediatrics, Oregon Health Sciences University, Portland. TI - Neonatal hyperparathyroidism and skeletal demineralization in an infant with familial hypocalciuric hypercalcemia. [Review] [9 refs] SO - Pediatrics 1993 Jan;91(1):144-5 <41> UI - 93370458 AU - Nance MA AU - Berry SA IN - Department of Pediatrics, University of Minnesota, Minneapolis. TI - Cockayne syndrome: review of 140 cases. [Review] [143 refs] SO - American Journal of Medical Genetics 1992 Jan 1;42(1):68-84 AB - To define diagnostic criteria for Cockayne Syndrome (CS) and to identify in detail the complications of the condition, a comprehensive review of 140 cases of CS was performed. Criteria required for the diagnosis include poor growth and neurologic abnormality; other very common manifestations include sensorineural hearing loss, cataracts, pigmentary retinopathy, cutaneous photosensitivity, and dental caries. The mean age of death in reported cases is 12 3/12 years, though a few affected individuals have lived into their late teens and twenties. Prenatal growth failure, congenital structural eye anomalies, severe neurologic dysfunction from birth, and the presence of cataracts within the first 3 years of life are predictors of severe disease and early death. In contrast with other disorders of chromosome or DNA repair, cancer has never been reported in a classical CS patient, and there appears to be no predisposition to infectious complications. The wide spectrum of symptoms and severity of the disease suggest that biochemical and genetic heterogeneity exist. CS is an uncommon but devastating genetic condition which will be better understood as the biochemical interrelationships between DNA replication and repair, and between growth, homeostasis, and oncogenesis are unraveled. [References: 143] <42> UI - 93268584 AU - Hallett KB AU - Radford DJ AU - Seow WK IN - Cardiology Department, The Prince Charles' Hospital, Brisbane, Australia. TI - Oral health of children with congenital cardiac diseases: a controlled study. SO - Pediatric Dentistry 1992 Jul-Aug;14(4):224-30 AB - Congenital cardiac disease (CCD) is one of the most common developmental anomalies in children. Affected children require special care in dentistry because of their susceptibility to infective endocarditis from oral infections, yet little information is available on the oral health of children with CCD. The present study, which investigated 39 children with CCD and 33 healthy control siblings, showed that CCD children generally suffered poorer oral health. In patients with primary dentitions, 52% of CCD children had enamel hypoplasia, compared with only 23% in the control group. In addition, CCD children had significantly more teeth with untreated dental decay (mean dmft 4.2 vs. 2.3), and more endodontically treated teeth. Children with CCD also had less than optimal professional and home dental care. Only 31% had professional advice regarding increased preventive dental health behavior, and only 15% used fluoride supplements, although the children resided in a nonfluoridated area. Furthermore, significantly fewer CCD children had parental help with tooth brushing compared to control children. This study shows that children with CCD should be targeted for vigorous preventive dental care. <43> UI - 93198772 AU - Bleiweis AS AU - Oyston PC AU - Brady LJ IN - University of Florida, Gainesville 32610. TI - Molecular, immunological and functional characterization of the major surface adhesin of Streptococcus mutans. [Review] [7 refs] SO - Advances in Experimental Medicine & Biology 1992;327:229-41 AB - In the 15 years since the last major NIH conference that dealt with anti-caries vaccines, we have learned much. Certainly, whole bacteria or bacterial fractions may not be proper immunogens due to the possibility of inducing tissue cross-reactivity. Our own experience (van de Rijn et al., 1976) illustrates that pitfall. But even in the era of genetically engineered vaccines, we first must understand the biological functions of our chosen immunogen before employing that pure protein in a vaccine. Our recent work (Brady et al., 1991c) indicates that antigen P1, a ubiquitous protein found on several oral streptococci, may possess different, but possibly overlapping, functional domains influencing reactions with fluid-phase salivary agglutinin (aggregation) versus fixed agglutinin (adherence). A proper vaccine would induce antibodies against the latter domain(s) thereby retarding colonization. An improper vaccine that induces antibodies against aggregation-related domains on P1 would lessen the host's ability to clear those bacteria from the oral cavity. After carefully identifying appropriate functional domains and obtaining sub-clones of the larger gene that yield truncated polypeptides typical of adherence-specific regions that are also immunogenic, we may be in a position to create the most effective vaccine. In studies employing the polymerase chain reaction (PCR) and standard cloning procedures, we have already begun to produce such polypeptides. Once a library of polypeptides is assembled, they may be tested for functional activity and for lack of induction of cross-reactivity with nonpathogenic streptococci (i.e., S. gordonii). Certain of these recombinant-specified polypeptides could serve as the basis for an anti-caries vaccine. Alternatively, peptides may be synthesized that resemble these sub-molecular regions for use in a vaccine or as competitive inhibitors of adherence but not aggregation. Clearly, a