Database: EMBASE <: international biomedical and pharmaceutical literature, 1988 - Aug 2000. [Trial access until 3/2001. Feedback welcome to medical.library@umich.edu] Search Strategy (You Saved Citations 1-233 From Set 76): ----------------------------------------------------------------------------- 1 Immunology/ 2913 2 exp immunity/ 453271 3 exp Immunopathology/ 241657 4 ((natural or disease) adj2 (immunity or resistan:)).mp. 3461 5 ("non-specific" adj (immunity or resistan:)).mp. 100 6 (bacteria$1 adj immun:).mp. 603 7 (bacteria$1 adj resistan:).mp. 986 8 (mucosa$1 adj immun:).mp. 2163 9 (immun: adj respons:).mp. 48912 10 (immun: adj recogni:).mp. 978 11 ((ADA or "adenosine deaminase") adj deficien$2).mp. 247 12 immunolog:.mp. 52323 13 immunity.mp. 34531 14 or/1-13 636668 15 exp Tooth demineralization/ 7753 16 demineralization.mp. 907 17 caries.mp. 1846 18 caires.mp. 0 19 craies.mp. 0 20 careis.mp. 1 21 carise.mp. 0 22 (teeth adj3 cavit:).mp. 32 23 (tooth adj3 cavit:).mp. 31 24 (dental adj3 cavit:).mp. 55 25 (dentin adj3 cavit:).mp. 14 26 (enamel adj3 cavit:).mp. 6 27 (teeth adj3 decay:).mp. 60 28 (tooth adj3 decay:).mp. 59 29 (dental adj3 decay:).mp. 48 30 (dentin adj3 decay:).mp. 0 31 (enamel adj3 decay:).mp. 1 32 (active adj decay).mp. 5 33 (rampant adj3 decay:).mp. 4 34 (recurrent adj3 decay:).mp. 3 35 (white adj spot:).mp. 229 36 carious.mp. 114 37 cariology.ti,ab. 2 38 (non-cavitated adj3 lesion:).mp. 0 39 (noncavitated adj3 lesion:).mp. 1 40 Tooth remineralization/ 819 41 (dental adj3 fissure:).mp. 7 42 (tooth adj3 fissure:).mp. 3 43 (teeth adj3 fissure:).mp. 1 44 caries-free.mp. 30 45 cariesfree.mp. 0 46 Cariogenic agents/ 3 47 precavit:.mp. 2 48 (filled adj3 teeth).mp. 47 49 (filled adj3 tooth).mp. 9 50 (oral adj fissure:).mp. 4 51 (tooth adj3 remineraliz:).mp. 1 52 (teeth adj3 remineraliz:).mp. 4 53 dft.mp. 583 54 dfs.mp. 1015 55 dmf:.mp. 1290 56 cariogeni:.mp. 169 57 or/15-56 12701 58 14 and 57 1704 59 exp Genetics/ 10525 60 (cn or ge).fs. 87348 61 gene$1.mp. 441975 62 genetic:.mp. 235931 63 genom:.mp. 69641 64 genotyp:.mp. 27632 65 chromosom:.mp. 104283 66 congenit:.mp. 48604 67 familial.mp. 25779 68 heritab:.mp. 3554 69 inherit:.mp. 27009 70 twin$1.mp. 9553 71 Diseases in twins/ 2748 72 exp Multiple birth offspring/ 3143 73 consanguin:.mp. 2251 74 or/59-73 680672 75 58 and 74 246 76 limit 75 to english language 233 77 from 76 keep 1-233 233 *************************** <1> UI - 2000284318 AU - Davies R AU - Bedi R AU - Scully C TI - Oral health care for patients with special needs. SO - British Medical Journal 19 AUG 2000Vol 321(7259) (pp 495-498), 2000. <2> UI - 2000280291 AU - Yoder S AU - Cao C AU - Ugen KE AU - Dao ML IN - Dr. K.E. Ugen, Dept. of Med. Microbiol./Immunol., Univ. of South Florida Coll. of Med., MDC10, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612; United States. E-Mail: kugen@hsc.usf.edu. TI - High-level expression of a truncated wall-associated protein A from the dental cariogenic Streptococcus mutans. SO - DNA & Cell Biology Vol 19(7) (pp 401-408), 2000. AB - Streptococcus mutans plays a primary role in the formation of dental caries. Previously, in our laboratory, an S. mutans genomic library was prepared, and the wapA gene was cloned into the shuttle vector, pSA4/4B2. To generate overexpression of wapA and to facilitate efficient purification of the WapA protein for use as an immunogen, an expression vector with the strong tac promoter was used. In order to answer questions regarding the optimization of solubility and expression based on gene size or the hydrophobicity of the protein product, 12 truncated constructs of the wapA gene were prepared using PCR. The truncated products were subcloned into the pGEX-6P-1 glutathione S-transferase (GST) fusion vector and expressed in E. coli BL21. The fusion proteins were analyzed by SDS-PAGE and confirmed by analysis with anti-GST and anti-WapA antibodies. Our study suggests that abrogation of the wapA promoter is necessary for expression of this gene in this expression system. Deletion of the signal peptide and the hydrophobic C terminus of WapA increased expression compared with the full-length construct, and truncation at the protease cleavage site of the C-terminal region greatly increased the stability of the protein without a loss in reactivity with the anti-WapA antibody. Western immunoblot analysis with anti-WapA antiserum clearly showed that the majority of the epitopes of the GST-WapA fusions are located in the N-terminal region of WapA. The immunogenicity of the various WapA fusion products is being examined in mice and rats to further map the immunologically dominant regions of the protein. This method effectively increased the expression of WapA and should contribute to the further understanding of gene expression of E. coli, as well as aid in the characterization of this protein for future immunologic evaluation. [References: 25] <3> UI - 2000272590 AU - Dutly F AU - Hinrikson HP AU - Seidel T AU - Morgenegg S AU - Altwegg M AU - Bauerfeind P IN - M. Altwegg, Dept. of Medical Microbiol., University of Zurich, Gloriastr. 30/32, CH-8028 Zurich; Switzerland. E-Mail: altwegg@immv.unizh.ch. TI - Tropheryma whippelii DNA in saliva of patients without Whipple's disease. SO - Infection Vol 28(4) (pp 219-222), 2000. AB - Tropheryma whippelii is the causative agent of Whipple's disease, a difficult to diagnose systemic illness. Amplification of part of its 165 ribosomal RNA gene(s) has become a standard diagnostic method because of increased sensitivity as compared to classical histopathological analysis. Recently we demonstrated the presence of T. whippelii DNA by PCR in duodenal biopsies and/or gastric juice of a considerable fraction of individuals without clinical signs of Whipple's disease. In this follow-up study, saliva and dental plaques of the same patients were screened for the presence of T. whippelii DNA. Six out of the 14 previously PCR-positive persons but none of the 17 controls had T. whippelii DNA in their saliva. Our results suggest that Whipple bacteria are ubiquitous environmental or commensal organisms causing Whipple's disease only in a particular subset of individuals, possibly those with an as yet uncharacterized immunological defect. [References: 17] <4> UI - 2000272322 AU - Stollerman GH TI - Vaccines from transgenic plants. SO - Hospital Practice 15 JUL 1998Vol 33(7) (pp 41-42), 1998. <5> UI - 2000262933 AU - Bartova J AU - Kratka-Opatrna Z AU - Prochazkova J AU - Krejsa O AU - Duskova J AU - Mrklas L AU - Tlaskalova H AU - Cukrowska B IN - J. Bartova, Institute of Dental Research, Vinohradska 48, 12060 Prague 2; Czech Republic. E-Mail: jirina.bartova@post.cz. TI - Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings. SO - Mediators of Inflammation Vol 9(2) (pp 115-120), 2000. AB - Early onset periodontitis (EOP) is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a.), a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC) were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL-4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL-4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL-4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour's hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes. [References: 31] <6> UI - 2000227702 AU - Ochs RL AU - Muro Y AU - Si Y AU - Ge H AU - Chan EKL AU - Tan EM IN - Dr. E.M. Tan, Autoimmune Disease Center, Scripps Research Institute, 10550 N Torrey Pines Rd, San Diego, CA 92037; United States. TI - Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. SO - Journal of Allergy & Clinical Immunology Vol 105(6 I) (pp 1211-1220), 2000. AB - Background: Sera of patients with atopic dermatitis (AD) were found to have autoantibodies that reacted with tissue culture cell substrates in immunohistochemistry to display a characteristic pattern of nuclear distribution of dense fine speckles. The sera also recognized a 70-kd protein on Western immunoblots, and the antigen was termed dense fine speckles 70 kd (DSF70). Objective: Because spontaneously occurring autoantibodies could be immune responses to proteins that might be participating in the disease process, it was of interest to identify the antigens driving the autoimmune antibody response. Methods: A serum containing high-titer antibodies to DFS70 was used to immunoscreen a complementary (c)DNA expression library to isolate cDNA encoding the antigen. After the cDNA was isolated, this was used to express recombinant protein to determine the prevalence of antibody in AD and other conditions. Results: Thirty percent of patients with AD were found to have antibody to recombinant DFS70 in Western immunoblots. Sixteen percent of patients with asthma and 9% of patients with interstitial cystitis had antibodies of the same specificities. The cDNA encoding DFS70 was identical to a transcription coactivator called p75, which had been shown to be required for RNA polymerase II-dependent transcription. Another important finding was that IgE antibodies to DFS70 were also present in AD sera. Conclusion: It is suggested that a common basis for the presence of autoantibodies to DFS70 might be related to AD in asthma, interstitial cystitis, and other conditions. A possible role of this antigen-antibody system in pathogenesis remains to be demonstrated, but it appears to be a marker for a subset of patients with AD. [References: 33] <7> UI - 2000220530 AU - Korzenik JR AU - Dieckgraefe BK IN - Dr. J.R. Korzenik, Division of Gastroenterology, Department of Internal Medicine, Washington Univ. School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110; United States. TI - Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease. SO - Digestive Diseases & Sciences Vol 45(6) (pp 1121-1129), 2000. AB - The current hypothesis for the etiology of Crohn's disease proposes an excessive immune response, largely T-cell driven, possibly against endogenous bacteria. Standard therapy is therefore directed towards suppression of this immune response. An alternative theory of pathogenesis accounts for epidemiologic and pathophysiologic observations that have been hitherto underemphasized, namely, (1) genetic disorders with deficiencies in neutrophil function can give rise to a clinical and pathologic syndrome indistinguishable from Crohn's; (2) abnormal neutrophil function is well described in Crohn's disease; (3) a group of bacteria implicated in other chronic inflammatory disorders causes impairment of neutrophil function; and (4) 20th century environmental risk factors for Crohn's disease may directly suppress neutrophil function and may have led to a shift in the dominant gut flora with similar effects. We propose that some cases of Crohn's disease result from the interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in failure to effectively clear intramucosal microbes effectively. While encompassing existing data, this hypothesis proposes a proximate defect in the mucosal immune response. If this paradigm were correct, new therapeutic approaches might involve strategies to alter intestinal flora and stimulate neutrophil function. [References: 97] <8> UI - 2000210914 AU - Thomas X AU - Dombret H AU - Cordonnier C AU - Pigneux A AU - Gardin C AU - Guerci A AU - Vekhoff A AU - Sadoun A AU - Stamatoullas A AU - Fegueux N AU - Maloisel F AU - Cahn JY AU - Reman O AU - Gratecos N AU - Berthou C AU - Huguet F AU - Kotoucek P AU - Travade P AU - Buzyn A AU - de Revel T AU - Vilque JP AU - Naccache P AU - Chomienne C AU - Degos L AU - Fenaux P IN - X. Thomas, Service d'Hematologie, Hopital Edouard Herriot, F-69437 Lyon Cedex 03; France. TI - Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. SO - Leukemia Vol 14(6) (pp 1006-1013), 2000. AB - The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 109/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% Cl 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging. [References: 42] <9> UI - 2000205613 AU - Anonymous IN - M. Bhargava, Department of Haematology, All India Institute Medical Sciences, AIIMS, New Delhi 110029. E-Mail: manorama@medinst.ernet.in. TI - Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India. SO - Leukemia Research Vol 24(7) (pp 575-582), 2000. AB - In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x109/l vs. 103.7x109/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x109/l vs. 63.4x109/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region. Copyright (C) 2000 Elsevier Science Ltd. [References: 28] <10> UI - 2000203414 AU - Kennedy HF AU - Smith AJ IN - H.F. Kennedy, Dept. of Microbiol., Royal Hosp. For