Database: MEDLINE <: biomedical, nursing & dental literature, 1966 - Nov 2000.> Search Strategy (You Saved Citations 1-115 From Set 76): ----------------------------------------------------------------------------- 1 "Allergy and immunology"/ 2437 2 exp Immunity/ 541498 3 ((natural or disease) adj2 (immunity or resistan:)).mp. 5385 4 ("non-specific" adj (immunity or resistan:)).mp. 359 5 (bacteria$1 adj immun:).mp. 1701 6 (bacteria$1 adj resistan:).mp. 1436 7 (mucosa$1 adj immun:).mp. 2320 8 (immun: adj respons:).mp. 56666 9 (immun: adj recogni:).mp. 1431 10 exp Immunologic deficiency syndromes/ 120868 11 ((ADA or "adenosine deaminase") adj deficien$2).mp. 520 12 immunolog:.mp. 144751 13 immunity.mp. 53402 14 or/1-13 764954 15 exp Tooth demineralization/ 22684 16 demineralization.mp. 1629 17 caries.mp. 15334 18 caires.mp. 1 19 craies.mp. 0 20 careis.mp. 4 21 carise.mp. 0 22 (teeth adj3 cavit:).mp. 422 23 (tooth adj3 cavit:).mp. 217 24 (dental adj3 cavit:).mp. 276 25 (dentin adj3 cavit:).mp. 256 26 (enamel adj3 cavit:).mp. 183 27 (teeth adj3 decay:).mp. 379 28 (tooth adj3 decay:).mp. 325 29 (dental adj3 decay:).mp. 251 30 (dentin adj3 decay:).mp. 12 31 (enamel adj3 decay:).mp. 20 32 (active adj decay).mp. 9 33 (rampant adj3 decay:).mp. 14 34 (recurrent adj3 decay:).mp. 30 35 (white adj spot:).mp. 513 36 carious.mp. 2083 37 cariology.ti,ab. 56 38 (non-cavitated adj3 lesion:).mp. 15 39 (noncavitated adj3 lesion:).mp. 2 40 Tooth remineralization/ 479 41 (dental adj3 fissure:).mp. 99 42 (tooth adj3 fissure:).mp. 50 43 (teeth adj3 fissure:).mp. 98 44 caries-free.mp. 606 45 cariesfree.mp. 17 46 Cariogenic agents/ 729 47 precavit:.mp. 8 48 (filled adj3 teeth).mp. 513 49 (filled adj3 tooth).mp. 117 50 (oral adj fissure:).mp. 6 51 (tooth adj3 remineraliz:).mp. 28 52 (teeth adj3 remineraliz:).mp. 24 53 dft.mp. 415 54 dfs.mp. 1266 55 dmf:.mp. 6412 56 cariogeni:.mp. 1789 57 or/15-56 32343 58 14 and 57 712 59 limit 58 to english language 586 60 exp Genetics/ 1206180 61 (cn or ge).fs. 901090 62 gene$1.mp. 443661 63 genetic:.mp. 259943 64 genom:.mp. 99495 65 genotyp:.mp. 48882 66 chromosom:.mp. 199850 67 congenit:.mp. 84285 68 familial.mp. 37802 69 heritab:.mp. 5915 70 inherit:.mp. 33803 71 twin$1.mp. 19323 72 Diseases in twins/ 8030 73 exp Multiple birth offspring/ 12476 74 consanguin:.mp. 6420 75 or/60-74 1589028 76 59 and 75 115 77 from 76 keep 1-115 115 *************************** <1> UI - 20399327 AU - Yoder S AU - Cao C AU - Ugen KE AU - Dao ML IN - Department of Biology, University of South Florida, Tampa, USA. TI - High-level expression of a truncated wall-associated protein A from the dental cariogenic Streptococcus mutans. SO - DNA & Cell Biology 2000 Jul;19(7):401-8 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. <2> UI - 20314570 AU - Ochs RL AU - Muro Y AU - Si Y AU - Ge H AU - Chan EK AU - Tan EM IN - W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. TI - Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. SO - Journal of Allergy & Clinical Immunology 2000 Jun;105(6 Pt 1):1211-20 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. <3> UI - 20270569 AU - Ball ED AU - Wilson J AU - Phelps V AU - Neudorf S IN - Department of Medicine, University of California San Diego, La Jolla, CA 92093-0960, USA. TI - Autologous bone marrow transplantation for acute myeloid leukemia in remission or first relapse using monoclonal antibody-purged marrow: results of phase II studies with long-term follow-up. SO - Bone Marrow Transplantation 2000 Apr;25(8):823-9 AB - One hundred and thirty-eight patients with AML underwent ABMT with monoclonal antibody plus complement-purged marrow between August 1984 and March 1997. One hundred and ten patients were in CR (CR1: 23; CR2/3: 87) and 28 were in first relapse (R1) at ABMT. Preparative regimens included busulfan (16 mg/kg) and CY (120 mg/kg) (n = 93), CY (120 mg/kg over 2 days) with TBI (1200 cGy) (n = 35), and busulfan (16 mg/kg) plus etoposide (60 mg/kg) (n = 10). CR1 patients treated with CY/TBI (n = 7) had 3- and 5-year disease-free survival (DFS) rates of 71% and 57%. CR1 patients treated with BU/CY (n = 12), had 3- and 5-year DFS rates of 45%. Three and 5-year DFS for CR2/3 patients treated with CY/TBI (n = 26) was 23%. Three- and 5-year DFS for patients in CR2/3 treated with BU/CY (n = 55) was 31 and 28%. Three- and 5-year DFS for patients in R1 treated with BU/CY (n = 26) was 37%. In multivariate analysis, increased age was associated with greater risk of death and relapse. For CR2/3 patients, the length of CR1 was a significant predictor of DFS. ABMT performed in CR or R1 results in excellent 5-year DFS and OS. The contribution of purging may require a randomized trial comparing purged vs unpurged stem cell infusions. <4> UI - 20231807 AU - Taubman MA AU - Smith DJ AU - Holmberg CJ AU - Eastcott JW IN - Department of Immunology, The Forsyth Institute, Boston, Massachusetts 02115, USA. mtaubman@forsyth.org TI - Coimmunization with complementary glucosyltransferase peptides results in enhanced immunogenicity and protection against dental caries. SO - Infection & Immunity 2000 May;68(5):2698-703 AB - Peptide constructs from the catalytic (CAT) and glucan-binding (GLU) regions of the mutans streptococcal glucosyltransferase enzymes (GTF) can provide immunity to dental caries infection. A strategy of coimmunization was tested to determine whether protection could be enhanced. Rats were immunized with one of the previously described peptide constructs from the CAT or GLU region of the GTF of mutans streptococci or coimmunized with a combination of these constructs (CAT-GLU). Coimmunized animals demonstrated significantly higher serum immunoglobulin G (IgG) and salivary IgA antibody levels to CAT or GTF than rats immunized with either construct alone. To assess the functional significance of coimmunization with these constructs, animals were immunized as above or with Streptococcus sobrinus GTF and then infected with S. sobrinus to explore the effects of immunization on immunological, microbiological, and disease (dental caries) parameters. Serum antibody from the communized group inhibited S. sobrinus GTF-mediated insoluble glucan synthesis in vitro above that of the individual-construct-immunized groups. Immunization with CAT or GLU constructs resulted in significantly reduced dental caries after infection with S. sobrinus compared with sham-immunized animals. Coimmunization produced greater reductions in caries than after immunization with either CAT or GLU. Also, significant elevations in lymphocyte proliferative responses to CAT, GLU, and GTF were observed after coimmunization with CAT-GLU compared with the responses after immunization with the individual constructs. The results suggested that increased numbers of memory T cells, which could proliferate to CAT, were generated by coimmunization. The experiments support the functional significance of these GTF domains in dental caries pathogenesis and present coimmunization as a simple alternative to intact GTF to enhance protective immunity against cariogenic microorganisms. <5> UI - 20252596 AU - Eissa S AU - Kassim SK AU - Imam M AU - Khalifa A IN - Biochemistry Department, Ain Shams Faculty of Medicine, Abbassia, Cairo, Egypt. samar:kassim@usa.net TI - Correlation between EBV DNA and rearrangement and expression of Bcl-2 gene in aggressive non-Hodgkin's lymphoma. SO - Iubmb Life 1999 Aug;48(2):231-6 AB - Previous in vitro studies have shown that bcl-2 expression can be induced by transfection of Epstein-Barr virus (EBV)-negative non-Hodgkin's lymphoma (NHL) cell lines with EBV. This induced expression of bcl-2 is important for the long survival of EBV-positive cells and might be a first step in tumorigenesis. The purpose of the present study was to investigate the possibility of similar correlation between bcl-2 expression and EBV infection in vivo in a cohort of patients with aggressive NHL, who were uniformly evaluated and treated with effective chemotherapy. The 42 patients included were 25-65 years old. None had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Fresh biopsied samples were obtained and stored frozen for analysis of bcl-2 gene rearrangement major break point and of EBV DNA by PCR. Bcl-2 protein expression was estimated by Western blot, and enzyme immunoassay. With a median follow-up of 30 months, overall survival (OS) and disease-free survival (DFS) were measured to determine the prognostic significance of these variables. Analyzable DNA was present in all samples, 24% demonstrating bcl-2 rearrangement and 33% showing EBV DNA. Patients with bcl-2 gene rearrangement tended to have shorter DFS, and OS than patients without translocation. Bcl-2 protein expression was not correlated to gene rearrangement and had no significant influence on survival. The presence of EBV DNA in NHL had no prognostic significance but was correlated to bcl-2 expression. EBV-positive tumors showed higher bcl-2 expression than EBV-negative tumors did. Our results suggest a role of EBV infection in inducing bcl-2 expression as a survival factor for EBV-positive cells. <6> UI - 20196979 AU - Talwar GP AU - Diwan M AU - Razvi F AU - Malhotra R IN - Talwar Research Foundation, New Delhi, India. TI - The impact of new technologies on vaccines. [Review] [75 refs] SO - National Medical Journal of India 1999 Nov-Dec;12(6):274-80 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 acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria 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 Haemophilus 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] <7> UI - 20120090 AU - Poole LB AU - Higuchi M AU - Shimada M AU - Calzi ML AU - Kamio Y IN - Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem 27157, NC, USA. lbpoole@wfubmc.edu TI - Streptococcus mutans H2O2-forming NADH oxidase is an alkyl hydroperoxide reductase protein. SO - Free Radical Biology & Medicine 2000 Jan 1;28(1):108-20 AB - Nox-1 from Streptococcus mutans, the bacteria which cause dental caries, was previously identified as an H2O2-forming reduced nicotinamide adenine dinucleotide (NADH) oxidase. Nox-1 is homologous with the flavoprotein component, AhpF, of Salmonella typhimurium alkyl hydroperoxide reductase. A partial open reading frame upstream of nox1, homologous with the other (peroxidase) component, ahpC, from the S. typhimurium system, was also identified. We report here the complete sequence of S. mutans ahpC. Analyses of purified AhpC together with Nox-1 have verified that these proteins act as a cysteine-based peroxidase system in S. mutans, catalyzing the NADH-dependent reduction of organic hydroperoxides or H2O2 to their respective alcohols and/or H2O. These proteins also catalyze the four-electron reduction of O2 to H2O2, clarifying the role of Nox-1 as a protective protein against oxygen toxicity. Major differences between Nox-1 and AhpF include: (i) the absolute specificity of Nox-1 for NADH; (ii) lower amounts of flavin semiquinone and a more prominent FADH2 to NAD+ charge transfer absorbance band stabilized by Nox-1; and (iii) even higher redox potentials of disulfide centers