vaccine against dental caries remains a real possibility for the future. [References: 7] <44> UI - 93198764 AU - Lehner T AU - Ma JK AU - Kelly CG IN - Department of Immunology, United Medical School, Guy's Hospital, London, United Kingdom. TI - A mechanism of passive immunization with monoclonal antibodies to a 185,000 M(r) streptococcal antigen. SO - Advances in Experimental Medicine & Biology 1992;327:151-63 AB - The cell surface streptococcal antigen (SA) I/II of 185,000 M(r) is an immunodominant molecule that expresses one or more adhesion determinants. A series of 14 monoclonal antibodies (MAb) to defined parts of SA I/II were generated and some of these were used in passive immunization of macaques. Topical administration of selected MAb to the teeth of macaques prevented colonization of endogenous or implanted exogenous Streptococcus mutans for a period of 1 year. Significant reduction of both smooth surface and fissure caries was found in macaques who had MAb (Guy's 1) applied to their teeth, as compared with saline-treated animals. A series of in vivo passive immunization experiments was then carried out in 57 human subjects. Topical application of MAb to SA I/II prevented colonization of both artificially implanted exogenous strains of S. mutans, as well as natural recolonization by indigenous S. mutans. The properties of the protective MAb were then investigated and the epitope specificity within the SA I/II molecule was found to be essential but not the isotype specificity of the immunoglobulin (Ig). The requirement for complement activating and the phagocyte binding sites of the Fc fragment of MAb was not essential, as the F(ab')2 fragment of the MAb was as protective as the intact IgG, but the Fab fragment failed to prevent recolonization of S. mutans. Prevention of recolonization was specifically restricted to S. mutans, as the proportion of other organisms, such as S. sanguis, failed to show a significant change. The surprising feature of these experiments was that protection of re-colonization of S. mutans lasted up to 2 years, although MAb was applied for only 3 weeks and functional MAb was detected on the teeth only 3 days following application of the MAb. The long-term protection could therefore not be accounted for by a persistence of MAb on the teeth, but may be due to a shift in the microbial balance in which other bacteria occupy the ecological niche vacated by S. mutans, resulting in colonization resistance to S. mutans. Gene cloning and sequencing the SA from S. mutans, S. sobrinus and S. sanguis identified a conserved region (residues 955-1213) which on Southern hybridization and partial DNA sequence analysis was also found in 19 alpha-haemolytic oral streptococci. The results suggest that the SA molecule may constitute a family of adhesins in oral alpha haemolytic streptococci.(ABSTRACT TRUNCATED AT 400 WORDS) <45> UI - 93181413 AU - Quevedo WC Jr AU - Holstein TJ IN - Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912. TI - Molecular genetics and the ontogeny of pigment patterns in mammals. [Review] [41 refs] SO - Pigment Cell Research 1992 Nov;5(5 Pt 2):328-34 AB - The conclusion that animal development is guided by a hierarchical system of gene expression and interaction has gained considerable support from recent molecular genetic studies on fruit flies (Drosophila melanogaster) and mice (Mus musculus). They demonstrate that the patterns of organization revealed by terminal differentiation of cells is anticipated by a myriad of transient prepatterns that channel the developing embryo toward its genetically-programmed target. The numerous white spotting mutants in mice exhibit some of the most dramatic and variable patterns of cutaneous melanin pigmentation. Until recently, the mechanisms of action of white spotting genes and their relationship to the developmental genetic hierarchy remained unknown. It now appears that certain white spotting genes may encode growth factors essential for melanoblast development. Others may be related to homeobox genes that play a number of developmental roles, the primary one being the determination of regional organization along the anterior-posterior axis of the early embryo. The patterns of homeobox gene expression are consistent with several of the developmental models for white spotting in mice and other mammals. It is evident that white spotting genes are not solely concerned with the terminal differentiation of melanoblasts into melanocytes. They are heterogeneous with regard to action and level of expression within the developmental hierarchy. [References: 41] <46> UI - 93170678 AU - Mirto S AU - Santoro A AU - Barbata G AU - Crescimanno A AU - Buscemi F AU - Carbone P AU - Caronia F IN - Dipartimento di Ematologia, Ospedale V. Cervello, USL 60, Palermo, Italy. TI - ANLL patients with normal karyotype are not a homogeneous prognostic group. SO - Haematologica 1992 Nov-Dec;77(6):484-6 AB - BACKGROUND AND METHODS. Karyotype in ANLL is referred as an independent prognostic factor. The prognosis of diploid ANLL subjects has been defined as "good" by some authors, or, more recently, "intermediate" by others. This is a retrospective study on 30 consecutive heavy treated ANLL diploid patients with the aim to make a correlation among age, normal karyotype and response. Chromosomal banding studies were performed at presentation with GTG technique. Diploid patients were divided into two age groups < 60 years (17 cases) and > or = 60 (13 cases). Data were analyzed by NCSS