Sick Children, Yorkhill NHS TRust, Glasgow G3 8SJ; United Kingdom. TI - Viridans streptococcal infection in the medically compromised. SO - Reviews in Medical Microbiology Vol 11(2) (pp 77-86), 2000. AB - Viridans streptococci form a heterogeneous group of bacteria traditionally associated with dental caries and recognised as the classical opportunistic cause of infective endocarditis. More recently these organisms have emerged as significant pathogens in immunocompromised patients with malignant disease. In addition to a marked increase in the number and severity of infections caused by viridans streptococci over the last two decades, resistance to antibiotics amongst these organisms has become widespread. Antimicrobial therapy must be prescribed prudently to prevent selective pressure towards overgrowth of resistant strains. Factors which may contribute to the development of infection by viridans streptococci include disease- or treatment-associated immunocompromise, mucosal damage and antibiotic selection pressure. Further studies on potential virulence determinants are required to enhance our knowledge of the mechanisms involved in progression from colonisation to infection. In the past accurate and universally recognised phenotypic identification schemes for viridans streptococci were elusive. With recent advances in molecular characterisation of viridans streptococci, controlled prospective studies may determine whether particular species are associated with specific patterns of infection or severity of disease. (C) 2000 Lippincott Williams and Wilkins. [References: 65] <11> UI - 2000175631 AU - Tabeta K AU - Yamazaki K AU - Hotokezaka H AU - Yoshie H AU - Hara K IN - Dr. K. Yamazaki, Department of Periodontology, Faculty of Dentistry, Niigata University, 5274, Gakkocho-Dori, 2-ban-cho, Niigata 951-8514; Japan. E-Mail: kaz@dent.niigata-u.ac.jp. TI - Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients. SO - Clinical & Experimental Immunology Vol 120(2) (pp 285-293), 2000. AB - The presence of antibodies to the 60-kD human and Porphyromonas gingivalis GroEL hsp60 in the sera and inflamed gingival tissues of periodontitiS patients was examined. In order to obtain the antigens, recombinant plasmids carrying human hsp60 and P. gingivalis GroEL genes were constructed and expressed as histidine-tagged recombinant proteins. Immunoreactivities of these proteins were confirmed by MoAbs specific to mammalian hsp60 and cross-reactive with both mammalian and bacterial hsp60. Western blot analysis clearly demonstrated that the number of periodontitis patients showing a positive response to P. gingivalis GroEL was higher than the number of periodontally healthy subjects. Furthermore, anti-P. gingivalis GroEL antibody was detected in all samples of gingival tissue extracts. For human hsp60, a higher frequency of seropositivity was found in the periodontitis patients than in the healthy subjects. In addition, the periodontitis patients demonstrated stronger reactivity compared with the healthy subjects. Quantitative analysis of serum antibodies by ELISA also demonstrated that the levels of antibodies in the sera of patients were significantly higher than those of control subjects. In the gingival tissue extracts, seven out of 10 patients demonstrated a positive response to human hsp60 and tso of these demonstrated strong positivity. Affinity-purified serum antibodies to human hsp60 and P. gingivalis GroEL from selected patients reacted with P. gingivalis GroEL and human hsp60, respectively, suggesting cross-reactivity of antibodies. These results suggest that molecular mimicry between GroEL of the periodontopathic bacterium P. gingivalis and autologous human hsp60 may play some role in immune mechanisms in periodontitis. [References: 28] <12> UI - 2000174865 AU - Yamashiro T AU - Fujiyama K AU - Fujiyoshi Y AU - Inaguma N AU - Takano-Yamamoto T IN - Dr. T. Takano-Yamamoto, Department of Orthodontics, Okayama University Dental School, 2-5-1 Shikato-cho, Okayama 700; Japan. TI - Inferior alveolar nerve transection inhibits increase in osteoclast appearance during experimental tooth movement. SO - Bone Vol 26(6) (pp 663-669), 2000. AB - To evaluate the role of sensory nerve innervation in alveolar bone remodeling during experimental tooth movement, we investigated histomorphometrically the influence of sensory nerve denervation on bone metabolism. Seven days after inferior alveolar nerve (IAN) transection or a sham operation in rats, orthodontic force was applied to the animals by inserting an elastic module interproximally between the lower first molar and second molar. Twenty-four hours after the application of the orthodontic force, osteoclast number, osteoclast surface, and osteoblast surface were measured on the trabecular bone surface in the interradicular septum of the lower second molar. The distribution of sensory nerve fibers immunoreactive to antibody against calcitonin gene-related peptide (CGRP) was also evaluated. In the sham-operated rats, CGRP-immunoreactive nerves were observed to be distributed along the blood vessels in the trabecular alveolar bone. Experimental tooth movement resulted in a fivefold increase in the number of osteoclasts and in increased immunoreactivity of nerves to anti-CGRP in the trabecular bone. However, IAN transection depleted the immunoreactivity to anti-CGRP and reduced the osteoclast number and osteoclast surface significantly. On the other hand, in the rats that were not subjected to experimental tooth movement, there was no significant difference in osteoclast number between sham-operated and IAN-transected rats. Significant changes were not observed in osteoblast surfaces associated with experimental tooth movement or nerve transection. These findings suggest that sensory nerves play an important role in regulating bone resorptive activity during experimental tooth movement. Copyright (C) 2000 Elsevier Science Inc. [References: 39] <13> UI - 2000166930 AU - O'Brien-Simpson NM AU - Black CL AU - Bhogal PS AU - Cleal SM AU - Slakeski N AU - Higgins TJ AU - Reynolds EC IN - E.C. Reynolds, Oral Health Sciences Unit, School of Dental Science, University of Melbourne, 711 Elizabeth St., Melbourne, Vic. 3000; Australia. E-Mail: e.reynolds@dent.unimelb.edu.au. TI - Serum immunoglobulin G (IgG) and IgG subclass responses to the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis in adult periodontitis. SO - Infection & Immunity Vol 68(5) (pp 2704-2712), 2000. AB - Serum immunoglobulin G (IgG), IgM, and IgG subclass responses to the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis were examined by enzyme-linked immunosorbent assay using adult periodontitis patients and age- and sex-matched controls. Twenty-five sera from subjects with adult periodontitis (diseased group) and 25 sera from healthy subjects (control group) were used for the study. Sera and subgingival plaque samples from 10 sites were collected from each patient at the time of clinical examination. The level of P. gingivalis in the plaque samples was determined using a DNA probe. Highly significant positive associations between the percentage of sites positive for P. gingivalis and measures of disease severity (mean pocket depth, mean attachment loss, and percentage of sites that bled on probing) were found. The diseased group had significantly higher specific IgG responses to the RgpA-Kgp complex than did the control group, and the responses were significantly associated with mean probing depths and percentage of sites positive for P. gingivalis. Analysis of the IgG subclass responses to the RgpA-Kgp complex revealed that the subclass distribution for both the diseased and control groups was IgG4 > IgG2 > IgG3 = IgG1. The IgG2 response to the complex was positively correlated with mean probing depth, whereas the IgG4 response was negatively correlated with this measure of disease severity. Immunoblot analysis of the RgpA-Kgp complex showed that sera from healthy subjects and those with low levels of disease, with high IgG4 and low IgG2 responses, reacted with the RgpA27, Kgp39, and RgpA44 adhesins; however, sera from diseased subjects with low IgG4 and high IgG2 responses reacted only with the RgpA44 and/or Kgp44 adhesins. Epitope mapping of the RgpA27 adhesin localized a major epitope recognized by IgG4 antibodies in sera from subjects with high IgG4 and low IgG2 responses to the RgpA-Kgp complex which was not recognized by sera from diseased subjects with low IgG4 and high IgG2 responses. [References: 61] <14> UI - 2000167955 AU - Cole BOI AU - Welbury RR AU - Bond E AU - Abinun M IN - B.O.I. Cole, Dept. of Child Dental Health, Dental Hospital and School, Richardson Road, Newcastle upon Tyne NE2 4AZ; United Kingdom. TI - Dental manifestations in severe combined immunodeficiency following bone marrow transplantation. SO - Bone Marrow Transplantation Vol 25(9) (pp 1007-1009), 2000. AB - Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency disorder with an estimated overall frequency of 1 in 75,000 live births. Bone marrow transplantation is the only curative treatment available. Using T cell-depleted HLA non-identical bone marrow requires preconditioning with a short course of cytotoxic chemotherapy. We report severe dental developmental anomalies in three such patients under longterm follow up. [References: 12] <15> UI - 2000147972 AU - Carlander D AU - Kollberg H AU - Wejaker P-E AU - Larsson A IN - A. Larsson, Department of Medical Sciences, University Hospital, S-751 85 Uppsala; Sweden. E-Mail: anders.larsson@klinkem.uas.lul.se. TI - Peroral immunotheraphy with yolk antibodies for the prevention and treatment of enteric infections. SO - Immunologic Research Vol 21(1) (pp 1-6), 2000. AB - Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are very good producers of specific antibodies. After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified. A laying hen produces more than 20 g of yolk antibodies (IgY) per year. These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent bacterial and viral infections. [References: 25] <16> UI - 2000116126 AU - Byers MR AU - Chudler EH AU - Iadarola MJ IN - M.R. Byers, Department of Anesthesiology, University of Washington, Seattle, WA 98195-6540; United States. E-Mail: byersm@u.washington.edu. TI - Chronic tooth pulp inflammation causes transient and persistent expression of Fos in dynorphin-rich regions of rat brainstem. SO - Brain Research 14 APR 2000Vol 861(2) (pp 191-207), 2000. AB - We have analyzed central Fos immunoreactivity (Fos-IR) brainstems of adult rats after three clinically relevant dental injuries: filled dentin (DF) cavities that cause mild pulp injury and heal within 1-2 weeks; open pulp exposures (PX) that cause gradual pulp loss and subsequent periodontal lesions; and filled pulp exposures (PXF). By 1 week after DF cavities, no Fos-IR remained except for sites such as lateral-ventral periolivary nucleus (LVPO) that had Fos-IR in all rats including controls. PX injury induced (1) a delayed transient expression of Fos at 1-2 weeks at three loci (ipsilateral neurons in dorsomedial nucleus oralis, paratrigeminal nucleus, and trigeminal tract), (2) persistent ipsilateral Fos for at least 4 weeks after injury in dynorphin (Dyn)-rich regions (rostral lateral solitary nucleus, periobex dorsal nucleus caudalis), and (3) late Fos-IR at 2-4 weeks (bilateral superficial cervical dorsal horn, contralateral dorsal nucleus caudalis, contralateral rostral lateral solitary nucleus). Rats with PXF injury were examined at 2 weeks, and they had greater numbers and more extensive rostro-caudal distribution of Fos neurons than the PX group. One week after PX injury, Fos-IR neurons were found in regions with strong Dyn-IR central fibers. Co-expression of Dyn and Fos was found in some unusually large neurons of the ipsilateral rostral lateral solitary nucleus, trigeminal tract, and dorsal nucleus caudalis. Immunocytochemistry for the p75 low affinity neurotrophin receptor (p75NTR) or for calcitonin gene-related peptide (CGRP) showed no consistent change in trigeminal central endings in any Fos-reactive brainstem areas, despite the extensive structural and cytochemical reorganization of the peripheral endings of the dental neurons. The Fos responses of central neurons to tooth injury have some unusual temporal and spatial patterns in adult rats compared to other trigeminal injury models. Copyright (C) 2000 Elsevier Science B.V. [References: 83] <17> UI - 2000110983 AU - Lopatin DE AU - Combs A AU - Sweier DG AU - Fenno JC AU - Dhamija S IN - D.E. Lopatin, Dept. of Biologic and Materials Sci., School of Dentistry, University of Michigan, 1011 North University Ave., Ann Arbor, MI 48109-1078; United States. E-Mail: lopatin@umich.edu. TI - Characterization of heat-inducible expression and cloning of HtpG (Hsp90 homologue) of Porphyromonas gingivalis. SO - Infection & Immunity Vol 68(4) (pp 1980-1987), 2000. AB - Porphyromonas gingivalis is implicated in the etiology of periodontal disease. Associations between microbial virulence and stress protein expression have been identified in other infections. For example, Hsp90 homologues in several microbial species have been shown to contribute to virulence. We previously reported that P. gingivalis possessed an Hsp90 homologue (HtpG) which cross-reacts with human Hsp90. In addition, we found that elevated levels of serum antibody to Hsp90 stress protein in individuals colonized with this microorganism were associated with periodontal health. However, the role of HtpG in P. gingivalis has not been explored. Therefore, we cloned the htpG gene and investigated the characteristics of HtpG localization and expression in P. gingivalis, htpG exists as a single gene of 2,052 bp from which a single message encoding a mature protein of approximately 68 kDa is transcribed. Western blot analysis revealed that the 68-kDa polypeptide was stress inducible and that a major band at 44 kDa and a minor band at 40 kDa were present at constitutive levels. Cellular localization studies revealed that the 44- and 40-kDa species were associated with membrane and vesicle fractions, while the 68-kDa polypeptide was localized to the cytosolic fractions. [References: 45] <18> UI - 2000102679 AU - Norris JM AU - Love DN IN - D.N. Love, Department of Veterinary Anatomy, University of Sydney, Sydney, NSW 2006; Australia. E-Mail: dlove@angis.usyd.edu.au. TI - Serum antibody responses of cats to soluble whole cell antigens of feline Porphyromonas gingivalis. SO - Veterinary Microbiology 04 APR 2000Vol 73(1) (pp 37-49), 2000. AB - The whole cell soluble antigens of two strains (VPB 3457 and VPB 3492) of feline Porphyromonas gingivalis were analysed by Western blotting using serum taken from 40 domestic cats with various grades of periodontal disease. Five strongly immunogenic protein bands (70, 34, 27, 24 and 19kDa) from VPB 3457 and seven from VPB 3492 (58, 44, 34, 27, 25, 24 and 21kDa) were selected for further study. A significant positive correlation was found between the serum antibody response to the 70, 34, 27, 24 and 19kDa bands of VPB 3457 and the 58, 44, 25, 24 and 21kDa bands of VPB 3492 and the overall periodontal grade. A significant positive correlation was also found between the serum antibody response to the 24kDa band of VPB 3457 and the total colony forming units of P. gingivalis. N-terminal sequencing of the 44kDa band of VPB 3492 showed 75% identity with the translated amino acids from the hag A (haemagglutinin) gene of a human strain of P. gingivalis and N-terminal amino acid sequence of the 27kDa band of VPB 3457 showed 88% identity with the amino acid sequences translated from DNA of purported genes coding for variously named proteinases of human strains of P. gingivalis. Copyright (C) 2000 Elsevier Science B.V. [References: 33] <19> UI - 2000096276 AU - Taylor DO IN - Dr. D.O. Taylor, Department of Medicine, Division of Cardiology 4A-100, University Utah Health Sciences Ctr., 50 N. Medical Drive, Salt Lake City, UT 84132; United States. TI - Immunosuppressive therapies after heart transplantation: Best, better, and beyond. SO - Current Opinion in Cardiology Vol 15(2) (pp 108-114), 2000. AB - Despite the significant advances in transplantation immunology and immunosuppressive therapies over the past 30 years, current immunosuppressive regimens are still inadequate in the majority of cardiac transplant recipients. Although short- and long-term survival rates have improved significantly, only 50% will survive 10 years and very few will survive 20 years. Complications of overimmunosuppression and underimmunosuppression account for the majority of these deaths. Only true 'immunologic' tolerance can provide the outcome we pursue, namely, prolonged allograft function and otherwise normal immune function without chronic immunosuppressive therapy and its risks. Until a successful tolerance-inducing protocol is developed, we must use the current and upcoming immunosuppressive agents and techniques. (C) 2000 Lippincott Williams and Wilkins, Inc. [References: 35] <20> UI - 2000087806 AU - Thomas DW AU - Newcombe RG AU - Osborne GR IN - Dr. D.W. Thomas, Dept. of Oral Surg. Med./Pathology, Univ. of Wales College of Medicine, Heath Park, Cardiff CF14 4XY; United Kingdom. E-Mail: woadwt@cf.ac.uk. TI - Risk factors in the development of cyclosporine-induced gingival overgrowth. SO - Transplantation Vol 69(4) (pp 522-526), 2000. AB - Background. Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of cyclosporine-A (CsA). Using the largest group of renal allograft recipients assembled for this purpose, in this study, we statistically modeled the genetic (HLA), medical, and dental risk factors for the development of GH subsequent to administration of CsA. Methods. Two hundred thirty-six renal transplant patients underwent full dental examination to quantify the extent and distribution of hyperplasia and dental disease (gingivitis, plaque, and calculus). Computerized data from all patients included pre-transplant medical history and dosage of nifedipine and azathioprine, as well as dose and serum levels of CsA and CsA microemulsion. Donor and host HLA haplotype were studied to investigate potential association of haplotype and donor-host mismatching with the development of GH. We evaluated the data by multivariate regression analysis, using Statistical Package for Social Sciences (SPSS). Results. There was no association with age, sex, duration of renal replacement therapy, or interval since transplantation or pre-transplant disease (P>0.05). There also was no association of disease with host HLA haplotype, but degree of HLA-A mismatching was protective for GH development (P<0.002). GH was associated with the dose and serum levels of CsA (P<0.001) and the last dose of CsA microemulsion (P=0.009) but not nifedipine (P=0.10). Gingival inflammation and plaque were also strongly associated with GH (P<0.0003). In multivariate analysis, however, the last recorded dose of CsA (P< 0.0001), presence of local gingival inflammation (P<0.0001), and gingivitis (P<0.003) were the independent predictors of the extent and severity of GH. Conclusions. Inter- patient variation in the extent and severity of GH is related to CsA dose and serum levels. Differences in host HLA phenotype do not explain individual susceptibility to GH, but donor-host HLA-A mismatching may be important. Inter-site variation in the extent and severity of the disease is related to local gingival inflammation. [References: 34] <21> UI - 2000067731 AU - Talwar GP AU - Diwan M AU - Razvi F AU - Malhotra R IN - G.P. Talwar, Talwar Research Foundation, New Delhi; India. TI - The impact of new technologies on vaccines. SO - National Medical Journal of India Vol 12(6) (pp 274-280), 1999. AB - Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by accellular purified fractions devoid of side-effects. Non- pathogenic but immunogenic mutants of tetanus and diphtheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophillus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti- inflammatory experimental vaccines against multiple sclerosis and insulin- dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual. [References: 75] <22> UI - 2000066892 AU - Liu B AU - Rayment SA AU - Gyurko C AU - Oppenheim FG AU - Offner GD AU - Troxler RF IN - R.F. Troxler, Department of Biochemistry, Boston University School of Medicine, Boston University Medical Center, Boston, MA 02118; United States. E-Mail: btrox@bu.edu. TI - The recombinant N-terminal region of human salivary mucin MG2 (MUC7) contains a binding domain for oral Streptococci and exhibits candidacidal activity. SO - Biochemical Journal 01 FEB 2000Vol 345(3) (pp 557-564), 2000. AB - MG2 (the MUC7 gene product) is a low-molecular-mass mucin found in human submandibular/sublingual secretions. This mucin is believed to agglutinate a variety of microbes and thus is considered an important component of the non-immune host defence system in the oral cavity. We have shown that MUC7 can bind to cariogenic strains of Streptococcus mutans and that this binding requires a structural determinant in the N-terminal region. In the present study an expression construct, pNMuc7, encoding the N-terminal 144 amino acids of MUC7 was generated, and the recombinant protein rNMUC7 was expressed in Escherichia coli. Purified rNMUC7 was characterized and the binding of this protein to oral bacteria was investigated in an established assay. The results showed that the recombinant protein bound to S. mutans ATCC 25175 and ATCC 33402, and that alkylation of the two cysteine residues (Cys45 and Cys50) resulted in the complete loss of bacterial binding. This suggests that binding of MUC7 to S. mutans occurs between the N-terminal region of the mucin molecule and the bacterial surface, and that this interaction is dependent on a cysteine-containing domain within this region of MUC7. In addition, the killing activity of rNMUC7 was compared with that of the candidacidal salivary protein histatin 5 in an established Candida albicans (ATCC 44505) blastoconidia killing assay. It was found that the LD50 values of rNMUC7 and histatin 5 were comparable, and that the recombinant protein displayed significant killing activity at the physiological concentration range of MUC7 in whole saliva. This study is the first to show that the N-terminal region of MUC7 contains a structural determinant for bacterial binding and that this region exhibits candidacidal activity. [References: 38] <23> UI - 2000045995 AU - Yokozawa T AU - Towatari M AU - Iida H AU - Takeyama K AU - Tanimoto M AU - Kiyoi H AU - Motoji T AU - Asou N AU - Saito K AU - Takeuchi M AU - Kobayashi Y AU - Miyawaki S AU - Kodera Y AU - Ohno R AU - Saito H AU - Naoe T IN - M. Towatari, First Department Internal Medicine, Nagoya University School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550; Japan. TI - Prognostic significance of the cell cycle inhibitor p27(Kip1) in acute myeloid leukemia. SO - Leukemia Vol 14(1) (pp 28-33), 2000. AB - There are few molecular biologic determinants that are prognostic for patients with acute myeloid leukemia (AML). Hence, we examined whether cellular levels of the cyclin-dependent kinase inhibitor p27(Kip1) in acute myeloid leukemia could be used to predict clinical outcome in AML. Using immunoblot analysis, levels of p27 were assessed in blast cells from 72 AML patients who were registered and treated by the identical chemotherapy protocol. AML cases were classified into three groups on the basis of the percentage of the expression level of p27 compared to a control cell line. AML cases exhibiting p27 expression at low, moderate, and high levels were 43, 9, and 20 cases, respectively. No significant differences in the rates of complete remission (CR) were observed among the three groups. Although the level of p27 expression was not correlated with any other possible prognostic markers, such as age, white blood cell count, chromosome abnormalities, and FAB subclasses, patients with high p27 expression had a significantly increased disease-free survival (DFS) (78 vs 19, P = 0.004). We further examined the expression of cyclin E at the protein level in all 72 AML cases. We observed a statistically significant correlation between a high cyclin E level and a high p27 level (P < 0.005). However, we failed to find any correlation between the rates of CR or DFS and cyclin E expression. The present study reveals that levels of p27 expression can be one of the useful prognostic molecular markers for AML. [References: 34] <24> UI - 2000039183 AU - Kozarov E AU - Miyashita N AU - Burks J AU - Cerveny K AU - Brown TA AU - McArthur WP AU - Progulske-Fox A IN - E. Kozarov, Department of Oral Biology, University of Florida, Box 100424 JHMHSC, Gainesville, FL 32610-0424; United States. E-Mail: kozarov@dent al.ufl.edu. TI - Expression and immunogenicity of hemagglutinin a from Porphyromonas gingivalis in an avirulent Salmonella enterica serovar typhimurium vaccine strain. SO - Infection & Immunity Vol 68(2) (pp 732-739), 2000. AB - Porphyromonas gingivalis is a major etiologic agent