relative to flavin for Nox-1. Although Nox-1 and AhpC from S. mutans were shown to play a protective role against oxidative stress in vitro and in vivo in Escherichia coli, the lack of a significant effect on deletion of these genes from S. mutans suggests the presence of additional antioxidant proteins in these bacteria. <8> UI - 20043984 AU - Huang CC AU - Song YL IN - Department of Zoology, National Taiwan University, Taipei. TI - Maternal transmission of immunity to white spot syndrome associated virus (WSSV) in shrimp (Penaeus monodon). SO - Developmental & Comparative Immunology 1999 Oct-Dec;23(7-8):545-52 AB - Beta-1,3-1,6-glucan, derived from bakers' yeast Saccharomyces cerevisiae, was used in the present study to investigate the extent to which glucan is able to protect spawners from white spot syndrome associated virus (WSSV), and whether this protection (if any) can be passed on to hatchlings via maternal transmission of immunity. Results showed that fewer spawners in the glucan-injected groups showed the clinical symptoms of red body coloration and white spots on the shell during the 15 days between eyestalk ablation and the end of repeated spawning. This suggests that the application of glucan might lead to a slight enhancement of disease resistance in spawners, although the differences were not statistically significant within the confidence limit chosen. Challenge results showed a significant increase in relative percent survival for larvae derived from groups of glucan-injected spawners compared to those derived from groups of untreated spawners. It therefore seems that a maternally transmitted disease resistance induced by glucan, protected the larvae against a WSSV infection. Glucan immersion was not only shown to be effective for nauplii derived from spawners that were not injected with glucan, it also provided additional, cumulative protection for nauplii which already had a maternally transmitted resistance to WSSV. This is the first documented demonstration of a maternal transmission of immunity in invertebrates. <9> UI - 20067241 AU - Slavkin HC IN - National Institute of Dental and Craniofacial Research, Bethesda, Md. 20892-2290, USA. TI - Streptococcus mutans, early childhood caries and new opportunities. SO - Journal of the American Dental Association 1999 Dec;130(12):1787-92 <10> UI - 20065968 AU - Bowden GH AU - Nolette N AU - Ryding H AU - Cleghorn BM IN - Department of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg, Canada. TI - The diversity and distribution of the predominant ribotypes of Actinomyces naeslundii genospecies 1 and 2 in samples from enamel and from healthy and carious root surfaces of teeth. SO - Journal of Dental Research 1999 Dec;78(12):1800-9 AB - The bacterial communities associated with root caries are highly diverse and undergo succession during lesion formation. Consequently, root caries is said to have a polymicrobic etiology, typified by variation in the predominant species among samples from different lesions. Despite the polymicrobic etiology, A. naeslundii genospecies 1 and 2 (previously A. viscosus) have consistently been shown to be associated with root caries in humans; they predominate in some lesions and have been suggested to play a significant role in the disease. Several genetic variants of A. naeslundii are known to be present among the oral A. naeslundii population of an individual. The current study was initiated to explore the possibility that a variant in these A. naeslundii populations had characteristics which made it best fitted to colonize or promote root-surface caries lesions. Using ribotyping to detect variants, we tested the hypothesis that 'a ribotype of A. naeslundii best fitted to the environment would be selected and predominate in the A. naeslundii population of lesions'. Samples of plaque from enamel, normal root surfaces, plaque overlying the lesion, and material from within the lesion were taken from nine patients with soft root caries. The flora from 14 lesions and 9 enamel sites was analyzed on selective and non-selective media, and A. naeslundii genospecies were identified by serology. We ribotyped 972 isolates, showing 54 different patterns. Between 6 and 20 ribotypes were isolated from eight of nine patients. In general, each site from a patient showed a similar distribution of ribotypes. These results do not support the hypothesis and suggest that any phenotypic characters that allow A. naeslundii genospecies 1 and 2 to colonize or contribute to the formation of root-caries lesions are common among strains identified by ribotyping. <11> UI - 20030876 AU - Acton RT AU - Dasanayake AP AU - Harrison RA AU - Li Y AU - Roseman JM AU - Go RC AU - Wiener H AU - Caufield PW IN - Department of Microbiology, Schools of Dentistry, Medicine and Public Health, University of Alabama at Birmingham 35294-4400, USA. 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 1999 Oct;60(10):984-9 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 < or = 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. <12> UI - 20038320 AU - Jespersgaard C AU - Hajishengallis G AU - Huang Y AU - Russell MW AU - Smith DJ AU - Michalek SM IN - Departments of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. TI - Protective immunity against Streptococcus mutans infection in mice after intranasal immunization with the glucan-binding region of S. mutans glucosyltransferase. SO - Infection & Immunity 1999 Dec;67(12):6543-9 AB - Here we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of the gtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) from Streptococcus mutans and thioredoxin from Escherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polypeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P < 0.01) which were sustained to the end of the study (experimental day 100). Following infection with S. mutans, sham-immunized mice maintained high levels of this cariogenic organism ( approximately 60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) in S. mutans colonization after 3 weeks (P < 0.05). The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) of S. mutans infection (P < 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P < 0.01). The protective effects against S. mutans colonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio-GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any immunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries. <13> UI - 99440939 AU - Brailsford SR AU - Tregaskis RB AU - Leftwich HS AU - Beighton D IN - Joint Microbiology Research Unit, Dental Institute, King's College School of Medicine and Dentistry, London. TI - The predominant Actinomyces spp. isolated from infected dentin of active root caries lesions. SO - Journal of Dental Research 1999 Sep;78(9):1525-34 AB - Actinomyces are Gram-positive pleomorphic rods (GPPR) which form a large proportion of the oral microflora of all mammals. They have been implicated in root caries, although their role in dental caries initiation and progression is not well-understood. Many studies have focused on Actinomyces naeslundii, but few reports have documented other members of the GPPR. Therefore, we investigated the GPPRs isolated from infected dentin of active root caries lesions (n = 9) to determine which species were the most frequently isolated. The GPPR were isolated under both aerobic and anaerobic conditions and identified by biochemical and physiological tests to the species level according to the new taxonomy. Of 654 GPPR isolates investigated, 607 were identified as belonging to the genus Actinomyces. Of these, 242 were identified as A. israelii, 225 as A. gerencseriae, 109 as A. naeslundii, 15 as A. odontolyticus, and 13 as A. georgiae. Individual strains of A. israelii (n = 56) and A. gerencseriae (n = 46) were also investigated at the DNA level by means of Repetitive Extragenic Palindromic polymerase chain-reactions (REP-PCR) for the study of clonal diversity. Although only a small number of isolates was investigated, REP-PCR showed that the genotypes of both A. gerencseriae and A. israelii populations were heterogeneous within individual root caries lesions. A. gerencseriae and A. israelii strains from the same lesions did not share the same REP-PCR patterns, showing the robustness of the identification scheme. A significantly greater proportion of A. gerencseriae was isolated from the aerobic plates (p < 0.05), while the proportion of A. israelii was significantly (p < 0.05) greater from anaerobic plates. The role of individual Actinomyces spp. in the root caries process remains unclear, since various populations of GPPRs were isolated from individual active root caries lesions. <14> UI - 99268361 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 - Department of Bone Marrow Transplantation and The Cancer and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel. TI - The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases. SO - Bone Marrow Transplantation 1999 May;23(9):861-5 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 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/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. <15> UI - 99309944 AU - Weinberg MA AU - Bral M IN - Department of Periodontics, New York University College of Dentistry, NY 10010, USA. TI - Laboratory animal models in periodontology. [Review] [50 refs] SO - Journal of Clinical Periodontology 1999 Jun;26(6):335-40 AB - Animal models are needed to objectively evaluate the pathogenesis of human periodontal diseases and its various treatment modalities. Selection of the appropriate animal model depends on the similarity of the periodontium and the nature of the disease to that of humans. The more commonly used animal models for studying the pathogenesis of periodontal disease, use of implants and guided tissue regeneration have been dogs and nonhuman primates. Periodontal disease in rodents has not been found to be as closely related to the human varieties. Rats and hamsters are best suited for caries and calculus research. Ferrets may be a promising new model for studying periodontal disease and calculus formation. Variables unique to each animal species are manifested by a wide range of clinical and histopathological features. Different species have distinct diets, habits, life spans, tissue structures, host defense mechanisms and genetic traits. This article describes the diversity seen in animal models used to study microbiological, immunological, and clinical features of periodontal disease and its prevention and treatment. [References: 50] <16> UI - 99256661 AU - Rupf S AU - Merte K AU - Eschrich K IN - Department of Operative Dentistry and Periodontology, University of Leipzig, Germany. TI - Quantification of bacteria in oral samples by competitive polymerase chain reaction. SO - Journal of Dental Research 1999 Apr;78(4):850-6 AB - Information about the total amount of bacteria in oral samples contributes to assessment of an individual's risk of contracting dental caries or developing periodontitis and the prediction of that individual's clinical course. Since existing