software. RESULTS AND CONCLUSIONS. CR rate for the two diploid age groups was 94% and 38% respectively (p = 0.002). Median DFS and overall survival were 14.4 and 23.3 months, 4 and 5 months for the two subgroups respectively: these data were not statistically significative. The probability of achieving CR was not affected by blood counts and Karnofsky performance status on admission, but only by age. Though ANLL patients with the same karyotype have the same course regardless of other prognostic factors, this does not occur in our series of diploid patients. We suggest that a normal karyotype, at least as defined with the GTG technique, does not characterize a homogeneous group of patient. Heterogeneity in this group might be due to submicroscopic or molecular genetic changes; it can enhance the age as prognostic factor. <47> UI - 93161944 AU - Maeda H AU - Yamagata A AU - Nishikawa S AU - Yoshinaga K AU - Kobayashi S AU - Nishi K AU - Nishikawa S IN - Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan. TI - Requirement of c-kit for development of intestinal pacemaker system. SO - Development 1992 Oct;116(2):369-75 AB - A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c-kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility. <48> UI - 93162848 AU - Nunn JH AU - Welbury RR AU - Gordon PH AU - Stretton-Downes S AU - Green-Abate C IN - Dental School, University of Newcastle upon Tyne. TI - Dental health of children in an integrated urban development programme for destitute mothers with twins in Addis Ababa. SO - International Dental Journal 1992 Dec;42(6):445-50 AB - The Ethiopian Gemini Trust in Addis Ababa is a charitable organisation which cares for mothers who have delivered twins or triplets. A dental preventive programme for the disadvantaged children in the Trust was begun and this paper describes the first objective of the programme, the determination of the levels of dental disease. Caries, periodontal disease, malocclusion and enamel opacities were recorded. <49> UI - 93131345 AU - Ainamo A AU - Osterberg T TI - Changing demographic and oral disease patterns and treatment needs in the Scandinavian populations of old people. [Review] [70 refs] SO - International Dental Journal 1992 Oct;42(5):311-22 <50> UI - 93115886 AU - Chen CK AU - Wilson ME IN - Department of Oral Biology, State University of New York, Buffalo. TI - Eikenella corrodens in human oral and non-oral infections: a review. [Review] [110 refs] SO - Journal of Periodontology 1992 Dec;63(12):941-53 AB - There is substantial evidence in support of the existence of distinct clinical forms of human periodontal disease. Moreover, these different forms of periodontal disease may be associated with relatively distinct subgingival microflora, often involving microaerophilic or anaerobic Gram-negative bacterial species. Eikenella corrodens is a facultative Gram-negative bacillus which is a common inhabitant of the oral cavity and the intestinal and genital tracts. Its primary ecologic niche within the oral cavity appears to be dental plaque, both in periodontally healthy individuals and in periodontitis patients. However, E. corrodens is recognized as an infrequent human pathogen capable of causing extraoral infections, either as the sole infectious agent or as part of a mixed infection, its potential role in the etiology of periodontal disease is not well understood. E. corrodens is often present in the supra- and subgingival plaque of periodontally healthy subjects. On the basis of cross-sectional and longitudinal studies, E. corrodens appears to be somewhat more prevalent in subgingival plaque samples of periodontitis subjects than periodontally healthy individuals. However, the percentage of E. corrodens in the total cultivable microflora did not vary between the two groups. Microbiologic studies attempting to define the relationship between E. corrodens and periodontal disease assume that this species is essentially homogeneous and that all strains exhibit comparable pathogenic potential. However, E. corrodens exhibits 1) variable colony morphology, biochemical and serologic reactivity; 2) marked phenotypic diversity with respect to outer membrane protein and lipopolysaccharide structure; and 3) marked diversity in the restriction patterns of total genomic DNA. Thus, it is possible that a limited number of clones of E. corrodens may be associated with periodontal disease and/or extraoral infection, while other strains are relatively harmless commensals. Additional studies, possibly employing strain-specific nucleic acid probes, may be required to define the role of E. corrodens as a human periodontal pathogen. [References: 110] <51> UI - 93122979 AU - Kuroda H AU - Chen YN AU - Kimura T AU - Sakakibara S IN - Peptide Institute Inc., Protein Research Foundation, Osaka, Japan. TI - Powerful solvent systems useful for synthesis of sparingly-soluble peptides in solution. SO - International Journal of Peptide & Protein Research 1992 Sep-Oct;40(3-4):294-9 AB - Our maximum protection strategy for the synthesis of human parathyroid hormone(1-84) indicates that fully protected peptide segments in the form of Boc-peptide phenacyl (Pac) ester are relatively soluble in ordinary organic solvents such as DMF, NMP or DMSO, which are suitable for coupling segments. However, about 1% of such segments synthesized were found to be insoluble even in the most polar solvent, DMSO. Thus, a more powerful solvent which can be used for their peptide synthesis was pursued. Among the solvent