of periodontitis, a chronic inflammatory disease that ultimately results in the loss of the supporting tissues of the teeth. Previous work has demonstrated the usefulness of avirulent Salmonella enterica serovar Typhimurium strains as antigen delivery systems for protective antigens of pathogens that colonize or cross mucosal surfaces. In this study, we constructed and characterized a recombinant S. enterica serovar Typhimurium avirulent vaccine strain which expresses hemagglutinin A and carries no antibiotic resistance markers. HagA, a major virulence-associated surface protein, is a potentially useful immunogen that contains an antigenic epitope which, in humans, elicits an immune response that is protective against subsequent colonization by P. gingivalis. The hagA gene, including its promoter, was cloned into a balanced-lethal Salmonella vector and transferred to the vaccine strain. Heterologous expression of HagA was demonstrated in both Escherichia coli JM109 and S. enterica serovar Typhimurium vaccine strain X4072. The HagA epitope was present in its native configuration as determined by immunochemistry and immunoelectron microscopy. Purified recombinant HagA was recognized by sera from mice immunized with the S. enterica serovar Typhimurium vaccine strain. The HagA-specific antigen of the vaccine was also found to be recognized by serum from a periodontal patient. This vaccine strain, which expresses the functional hemagglutinin protein, induces a humoral immune response against HagA and may be useful for developing a protective vaccine against periodontal diseases associated with P. gingivalis. [References: 60] <25> UI - 2000039181 AU - Kumagai Y AU - Konishi K AU - Gomi T AU - Yagishita H AU - Yajima A AU - Yoshikawa M IN - Y. Kumagai, Department of Microbiology, Nippon Dental University, Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159; Japan. E-Mail: yumi-mic@tokyo.ndu.ac.jp. TI - Enzymatic properties of dipeptidyl aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis and its participation in virulence. SO - Infection & Immunity Vol 68(2) (pp 716-724), 2000. AB - Porphyromonas gingivalis is a major pathogen associated with adult periodontitis. We cloned and sequenced the gene (dpp) coding for dipeptidyl aminopeptidase IV (DPPIV) from P. gingivalis W83, based on the amino acid sequences of peptide fragments derived from purified DPPIV. An Escherichia coli strain overproducing P. gingivalis DPPIV was constructed. The enzymatic properties of recombinant DPPIV purified from the over-producer were similar to those of DPPIV isolated from P. gingivalis. The three amino acid residues Ser, Asp, and His, which are thought to form a catalytic triad in the C- terminal catalytic domain of eukaryotic DPPIV, are conserved in P. gingivalis DPPIV. When each of the corresponding residues of the enzyme was substituted with Ala by site-directed mutagenesis, DPPIV activity significantly decreased, suggesting that these three residues of P. gingivalis DPPIV are involved in the catalytic reaction. DPPIV-deficient mutants of P. gingivalis were constructed and subjected to animal experiments. Mice injected with the wild-type strain developed abscesses to a greater extent and died more frequently than those challenged with mutant strains. Mice injected with the mutants exhibited faster recovery from the infection, as assessed by weight gain and the rate of lesion healing. This decreased virulence of mutants compared with the parent strain suggests that DPPIV is a potential virulence factor of P. gingivalis and may play important roles in the pathogenesis of adult periodontitis induced by the organism. [References: 45] <26> UI - 2000030167 AU - Ingram DA AU - Yang F-C AU - Travers JB AU - Wenning MJ AU - Hiatt K AU - New S AU - Hood A AU - Shannon K AU - Williams DA AU - Clapp DW IN - D.W. Clapp, Indiana University, School of Medicine, Cancer Research Institute, 1044 W. Walnut St., Indianapolis, IN 46202; United States. E-Mail: dclapp@iupui.edu. TI - Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. SO - Journal of Experimental Medicine 03 JAN 2000Vol 191(1) (pp 181-187), 2000. AB - Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms; NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's 'two hit' model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W41 mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to steel factor, the ligand for c- kit. Furthermore, haploinsufficiency was associated with enhanced Ras- mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W41) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types. [References: 33] <27> UI - 2000023798 AU - Norris JM AU - Love DN IN - D.N. Love, Dept. Veterinary Anatomy/Pathology, University of Sydney, Sydney, NSW 2006; Australia. E-Mail: dlove@angis.usyd.edu.au. TI - The association of two recombinant proteinases of a feline strain of Porphyromonas gingivalis with periodontal disease in cats. SO - Veterinary Microbiology Vol 71(1-2) (pp 69-80), 2000. AB - Serum from 40 domestic cats with various grades of periodontal disease was used to probe two recombinant functional proteinases from feline strain VPB 3457 of Porphyromonas gingivalis expressed in E. coli. One recombinant proteinase (VPB 2856) was constructed using polymerase chain reaction and had 91% DNA identity with the prtC collagenase gene of the human type strain of P. gingivalis, while the other proteinase (VPB 2814) was isolated from a size selected genomic library and had an amino-terminal sequence with no significant identity with deposited sequences. Thirteen of 40 cats showed a serum antibody response to VPB 2856 using Western immunoblot detection. All the 13 cats had an overall periodontal grade of 3 or greater and greater than 1.68x105 cfu P. gingivalis at the canine and premolar periodontium sample sites. Fourteen of 40 cats showed a serum antibody response to VPB 2814. Thirteen of these 14 cats had an overall periodontal grade of 3 or greater. Regression analysis of overall periodontal grade against the serum antibody response showed significant positive relationships for both VPB 2856 (r2=0.351; p<0.001) and VPB 2814 (r2=0.247; p<0.001). Regression analysis of the total colony forming units of feline strain P. gingivalis against the grade of serum antibody response showed a positive relationship for both VPB 2856 (r2=0.662; p<0.001) and VPB 2814 (r2=0.531; p<0.001). These data provide strong evidence that the recombinant proteinases of feline P. gingivalis expressed in E. coli clones VPB 2856 and VPB 2814 are associated with periodontal disease in cats. Copyright (C) 2000 Elsevier Science B.V. [References: 34] <28> UI - 2000020183 AU - Dickinson CJ IN - Dr. C.J. Dickinson, Wolfson Inst. Preventive Medicine, Charterhouse Square, London EC1M 6BQ; United Kingdom. E-Mail: c.j.dickinson@mds.qmw.ac.uk. TI - The possible role of osteoclastogenic oral bacterial products in etiology of Paget's disease. SO - Bone Vol 26(2) (pp 101-102), 2000. <29> UI - 1999427504 AU - Prasad SK IN - Prof. S.K. Prasad, Dept. of ENT, Patna Medical College, Patna 800004; India. TI - Preventive Otorhinolaryngology. SO - Indian Journal of Otolaryngology Vol 51(2) (pp 86-89), 1999. AB - Curative medicine and curative surgery are no doubt of interest to every body. However, a host of diseases in the area of ear, nose and throat are curable, on the other hand, a number of them are only controllable, not curable. Several amongst them are preventable as such or their complications and sequelae can be prevented or minimised. It is high time that more awareness is created towards better understanding of the preventive aspect of Otorhinolaryngology practice. The time and energy spent on managing complications and sequelae can be easily saved and easily utilized in a better way in improving expertise to cure the diseases through more research and interaction. <30> UI - 1999402742 AU - Rice HE AU - Chuang E IN - Dr. H.E. Rice, Division of Pediatric Surgery, Box 3815, Duke University Medical Center, Durham, NC 27710; United States. TI - Current management of pediatric inflammatory bowel disease. SO - Seminars in Pediatric Surgery Vol 8(4) (pp 221-228), 1999. AB - Inflammatory bowel disease (IBD) is a relatively rare condition of childhood, although the wide range of presenting complaints, scope of complications, and choices of therapy for this condition make it particularly difficult to treat in children. Novel approaches to the management of Crohn's disease and ulcerative colitis have gained recent favor. This report summarizes the current medical and surgical management of IBD, recent advancements in clinical therapies, and particular aspects of IBD care for children. [References: 36] <31> UI - 1999384778 AU - Acton RT AU - Dasanayake AP AU - Harrison RA AU - Li Y AU - Roseman JM AU - Go RCP AU - Wiener H AU - Caufield PW IN - Dr. R.T. Acton, Immunogenetics Program, University of Alabama, PAB 221, 1025 18th Street South, Birmingham, AL 35294-4400; United States. E-Mail: Acton@iprsh.igpmd.uab.edu. TI - Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women. SO - Human Immunology Vol 60(10) (pp 984-989), 1999. AB - The aim of this investigation was to evaluate the relationship between MHC alleles at the HLA-DRB1, DQB1 and TNFa microsatellite loci and levels of oral bacteria that play a role in the etiology of dental caries, and the DMFS index in 186 AA primparous women. The average age of the cohort was 20.8 +/- 3.7 years. The median DMFS index was 9 (range 0-68). High levels of S. mutans were positively associated with DRB1*3 and DRB1*4 presence (p <= 0.005). DRB1*8 was positively associated with higher levels of S. mutans as a percentage of total Streptococci (p = 0.04). DRB1*1 was positively associated with high levels L. casei (p = 0.04). DQB1 alleles were not observed associated with oral bacterial levels. TNFa allele 103 was negatively associated (p = 0.04), and TNFa 117 was positively associated (p = 0.007), with high levels of L. acidophilus. No significant associations were observed between any DRB1, DQB1 or TNFa allele and the DMFS index. These results support an hypothesis of an association between host HLA class II and TNFa genetic profile and colonization of S. mutans, L. casei, and L. acidophilus thought to be pathogens involved in the etiology of dental caries. [References: 21] <32> UI - 1999359773 AU - Price P AU - Calder DM AU - Witt CS AU - Allcock RJN AU - Christiansen FT AU - Davies GR AU - Cameron PU AU - Rogers M AU - Baluchova K AU - Moore CB AU - French MA IN - Dr. P. Price, Dept. of Clinical Immunology, Royal Perth Hospital, Perth, 6001; Australia. E-Mail: pprice@cyllene.uwa.edu.au. TI - Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3). SO - Tissue Antigens Vol 54(4) (pp 391-399), 1999. AB - Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.xm. [References: 35] <33> UI - 1999354625 AU - Berrozpe G AU - Timokhina I AU - Yukl S AU - Tajima Y AU - Ono M AU - Zelenetz AD AU - Besmer P IN - Dr. P. Besmer, Memorial Sloan-Kettering Can. Center, 1275 York Ave, New York, NY 10021; United States. E-Mail: p-besmer@ski.mskcc.org. TI - The W(sh), W57, and Ph Kit expression mutations define tissue-specific control elements located between -23 and -154 kb upstream of Kit. SO - Blood Vol 94(8) (pp 2658-2666), 1999. AB - The Kit and PDGFRa receptor tyrosine kinases are encoded in close proximity at the murine white spotting (W) and patch (Ph) loci. Whereas W mutations affect hematopoiesis, melanogenesis, and gametogenesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. The W(sh), W57, and Ph mutations diminish Kit expression in certain cell types such as mast cells and enhance it in others. The W(sh), W57, and Ph mutations arose from deletions and inversions affecting sequences in between the Kit and PDGFRa genes. We have determined the precise location of the breakpoint of the W(sh) inversion and the endpoints of the W57 deletion upstream of the Kit transcription start site and examined the effect of these mutations on Kit expression in mast cells and hematopoietic stem cells and lineage progenitors. Our results indicate that positive elements controlling Kit expression in mast cells mapping in between -23 and -154 kb from the transcription start site can be dissociated from negative elements controlling Kit misexpression during embryonic development in the vicinity of the PDGFRa gene. In addition, we have identified two clusters of hypersensitive sites in mast cells at -23 -28 kb and -147 -154 kb from the Kit gene transcription start site. Analysis of these hypersensitive