techniques are often time-consuming and expensive, it seemed attractive to look for alternative methods for the quantification of eubacteria. With their high specificity and sensitivity, polymerase chain-reaction (PCR) techniques have the potential of supplying fast and reliable results. We developed a method of competitive PCR for the quantification of eubacteria. We designed forward and reverse PCR primers which bind to highly conserved sequences of the bacterial 16S rRNA gene. A homologous competitor was synthesized with Escherichia coli 16S rDNA as a template, with the reverse primer and a hybrid primer which binds 67 bases downstream to the forward primer and carries the forward primer sequence at its 5' end. Specificity controls with 30 different bacterial species, 5 Archaea, 3 fungi, human astrocytoma cells, and rat hepatoblastoma cells were carried out. Results were positive for all eubacteria and negative for all other cells tested. Calibration curves were obtained by co-amplification of known amounts of E. coli cells in the presence of the homologous competitor. The developed method was successfully applied to assessment of the accumulation of bacteria during an oral hygiene cessation experiment. The competitive PCR method proved to be a reliable and fast method for the quantification of bacterial DNA and cultured eubacteria, as well as of bacteria in biological samples. It may find further applications not only in periodontology and cariology but also in other fields of medical microbiology. <17> UI - 99220708 AU - Rudney JD AU - Larson CJ IN - Department of Oral Science, School of Dentistry, University of Minnesota, Minneapolis 55455, USA. TI - Identification of oral mitis group streptococci by arbitrarily primed polymerase chain reaction. SO - Oral Microbiology & Immunology 1999 Feb;14(1):33-42 AB - "Mitis group" streptococci are commensal but may play some role in dental caries, septicemia or endocarditis. Rapid genotypic identification would aid studies of dental plaque ecology, or diagnostic use. AP-PCR with 58 unpaired arbitrary primers was used to characterize 7 Streptococcus gordonii, 11 Streptococcus sanguis, 2 Streptococcus crista, 5 Streptococcus parasanguis, 18 Streptococcus oralis, and 36 Streptococcus mitis (22 biovar 1 and 14 biovar 2). S. parasanguis 16S rRNA variable region primer RR2 produced species-specific bands with all S. gordonii and S. sanguis. Human V beta 1 T-cell receptor primer 434 yielded concordant genotypic identification of all phenotypically defined S. crista and S. parasanguis, 83% of S. oralis, and 74% of S. mitis biovar 1. Amplicon patterns for S. mitis biovar 2 were heterogeneous. Findings suggest that primers RR2 and 434 in succession will allow rapid identification of genotypic groups corresponding closely to mitis group species established by phenotype. <18> UI - 99110710 AU - Loftenius A AU - Andersson B AU - Butler J AU - Ekstrand J IN - Division of Dental Toxicology, Department of Basic Oral Sciences, Karolinska Institute, Huddinge, Sweden. Annika.Loftenius@ofa.ki.se TI - Fluoride augments the mitogenic and antigenic response of human blood lymphocytes in vitro. SO - Caries Research 1999;33(2):148-55 AB - It has been shown that fluoride, the agent responsible for reduction of dental caries worldwide and a recognized proliferative agent, is an adjuvant when given intragastrically to rats. Furthermore, plasma fluoride levels increase in humans after various fluoride treatments. The studies presented here show that fluoride also has the ability to affect the cells of the human immune system. This was tested by measuring the effect of sodium fluoride (NaF) on cytokine production by human whole blood cells stimulated in vitro. These studies revealed that NaF augments the human lymphocyte response from human blood to a mitogen (phytohemagglutinin, PHA) or a specific antigen (morbilli antigen from infected cells, MorbAg). The cytokine interferon-gamma (IFN-gamma), released from activated T and/or NK cells, was significantly (p<0.01) increased when whole blood cells were simultaneously incubated with 0.62 mmol/l NaF and PHA compared to PHA alone. This tendency was also true for NaF and MorbAg. The lymphocyte activation marker interleukin-2 receptor (measured in soluble form) increased after simultaneous stimulation of the cells with PHA and 0.62 mmol/l NaF compared to stimulation with PHA only. However, 0.62 mmol/l NaF did not enhance interleukin-6 release, in blood mainly produced by monocytes. The ability to influence the IFN-gamma release during an immune response could be one of the primary means by which the fluoride ion influences the immune system. <19> UI - 99051259 AU - Russell MW AU - Hajishengallis G AU - Childers NK AU - Michalek SM IN - Microbiology, University of Alabama at Birmingham, Ala. 35294-2170, USA. MWR@uab.edu TI - Secretory immunity in defense against cariogenic mutans streptococci. [Review] [105 refs] SO - Caries Research 1999;33(1):4-15 AB - Specific immune defense against cariogenic mutans streptococci is provided largely by salivary secretory IgA antibodies, which are generated by the common mucosal immune system. This system is functional in newborn infants, who develop salivary IgA antibodies as they become colonized by oral microorganisms. The mechanisms of action of salivary IgA antibodies include interference with sucrose-independent and sucrose- dependent attachment of mutans streptococci to tooth surfaces, as well as possible inhibition of metabolic activities. The goal of protecting infants against colonization by mutans streptococci might be accomplished by applying new strategies of mucosal immunization that would induce salivary IgA antibodies without the complications of parenteral immunization. Strategies of mucosal immunization against mutans streptococci currently under development include the use of surface adhesins and glucosyltransferase as key antigens, which are being incorporated into novel mucosal vaccine delivery systems and adjuvants. The oral application of preformed, genetically engineered antibodies to mutans streptococcal antigens also offers new prospects for passive immunization against dental caries. [References: 105] <20> UI - 99445375 AU - Berrozpe G AU - Timokhina I AU - Yukl S AU - Tajima Y AU - Ono M AU - Zelenetz AD AU - Besmer P IN - Molecular Biology Program Sloan-Kettering Institute, New York, NY, USA. TI - The W(sh), W(57), and Ph Kit expression mutations define tissue-specific control elements located between -23 and -154 kb upstream of Kit. SO - Blood 1999 Oct 15;94(8):2658-66 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), W(57), and Ph mutations diminish Kit expression in certain cell types such as mast cells and enhance it in others. The W(sh), W(57), 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 W(57) 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. <21> UI - 20027791 AU - Meiller TF AU - Jabra-Rizk MA AU - Baqui Aa AU - Kelley JI AU - Meeks VI AU - Merz WG AU - Falkler WA IN - Department of Oral Medicine and Diagnostic Sciences, Dental School, University of Maryland, Baltimore 21201, USA. TI - Oral Candida dubliniensis as a clinically important species in HIV-seropositive patients in the United States. SO - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, & Endodontics 1999 Nov;88(5):573-80 AB - OBJECTIVE: Interest in Candida dubliniensis has led to renewed clinical investigations regarding incidence, drug resistance, pathogenesis, and epidemiology of fungal infections in patients with HIV. C dubliniensis phenotypically resembles Candida albicans in many respects, yet it can be identified and differentiated as a unique Candida species by its phenotypic and genetic profiles. The purpose of this study was to prospectively evaluate the prevalence of C dubliniensis in clinical isolates and determine the clinical and demographic characteristics of patients harboring C dubliniensis. STUDY DESIGN: Over a 6-week period, 24 yeast-positive isolates from HIV-positive dental patients were screened for C dubliniensis through use of phenotypic criteria. HIV viral load, CD4 count, and complete oral health evaluations were performed on each patient at the same visit during which the oral fungal surveillance culture was taken. RESULTS: Six isolates from 24 HIV-seropositive and yeast-positive patients were shown to be consistent phenotypically and by electrophoretic karyotyping with the European reference strain of C dubliniensis. Dose-dependent susceptibility to fluconazole was shown in one of the C dubliniensis isolates. Five of the 6 patients demonstrated moderate to high viral loads. General oral health, as evidenced by the presence of advanced periodontal lesions and a high decayed, missing, and filled teeth index (>20), was poor in 3 of the 6 patients with C dubliniensis and 7 of the 18 patients with C albicans. A history of intravenous drug abuse was present in 50% of the C dubliniensis -positive patients, which is representative of the HIV-positive population at the hospital. CONCLUSIONS: In this small sample, C dubliniensis represented 25% of the yeast-positive cultures. The clinical significance of this interesting species in the United States may be related to high viral load, rapid AIDS progression, and/or concomitant oral disease, such as a high caries index or periodontal disease. <22> UI - 99449274 AU - Sakurai K AU - Okiji T AU - Suda H IN - Department of Endodontics, Faculty of Dentistry, Tokyo Medical and Dental University, Japan. TI - Co-increase of nerve fibers and HLA-DR- and/or factor-XIIIa-expressing dendritic cells in dentinal caries-affected regions of the human dental pulp: an immunohistochemical study. SO - Journal of Dental Research 1999 Oct;78(10):1596-608 AB - Neuro-immune interaction has been suggested to play some modulatory role in the immunodefense of the dentin/pulp complex. In this study, we performed a simultaneous immunohistochemical observation of neural elements and pulpal dendritic cells (PDCs) on human carious teeth, to obtain morphological evidence for neuro-immune interaction in response to dentinal tubule-derived carious stimuli. Human third molars bearing a pulp-exposure-free caries lesion were studied. Immunoperoxidase staining was performed with anti-HLA-DR, anti-coagulation factor XIIIa, and anti-CD14 as PDC markers, and anti-low-affinity nerve growth factor receptor (NGFR), anti-protein gene products 9.5, and anti-calcitonin gene-related peptide as nerve markers. The carious teeth usually exhibited localized accumulation of both PDCs and nerve fibers immunoreactive to each marker, in the para-odontoblastic region corresponding to the pulpal end of carious dentinal tubules. Semi-quantitative digital densitometry revealed that pixel numbers corresponding to factor-XIIIa- and NGFR-immunoreactivity were significantly higher in the carious regions than those in the non-carious regions of the same teeth as well as those in the corresponding regions of intact teeth. Classification of specimens with respect to caries depth showed that the co-increase was most apparent in teeth with