systems tested, a mixture of trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) and trichloromethane (TCM) or dichloromethane (DCM) was found to be most powerful for dissolving such sparingly-soluble protected peptides. These solvent systems were confirmed to be useful for the removal reaction of the carboxy-terminal Pac esters from the sparingly-soluble segments. They were then tested for the coupling reactions of fully protected Boc-peptides with other sparingly-soluble peptide esters. The TFE/TCM or TFE/DCM system was extremely useful for coupling segments without danger of racemization and of trifluoroester formation, if WSCI was used as the coupling reagent in the presence of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HOOBt). <52> UI - 93115891 AU - Mellonig JT AU - Prewett AB AU - Moyer MP TI - HIV inactivation in a bone allograft. SO - Journal of Periodontology 1992 Dec;63(12):979-83 AB - The use of exclusionary techniques in the procurement of donors for bone allografts greatly reduces chances for disease transmission. Furthermore, treatment of HIV with either chemical agents or strong acids will effectively inactivate the AIDS virus. These data are taken as indirect proof that the risk of obtaining AIDS from a freeze-dried bone allograft is highly remote. The purpose of this study is to obtain direct evidence that the processing of a demineralized freeze-dried bone allograft would render the allograft safe for human use. In Part I, human cortical bone was obtained from a cadaveric source and tested to be free of HIV contamination. The bone was spiked with 5.26 x 10(9) viral particles. This corresponded to 148 micrograms of total viral protein. In Part II, cortical bone was procured from a donor who died of AIDS. In both Parts I and II, the cortical bone was ground to yield particle sizes of 90 to 500 microns. Test samples were treated with a virucidal agent and demineralized in HCl. Control samples were left untreated. All samples were cocultivated with stimulated peripheral blood lymphocytes and assayed for p24 core protein, reverse transcriptase, and viral gag gene by polymerase chain reaction (PCR). In Part I, the HIV spiking experiment, untreated virus infected particulate bone was positive for HIV replication. Treated samples were negative when assayed for HIV. Bone samples in Part II, HIV infected bone, were positive by PCR. Replication of viable HIV could not be demonstrated after treatment. It was concluded that demineralization and treatment with a virucidal agent inactivates HIV in spiked and infected bone. <53> UI - 93122807 AU - Johansson M AU - Ellegren H AU - Marklund L AU - Gustavsson U AU - Ringmar-Cederberg E AU - Andersson K AU - Edfors-Lilja I AU - Andersson L IN - Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala. TI - The gene for dominant white color in the pig is closely linked to ALB and PDGRFRA on chromosome 8. SO - Genomics 1992 Dec;14(4):965-9 AB - White is a widespread coat color among domestic pig breeds and is controlled by an autosomal dominant gene I. The segregation of this gene was analyzed in a reference pedigree for gene mapping developed by crossing the European wild pig and a Large White domestic breed. The gene for dominant white color was shown to be closely linked to the genes for albumin (ALB) and platelet-derived growth factor receptor alpha (PDGFRA) on chromosome 8. An unexpected phenotype with patches of colored and white coat was observed among the F1 and F2 animals. The segregation data indicated that the phenotype was controlled by a third allele, denoted patch (Ip), most likely transmitted by one of the Large White founder animals. It is shown that the ALB, PDGFRA, I linkage group shares homologies with parts of mouse chromosome 5, human chromosome 4, and horse linkage group II, all of which contain dominant genes for white or white spotting. Candidate genes for the dominant white and patch mutations in the pig are proposed on the basis on these linkage homologies and the recent molecular definition of the dominant white spotting (W) and patch (Ph) mutations in the mouse. <54> UI - 93141212 AU - Johansson I AU - Ryberg M AU - Steen L AU - Wigren L IN - Department of Cariology, University of Umea, Sweden. TI - Salivary hypofunction in patients with familial amyloidotic polyneuropathy. SO - Oral Surgery, Oral Medicine, Oral Pathology 1992 Dec;74(6):742-8 AB - Patients who suffer from familial amyloidotic polyneuropathy frequently complain of mouth dryness and an increased need for dental treatment. The aim of the present investigation was to study saliva secretion rate and composition and other factors related to the risk of dental caries in patients with familial amyloidotic polyneuropathy. Thirty patients with familial amyloidotic polyneuropathy volunteered for the study and were compared with a matched control group. Samples of unstimulated and stimulated whole saliva were collected in a standardized manner. The secretion rates were calculated, and the concentrations of electrolytes, glycoprotein markers, and proteins with antibacterial properties were analyzed. Dental caries and variables related to the risk of dental caries were also scored. The results show that familial amyloidotic polyneuropathy patients frequently have a decreased rate of saliva secretion and that the degree of salivary hypofunction is positively correlated to the progress of familial amyloidotic polyneuropathy. Forty-three percent of the familial amyloidotic polyneuropathy patients in this