sites in mutant mast cells indicates a role for HS4-6 in Kit expression in mast cells. These findings provide a molecular basis for the phenotype of these Kit expression mutations and they provide insight into the complex mechanisms governing the regulation of Kit expression. [References: 36] <34> UI - 1999348013 AU - Hale GA AU - Heslop HE AU - Bowman LC AU - Rochester RA AU - Pui C-H AU - Brenner MK AU - Krance RA IN - Dr. H.E. Heslop, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates St., Houston, TX 77030; United States. TI - Bone marrow transplantation for therapy-induced acute myeloid leukemia in children with previous lymphoid malignancies. SO - Bone Marrow Transplantation Vol 24(7) (pp 735-739), 1999. AB - Twenty-one children who developed therapy-related acute myeloid leukemia after treatment for acute lymphoblastic leukemia received allogeneic bone marrow transplants between January 1990 and June 1997. All had previously received epipodophyllotoxin-containing regimens and 11 had cytogenetic abnormalities involving 11q23. Induction chemotherapy was given to 13 patients and eight patients went directly to BMT. Eleven received marrow from matched siblings, eight from matched unrelated donors and two from haploidentical family members. Conditioning regimens included cyclophosphamide (CY), cytarabine, and total body irradiation. Four patients are alive disease-free between 1118 and 1825 days post-BMT resulting in a 3-year DFS of 19%. Ten patients relapsed at a median of 150 days (range 30-664 days) post-BMT and all eventually died of disease. Seven patients died of regimen-related toxicity. The outlook for patients with therapy-related AML/MDS remains poor and more effective therapy is needed. [References: 22] <35> UI - 1999340610 AU - Yu H AU - Levesque MA AU - Clark GM AU - Diamandis EP IN - E.P. Diamandis, Dept. Pathology Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont. M5G 1X5; Canada. TI - Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. SO - British Journal of Cancer Vol 81(3) (pp 490-495), 1999. AB - p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan-Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P= 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(-)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(-) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. [References: 45] <36> UI - 1999328733 AU - Becker M AU - Weizenegger M AU - Bartel J IN - Dr. M. Weizenegger, Lab. Gemeinschaftspraxis Heidelberg, Im Breitspiel 15, D-69126 Heidelberg; Germany. TI - Reverse hybridization assay for rapid identification of periodontitis-associated interleukin-1 alleles. SO - Clinical Laboratory Vol 45(9-10) (pp 499-505), 1999. AB - Periodontitis is a chronic inflammatory disease of the periodontium characterized by an interaction between specific bacteria and the host inflammatory response. Advanced periodontal disease usually results in alveolar bone loss and loss of masticatory function. Although periodontopathic bacteria are essential for the initiation of periodontitis, the quality and quantity of plaque formation is not sufficient to explain the different progression in disease severity. The activated host defense cells produce and release immunopathologic mediators such as cytokines or proteases. Interleukin-1 (IL-1) is one of these cytokines which is of special interest in the context of periodontitis due to its osteoclast activity properties leading to alveolar bone resorption. In the cluster of IL-1 genes there are several polymorphisms that influence the biological effects and functionality of the mature protein. In 1997, Kornman et al. identified two of these polymorphisms, which are significantly associated with severe periodontitis when found in the composite genotype comprising allele 2 of the IL-1A -889 polymorphism plus allele 2 of the IL-1B +3953 polymorphism. The genetic marker is a prognostic marker for susceptibility and predisposition to severe periodontitis. The aim of this project was to develop a reverse hybridization assay to detect the respective IL-1-polymorphisms in order to identify individuals who are highly susceptible to periodontitis. The genotyping test may provide important information and data to dentists and clinicians for treatment planning and will improve the clinicians ability to assess prognosis and predict tooth survival. [References: 36] <37> UI - 1999321134 AU - Thurnheer T AU - Guggenheim B AU - Gruica B AU - Gmur R IN - R. Gmur, Inst. Oral Microbiol. Gen. Immunol., University of Zurich, Plattenstrasse 11, CH-8028 Zurich; Switzerland. E-Mail: gmuer@zzmk.unizh.ch. TI - Infinite serovar and ribotype heterogeneity among oral Fusobacterium nucleatum strains?. SO - Anaerobe Vol 5(2) (pp 79-92), 1999. AB - Fusobacterium nucleatum is part of the residential human microbiota and is associated with various infections. It is characterised by broad genetic heterogeneity, but reliable phenotypic markers are lacking. The purpose of the present study was to generate antibodies for the detection of F. nucleatum, to characterise expression patterns of the detected surface antigens on oral isolates, to investigate the prevalence of distinguishable subtypes in clinical samples from the oral cavity, and to compare antigenic with ribotype heterogeneity. Thirty-seven monoclonal antibodies (mAbs) were generated and characterised using strains from 52 taxa. Antibody-binding bacteria were monitored in 35 samples of supra- and subgingival plaque from healthy sites and sites affected by gingivitis or periodontitis. Results indicated broad but structured antigenic heterogeneity. Detecting at least 28 different epitopes, the mAbs defined 19 serovars. Epitopes were expressed on periodate-sensitive polysaccharide chains. Ribotyping of 40 oral F. nucleatum strains (PvuII digestion) resulted in the detection of similarly broad genetic heterogeneity, which rarely corresponded to the observed phenotypic diversity. Clinical samples were generally positive for multiple (up to eight) serovars of which some colonised supra- and subgingival plaques from both healthy and diseased sites, whereas others were restricted to inflamed sites. The majority of the studied isolates could not be grouped with reference strains of the five established subspecies of F. nucleatum, corroborating doubts about the usefulness of the current classification scheme. Although, as a whole the described monoclonal antibodies can only recognise a part of the overwhelming heterogeneity of this 'species', they should prove of value to investigations of the importance, the antigenic stability and the origin of positive subtypes of F. nucleatum from human infections. [References: 48] <38> UI - 1999307494 AU - Okamoto M AU - Maeda N AU - Kondo K AU - Leung KP IN - M. Okamoto, Department Oral Bacteriology, Tsurumi University, School of Dental Medicine, 2-1-3 Tsurumi, Yokohama, Kanagawa 230-5801; Japan. E-Mail: pb8m-okmt@asahi-net.or.jp. TI - Hemolytic and hemagglutinating activities of Prevotella intermedia and Prevotella nigrescens. SO - FEMS Microbiology Letters Vol 178(2) (pp 299-304), 1999. AB - A total of 91 isolates of Prevotella intermedia or Prevotella nigrescens from subgingival sites were identified by PCR using primers specific for sequences of 16S rRNA. The hemolytic and hemagglutinating activities of the P. intermedia isolates exhibited significantly higher levels compared to those of the P. nigrescens isolates by quantitative analysis. The hemagglutinin gene (phg) was found in 23 of 26 P. intermedia isolates (88.5%), whereas it was found in only two of 44 isolates (4.5%) of P. nigrescens. The high hemolytic and hemagglutinating activities of P. intermedia may be involved in the pathogenicity of P. intermedia in the progression of periodontal disease. Copyright (C) 1999 Federation of European Microbiological Societies. [References: 25] <39> UI - 1999305950 AU - Hodge PJ AU - Riggio MP AU - Kinane DF IN - Dr. P.J. Hodge, Periodontal Oral Immunology Research, Glasgow Dental Hospital and School, 378 Sauchiehall Street, Glasgow G2 3JZ; United Kingdom. E-Mail: pjh@hodgeqc.freeserve.co.uk. TI - No association with HLA-DQB1 in European Caucasians with early-onset periodontitis. SO - Tissue Antigens Vol 54(2) (pp 205-207), 1999. AB - Periodontitis is a chronic inflammatory disease of the supporting tissues of the teeth that may ultimately result in tooth loss. The human leukocyte antigen (HLA) complex plays an important role in immune responsiveness and may be involved in antigen recognition of periodontal pathogens. A recent report of a Japanese population found an association between an atypical BamHI site in the HLA-DQB1 gene and a severe form of early-onset periodontitis (EOP). The aim of the present study was to test for the existence of the site in a European Caucasian EOP population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No statistically significant differences were found between the patients and controls with regard to the presence of the BamHI site. It was concluded that this lack of association could reflect racial genetic variation in HLA allelic frequencies. [References: 15] <40> UI - 1999299550 AU - Stashenko P AU - Teles R AU - D'Souza R IN - P. Stashenko, Department of Cytokine Biology, Forsyth Dental Center, 140 The Fenway, Boston, MA; United States. TI - Periapical inflammatory responses and their modulation. SO - Critical Reviews in Oral Biology & Medicine Vol 9(4) (pp 498-521), 1998. AB - Periapical inflammatory responses occur as a consequence of bacterial infection of the dental pulp, as a result of caries, trauma, or iatrogenic insult. Periapical inflammation stimulates the formation of granulomas and cysts, with the destruction of bone. These inflammatory responses are complex and consist of diverse elements. Immediate-type responses - including vasodilatation, increased vascular permeability, and leukocyte extravasation - are mediated by endogenous mediators, including prostanoids, kinins, and neuropeptides. Non-specific immune responses - including polymorphonuclear leukocyte and monocyte migration and activation, and cytokine production - are elicited in response to bacteria and their products. Interleukin-I and prostaglandins in particular have been implicated as central mediators of periapical bone resorption. Chronic periapical inflammation further involves specific T- and B-cell-mediated anti-bacterial responses, and activates a network of regulatory cytokines which are produced by Th1- and Th2-type T-lymphocytes. Various naturally occurring and genetically engineered models of immunodeficiency are beginning to help elucidate those components of the immune system which protect the pulpal/periapical complex. Both specific and non-specific responses interface with and are regulated by the neural system. The modulation of these responses by immune response modifiers, cytokine antagonists, and other novel therapeutic agents is discussed. As an experimental model, periapical inflammation has many advantages which permit it to be used in studies of microbial ecology and pathogenesis, host response, neuroimmunology, and bone resorption and regeneration. [References: 272] <41> UI - 1999298544 AU - Schenkein HA AU - Gunsolley JC AU - Best AM AU - Harrison MT AU - Hahn C-L AU - Wu J AU - Tew JG IN - H.A. Schenkein, VCU School of Dentistry, MCV Station Box 980566, Richmond, VA 23298; United States. E-Mail: hschenke@hsc.vcu.edu. TI - Antiphosphorylcholine antibody levels are elevated in humans with periodontal diseases. SO - Infection & Immunity Vol 67(9) (pp 4814-4818), 1999. AB - Human immunoglobulin G2 (IgG2) serum concentrations and the IgG2 antibody response to Actinobacillus actinomycetemcomitans can be influenced by genes, by environmental factors such as smoking, and by periodontal disease status. Examination of the IgG2 response to phosphorylcholine (PC), a response thought to be mainly induced by the C polysaccharide of Streptococcus pneumoniae, suggested that periodontal disease status was also associated with this response. This prompted the hypothesis that PC is an important oral antigen associated with organisms in the periodontal flora and that anti-PC antibody is elevated as a consequence of periodontal disease. Subjects in various periodontal disease diagnostic categories in which attachment loss is exhibited were tested for anti-PC in serum. Those with adult periodontitis, localized juvenile periodontitis, generalized early- onset periodontitis, and gingival recession all had similar levels of anti-PC IgG2 serum antibody which