superficial caries. The increase of PDCs was less pronounced in carious teeth with reparative dentin. These findings suggest that both pulpal nerves and PDCs respond promptly and actively to dentinal tubule-derived carious stimuli. The synchronized accumulation of the two structures suggests an increased opportunity for neuro-immune interaction that may be of significance in the modulation of pathological processes in the dental pulp. <23> UI - 20018861 AU - Kato H AU - Takeuchi H AU - Oishi Y AU - Senpuku H AU - Shimura N AU - Hanada N AU - Nisizawa T IN - Department of Oral Science, National Institutes of Infectious Diseases, Tokyo, Japan. TI - The immunogenicity of various peptide antigens inducing cross-reacting antibodies to a cell surface protein antigen of Streptococcus mutans. SO - Oral Microbiology & Immunology 1999 Aug;14(4):213-9 AB - A cell surface protein antigen (PAc) of Streptococcus mutans may be involved in the binding of bacteria to the tooth surface, and has long been focused upon as a candidate for a preventive vaccine of dental caries. Previously the peptide PAc (365-377) was shown to raise an antibody in B10.D2 mice which inhibited the binding of salivary components to the PAc molecule. Using this peptide as a unit peptide, two constructs based on multiple antigenic peptides, and several types of tandem repeats of two or three copies were synthesized to estimate the immunogenicity of these peptides. Increase in the immunogenicity was observed for all constructs with the use of an adjuvant compared to the unit peptide alone. However, the tandem repeat constructs generally induced antibody production in the absence of adjuvant, while the multiple antigenic peptide constructs did not induce antibody production under the same condition. Although such a phenomenon may be restricted to this particular peptide sequence, these results may influence the strategy for the design of peptide vaccines. <24> UI - 99042665 AU - Stashenko P AU - Teles R AU - D'Souza R IN - Department of Cytokine Biology, Forsyth Dental Center, Boston, Massachusetts, USA. TI - Periapical inflammatory responses and their modulation. [Review] [272 refs] SO - Critical Reviews in Oral Biology & Medicine 1998;9(4):498-521 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-1 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 modifies, 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] <25> UI - 99051089 AU - Larrick JW AU - Yu L AU - Chen J AU - Jaiswal S AU - Wycoff K IN - Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043, USA. TI - Production of antibodies in transgenic plants. [Review] [40 refs] SO - Research in Immunology 1998 Jul-Aug;149(6):603-8 AB - Plants offer a cost-effective bioreactor to produce antibodies of diverse types. Recent studies demonstrate that secretory IgA, the predominant antibody isotype of the mucosal immune system, can be made in large quantities in plants. CaroRx, the lead SIgA antibody being developed by Planet Biotechnology Inc., has demonstrated activity in pilot phase II trials versus S. mutans, the major pathogen contributing to development of dental caries. Numerous other SIgA plantibodies are in preclinical development. [References: 40] <26> UI - 99005342 AU - Kramer MH AU - Hermans J AU - Wijburg E AU - Philippo K AU - Geelen E AU - van Krieken JH AU - de Jong D AU - Maartense E AU - Schuuring E AU - Kluin PM IN - Departments of Pathology and Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. TI - Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. SO - Blood 1998 Nov 1;92(9):3152-62 AB - Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers. Copyright 1998 by The American Society of Hematology <27> UI - 99032195 AU - Evans PA AU - Short MA AU - Owen RG AU - Jack AS AU - Forsyth PD AU - Shiach CR AU - Kinsey S AU - Morgan GJ IN - Department of Haematology, The General Infirmary at Leeds, United Kingdom. TI - Residual disease detection using fluorescent polymerase chain reaction at 20 weeks of therapy predicts clinical outcome in childhood acute lymphoblastic leukemia. SO - Journal of Clinical Oncology 1998 Nov;16(11):3616-27 AB - PURPOSE: Ninety-five percent of children with acute lymphoblastic leukemia (ALL) will achieve a remission, but approximately 25% will relapse. Identifying these patients is difficult, as patients with adverse prognostic features at presentation are rare and the majority are standard risk. Analysis of minimal residual disease (MRD) may be able to determine those at risk of relapse, but the best method by which this can be accomplished has yet to be defined. The object of this study was to determine the predictive value of residual disease detection in a group of standard-risk patients with precursor-B ALL at a fixed point in therapy (week 20) using a simple fluorescent consensus immunoglobulin H (IgH) heavy chain polymerase chain reaction (PCR). PATIENTS AND METHODS: Forty-two patients who presented with precursor-B ALL with standard-risk clinical features and treated according to either the Medical Research Council (MRC) UKALL X or XI protocols were assessed using a combination of both fluorescent consensus framework I and framework III Ig heavy-chain PCR. The results of the PCR were analyzed on an ABI 373 gene sequencer with genescan software (Applied Biosystems, Foster City, CA). Clonal rearrangements detected at presentation were looked for at week 20. RESULTS: Of 42 patients, 35 had a clonal population detectable at presentation; of these, seven had more than two clonal rearrangements; this latter group showed a similar disease-free survival (DFS) to the group as a whole. Thirty of 35 patients were analyzed before their second course of intensification therapy at week 20. At this point, nine of 30 had a detectable clonal rearrangement, eight (89%) of whom have since relapsed with a median DFS of 27.5 months. Of the rest of the group (n=21), in whom no clonal rearrangement was detectable, only six (21%) have relapsed. CONCLUSION: Fluorescent IgH PCR at week 20 provides a sensitive and specific means to predict ultimate relapse (57% and 89%, respectively) and is a simple yet promising technique for the identification of patients at risk of poor outcome. <28> UI - 98386608 AU - van't Erve EH AU - Wijnand E AU - Bol M AU - Seinen W AU - Pieters RH IN - Research Institute of Toxicology, Immunotoxicology, Utrecht University, The Netherlands. vantErve@ritox.dgk.ruu.nl TI - The vehicle modulates cellular and humoral responses in contact hypersensitivity to oxazolone. SO - Toxicological Sciences 1998 Jul;44(1):39-45 AB - The development of contact hypersensitivity (CHS) greatly depends on the allergenicity of the inducing agent. However, various cofactors are known to influence the outcome of the response as well. From this perspective, we have compared the effects of five different vehicles: acetone, ethanol, dimethyl formamide (DMF), dimethyl sulfoxide (DMSO), and a 4 to 1 mixture of acetone and olive oil (AOO) on the cellular and humoral immune responses to epicutaneously applied oxazolone in female BALB/c mice. A single application of 0.2% oxazolone dissolved in acetone or ethanol induced stronger proliferative responses and higher lymph node cell numbers than the other three vehicles. Moreover, both vehicles led to higher numbers of oxazolone-specific Ab forming cells in the draining lymph nodes of sensitized animals. When the IgG2a/IgG1 ratios were determined to indicate the type of T helper cell involved, the highest values were obtained with AOO and lowest with DMF and DMSO, while acetone and ethanol were in between. Moreover, no correlation was found between oxazolone-specific antibody production and cellular responses, measured as [3H]thymidine incorporation of draining lymph node cells after sensitization and increased ear thickness after challenge. From this study it can be concluded that cellular and humoral responses in CHS to oxazolone are dissimilarly affected by the vehicles used. <29> UI - 98361686 AU - Thomas X AU - Thiebaut A AU - Olteanu N AU - Danaila C AU - Charrin C AU - Archimbaud E AU - Fiere D IN - Service d'Hematologie, Hopital Edouard Herriot, Lyon, France. TI - Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. SO - Hematology & Cell Therapy 1998 Jun;40(3):119-28 AB - Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is an aggressive form of acute leukemia that represents about one third of all adult ALL. Between 1984 and 1996, forty-three cases of Ph+ ALL (22 males and 21 females) were diagnosed in our institution by successful cytogenetic studies and/or molecular biology. Median age was 42 years (range, 20-71 years) with 28 patients aged below 50 years. Median leukocyte count was 39.7 x 10(9)/l on admission. Tumoral syndrome was seen only in 21 patients (49%) of which 4 cases presented with central nervous system (CNS) involvement. Among the 38 patients classified according to the French-American-British (FAB) criteria, 26 showed L1 and 9 L2 morphology. Three patients showed undifferentiated leukemia. Immunological study at diagnosis only showed B-cell lineage ALL with 95% of patients expressing CD10 and 50% expressing CD20. The Ph+ as sole anomaly was seen in 13 patients (31%), while additional chromosome changes were observed in 28 cases. Two patients were diagnosed only on molecular biology showing a Bcr/Abl rearrangement. Thirty-nine patients treated according to LALA protocols were eligible for the analysis of treatment outcome. Complete remission (CR) was achieved in 25 cases (64%, 95% CI: 47-79%). The median disease-free survival (DFS) and the median overall survival were 6 and 9 months respectively. Relapse was observed in 16 cases (64% of patients achieving CR). Initial parameters associated with a statistically significant worse prognosis were "blastic" fever, hyperuricemia, the presence of an extra Ph chromosome and patients whose marrow does not contain any normal mitosis (AA cases). As post-induction therapy, 13 cases followed a chemotherapy program (group 1) while 11 received early bone marrow (BM) or peripheral stem cell (PSC) transplantation (group 2) (5 allogeneic BM transplantation and 6 autologous BM or PSC transplantation). One patient did not receive any post-induction therapy. In group 1, the median DFS and overall survival were of 5 and 11 months respectively, while they were of 9 months and not reached respectively in group 2 with a 2-year survival rate of 51% (95% CI: 21-83%) confirming the requirement for intensified therapy in Ph+ ALL. <30> UI - 98341935 AU - Tomas JF AU - Lopez-Lorenzo JL AU - Requena MJ AU - Aguilar R AU - Steegmann JL AU - Camara R AU - Alegre A AU - Arranz R AU - Figuera A AU - Fernandez-Ranada JM IN - Department of Hematology, Universidad Autonoma de Madrid, Hospital Universitario La Princesa, Spain. TI - Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia. SO - Bone Marrow Transplantation 1998 Jul;22(1):47-51 AB - Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study. <31> UI - 98305521 AU - Suzuki N AU - Kurihara Y AU - Kurihara Y IN - Department of Pedodontics, Nihon University School of Dentistry at