study had no detectable secretion of unstimulated saliva. A low secretion rate of stimulated saliva (< 0.7 ml/min) was found in 33% of the patients. The concentrations of salivary protein, amylase, lysozyme, salivary peroxidase, secretory IgA, hexosamines, sialic acid, fucose, phosphate, potassium, and the degree of protein glycosylation were higher in the familial amyloidotic polyneuropathy patients than in the control patients. We conclude that patients with familial amyloidotic polyneuropathy have a reduced saliva secretion and are subsequently at risk for increased development of dental caries. <55> UI - 93114502 AU - Takeda H AU - Yoshiki A AU - Nishikawa S AU - Nishikawa S AU - Kunisada T AU - Sakakura T AU - Amanuma H AU - Kusakabe M IN - Laboratory of Gene Technology and Safety, Institute of Physical and Chemical Research, Ibaraki, Japan. TI - Expression of c-kit, a proto-oncogene of the murine W locus, in cerebella of normal and neurological mutant mice: immunohistochemical and in situ hybridization analysis. SO - Differentiation 1992 Oct;51(2):121-7 AB - The c-kit proto-oncogene encodes a receptor tyrosine kinase and is allelic with the murine white-spoting (W) locus. Although no apparent defects in the brain have been reported in W mutant mice, brain tissue, especially cerebellum, shows a high level of c-kit transcription. In the present study, sites of c-kit expression in the cerebellum were exained by immunohistochemical and in situ hybridization techniques. Immunohistochemistry with a monoclonal antibody against c-Kit protein revealed that the c-Kit protein was localized close to the Purkinje cell soma in the region facing the granular cell layer. Similar distribution of the c-Kit protein was observed in cerebella of mutant mice in which the Purkinje cell (pcd) or the granular cell layer (weaver) is missing. These data suggest that the c-Kit protein is produced not by the Purkinje cell nor by the granular cell but by the cells present in the molecular layer and that the protein is then transported to the region around the Purkinje cell soma. This interpretation was supported by in situ hybridization analysis: cells containing the c-kit transcripts were found only in the molecular layer, while the granular and Purkinje cells were negative. <56> UI - 93101693 AU - Finkelman RD AU - Bell NH AU - Strong DD AU - Demers LM AU - Baylink DJ IN - Department of Periodontics, Loma Linda University, CA. TI - Ovariectomy selectively reduces the concentration of transforming growth factor beta in rat bone: implications for estrogen deficiency-associated bone loss. SO - Proceedings of the National Academy of Sciences of the United States of America 1992 Dec 15;89(24):12190-3 AB - Previous work showed that production of transforming growth factor beta (TGF-beta) by osteoblast-like rat UMR 106 cells was increased by 17 beta-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-beta in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-beta in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-beta was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-beta deficit. To determine whether 17 beta-estradiol increased TGF-beta production by normal bone cells, mouse osteoblasts were treated for 2 days with 17 beta-estradiol. The production of TGF-beta was increased almost 2-fold by 1 nM 17 beta-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-beta 1 mRNA. We conclude that ovariectomy reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-beta may be necessary for normal maintenance of the skeleton in female rats. <57> UI - 93091143 AU - Ueyama N AU - Ueno S AU - Nakamura A AU - Wada K AU - Matsubara H AU - Kumagai S AU - Sakakibara S AU - Tsukihara T IN - Department of Macromolecular Science, Faculty of Science, Osaka University, Japan. TI - A synthetic analogue for the active site of plant-type ferredoxin: two different coordination isomers by a four-cys-containing [20]-peptide. SO - Biopolymers 1992 Nov;32(11):1535-44 AB - The (Fe2S2)2+ complex of an artificial 20-peptide ligand, Ac-Pro-Tyr-Ser-Cys-Arg-Ala-Gly-Ala-Cys-Ser-Thr-Cys-Ala-Gly-Pro-Leu-Leu-T hr-Cys- Val-NH2, containing an invariant Cys-A-B-C-D-Cys-X-Y-Cys (A, B, C, D, X, Y = amino acid residues) fragment of plant-type ferredoxins was synthesized by a ligand exchange method with [Fe2S2(S-t-Bu)4]2-. 1H-nmr spectroscopic and electrochemical data of the complex indicate the presence of two coordination isomers. One of them having a Cys-X-Y-Cys bridging coordination to the two Fe(III) ions, has the (Fe2S2)2+ core environment similar to those of the denatured plant-type ferredoxins and exhibits a positive shifted redox potential at -0.64 V vs saturated colonel electrode (SCE) in N,N-dimethylformamide (DMF). Another isomer with the Cys-A-B-C-D-Cys bridging coordination shows a negative redox potential at -0.96 V vs SCE in DMF. <58> UI - 93100555 AU - Manova K AU - Bachvarova RF AU - Huang EJ AU - Sanchez S AU - Pronovost SM AU - Velazquez E AU - McGuire B AU - Besmer P IN - Molecular Biology Department, Sloan Kettering Institute, New York, New York 10021. TI - c-kit receptor and ligand expression in postnatal development of the mouse cerebellum suggests a function for c-kit in inhibitory interneurons. SO - Journal of Neuroscience 1992 Dec;12(12):4663-76 AB - The c-kit receptor and its cognate ligand, KL, are encoded at the white spotting locus (W) and the steel locus (Sl) of the mouse, respectively. Sl and W mutations affect the same cellular targets in melanogenesis, gametogenesis