were significantly greater than in the group of subjects with no attachment loss. Analysis of plaque samples from subgingival and supragingival sites in all diseases categories for reactivity with the anti-PC specific monoclonal antibody TEPC-15 revealed that a substantial proportion of the bacteria in dental plaque (30 to 40%) bear PC antigen; this antigen was not restricted to morphotypes resembling only cocci but was also present on rods and branched filamentous organisms. We found that S. mitis, S. oralis, and S. sanguis, as well as oral actinomycetes, including A. viscosus, A. odontolyticus, and A. israelii, incorporated substantial amounts of [3H]choline from culture media. Further analysis of antigens derived from these organisms by Western blot indicated that S. oralis, S. sanguis, A. viscosus, A. odontolyticus, and A. israelii contained TEPC15-reactive antigens. The data show that many commonly occurring bacterial species found in dental plaque contain PC antigen and that immunization with plaque-derived PC antigens as a consequence of inflammation and periodontal attachment loss may influence systemic anti-PC antibody concentrations. [References: 27] <42> UI - 1999298483 AU - Katz J AU - Black KP AU - Michalek SM IN - J. Katz, Department of Oral Biology, University of Alabama, 845 South 19th St., Birmingham, AL 35294-2170; United States. TI - Host responses to recombinant hemagglutinin B of Porphyromonas gingivalis in an experimental rat model. SO - Infection & Immunity Vol 67(9) (pp 4352-4359), 1999. AB - Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Several hemagglutinin genes have been identified, cloned, and expressed in Escherichia coli. The purpose of this study was to characterize host responses to purified recombinant hemagglutinin B (rHag B), using the conventional Fischer rat as the experimental animal model. The effectiveness of immunization with rHag B on protection against experimental periodontal bone loss following infection with P. gingivalis was also evaluated. Groups of rats were immunized by the subcutaneous route with rHag B in complete Freund's adjuvant, immunized with rHag B and orally infected with P. gingivalis, nonimmunized and noninfected, or orally infected with P. gingivalis only. Serum and saliva samples were collected throughout the experiment and evaluated for serum immunoglobulin G (IgG) and IgM and salivary IgA antibody activity by enzyme-linked immunosorbent assay. No salivary IgA anti-Hag B activity was detected in the various groups of rats. A slight serum IgM response similar to that seen in preimmune samples was observed. Serum IgG antibody activity to Hag B was detected only in samples from rats immunized with rHag B. This response was primarily of the IgG1 and IgG2a subclasses, followed by IgG2b and low levels of IgG2c. Supernatants from rHag B-stimulated splenic lymphoid cell cultures from immunized rats contained high levels of gamma interferon, followed by interleukin-2 (IL-2), IL-10, and then IL-4. These results are consistent with the induction of T helper type 1 (Th1)- and Th2-like responses. Western blot analysis of sera derived from rHag B-immunized rats reacted with trichloroacetic acid (TCA) precipitates of P. gingivalis 33277, 381, A7A1-28, and W50, revealing a 50-kDa band reflective of Hag B. However, sera derived from rats immunized with P. gingivalis whole cells or from rats infected with P. gingivalis only did not react with rHag B but did react with TCA precipitates of P. gingivalis strains. Finally, radiographic measurements of periodontal bone loss indicated that rats immunized with rHag B had less bone loss than those infected with P. gingivalis only. These results demonstrate the effectiveness of purified rHag B in inducing a protective immune response and support the potential usefulness of this component of P. gingivalis in the development of a vaccine against adult periodontitis. [References: 47] <43> UI - 1999283004 AU - Kato T AU - O'Brien CB AU - Nishida S AU - Hoppe H AU - Gasser M AU - Berho M AU - Rodriguez MJ AU - Ruiz P AU - Tzakis AG IN - Dr. T. Kato, Professional Arts Bldg, 1150 N.W. 14th St., Miami, FL 33136; United States. TI - The first case report of the use of a zoom videoendoscope for the evaluation of small bowel graff mucosa in a human after intestinal transplantation. SO - Gastrointestinal Endoscopy Vol 50(2) (pp 257-261), 1999. AB - Background: Control of allograft rejection remains the most difficult dilemma in intestinal transplantation. Standard endoscopic surveillance to date has not been always accurate in the diagnosis of rejection. We describe the first application of a zoom video endoscope in monitoring graft mucosa in humans after intestinal transplantation. Method: A zoom video endoscope, which can magnify the image up to 100-fold, was used in this study. The patient was a 31-year-old man who received an isolated intestinal transplant. Surveillance endoscopy with the zoom video endoscope was performed through the ileostomy. Endoscopic biopsies were done at the same time. Results: The zoom video endoscope showed the microscopic architecture of the graff mucosa such as villi and crypts with outstanding quality. We found that an enlargement of the crypt areas appeared to correlate with morphologic changes of early rejection. This finding was reversed with the treatment of rejection. Conclusions: The zoom video endoscope successfully showed the detailed information of intestinal mucosa. The ability to visualize a more representative view of the graff mucosa could lead to better detection of early rejection. A greater experience with this unique method will provide more accurate assessment of the intestinal allograft. [References: 17] <44> UI - 1999266498 AU - Caimano MJ AU - Bourell KW AU - Bannister TD AU - Cox DL AU - Radolf JD IN - J.D. Radolf, Univ. of Connecticut Health Center, Center for Microbial Pathogenesis, 263 Farmington Ave., Farmington, CT 06030-3710; United States. E-Mail: Jradolf@up.uchc.edu. TI - The Treponema denticola major sheath protein is predominantly periplasmic and has only limited surface exposure. SO - Infection & Immunity Vol 67(8) (pp 4072-4083), 1999. AB - The recent discovery that the Treponema pallidum genome encodes 12 orthologs of the Treponema denticola major sheath protein (Msp) prompted us to reexamine the cellular location and topology of the T. denticola polypeptide. Experiments initially were conducted to ascertain whether Msp forms an array on or within the T. denticola outer membrane. Transmission electron microscopy (EM) of negatively stained and ultrathin-sectioned organisms failed to identify a typical surface layer, whereas freeze-fracture EM revealed that the T. denticola outer membrane contains heterogeneous transmembrane proteins but no array. In contrast, a lattice-like structure was observed in vesicles released from mildly sonicated treponemes; combined EM and biochemical analyses demonstrated that this structure was the peptidoglycan sacculus. Immunoelectron microscopy (IEM) subsequently was performed to localize Msp in T. denticola. Examination of negatively stained whole mounts identified substantial amounts of Msp in sonicated organisms. IEM of ultrathin-sectioned, intact treponemes also demonstrated that the preponderance of antigen was unassociated with the outer membrane. Lastly, immunofluorescence analysis of treponemes embedded in agarose gel microdroplets revealed that only minor portions of Msp are surface exposed. Taken as a whole, our findings challenge the widely held belief that Msp forms an array within the T. denticola outer membrane and demonstrate, instead, that it is predominantly periplasmic with only limited surface exposure. These findings also have implications for our evolving understanding of the contribution(s) of Msp/Tpr orthologs to treponemal physiology and disease pathogenesis. [References: 60] <45> UI - 1999257164 AU - Sugita N AU - Yamamoto K AU - Kobayashi T AU - Van Der Pol WL AU - Horigome T AU - Yoshie H AU - Van De Winkel JGJ AU - Hara K IN - Dr. H. Yoshie, Department of Periodontology, Niigata Univ. School of Dentistry, Gakko-cho 2-5274, Niigata 951-8514; Japan. E-Mail: psugita@dent.niigata-u.ac.jp. TI - Relevance of FcgammaRIIIa-158V-F polymorphism to recurrence of adult periodontitis in Japanese patients. SO - Clinical & Experimental Immunology Vol 117(2) (pp 350-354), 1999. AB - The immunoglobulin receptor FcgammaRIIIa (CD 16) is distributed on natural killer (NK) cells, macrophages, and gammadelta T cells, and is polymorphic. FcgammaRIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined FgammaRIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over- representation of FcgammaRIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making FcgammaRIIIA a candidate gene for recurrence risk of adult periodontitis. [References: 37] <46> UI - 1999251468 AU - Hansen HC IN - Dr. H.C. Hansen, Pain Relief Centers, PO Box 5956, Statesville, NC 28687; United States. TI - Treatment of chronic pain with antiepileptic drugs: A new era. SO - Southern Medical Journal Vol 92(7) (pp 642-649), 1999. AB - Background. Shortcomings of traditional pain relief agents have led physicians to investigate other alternatives, such as antiepileptic drugs. Safe, effective, nonhabituating agents are currently available to enhance pain treatment strategies. Methods. In this article, various pharmacologic options and their mechanisms of action are reviewed briefly, with a focus on treatment of chronic pain with antiepileptic drugs (AEDs). Results. Antiepileptic drugs have been widely studied and prescribed for the relief of acute and chronic pain. Similarities in the neurophysiology of pain and epilepsy suggest that AEDs may be a suitable adjunct in the management of chronic pain. Of the newer AEDs, gabapentin shows the greatest potential and appears to be well tolerated by patients. Conclusions. Treatment of chronic pain remains a challenge for physicians and patients. Further research is required to identify the role of various agents and their effect on patient return to function and quality of life. [References: 66] <47> UI - 1999230383 AU - Au WY AU - Lie AKW AU - Ma SK AU - Chan LC AU - Lee CK AU - Kwong YL AU - Chim CS AU - Chan TK AU - Chiu E AU - Liang R IN - R. Liang, University Medical Unit, Queen Mary Hospital, 4/F Professorial Block, Pokfulam; Hong Kong. E-Mail: rliang@hkucc.hku.hk. TI - Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: A single-centre experience. SO - Hematological Oncology Vol 16(4) (pp 163-168), 1998. AB - Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n= 15), VP16-Cy-TBI(n= 12), CBV (n= 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patientS died of transplant- related complications before 100 days. Relapse occurred in i 1 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment- related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p=0.39). No long-term DFS is obtained from patients with resistant disease (n=4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p=0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results. [References: 34] <48> UI - 1999226993 AU - Ito Y AU - Matsuura N AU - Sakon M AU - Miyoshi E AU - Noda K AU - Takeda T AU - Umeshita K AU - Nagano H AU - Nakamori S AU - Dono K AU - Tsujimoto M AU - Nakahara M AU - Nakao K AU - Taniguchi N AU - Monden M IN - Prof. N. Matsuura, Department of Pathology, Osaka University, Faculty of Medicine, 1-7, Yamadaoka, Suita, Osaka 565; Japan. E-Mail: matsuura@sahs.med.osaka-u.ac.jp. TI - Expression and prognostic roles of the G1-S modulators in hepatocellular carcinoma: p27 Independently predicts the recurrence. SO - Hepatology Vol 30(1) (pp 90-99), 1999. AB - Expression of cell-cycle modulators at the G1-S boundary, retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1, and cyclin E was investigated with 104 hepatocellular carcinomas (HCC), as well as 90 of their adjacent noncancerous lesions and 9 normal liver control specimens. The labeling indices (LI) of pRb, p21, p16, and p27 were higher in HCC lesions than in the adjacent noncancerous lesions and normal controls. Especially, p27 LI in noncancerous lesions was significantly higher than that in normal livers (P = .011). Aberrant p53 expression and cyclin D1 and E overexpression were observed exclusively in HCC lesions, pRb was positive in 85.6% of the HCC cases and was not related to any clinicopathological parameters. The p21 LI was generally low (average, 5.5 +/- 9.8). Although a negative regulator, p21 LI was higher in cases with intrahepatic metastasis (P = .0359). The p16 LI was significantly decreased (P = .0121) in cases with advanced stage, p27 LI was significantly decreased in cases with portal invasion (P = .0409), poor differentiation (P < .0001), larger size (P = .0421), and intrahepatic metastasis (P = .0878, borderline significance). On the other hand, aberrant p53 expression showed positive relationships with poor differentiation (P = .0004) and Ki-67 LI (P = .0047). Cyclin D1 overexpression was found in 32.6% of the cases and occurred more frequently in those with high Ki-67 LI (P = .0032), pRb expression (P = .0202), poor differentiation (P = .0612, borderline significance), and intrahepatic metastasis (P = .0675, borderline significance). Cyclin E was overexpressed in 35.5% and had positive relationships with Ki-67 LI (P = .0269)and stage (P = .0125). In univariate analysis, cases with p27 LI < 50 (P = :0004), cyclin D1 overexpression (P = .0041), and cyclin E overexpression (P = .05 72, borderline significance) showed poorer outcomes for disease-free survival (DFS). In multivariate analysis, p27 expression could be recognized as an independent prognostic marker for DFS. These findings suggest that in HCC: 1) p27 is active against HCC progression in early phases and, possibly, hepatocarcinogenesis as a negative regulator and can be a novel prognostic marker for DFS; and 2) cyclin D1 predominantly works for cell-cycle progression at the G1-S boundary. [References: 67] <49> UI - 1999226853 AU - Cassatella MA IN - M.A. Cassatella, Department of Pathology, Faculty of Medicine, University of Verana, 37134 Verona; Italy. TI - Neutrophil-derived proteins: Selling cytokines by the pound. SO - Advances in Immunology Vol 73 (pp 369-509), 1999. <50> UI - 1999214953 AU - Saito K AU - Mori S AU - Tanda N AU - Sakamoto S IN - Dr. K. Saito, Department of Preventive Dentistry, School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575; Japan. TI - Expression of p53 protein and Ki-67 antigen in gingival hyperplasia induced by nifedipine and phenytoin. SO - Journal of Periodontology Vol 70(6) (pp 581-586), 1999. AB - Background: Although it has been thought that drug-induced gingival hyperplasia is not related to tumorigenesis, recent case reports have shown that squamous cell carcinomas may arise in gingival hyperplasia induced by cyclosporin and phenytoin. The possible implications between the pathogenesis of this disease and tumorigenesis have not been elucidated and remain to be studied. Methods: We immunohistochemically examined the expression of tumor- related markers such as p53 protein and Ki-67 antigen in 11 hyperplastic gingival tissues induced by nifedipine and phenytoin, as well as 5 control tissues using an avidin-biotin-peroxidase complex method. Results: Two specimens out of 4 nifedipine-induced and 4 out of 7 phenytoin-induced hyperplastic gingival tissues revealed the expression of p53 protein in the nuclei of epithelial cells, while no expression of p53 protein was observed in the epithelia of the 5 non-hyperplastic control tissues. The immunoreactions against p53 protein showed sporadic distribution in the suprabasal layers of hyperplastic epithelia. The mean percentage of epithelial cells expressing Ki-67 antigen in the hyperplastic gingival tissues was more than 10% higher than that in the controls. The expression of Ki-67 antigen was suppressed in the typical rete pegs deeply elongated into lamina propria of hyperplastic gingival tissues. Intense immunostaining of Ki-67 antigen was found in fibroblasts of hyperplastic gingival tissues, while that of the control tissues was negligible. Conclusions: The expression of p53 protein in gingival hyperplasia suggests that the pathogenesis of this disease is involved with impaired DNA, while the growth arrest observed in the hyperplastic epithelia with typically elongated rete pegs as expressed with Ki-67 antigen may prevent the invasive expansion of epithelial cells undergoing DNA damage within gingival tissues and may consequently suppress tumorigenic progression. [References: 47] <51> UI - 1999208171 AU - Yoshida Y AU - Nakano Y AU - Nezu T AU - Yamashita Y AU - Koga T IN - Y. Nakano, Dept. of Preventive Dentistry, Kyushu Univ. Faculty of Dentistry, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582; Japan. E-Mail: yosh@dent.kyushu-u.ac.jp. TI - A novel NDP-6-deoxyhexosyl-4-ulose reductase in the pathway for the synthesis of thymidine diphosphate-D-fucose. SO - Journal of Biological Chemistry 11 JUN 1999Vol 274(24) (pp 16933-16939), 1999. AB - The serotype-specific polysaccharide antigen of Actinobacillus actinomycetemcomitans Y4 (serotype b) consists of D-fucose and L-rhamnose. Thymidine diphosphate (dTDP)-D-fucose is the activated nucleotide sugar form of D-fucose, which has been identified as a constituent of structural polysaccharides in only a few bacteria. In this paper, we show that three dTDP-D-fucose synthetic enzymes are encoded by genes in the gene cluster responsible for the synthesis of serotype b-specific polysaccharide in A. actinomycetemcomitans. The first and second steps of the dTDP-D-fucose synthetic pathway are catalyzed by D-glucose-1-phosphate thymidylyltransferase and dTDP-D-glucose 4,6-dehydratase, which are encoded by rmlA and rmlB in the gene cluster, respectively. These two reactions are common to the well studied dTDP-L-rhamnose synthetic pathway. However, the enzyme catalyzing the last step of the dTDP-D-fucose synthetic pathway has never been reported. We identified the fcd gene encoding a dTDP-4-keto-6- deoxy-D-glucose reductase. After purifying the three enzymes, their enzymatic activities were analyzed by reversed-phase high performance liquid chromatography. In addition, nuclear magnetic resonance analysis and gas- liquid chromatography analysis proved that the fcd gene product converts dTDP-4-keto-6-deoxy-D-glucose to dTDP-D-fucose. Moreover, kinetic analysis of the enzyme indicated that the K(m) values for dTDP-4-keto-6-deoxy-D-glucose and NADPH are 97.3 and 28.7 muM, respectively, and that the enzyme follows the sequential mechanism. This paper is the first report on the dTDP-D- fucose synthetic pathway and dTDP-4-keto-6-deoxy-D-glucose reductase. [References: 43] <52> UI - 1999200170 AU - Ormerod LD AU - Dailey JP IN - Dr. L.D. Ormerod, Mason Eye Institute, University of Missouri-Columbia, One Hospital Drive, Columbia, MO 65212; United States. TI - Ocular manifestations of cat-scratch disease. SO - Current Opinion in Ophthalmology Vol 10(3) (pp 209-216), 1999. AB - Bartonella henselae has only recently been isolated, characterized, and found to be the principal cause of cat-scratch disease (CSD). The availability of specific serologic investigations has allowed the recognition of a spectrum of ocular CSD syndromes that previously were ill defined and considered idiopathic. The primary inoculation complex causing regional lymphadenopathy is represented in the eye by Parinaud's oculoglandular syndrome; B. henselae is the most common cause. Leber's neuroretinitis has been identified for 80 years, and new data suggest that it is commonly a manifestation of CSD; the extent of the association remains to be determined, CSD optic neuritis is also described. The vitreoretinal manifestations include anterior uveitis, vitritis, pars planitis, focal retinal vasculitis, a characteristic retinal white spot syndrome, Bartonella retinitis, branch retinal arteriolar or venular occlusions, focal choroiditis, serous retinal detachments, and peripapillary angiomatous lesions. The pattern of ocular disease in AIDS-associated B, henselae infections is poorly delineated; unusual manifestations include conjunctival and retinal bacillary angiomatosis. The benefit of antimicrobial therapy for CSD in immunocompetent individuals has been difficult to establish, partly because most infections are self limited. Empirically, azithromycin, ciprofloxacin, rifampin, parenteral gentamicin, or trimethoprim-sulfamethoxazole provide the best therapeutic choices to minimize damage to the eye. [References: 72] <53> UI - 1999189222 AU - Czuczman MS AU - Dodge RK AU - Stewart CC AU - Frankel SR AU - Davey FR AU - Powell BL AU - Szatrowski TP AU - Schiffer CA AU - Larson RA AU - Bloomfield CD IN - Dr. M.S. Czuczman, Roswell Park Cancer Institute, Elm and Carlton St, Buffalo, NY 14263; United States. TI - Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: Cancer and leukemia group B study 8364. SO - Blood 01 JUN 1999Vol 93(11) (pp 3931-3939), 1999. AB - The prognostic value of immunophenotype in adult acute lymphoblastic leukemia (ALL) has varied based on the methods used, surface markers studied, and therapy administered. From April 1991 to September 1996, samples of leukemic marrow or blood from 259 eligible and evaluable adult ALL patients entering dose-intensive Cancer and Leukemia Group B (CALGB) front-line treatment protocols were prospectively studied for immunophenotypic classification by multiparameter flow cytometry (MFC) in a central laboratory. A B-lineage (B-LIN) phenotype was expressed in 79% of cases, with one third coexpressing myeloid antigens. A T-lineage (T-LIN) phenotype was expressed in 17% of cases, with one quarter coexpressing myeloid antigens. Since the advent of more intensive CALGB therapy which incorporated cyclophosphamide and the early use of L-asparaginase into the backbone of daunorubicin, vincristine and prednisone, together with central nervous system prophylaxis for adult ALL, no significant differences in response rates, remission duration, or survival have been seen in those patients coexpressing myeloid antigens. The T-LIN phenotype was associated with younger age (P= .01), a higher male to female ratio (P = .01), higher white blood cell count (P = .001) and hemoglobin (P < .001) levels, presence of a mediastinal mass (P < .001), and longer survival (P = .01) and disease-free survival (DFS) (P = .01) when compared to patients with a B-LIN phenotype. The 3-year probability of survival and DFS (95% confidence interval [CI]) of T-LIN adult ALL was 0.62 (0.46 to 0.76) and 0.62 (0.44 to 0.77), respectively. Comparatively, the 3-year probability of survival and DFS (95% CI) of B-LIN adult ALL was 0.42 (0.35 to 0.50) and 0.39 (0.31 to 0.47), respectively. The number of T markers expressed in T-LIN ALL cases was shown to have prognostic significance. In particular, patients expressing six or more markers compared with patients expressing three or fewer markers had longer DFS (P = .003)and survival (P = .004). The presence of the Philadelphia chromosome was significantly associated with B-LIN ALL cases which coexpressed CD19+, CD34+, and CD10+ (49%; P= .003), whereas the majority of t(4;11) cases were CD19+, CD34+ but CD10-. The knowledge gained from this study of MFC of a large number of patients will permit a reduction in the number of antigens to be evaluated in future studies. Overall, this should lead to cost savings without loss of valuable information. A rational approach for future studies would be to use four- color flow cytometry (instead of the current three-color) to help further streamline the study of immunophenotype of adult ALL by MFC. [References: 32] <54> UI - 1999161421 AU - Rosales F AU - Peylan-Ramu N AU - Cividalli G AU - Varadi G AU - Or R AU - Naparstek E AU - Slavin S AU - Nagler A IN - Dr. A. Nagler, Bone Marrow Transplantation Dept., Hadassah University Hospital, POB 12000, Jerusalem 91120; Israel. TI - The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases. SO - Bone Marrow Transplantation Vol 23(9) (pp 861-865), 1999. AB - Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC > 1.0 x 109/l at day +19 (10-33), ANC > 0.5 x 109/l at day +22 (10-56) and platelets > 25 x 109/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions. [References: 39] <55> UI - 1999131538 AU - Nguyen Dinh Khoa AU - Hasunuma T AU - Kobata T AU - Kato T AU - Nishioka K IN - Dr. K. Nishioka, Rheumatol., Immunol.,/Genet. Program, Institute of Medical Science, St. Marianna Univ. Sch. of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512; Japan. TI - Expression of murine HOXD9 during embryonic joint patterning and in human T lymphotropic virus type I tax transgenic mice with arthropathy resembling rheumatoid arthritis. SO - Arthritis & Rheumatism Vol 42(4) (pp 686-696), 1999. AB - Objective. To characterize the expression of murine HOXD9 during normal joint development and in arthritic joints of human T lymphotropic virus type I (HTLV-I) tax transgenic mice and the role of HTLV-I tax in HOXD9 expression. Methods. Expression of