Matsudo, Japan. TI - Dental caries susceptibility in mice is closely linked to the H-2 region on chromosome 17. SO - Caries Research 1998;32(4):262-5 AB - The generation of dental caries in humans is thought to be regulated by many intrinsic and social factors. In this study, we examined the effect of MHC on susceptibility to dental caries in mice. The mean carious score of BALB.K/Ola, a H-2 congenic strain in which the H-2 region derived from C3H/HeJ (H-2(k/k)) is introduced into BALB/cJ (H-2(d/d)), was markedly reduced as compared with that of its recipient strain (BALB/cJ). Mating experiments confirmed a strong genetic linkage between H-2 haplotype and caries susceptibility. These results demonstrate that one of the genetic factors of the susceptibility in the mouse is mapped within the H-2 region. This finding of a host genetic factor influencing the generation of dental caries will help in developing clinical preventive strategies. <32> UI - 98264927 AU - Yamamoto T AU - Katayama I AU - Nishioka K IN - Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Japan. TI - Restricted usage of the T-cell receptor V beta repertoire in tonsillitis in association with palmoplantar pustulosis. SO - Acta Dermato-Venereologica 1998 May;78(3):161-3 AB - Focal infections such as chronic tonsillitis or dental caries occasionally play a role in the induction or exacerbation of palmoplantar pustulosis (PPP). Arthro-osteitis is sometimes a complication in severe cases of PPP. To study the effects of bacterial infection on the exacerbation of cutaneous lesions and arthralgia, we investigated the T-cell receptor V beta repertoire in peripheral blood mononuclear cells (PBMC) and tonsil tissue after tonsillectomy in 4 cases, who had chronic tonsillitis and a history of exacerbation of cutaneous lesions following a sore throat. First, serum levels of interleukin-6 (IL-6) and IL-8 were measured before and after tonsillectomy by enzyme-linked immunosorbent assay (ELISA). Second, 3H-TdR incorporation was used to examine the effects of the culture supernatant on the PBMC of the autologous patients, other PPP patients without tonsillitis and normal controls. T-cell receptor V beta repertoire was examined by the reverse transcriptase-polymerase chain reaction method. Results showed that IL-8 was significantly high in the serum and abundantly released from tonsillar lymphocytes, which may play a role in the accumulation of neutrophils in lesional skin. T-cell receptors V beta 6 and 12 were preferentially expressed on tonsillar lymphocytes, and V beta 4, 7, 9, 17 and 18 were detected relatively frequently. These data suggest that restricted usage of T-cell receptor V beta subsets may play a crucial role in the induction of tonsillitis associated with PPP. <33> UI - 98196384 AU - Yamamoto T AU - Katayama I AU - Nishioka K IN - Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, Japan. TI - Possible involvement of interleukin-1 in the pathogenesis of dermatofibroma. SO - Acta Dermato-Venereologica 1998 Mar;78(2):99-102 AB - Dermatofibroma (DF) is histologically characterized by proliferation of fibroblasts in the dermis. Multiple DFs occasionally develop in patients with autoimmune disorders under immunosuppressive therapy; however, the pathogenesis of DF is still unclear. To elucidate immunological involvement in the mechanism of the fibrosis in DF, we studied the role of interleukin-1 (IL-1), which has a number of biological functions, including proliferation and collagen production of fibroblasts, on DF-derived fibroblasts. 3H-thymidine incorporation was used to examine the effects of Il-1 alpha and IL-1 beta in 4 cultured fibroblast strains derived from DF and 5 fibroblast strains from normal skin. Expression of mRNA of IL-1 was also analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). Basal 3H-TdR incorporation without stimulant of DF-derived fibroblasts showed a significantly greater growth activity than normal skin-derived fibroblasts (2, 632 +/- 525 vs. 762 +/- 144 dpm, p < 0.01). Both IL-1 alpha and IL-1 beta showed a stronger growth-stimulatory activity on DF-derived fibroblasts in a dose-dependent manner than normal fibroblasts, and the percent 3H-TdR uptake of DF was 1.4-fold (IL-1 alpha; 1,000 U/ml) and 1.3-fold (IL-1 beta; 1,000 U/ml) as compared with normal fibroblasts; however, the differences did not reach any significance. When increasing concentrations of IL-1 receptor antagonist (IL-1 alpha) were added to culture medium stimulated with IL-1 alpha, the proliferative response of fibroblasts was significantly reduced. Expression of IL-1 beta and RNA was detected on both DF-derived and normal skin-derived fibroblasts, while that of IL-1 alpha mRNA was detected only on DF-derived fibroblasts. Our results suggest that IL-1 may be involved in the fibrotic process in DF at the transcriptional level and play a role in the fibroblast proliferation in an autocrine manner. <34> UI - 98097417 AU - Archimbaud E AU - Charrin C AU - Magaud JP AU - Campos L AU - Thomas X AU - Fiere D AU - Rimokh R IN - Service d'Hematologie, Hopital Edouard Herriot, Lyon, France. TI - Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint. SO - Leukemia 1998 Jan;12(1):25-33 AB - Although the presence of a chromosome 11q23 breakpoint is of recognized poor prognosis in acute lymphoblastic leukemia, its prognostic significance in acute myeloid leukemia (AML) has been the object of conflicting reports, perhaps reflecting the possibility of different entities. It has been found that only typical and generally balanced 11q23 chromosomal anomalies involve the MLL gene while atypical and generally unbalanced do not. To determine whether these two categories of AML patients had different initial characteristics and evolution, supporting different pathogenetic mechanisms, we analyzed clinical and biologic characteristics of newly diagnosed AML patients with balanced 11q23 breakpoint and/or MLL rearrangement seen over a 10-year period in our institution and compared them to cases with unbalanced 11q23 anomaly seen over the same period. These two categories of patients were compared with newly diagnosed patients with normal karyotype and no MLL rearrangement when tested, seen over the same period of time and treated similarly. Over this period, 442 newly diagnosed adult (> 15 years) AML seen in our institution had a successful karyotype performed before any therapy. Thirty-six cases (8%) had a chromosome 11q23 breakpoint including 19 cases with a balanced translocation or inversion and 17 cases with an unbalanced anomaly. Eighty-seven recently diagnosed cases of AML, for whom frozen cellular material was available, were analyzed by Southern blot for the presence of MLL gene rearrangement. Fourteen cases (16% of the tested cases) had a rearrangement of the MLL gene, including seven cases with an apparently successful karyotype not showing any 11q23 breakpoint and two cases with no available karyotype. The only case with unbalanced 11q23 chromosomal anomaly which was tested had no MLL rearrangement. There was a clear-cut clinical difference between the 28 patients having a balanced 11q23 anomaly/MLL rearrangement and the 17 patients having an unbalanced chromosomal anomaly: AML with unbalanced 11q23 anomalies occurred in older patients (P = 0.07) tended to be less frequently associated with previous exposure to topoisomerase II-active drugs and with M4/M5 FAB cytological subtypes, were always associated with other chromosomal anomalies (P < 0.0001), expressed more frequently the CD34 antigen (P = 0.05) and were of considerably poorer prognosis for achievement of CR (P = 0.005) and survival (P = 0.0005). When compared to the control population, patients with balanced anomalies had more frequent history of toxic exposure (P = 0.0003) particularly to topoisomerase II-active drugs, tended to be more frequently of M4/M5 FAB subtypes (P = 0.07), expressed more frequently HLA-DR antigen (P = 0.02) and had shorter DFS (P = 0.02). Patients with unbalanced anomalies had more frequent splenomegaly (P = 0.009), lower WBC count (P = 0.04), and much poorer prognosis for CR achievement (P = 0.0001), survival (P < 0.0001) and DFS (P = 0.01). This study confirms the high frequency of 11q23 chromosomal breakpoint/MLL rearrangement in adult AML and the probable existence of two different entities with different clinical features according to the presence of a balanced or unbalanced cytogenetic abnormality, the latter being not associated with MLL rearrangement. <35> UI - 98061465 AU - Senpuku H AU - Kato H AU - Takeuchi H AU - Noda A AU - Nisizawa T IN - Department of Oral Science, National Institute of Health, Tokyo, Japan. TI - Identification of core B cell epitope in the synthetic peptide inducing cross-inhibiting antibodies to a surface protein antigen of Streptococcus mutans. SO - Immunological Investigations 1997 Aug-Dec;26(5-7):531-48 AB - A surface protein antigen (PAc) of Streptococcus mutans, in particular, A-region of the molecule, has been considered as a possible target for the development of an effective anticaries vaccine. This region might be implicated in the induction of dental caries via interaction with salivary components. We have recently specified a unique peptide, TYEAALKQYEADL, as one of the minimum peptides that completely corresponds to the amino acid sequence of a part of the A-region. The unique peptide contains both T and B cell epitopes for the induction of cross-reacting antibodies to the PAc. In this study, we synthesized valine or glycine-substituted peptide analogs of this peptide and examined core B cell epitopes of this unique peptide by using ELISA inhibition assay. As a result, the core amino acid residues of -Y------Y---- for B cell recognition were found to likely be not only important amino acids stabilizing the structure, but also might be essential for induction of the cross-inhibiting antibodies against PAc. These results will hopefully provide us with useful information for the design of an effective anticaries peptide vaccine. <36> UI - 98013064 AU - Smith DJ AU - Shoushtari B AU - Heschel RL AU - King WF AU - Taubman MA IN - Department of Immunology, Forsyth Dental Center, Boston, Massachusetts 02115, USA. TI - Immunogenicity and protective immunity induced by synthetic peptides associated with a catalytic subdomain of mutans group streptococcal glucosyltransferase. SO - Infection & Immunity 1997 Nov;65(11):4424-30 AB - We examined the immunogenicity and induction of protective immunity of two 19-mer sequences (GGY and AND) which overlapped a highly conserved region which has recently been implicated in the enzymatic activity of glucosyltransferases (GTFs) of the mutans group streptococci. These peptides were synthesized as eight-branched constructs on a lysine core. Serum immunoglobulin G (IgG) antibody, induced by subcutaneous (s.c. [salivary gland vicinity]) injection with these peptide constructs, reacted with the inciting antigen, with mutans streptococcal GTFs, and with a 21-mer peptide (CAT) containing an aspartate previously shown to covalently bind sucrose. Several