and hematopoiesis during embryonic development and in adult life. c-kit is expressed in cellular targets of W and Sl mutations, whereas KL is expressed in the microenvironment of these targets. c-kit and KL, however, are also expressed in tissues and cell types that are not targets of W and Sl mutations, including the brain. The cerebellum contains a small number of neural cell types whose developmental origins, pathways of migration, and synaptic contacts are known. We have investigated the patterns of expression of the c-kit and KL RNA and protein products in postnatal cerebellar development of the mouse. In the adult cerebellum, c-kit RNA and protein expression was evident in basket, stellate, and Golgi neurons. Most strikingly, the c-kit protein is expressed in the basket cell axons that form "basket" and "pinceau" structures entwining the Purkinje cell soma and the initial segment of the Purkinje cell axon. KL RNA expression was found in Purkinje cells, and the KL protein was detected in Purkinje cell bodies and dendrites. Soluble KL protein was also present in c-kit-expressing basket, stellate, and Golgi cells, presumably as a result of internalization of ligand-receptor complexes. During postnatal development, c-kit and KL RNA and protein expression in Golgi and Purkinje neurons, respectively, was evident by day 0 and persisted subsequently. c-kit expression in basket and stellate cells was detected from their time of birth, starting at day 4. These results suggest a role for the c-kit receptor system in postnatal development of the cerebellum. <59> UI - 93041010 AU - Schroeter CA AU - De Potter CR AU - Rathsmann K AU - Willighagen RG AU - Greep JC IN - Department of Surgery, University Hospital, Maastricht, The Netherlands. TI - c-erbB-2 positive breast tumours behave more aggressively in the first years after diagnosis. SO - British Journal of Cancer 1992 Oct;66(4):728-34 AB - In a retrospective study the expression of the c-erbB-2 oncogene was determined immunohistochemically in 276 breast cancer samples from 253 patients with the antibody 21N. The follow-up period was between 7 and 12 years. This study showed a trend for an inverse relationship between c-erbB-2 positive tumours and estrogen receptors (ER). A correlation was assessed between c-erbB-2 positive tumours and histological grade, liver metastases as first site of metastases, disease free survival time (DFS) in the second and third year after diagnosis and overall survival time (OST) in the third and fourth year after diagnosis. A trend was seen between c-erbB-2 positive tumours and tumour size. No correlation was found between c-erbB-2 positive tumours and age at diagnosis. The method of operation and lymph node involvement. From this study we conclude that there is a significant difference in prognosis the first years after diagnosis, but this difference seems to vanish in a longer follow-up period of 12 years. This provides us with an explanation for the discrepancies in literature concerning c-erbB-2 expression and prognosis in breast cancer. Some investigators did not show differences in prognosis between positive and negative cases after a long follow-up period whereas investigations with a short term follow-up period up to 2-3 years have indeed established a more aggressive behaviour of c-erbB-2 overexpressionary tumours. <60> UI - 93053213 AU - Miyazawa T AU - Otomatsu T AU - Fukui Y AU - Yamada T AU - Kuwata S IN - Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan. TI - Simultaneous use of 1-hydroxybenzotriazole and copper(II) chloride as additives for racemization-free and efficient peptide synthesis by the carbodiimide method. SO - International Journal of Peptide & Protein Research 1992 Apr;39(4):308-14 AB - In the carbodiimide mediated coupling of Z-Gly-L-Val-OH with H-L-Val-OMe in DMF, the simultaneous use of HOBt and copper(II) chloride as additives was found to give the desired peptide in a high yield without racemization. In the presence of HOBt, reducing the amount of copper(II) chloride produced a higher yield. Besides improving the coupling efficiency as compared with the case using copper(II) chloride alone as an additive, the present procedure offered another advantage for racemization suppression. Thus, even for the couplings where a low level of racemization was observed in the presence of copper(II) chloride, the simultaneous addition of HOBt and copper(II) chloride resulted in the elimination of racemization. The effectiveness of this new procedure using the two carbodiimide additives in the synthesis of biologically active peptides was assessed by the preparation of a protected Leu-enkephalin. In the 4 + 1 segment condensation using HOBt and copper(II) chloride simultaneously as additives, no racemization was detected and the yield was high enough. The elimination of racemization and improvement of coupling efficiency produced by the present procedure can be attributable to a reduced tendency for the activated forms of the carboxyl component to form a 5(4H)-oxazolone by the action of HOBt, and to the prevention of racemization by copper(II) chloride of the small amount of the oxazolone formed which is not eliminated by the action of HOBt alone. <61> UI - 93058686 AU - Zhang CZ AU - Young WG AU - Li H AU - Rolinson S AU - Waters MJ IN - Faculty of Dentistry, University of Queensland, Australia. TI - Growth hormone regulates nucleolar organizer regions during odontogenesis in the rat. SO - Journal of Oral Pathology & Medicine 1992 Oct;21(9):395-400 