HOXD9, HOXD10, HOXD11, HOXD12, and HOXD13 genes in joint tissues at the ankle/foot regions of mouse embryos at day 10 to day 18 of gestation (E10-E18) and neonates within 10 days after birth was determined by reverse transcriptase-polymerase chain reaction and in situ reverse transcription methods. Adult synovial tissues from 5 HTLV-I tax transgenic mice with chronic polyarthritis and 4 nontransgenic (normal) mice were also examined for expression of these HOXD genes. The effect of HTLV-I on HOXD9 expression in cultured synoviocytes was studied by in vitro infection and transfection experiments. Results. Expression of HOXD9 was detected in embryonic joints, preferentially on articular cartilage, only during the early stages of joint development (up to E15), whereas other HOXD genes were expressed throughout the embryonic and neonatal stages. In adult mice, transcripts of HOXD9 were specifically detected in synovial tissues from 4 of 5 arthritic mice, especially in the lining and sublining synovial cells, but not in synovial tissues of normal mice. Activation of HOXD9 was observed in cultured synoviocytes infected with HTLV-I in vitro as well as in those transfected with HTLV-I tax. Conclusion. Our findings suggest that HOXD9 is involved not only in the early stages of normal joint development, but may also be involved in the pathologic process of arthritis. HTLV-I tax appeared as an activator of this HOX gene in cultured synoviocytes. [References: 30] <56> UI - 1999115392 AU - Denton MD AU - Magee CC AU - Sayegh MH IN - Dr. M.H. Sayegh, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; United States. E-Mail: msayegh@rics.bwh.harvard.edu. TI - Immunosuppressive strategies in transplantation. SO - Lancet 27 MAR 1999Vol 353(9158) (pp 1083-1091), 1999. <57> UI - 1999101494 AU - Barry JM IN - Dr. J.M. Barry, Div. Urology Renal Transplantation, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201; United States. TI - Renal transplantation. SO - Current Opinion in Urology Vol 9(2) (pp 121-127), 1999. AB - There has been an increase in the transplantation of kidneys from living, genetically unrelated donors and from extended criteria cadaver donors. The past policies about paid renal donors are being reconsidered. Techniques have been developed to reduce morbidity for the living renal donor. The variety of immunosuppressants allows individuation of therapy. Guidelines for conception and pregnancy have been established. [References: 37] <58> UI - 1999083848 AU - Sawa T AU - Nishimura F AU - Ohyama H AU - Takahashi K AU - Takashiba S AU - Murayama Y IN - Y. Murayama, Dept. of Periodontology/Endodontol., Okayama University Dental School, 2-5-1 Shikata-cho, Okayama 700-8525; Japan. E-Mail: murayama@dcnt.okayama-u.ac.jp. TI - In vitro induction of activation-induced cell death in lymphocytes from chronic periodontal lesions by exogenous fas ligand. SO - Infection & Immunity Vol 67(3) (pp 1450-1454), 1999. AB - Periodontitis is a chronic inflammatory disease which gradually destroys the supporting tissues of the teeth, leading to tooth loss in adults. The lesions are characterized by a persistence of inflammatory cells in gingival and periodontal connective tissues. To understand what mechanisms are involved in the establishment of chronic lesions, we hypothesized that infiltrating lymphocytes might be resistant to apoptosis. However, both Bcl- 2 and Bcl-xL were weakly detected in lymphocytes from the lesions, compared with those from peripheral blood, suggesting that these cells are susceptible to apoptosis. Nevertheless, very few apoptotic cells were observed in tissue sections from the lesions, Lymphocytes from the lesions expressed mRNA encoding Fas, whereas Fas-ligand mRNA was very weakly expressed in lymphocytes from the lesions and in periodontal tissues. Since the results indicated that lymphocytes in the lesions might be susceptible to Fas- mediated apoptosis but lack the death signal, we next investigated if these lymphocytes actually undergo apoptosis by the addition of anti-Fas antibodies in vitro. Fas-positive lymphocytes from the lesions underwent apoptosis by these antibodies, but Fas-negative lymphocytes and Fas-positive peripheral lymphocytes did not undergo apoptosis by these antibodies. These results indicate that lymphocytes in the lesions are susceptible to activation- induced cell death and are induced to die by apoptosis after the addition of exogenous Fas ligand. [References: 20] <59> UI - 1999083815 AU - Crowley PJ AU - Brady LJ AU - Michalek SM AU - Bleiweis AS IN - A.S. Bleiweis, Department of Oral Biology, University of Florida, P.O. Box 100424, Gainesville, FL 32610-0424; United States. E-Mail: bleiweis@dental.ufl.edu. TI - Virulence of a spaP mutant of Streptococcus mutans in a gnotobiotic rat model. SO - Infection & Immunity Vol 67(3) (pp 1201-1206), 1999. AB - Streptococcus mutans, the principal etiologic agent of dental caries in humans, possesses a variety of virulence traits that enable it to establish itself in the oral cavity and initiate disease. A 185-kDa cell surface- localized protein known variously as antigen I/II, antigen B, PAc, and P1 has been postulated to be a virulence factor in S. mutans. We showed previously that P1 expression is necessary for in vitro adherence of S. mutans to salivary agglutinin-coated hydroxyapatite as well as for fluid-phase aggregation. Since adherence of the organism is a necessary first step toward colonization of the tooth surface, we sought to determine what effect deletion of the gene for P1, spaP, has on the colonization and subsequent cariogenicity of this organism in vivo. Germ-free Fischer rats fed a diet containing 5% sucrose were infected with either S. mutans NG8 or an NG8- derived spaP mutant strain, PC3370, which had been constructed by allelic exchange mutagenesis. At 1-week intervals for 6 weeks after infection, total organisms recovered from mandibles were enumerated. At week 6, caries lesions also were scored. A significantly lower number of enamel and dentinal carious lesions was observed for the mutant-infected rats, although there was no difference between parent and mutant in the number of organisms recovered from teeth through 6 weeks postinfection. Coinfection of animals with both parent and mutant strains resulted in an increasing predominance of the mutant strain being recovered over time, suggesting that P1 is not a necessary prerequisite for colonization. These data do, however, suggest a role for P1 in the virulence of S. mutans, as reflected by a decrease in the cariogenicity of bacteria lacking this surface protein. [References: 25] <60> UI - 1999065537 AU - Davis CJ AU - Davison R AU - Conway GS IN - C.J. Davis, Department of Obstetrics Gynaecology, University College Hospitals, London; United Kingdom. TI - Familial premature ovarian failure: Clinical and genetic features. SO - Contemporary Reviews in Obstetrics & Gynaecology Vol 10(4) (pp 289-294), 1998. AB - Premature ovarian failure (POF) occurs in approximately 1% of women, with potentially serious consequences in terms of reduced fertility cardiovascular and bone demineralization risks. In the majority of cases the cause is unknown; however, certain families demonstrate variable patterns of inheritance, ranging between autosomal dominant, recessive and X linked. Familial POF accounts for 5% of cases and is characterized by a trend toward primary amenorrhoea and negative autoimmunity, suggesting a genetic predisposition. There are a number of genetic syndromes causing POF which include Turner's syndrome, galactosaemia, fragile X premutation and follicle stimulating hormone receptor abnormalities. Despite there being no male phenotype for POF, the genetic mode of inheritance is clearly transmitted through males in certain families. Although it is likely that several genes are responsible for ovarian development, a number of candidate genes, harbouring mutations, on both the X chromosome and the autosomes have been identified as potential genetic causes of POF. The analysis of these may allow the possibility for gene therapy in the future. [References: 40] <61> UI - 1999033840 AU - Smith DJ AU - King WF AU - Wu CD AU - Shen BI AU - Taubman MA IN - D.J. Smith, Department of Immunology, Forsyth Dental Center, 140 The Fenway, Boston, MA 02115; United States. E-Mail: dsmith@forsyth.org. TI - Structural and antigenic characteristics of Streptococcus sobrinus glucan binding proteins. SO - Infection & Immunity Vol 66(11) (pp 5565-5569), 1998. AB - Three purified glucan binding proteins (GBP-2, GBP-3, and GBP-5) from Streptococcus sobrinus 6715 were compared structurally by mass spectroscopy of tryptic fragments and antigenically by Western blot analysis with rat antisera to each GBP or to peptides containing putative glucan binding epitopes of mutans streptococcal glucosyltransferases. Structural and antigenic analyses indicated that GBP-3 and GBP-5 are very similar but that both are essentially unrelated to GBP-2. None of these S. sobrinus GBPs appeared to have a strong antigenic relationship with GBPs from Streptococcus mutans. Thus, S. sobrinus GBP-2 and GBP-3 appear to be distinct proteins with potentially different functions. S. sobrinus GBP-5 may be a proteolytic fragment of GBP-3, or, alternatively, the genes coding for these proteins may be closely related. [References: 19] <62> UI - 1999030385 AU - Munoz A AU - Bureo E AU - Ortega JJ AU - Richard C AU - Olive T AU - Maldonado MS AU - Madero L AU - Diaz MA IN - Dr. A. Munoz, Servicio de Pediatria, Hospital Ramon y Cajal, 28034 Madrid; Spain. TI - Treatment of Ph1-positive chronic myelogenous leukemia in children: Comparison between allogeneic bone marrow transplantation and conventional chemotherapy. SO - Haematologica Vol 83(11) (pp 981-984), 1998. AB - Background and Objective. To compare the estimated survival and disease- free survival between children with Ph1-positive chronic myeloid leukemia treated with allogeneic bone marrow transplantation or conventional chemotherapy. Design and Methods. In this retrospective study we compared the results obtained in a group of 14 children who received allogeneic bone marrow transplantation (BMT) between 1983 and 1993, and another group of 27 children treated with busulfan, hydroxyurea or alpha-interferon during the same time period. Patients were transplanted at a median of 7 months from diagnosis and all except one were in their first chronic phase. Conditioning consisted in total body irradiation and cyclophosphamide in 12 cases, and busulfan was added in two. Results. Of the 14 patients treated with BMT, two died of transplant-related complications and two relapsed 18 and 48 months after the BMT. Ten children remain alive and disease free at a median follow up of 60 months. The probability of DFS at 5 years is 70%. Of the 27 patients treated with chemotherapy, 22 have died at a median of 36 months from diagnosis. The probability of survival at 5 years is 5% versus 83% for the BMT group (p = 0.001). Interpretation and Conclusions. Allogeneic BMT is a safe and very effective treatment for Ph-positive CML in children. Patients who have an HLA-identical sibling donor must receive a transplant as soon as possible after being diagnosed. [References: 20] <63> UI - 1999024166 AU - Sims TJ AU - Mancl LA AU - Braham PH AU - Page RC IN - R.C. Page, Research Center in Oral Biology, Box 357480, University of Washington, Seattle, WA 98195; United States. E-Mail: rcobiol@u.washing ton.edu. TI - Antigenic variation in Bacteroides forsythus detected by a checkerboard enzyme-linked immunosorbent assay. SO - Clinical & Diagnostic Laboratory Immunology Vol 5(5) (pp 725-731), 1998. AB - Evidence indicating that multiple serotypes of Bacteroides forsythus participate in rapidly progressing periodontal infections has not been reported previously. Our aim was to develop an assay for detecting subsets of B. forsythus clinical isolates which differ in serogroup membership and subsets of patients with immunoglobulin G (IgG) responses which differ in serogroup recognition. A checkerboard enzyme-linked immunosorbent assay (ELISA) was used to assess variation in the IgG binding profiles of 22 clinical isolates in sera from 28 patients with early-onset rapidly progressive periodontitis. To accommodate the maximum number of isolates and sera in a given assay run, a multiplate assay grid with standard 96-well microtest plates was established. Single dilutions of individual sera were placed in rows crossing columns of isolate-coated wells, and antigenspecific IgG immobilized in the we