of these antisera also inhibited the ability of Streptococcus sobrinus GTF to synthesize insoluble glucan. Significant levels of salivary IgA antibody were also induced by GGY and AND peptide constructs after s.c. injection. The effect of immunization with the GGY and AND peptide constructs on the cariogenicity of Streptococcus mutans was studied in three experiments by immunization of weanling Sprague-Dawley rats, twice at 7- to 14-day intervals with peptides, S. sobrinus GTF, or phosphate-buffered saline. All rats were then orally infected with S. mutans SJ. After 63-day infection periods, the GGY and AND-injected groups had significant dental caries reductions compared with sham-injected groups in most experiments. These studies support the existence of an additional catalytic subdomain within the sequence defined by the GGY and AND peptides. Furthermore, the epitopes defined in these sequences have significant immunogenicity, can induce immune responses which interfere with GTF-mediated glucan synthesis in vitro, and can protect rats from experimental dental caries. <37> UI - 97351083 AU - Gascoyne RD AU - Adomat SA AU - Krajewski S AU - Krajewska M AU - Horsman DE AU - Tolcher AW AU - O'Reilly SE AU - Hoskins P AU - Coldman AJ AU - Reed JC AU - Connors JM IN - Department of Pathology, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada. TI - Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. SO - Blood 1997 Jul 1;90(1):244-51 AB - The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs. <38> UI - 97158708 AU - Kluppel M AU - Nagle DL AU - Bucan M AU - Bernstein A IN - Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. TI - Long-range genomic rearrangements upstream of Kit dysregulate the developmental pattern of Kit expression in W57 and Wbanded mice and interfere with distinct steps in melanocyte development. SO - Development 1997 Jan;124(1):65-77 AB - Mutations in the murine dominant white spotting (W) locus cause pleiotropic developmental defects that affect hematopoietic cells, melanocytes, germ cells and the interstitial cells of Cajal in the gut. W mutations either alter the coding sequence of the Kit receptor tyrosine kinase, resulting in a receptor with impaired kinase activity, or affect Kit expression. Here we describe the molecular and cell-type-specific developmental defects of two of the latter class of regulatory W alleles, W57 and Wbanded(bd). In both mutants, the temporal and spatial patterns of Kit expression are dysregulated during embryogenesis and in adult animals. In Wbd mice, ectopic expression of Kit in the dermatome of the somites at days 10.8 and 11.8 of development seemed to interfere with melanoblast development. In contrast, the W57 allele leads to an intrinsic pigmentation defect by downregulating developmental Kit expression in trunk melanoblasts, but not melanoblasts around the otic vesicle. Both mutations affect transcriptional initiation of the Kit gene. The W57 allele is associated with a 80 kb deletion 5' of the Kit-coding region while Wbd is associated with a 2.8 Mb genomic inversion of chromosome 5 with the distal breakpoint between Kit and the platelet-derived growth factor receptor alpha (Pdgfra) gene, and the proximal breakpoint between the genes for the GABA receptor beta 1 (Gabrb1) and the Tec tyrosine kinase, juxtaposing the Kit and Tec tyrosine kinase genes. Neither W57 nor Wbd affect genomic sequences previously suggested in in vitro experiments to control cell-type-specific expression of Kit. These results link specific mechanisms of cellular and developmental defects to long-range genomic rearrangements that positively and negatively affect Kit transcription in different cell lineages as well as in different subpopulations of the same lineage. <39> UI - 97153252 AU - Cellier M AU - Shustik C AU - Dalton W AU - Rich E AU - Hu J AU - Malo D AU - Schurr E AU - Gros P IN - Department of Biochemistry, McGill University, Montreal, Canada. TI - Expression of the human NRAMP1 gene in professional primary phagocytes: studies in blood cells and in HL-60 promyelocytic leukemia. SO - Journal of Leukocyte Biology 1997 Jan;61(1):96-105 AB - In the mouse, mutations at the natural resistance-associated macrophage protein 1 (Nramp1) gene abrogate resistance to infection with antigenically unrelated intracellular parasites such as Mycobacterium, Salmonella, and Leishmania. Nramp1 expression is restricted to reticuloendothelial organs and peripheral blood leukocytes, where the protein may function as a membrane transporter of an as yet to be identified substrate. To identify the human blood cell type(s) expressing NRAMP1 mRNA and determine how Nramp1 expression is regulated in these cells, we have examined separated populations of peripheral blood leukocytes and in vitro cell lines. We observed that polymorphonuclear leukocytes (PMN) are the major site of NRAMP1 expression, followed to a lesser degree by monocytes (MN). Migration of MN to tissues (alveolar macrophages) or maturation in vitro (long-term culture) was associated with a higher level of NRAMP1 expression compared with blood MN. Northern analyses of RNA from model cultured cells showed absence of NRAMP1 expression in transformed cell lines from either erythroid or lymphoid T or B lineages as well as progenitors of the monocyte/macrophage pathway (KG1, U937, THP1), and the HL-60 promyelocytic leukemia. Induction of differentiation of HL-60 cells toward either the monocyte/macrophage (vitamin D3, phorbol ester) or the granulocyte pathways (DMF, DMSO), as measured by induction of IL8-Rb, c-FMS, and CD14 marker gene expression, was concomitant with a strong induction of NRAMP1 expression. These results suggest that NRAMP1 expression is specific to the myeloid lineage and is acquired during the maturation of PMN and MN. The possibility that NRAMP1 may be a component of the phagosomal/endosomal apparatus common to PMN and MN is discussed. <40> UI - 97180036 AU - Igarashi T AU - Yamamoto A AU - Goto N IN - Department of Oral Microbiology, Showa University School of Dentistry, Tokyo, Japan. TI - Direct detection of Streptococcus mutans in human dental plaque by polymerase chain reaction. SO - Oral Microbiology & Immunology 1996 Oct;11(5):294-8 AB - Streptococcus mutans is an etiological agent in human dental caries. A method for the detection of S. mutans directly from human dental plaque by polymerase chain reaction has been developed. Oligonucleotide primers specific for a portion of the dextranase gene (dexA) of S. mutans Ingbritt (serotype c) were designed to amplify a 1272-bp DNA fragment by polymerase chain reaction. The present method specifically detected S. mutans (serotypes c, e and f), but none of the other mutans streptococci: S. cricetus (serotype a), S. rattus (serotype b), S. sobrinus (serotypes d and g), and S. downei (serotype h), other gram-positive bacteria (16 strains of 12 species of cocci and 18 strains of 12 species of bacilli) nor gram-negative bacteria (1 strain of 1 species of cocci and 20 strains of 18 species of bacilli). The method was capable of detecting 1 pg of the chromosomal DNA purified from S. mutans Ingbritt and as few as 12 colony-forming units of S. mutans cells. The S. mutans cells in human dental plaque were also directly detected. Seventy clinical isolates of S. mutans isolated from the dental plaque of 8 patients were all positive by the polymerase chain reaction. These results suggest that the dexA polymerase chain reaction is suitable for the specific detection and identification of S. mutans. <41> UI - 97156856 AU - Trahan L AU - Bourgeau G AU - Breton R IN - Groupe de Recherche en Ecologie Buccale, Faculte de medecine dentaire, Universite Laval, Quebec, Canada. TI - Emergence of multiple xylitol-resistant (fructose PTS-) mutants from human isolates of mutans streptococci during growth on dietary sugars in the presence of xylitol. SO - Journal of Dental Research 1996 Nov;75(11):1892-900 AB - The growth inhibition of mutans streptococci is one of the proposed mechanisms of action of xylitol, a caries-preventive natural carbohydrate sweetener. Xylitol is taken up and accumulated as non-metabolizable, toxic xylitol phosphate via a constitutive fructose PTS, and selects, during in vitro growth at the expense of glucose, for natural xylitol-resistant mutants that lack constitutive fructose PTS activity. Since long-term xylitol consumption leads to the emergence of xylitol-resistant mutans populations in humans in an oral environment containing sugars of dietary origin, we wanted to test the hypothesis that xylitol-resistant cells could be selected from mutans streptococci strains during in vitro growth on fructose, sucrose, or lactose. Three laboratory strains and three fresh mutans streptococcal isolates were repeatedly transferred in trypticase-yeast extract medium supplemented with glucose, fructose, sucrose, or lactose in the presence and absence of xylitol. Depending on the growth sugar, the presence of xylitol resulted in the selection of xylitol-resistant populations for several of the six strains tested, but not necessarily in the presence of all four sugars. All six strains rapidly became xylitol-resistant when grown on glucose in the presence of xylitol. All three fresh isolates became xylitol-resistant after 9 to 16 transfers in the presence of fructose or sucrose plus xylitol, while none of the laboratory strains became xylitol-resistant after 16 transfers in the presence of these sugars. The growth rates of 12 xylitol-resistant mutants in the presence of eight sugars suggested the existence of various types of xylitol-resistant mutants. The data partially explain the occurrence of xylitol-resistant mutans populations in long-term xylitol consumers and suggest a mechanism consistent with a selection process. Since various preliminary results suggest that xylitol-resistant natural mutants may be less virulent and less cariogenic than their parent strains, this selection process may alter, for the better, the mutans streptococci population of the plaque and play a role in the caries-preventive action of xylitol. <42> UI - 97000543 AU - Redman TK AU - Harmon CC AU - Michalek SM IN - Department of Microbiology, University of Alabama at Birmingham 35294-2170, USA. TI - Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats. SO - Vaccine 1996 Jun;14(9):868-78 AB - Recombinant strains of Salmonella typhimurium have been studied as antigen delivery systems to determine their effectiveness as multivalent vaccines. Here we compare the efficacy of two strains of S. typhimurium. chi 4072 (pYA2905) and chi 3987 (pYA2905), expressing SpaA of Streptococcus sobrinus 6715 as oral vaccines for dental caries. Both strains are attenuated delta cya delta crp delta asd mutants with their Asd phenotypes complemented by the Asd+ plasmid pYA2905, which also encodes a peptide fragment of SpaA. S. typhimurium chi 3987 (pYA2905), unlike S. typhimurium chi 4072 (pYA2905), contains the 100 kb S. typhimurium virulence plasmid. Fischer rats were orally immunized with approximately 10(9) S. typhimurium chi 3987 (pYA2905) or chi 4072 (pYA2905) and then challenged with cariogenic S. sobrinus 6715. Rats orally immunized with either strain of recombinant Salmonella developed salivary IgA anti-SpaA responses and had lower levels of S. sobrinus-induced dental caries than nonimmunized, infected animals. In a second series of experiments, the kinetics and isotype of the serum and salivary antibody responses were determined in rats orally immunized with S. typhimurium chi 3987 (pYA2905) or chi 4072 (pYA2905) on weeks 0 and 8. IgG and IgM serum antibody responses to SpaA and S. typhimurium were detected after the primary and secondary immunizations, and the secondary immunization boosted serum IgG anti-Salmonella activity. In general, animals immunized with chi 3987 (pYA2905) had higher serum anti-SpaA, as well as serum and salivary anti-Salmonella, responses than animals immunized with chi 4072 (pYA2905). This study demonstrates the effective use of two recombinant S. typhimurium strains as oral vaccines for inducing protective and sustained immune responses against a mucosal pathogen and suggests that the recombinant Salmonella vaccine strain carrying the virulence plasmid induced similar or higher protective immune responses than the strain lacking the virulence plasmid. <43> UI - 97090461 AU - Lee KK AU - Yu SR AU - Yang TI AU - Liu PC AU - Chen FR IN - Department of Aquaculture, National Taiwan Ocean University, Keelung, ROC. TI - Isolation and characterization of Vibrio alginolyticus isolated from diseased kuruma prawn, Penaeus japonicus. SO - Letters in Applied Microbiology 1996 Feb;22(2):111-4 AB - Outbreaks of serious mortality among cultured kuruma prawns (Penaeus japonicus) with white spotted syndrome in the carapace occurred in the summer of 1993 in I-Lan, Taiwan. A swarming bacterium, strain Swy, was isolated from the hepatopancreas of the moribund prawns using tryptic soy agar supplemented with 1% NaCl and/or thiosulphate citrate bile salt sucrose agar. This strain was characterized and identified as Vibrio alginolyticus on the basis of a number of biochemical tests. The Swy strain was virulent to both kuruma prawns (P. japonicus) and tiger prawns (P. monodon) with LD50 values of 4.43 x 10(4) and 1.57 x 10(5) cfu g body weight-1, respectively. <44> UI - 97096943 AU - Senpuku H AU - Nakai M AU - Koga T AU - Hanada N AU - Nisizawa T IN - Department of Oral Science, National Institute of Health, Tokyo, Japan. TI - Identification of a repeated epitope recognized by human serum antibodies in a surface protein antigen of Streptococcus mutans. SO - Oral Microbiology & Immunology 1996 Apr;11(2):121-8 AB - This study determined the antigen determinants of a 190-kDa protein antigen of Streptococcus mutans that is involved in the initial attachment to the tooth surface. In 5 subjects, the reactivities of serum antibodies to 7 overlapping surface protein antigen fragments covering the entire antigen molecule and 19 sequential overlapping synthetic 19-mer peptides covering the entire A-region of the surface protein antigen were examined with enzyme-linked immunosorbent assay (ELISA). The study showed that the A-region of the antigen is strongly immunogenic in humans and contains several widely distributed epitopes. In addition, an amino acid sequence of the one of dominant epitopes in a certain subject was identified as LTAENTAI with ELISA inhibition assays using the relevant truncated peptides. This epitope was located both at the positions from L-346 to I-364 and L-430 to E-437 of the antigen molecule, and serum antibodies against the epitope were found in 3 of the 5 subjects. <45> UI - 96366120 AU - Peplinski GR AU - Tsung K AU - Meko JB AU - Norton JA IN - Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA. TI - Prevention of murine breast cancer by vaccination with tumor cells modified by cytokine-producing recombinant vaccinia viruses [published erratum appears in Ann Surg Oncol 1996 Mar;3(2):231]. SO - Annals of Surgical Oncology 1996 Jan;3(1):15-23 AB - BACKGROUND: Cancer gene therapy expressing specific levels of multiple genes has not been adequately tested. This study investigates the antitumor effects of recombinant vaccinia viruses (recVVs) that express predictable levels of single and multiple cytokines in a passive immunization murine breast cancer (C3HBA) model. METHODS: Seventeen recVVs encoding different cytokine combinations under weak and strong VV promoters were constructed. Cytokine production was measured in vitro by enzyme-linked immunosorbent assay. Mice were immunized with infected C3HBA cells and rechallenged 10 days later with 10(6) parental tumor cells. Controls were treated with saline or recVVs not expressing cytokines. Tumors were measured for 24 days. Data were analyzed using Fisher's exact test and the Breslow-Gehan-Wilcoxon test. RESULTS: recVVs encoding multiple cytokines induced secretion of each cytokine at predictable levels corresponding to VV promoter strength. Ten of 10 controls developed tumors by day 11 after rechallenge. recVVs producing large but not small amounts of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) alone resulted in complete protection in all immunized mice (p = 0.0003) for 24 days and disease-free survival (DFS) was significantly prolonged versus controls (p < 0.001). GM-CSF under a weak promoter was also effective in combination with human interleukin-1 beta (hIL-1 beta; p = 0.0220; DFS, p = 0.031) or interferon-gamma (IFN-gamma; p = 0.0037; DFS, p = 0.003). Effectiveness of hIL-1 beta and IFN-gamma vaccines depended on cytokine combinations and not the amount of cytokine produced. IL-2 or tumor necrosis factor-alpha vaccines had no significant antitumor effect. CONCLUSIONS: (a) recVVs can simultaneously express controllable levels of two cytokines; (b) tumor cells modified by recVVs generate systemic antitumor immunity; and (c) strength of immunity appears to be related to the amounts and specific cytokine(s) produced. <46> UI - 96265344 AU - Madigan A AU - Murray PA AU - Houpt M AU - Catalanotto F AU - Feuerman M IN - Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, USA. TI - Caries experience and cariogenic markers in HIV-positive children and their siblings. SO - Pediatric Dentistry 1996 Mar-Apr;18(2):129-36 AB - The purpose of this cross-sectional, masked study was to compare the oral status of perinatally HIV-infected children with their uninfected siblings living in the same environment. A secondary purpose was to compare HIV-positive children for differences in oral health with respect to disease advancement. One hundred forty-seven children were examined in their homes and meeting places, using NIH criteria for caries diagnosis. Significant differences were found in the number of caries-free children (P < 0.05), past caries experience (P < 0.003), subsurface demineralizations (P < 0.0001), and caries-related bacteria (P < 0.05). However, differences in caries prevalence were not found in the 3- to 6-year-old subgroup. Caries prevalence (P < 0.001) and levels of caries-related flora in saliva were correlated to years since diagnosis (mutans streptococci P < 0.008, lactobacilli P < 0.02). Children with a more advanced disease stage had significantly more caries (P < 0.02). Among the HIV-infected children, the frequency of carbohydrate intake was clearly correlated to caries (P < 0.003) and to lactobacilli levels (P < 0.0001). It is concluded that children with perinatally acquired HIV are at greater risk for caries than their siblings, more so with advancing disease. <47> UI - 96288265 AU - Senpuku H AU - Iizima T AU - Yamaguchi Y AU - Nagata S AU - Ueno Y AU - Saito M AU - Hanada N AU - Nisizawa T IN - Department of Oral Science, National Institute of Health, Tokyo, Japan. TI - Immunogenicity of peptides coupled with multiple T-cell epitopes of a surface protein antigen of Streptococcus mutans. SO - Immunology 1996 Jun;88(2):275-83 AB - A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of the molecule, has been noted as a possible target of effective dental caries vaccine. We have previously shown that two peptides of 19 amino acids (residues 361-379, NAKATYEAALKQYEADLAA, and residues 301-319, ANAANEADYQAKLTAYQTE), which correspond to parts of the A-region, contain both T- and B-cell epitopes for the induction of cross-reacting antibodies to the PAc. In this study, for development of an appropriate antigen as a peptide vaccine for use in prophylactic dentistry, we analysed in detail the localization of the T- and B-cell epitopes of PAc(361-379) peptide and the T-cell epitope of PAc(301-319) peptide in B10 congenic mice. In four murine major histocompatibility complex (MHC) haplotypes (H-2f,d,a and k), PAc(361-377) peptide showed T- and B-cell epitopes forming a cluster. It was found that the antibody which was induced by the immunization with the peptide was strongly cross-reactive with recombinant (r)PAc. Meanwhile, PAc(305-318) peptide, recognised by five strains of mice of different MHC haplotypes (H-2f,d,a,k and s), also bore multiple T-cell epitopes. PAc(361-377) peptide coupled to PAc(305-318) significantly elevated cross-reacting antibody levels compared to immunization with PAc(361-377) only in four H-2 haplotypes. Moreover, a peptide with PAc(305-318) coupled to the N-terminal region of PAc(361-377) produced significant cross-reacting antibody against rPAc, even in B10.S mice which had not responded to immunization with PAc(361-379) peptide. Therefore, it was suggested that coupling among the peptides forming a cluster might be effective in increasing immunogenicity. These results may provide us with a useful strategy for the design of peptide-based vaccines for S. mutans in the future. <48> UI - 96276467 AU - Lanza C AU - Gottardi E AU - Gaidano G AU - Vivenza C AU - Parziale A AU - Perfetto F AU - Fornaci M AU - Barisone E AU - Madon E AU - Basso G AU - Saglio G IN - Laboratorio di Medicina e Oncologia Molecolare, Ospedale San Lulgi Gonzaga, Orbassano, Italy. TI - Persistence of E2A/PBX1 transcripts in t(1;19) childhood acute lymphoblastic leukemia: correlation with chemotherapy intensity and clinical outcome. SO - Leukemia Research 1996 May;20(5):441-3 AB - The occurrence of t(1;19) translocation was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) for the E2A/PBX1 hybrid message in a panel of 37 consecutive childhood acute lymphoblastic leukemias (ALLs). Three patients with B-precursor ALL were found to be positive at diagnosis and were re-tested during follow-up to assess the presence of minimal residual disease (MRD). Two of them became PCR-negative during treatment, whereas one remains positive 3 years after diagnosis. Since all three patients are presently in clinical and hematological complete remission, PCR detection of persistent E2A/ PBX1 transcript does not seem to affect significantly the DFS at 3 years. However, the predictivity for an eventual late relapse still remains to be assessed. <49> UI - 96264093 AU - Todryk SM AU - Kelly CG AU - Munro GH AU - Lehner T IN - Department of Immunology, United Medical and Dental Schools of Guy's & St Thomas's, London, UK. TI - Induction of