AB - Nucleolar organizers are major sites of ribosomal RNA synthesis and provide an index of transcriptional activity. In order to further define growth hormone actions on nucleolar organizer regions in tooth forming cells, hypophysectomized rats treated with growth hormone for 4 and 24 h, hypophysectomized and sham-operated animals were used. After demineralization and standard paraffin embedding, longitudinal sections of maxillary incisors were stained by a silver stain technique to reveal nucleolar organizer regions. The area of these regions per nucleus was measured using a modified microdensitometer. Analyses of variance of the resulting data showed that preameloblasts and preodontoblasts have greater silver stained nucleolar organizer region values than ameloblasts and odontoblasts. Hypophysectomy reduced and growth hormone partly restored the level of nucleolar organizer regions in preameloblasts and preodontoblasts, but not in mature ameloblasts or odontoblasts. In the case of the younger preameloblasts and preodontoblasts, the effect of growth hormone was seen within 4 h of growth hormone injection. In conclusion, rRNA synthesis, as revealed by the specific silver staining of nucleolar organizer regions in tooth forming cells, appears to be regulated by growth hormone over a relatively short time frame. <62> UI - 93012940 AU - Brannan CI AU - Bedell MA AU - Resnick JL AU - Eppig JJ AU - Handel MA AU - Williams DE AU - Lyman SD AU - Donovan PJ AU - Jenkins NA AU - Copeland NG IN - Mammalian Genetics Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702. TI - Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail. SO - Genes & Development 1992 Oct;6(10):1832-42 AB - The murine dominant White spotting (W) and Steel (Sl) loci encode the c-kit tyrosine kinase receptor and its cognate ligand steel factor (SLF), respectively. Mutations at either locus produce deficiencies in the same three migratory cell populations--those giving rise to pigment cells, germ cells, and blood cells. The identification of the gene products of these two loci combined with the plethora of W and Sl mutations available for molecular analysis offers a unique opportunity to dissect the role of a tyrosine kinase receptor and its cognate ligand during development in a fashion not possible for most other mammalian genes. Among the most interesting Sl mutations available for study are those that induce sterility in only one sex. In studies described here, we show that one of these alleles, Sl17H, which in the homozygous condition induces sterility in males but not females, is the result of a splicing defect in the SLF cytoplasmic tail. We also characterize the nature of the germ cell defects in male and female Sl17H mice and show that both sexes are affected equally during embryonic but not postnatal development. These studies provide new insights into the role of SLF in germ cell development and indicate that the cytoplasmic domain of SLF is important for its normal biological function. <63> UI - 93003922 AU - Horie K AU - Fujita J AU - Takakura K AU - Kanzaki H AU - Kaneko Y AU - Iwai M AU - Nakayama H AU - Mori T IN - Department of Gynecology, Faculty of Medicine, Kyoto University, Japan. TI - Expression of c-kit protein during placental development. SO - Biology of Reproduction 1992 Oct;47(4):614-20 AB - The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and is shown to be allelic with the white-spotting locus (W) of the mouse. In order to elucidate the role of c-kit protein during placental development, we have examined the expression of c-kit protein in the uterus and placenta of mice at pre- and post-implantation stages by the avidin-biotin-peroxidase (ABC) method using rat anti-mouse c-kit monoclonal antibody. At Days 3 and 5 of pregnancy and pseudo-pregnancy, c-kit protein was detected in the glandular epithelium, but little expression was observed in the luminal epithelium. At Day 7 of pregnancy, expression was detected in the stromal cells around the uterine crypts of the mesometrial portion, but not in the vigorously proliferating decidual cells around the developing embryo. At Days 9 and 10 of pregnancy, the decidua basalis facing invading trophoblasts gradually expressed c-kit protein. In the mature placenta, c-kit protein was detected in the labyrinthine and decidual layers, but in neither the giant trophoblastic nor the spongiotrophoblastic layer. By Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), c-kit mRNA was detected at the stages of periimplantation and placental development. These results suggested that the c-kit protein might be involved in the proliferation and differentiation of placenta. <64> UI - 93014235 AU - Seiji K AU - Inoue O AU - Cai SX AU - Kawai T AU - Watanabe T AU - Ikeda M IN - Tohoku Rosai Hospital, Sendai, Japan. TI - Increase in sister chromatid exchange rates in association with occupational exposure to N,N-dimethylformamide. SO - International Archives of Occupational & Environmental Health 1992;64(1):65-7 AB - The effects of occupational exposure to N,N-dimethylformamide (DMF) on sister chromatid exchange (SCE) rates were studied in peripheral lymphocytes from 22 DMF-exposed women (aged 22-52 years) in comparison with 22 sex-, age-, and residence-matched controls. All subjects were nonsmokers and nondrinkers as confirmed by medical interview. The 22 pairs were divided by the intensity of exposure to DMF into 3 subgroups of high-exposed (8 pairs with mean DMF exposure at 5.8 ppm), middle-exposed (5 pairs with DMF at 0.7 ppm in combination with toluene at 0.9 ppm), and low-exposed (9 pairs with DMF at 0.3 ppm). The SCE rates were significantly higher in the high (P less than 0.005) and middle (P less than 0.01) exposed than in their matched pairs, and the increase was related to the intensity of DMF exposure. <65> UI - 93014526 AU - Miyazawa T AU - Otomatsu T AU - Fukui Y AU - Yamada T AU - Kuwata S IN - Department of Chemistry, Faculty of Science, Konan University, Kobe, Japan. TI - Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the carbodiimide method. SO - International Journal of Peptide & Protein Research 1992 Mar;39(3):237-44 AB - Copper(II) chloride was found to be an extremely efficient racemization-suppressing additive in the DCC method as compared with the hitherto known ones, by employing the model coupling Z-Gly-L-Val-OH + H-L-Val-OMe in DMF. Although some other copper salts also had a profound effect, copper(II) chloride was the best from the viewpoint of both racemization suppression and coupling efficiency. The effectiveness of copper(II) chloride was further confirmed by employing the EDC-mediated couplings of Z-Gly-containing dipeptides with amino acid esters or dipeptide esters, and those of Z-L-Ala (or L-Val)-L-Val-OH with amino acid esters or dipeptide esters. In almost all the cases studied, no detectable amount (less than 0.1%) of epimer was observed by the HPLC analysis in the presence of copper(II) chloride. This was also the case even with an extremely stringent coupling system Z-L-Pro-L-Val-OH + H-L-Pro-OMe. With reference to the mechanism of racemization suppression, it was found that copper(II) chloride has a strong ability to suppress the racemization of the 5(4H)-oxazolone, which may be formed from an activated carboxyl component during the coupling. <66> UI - 93026606 AU - Smorawinska M AU - Kuramitsu HK IN - University of Texas Health Science Center, San Antonio. TI - DNA probes for detection of cariogenic Streptococcus mutans. SO - Oral Microbiology & Immunology 1992 Jun;7(3):177-81 AB - Streptococcus mutans has been identified as the principal etiological agent in human dental caries. Therefore, the specificity and sensitivity of 3 potential gene probes derived from S. mutans GS5 have been examined as potential reagents for detecting the cariogenic bacteria. The gene probes derived from the cloned gtfB, gtfD and ftf genes were examined in Southern blots with a panel of representative oral bacteria. The gtfB and ftf genes were apparently specific for S. mutans under high-stringency hybridization conditions. However, the gtfD gene fragment did cross-hybridize with the DNA from other mutans streptococci. These results suggest that gtfB and ftf gene fragments may be used as specific probes for S. mutans. <67> UI - 93020430 AU - Komiyama K AU - Khandelwal RL IN - Department of Oral Biology, University of Saskatchewan, Saskatoon, Canada. TI - Acid production by Actinomyces viscosus of root surface caries and non-caries origin during glycogen synthesis and degradation at different pH levels. SO - Journal of Oral Pathology & Medicine 1992 Sep;21(8):343-7 AB - Actinomyces viscosus strains, freshly isolated from root surface caries lesions and intact root surfaces, were studied for their glycogen synthetic and degradative activities at pH 4.5, 5.0, and 7.0 in a pH-stat. At all three pH levels, root caries origin of A. viscosus synthesized up to three times as much glycogen compared to non-root caries origin. Since root caries origin of A. viscosus strains initially synthesized large amounts of glycogen, a longer period of time was required to deplete this polymer, resulting in an extended period of acid production, even at pH 4.5 and pH 5.0. This study suggests that the ability of A. viscosus of root caries origin to synthesize large quantities of glycogen and subsequently degrade this stored polymer slowly with acid production, at acidic pH levels, may play an important role in the root caries process. <68> UI - 93026210 AU - Mass E AU - Sarnat H AU - Ram D AU - Gadoth N IN - Department of Pediatric Dentistry, Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Israel. TI - Dental and oral findings in patients with familial dysautonomia. SO - Oral Surgery, Oral Medicine, Oral Pathology 1992 Sep;74(3):305-11 AB - Familial dysautonomia is an inherited autosomal recessive disease found almost exclusively in Ashkenazi Jews. It is characterized by selective damage to the sensory, motor, and autonomic peripheral nervous system. The main clinical features include decreased pain sensation, impaired temperature and blood pressure regulation, lack of tearing, absent tendon reflexes, and fungiform papillae on the tongue. The purpose of this study was to explore in depth and to verify the oral and dental status in familial dysautonomia. Twenty-two patients and 44 match-paired healthy persons of Ashkenazi descent were examined. Patients and parents had only little concern for their oral condition. Caries prevalence was lower than normal and plaque accumulation increased in all patients. Dental trauma was found in 59% of the patients, and 32% showed orodental self-mutilation. Dental age was within normal range, and dental arch measurements implied proportionally small jaws and little crowding. The low caries rate may be related to the known "hypersalivation" in familial dysautonomia and/or a possible change in the salivary composition and content, caused by chronic autonomic denervation. <69> UI - 93029619 AU - Tsushima Y AU -