immune responses to functional determinants of a cell surface streptococcal antigen. SO - Immunology 1996 Jan;87(1):55-63 AB - Antibodies directed against the cell surface adhesin, termed streptococcal antigen I/II of Streptococcus mutans can protect against dental caries. Streptococcal antigen I/II (SA I/II) interacts with salivary glycoproteins and promotes adhesion to the tooth surface. Topical application of monoclonal antibodies which recognize a domain within residues 816-1213 (fragment 3) prevents colonization by S. mutans in primates. In this study the immunogenicity and antigenicity of fragment 3 was investigated in five strains of mice. Fragment 3 induced an immune response following immunization with whole cells of S. mutans in all strains of mice. Immunization with recombinant fragment 3 also induced T-cell proliferative and antibody responses both to fragment 3 and to the SA I/II. Antibody responses to the previously defined adhesion determinants (residues 1005-1044) were weak or undetectable. Immunization of three representative strains of mice with a recombinant polypeptide (residues 975-1044) comprising this adhesion epitope and an adjacent T-cell epitope (residues 975-1004) elicited both T- and B-cell responses to the polypeptide and to native SA I/II. The B-cell epitopes overlapped with the adhesion determinant. These findings provide a means of directing immune responses to functional determinants of SA I/II. <50> UI - 96231141 AU - Nimgaonkar M AU - Kemp A AU - Lancia J AU - Ball ED IN - Department of Medicine, University of Pittsburgh Medical Center, PA 15213, USA. TI - A combination of CD34 selection and complement-mediated immunopurging (anti-CD15 monoclonal antibody) eliminates tumor cells while sparing normal progenitor cells. SO - Journal of Hematotherapy 1996 Feb;5(1):39-48 AB - Autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML) in first complete remission (CR) results in a prolonged disease-free survival (DFS) of 34%-57%. Relapse of the underlying disease is the major cause for failure of ABMT. Relapse can result fom tumor cells either surviving in the patient or reinfused in the autograft. Genetic marking of autografted cells has demonstrated that transplanted cells contribute to relapse. This finding supports the use of purged autografts. Several purging techniques have been used. Immunologic purging using the monoclonal antibody (mAb) PM-81 (anti-CD15) has been used by our center with a long-term DFS in 50% of AML patients. PM-81 reacts with 90% of AML patients, and we have used it for over 10 years. We have investigated a two-stage purging technique involving initial selection for CD34+ cells followed by mAb purging in bone marrow (BM) and peripheral blood stem cell (PBSC) harvests. This method achieved up to a 7 log diminution in leukemic cells and 1-4 log reduction in CD15+ cells, without a significant loss of hematopoietic progenitor cells. This double-purging technique has the advantages of cytoreduction, elimination of CD34- leukemic cells, and possible improvement in the clinical efficacy of purging by concentrating for CD34+ cells. Cytoreduction by CD34 enrichment followed by purging may facilitate the use of PBSC transplants in AML. <51> UI - 96110911 AU - Laloi P AU - Munro CL AU - Jones KR AU - Macrina FL IN - Centre de Genetique Moleculaire et Cellulaire, UMR CNRS 106, Universite Claude Bernard, Villeurbanne, France. TI - Immunologic characteristics of a Streptococcus mutans glucosyltransferase B sucrose-binding site peptide-cholera toxin B-subunit chimeric protein. SO - Infection & Immunity 1996 Jan;64(1):28-36 AB - Glucosyltranferases (Gtfs) produced by the mutans streptococci are recognized as virulence factors in dental caries, and the inhibition of Gtfs by secretory immunoglobulin A is predicted to provide protection against this disease. The basis of such mucosal immunity is linked to the ability to reliably stimulate production of secretory immunoglobulin A against Gtfs. In this regard, we are exploring the immunogenicities of various Gtf peptides genetically fused to the B subunit of cholera toxin (CTB), a known mucosal adjuvant. In this work, we have created a gene fusion linking the GtfB active-site (AS) peptide DANFDSIRVDAVDNVDADLLQIA to the amino terminus of CTB. This sequence, deduced from the nucleotide sequence of gtfB from Streptococcus mutans GS5, has been found to be strongly conserved in Gtfs from several mutans streptococci. We have purified this recombinant protein (AS:CTB) from Escherichia coli carrying the fusion gene under the control of the lactose operon promoter. This protein was immunogenic in rabbits and produced specific serum antibodies against both the Gtf peptide and the CTB moiety. The antiserum was tested for its ability to inhibit GtfB activity obtained from a mutant of S. mutans able to make only this enzyme and none of the other usual Gtfs or fructosyltransferase. Approximately 50% of the GtfB activity was inhibited in such assays. These results suggest that the AS of this enzyme is accessible to antibody binding and that this region of the protein may be considered a vulnerable target for vaccine design and development. The AS:CTB was able to bind GM1, ganglioside in enzyme-linked immunosorbent assays, indicating that the recombinant protein retained this property, which is though to be critical to the mucosal immunoadjuvant properties of CTB. Thus, this protein may be promising as a candidate anticaries vaccinogen alone or in combination with other Gtf peptides or conjugates. <52> UI - 96141405 AU - Ferreira MA AU - Tooley PW AU - Hatziloukas E AU - Castro C AU - Schaad NW IN - Departmento de Biologia Celular, Universidade de Brasilia, D.F., Brazil. TI - Isolation of a species-specific mitochondrial DNA sequence for identification of Tilletia indica, the Karnal bunt of wheat fungus. SO - Applied & Environmental Microbiology 1996 Jan;62(1):87-93 AB - Mitochondrial DNA (mtDNA) from five isolates of Tilletia indica was isolated and digested with several restriction enzymes. A 2.3-kb EcoRI fragment was chosen, cloned, and shown to hybridize with total DNA restricted with EcoRI from T. indica and not from a morphologically similar smut fungus, Tilletia barclayana. The clone was partially sequenced, and primers were designed and tested under high-stringency conditions in PCR assays. The primer pair Ti1/Ti4 amplified a 2.3-kb fragment from total DNA of 17 T. indica isolates from India, Pakistan, and Mexico. DNA from 25 isolates of other smut fungi (T. barclayana, Tilletia foetida, Tilletia caries, Tilletia fusca, and Tilletia controversa) did not produce any bands, as detected by ethidium bromide-stained agarose gels and Southern hybridizations. The sensitivity of the assay was determined and increased by using a single nested primer in a second round of amplification, so that 1 pg of total mycelial DNA could be detected. The results indicated that the primers which originated from a cloned mtDNA sequence can be used to differentiate T. indica from other Tilletia species and have the potential to identify teliospores contaminating wheat seeds. <53> UI - 96096468 AU - Klimpel GR AU - Chopra AK AU - Langley KE AU - Wypych J AU - Annable CA AU - Kaiserlian D AU - Ernst PB AU - Peterson JW IN - Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1019, USA. TI - A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin. SO - Journal of Experimental Medicine 1995 Dec 1;182(6):1931-42 AB - The role of stem cell factor (SCF) and its receptor (c-kit) in the intestinal secretory response to cholera toxin (CT) was investigated using a ligated intestinal loop model in mice having mutations in the dominant white spotting (W) locus and the steel (Sl) locus. W/Wv mice, which express an aberrant form of the c-kit protein, failed to give an intestinal secretory response after luminal CT challenge. In contrast, W/Wv mice and their control littermates had equivalent intestinal secretory responses to Escherichia coli heat-stable enterotoxin (STa). Sl/Sld mice, which express only a soluble truncated form of SCF, also gave a significantly reduced intestinal secretory response to CT when compared to the secretory response of their littermate controls. The unresponsiveness of W/Wv mice to CT was restricted to the intestinal tract since these mice had foot pad swelling responses to CT challenge that were equivalent to their littermate controls. Restoration of mast cells in W/Wv mice by bone marrow transplantation of control littermate bone marrow did not reverse the CT-unresponsiveness of the intestinal tract. Histological evaluation of the gastrointestinal tract from W/Wv mice showed a normal distribution of enterochromaffin cells (ECC). CT challenge of either ligated intestinal loops from C57B1/6 mice or a mouse intestinal epithelial cell line (MODE-K) resulted in elevated levels of mRNA for SCF. MODE-K cells exposed to CT also had enhanced expression of c-kit. Finally, fluid obtained from CT-challenged ligated intestinal loops from C57B1/6 mice contained significant levels of SCF. Taken together, the above results suggest that CT-induced intestinal secretory responses are dependent upon SCF-c-kit interactions. These interactions appear to be induced as a consequence of CT stimulation of the intestinal tract and may also play a role in the development or functionality of the enteric nervous system. <54> UI - 96071888 AU - Senpuku H AU - Miyauchi T AU - Hanada N AU - Nisizawa T IN - Department of Oral Science, National Institute of Health, Tokyo, Japan. TI - An antigenic peptide inducing cross-reacting antibodies inhibiting the interaction of Streptococcus mutans PAc with human salivary components. SO - Infection & Immunity 1995 Dec;63(12):4695-703 AB - A 190-kDa surface protein antigen (PAc) of Streptococcus mutans, in particular the A region of this molecule, may be implicated in the induction of dental caries via an interaction with salivary components. For this reason, it was probably used successfully as an antigenic component for experimental vaccination to prevent dental caries in animals. While developing a synthetic peptide vaccine for dental caries, as reported herein, we have identified a unique peptide, TYEAALKQYEADL, as a candidate vaccinal immunogen. The amino acid sequence of this peptide completely corresponds to the sequence of a B-cell epitope in the A region of PAc and additionally contains its own T-cell epitope for B10.D2 mice within the molecule. This peptide strongly induces the production of only cross-reacting antibodies against PAc. In addition, as demonstrated by surface plasmon resonance analysis using the BIAcore system, these cross-reacting antibodies inhibit approximately 50% of the binding of fluid-phase salivary components to immobilized recombinant PAc. <55> UI - 95359467 AU - Attal M AU - Blaise D AU - Marit G AU - Payen C AU - Michallet M AU - Vernant JP AU - Sauvage C AU - Troussard X AU - Nedellec G AU - Pico J AU - et al IN - Department of Hematology, Hopital Purpan, Toulouse, France. TI - Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone marrow transplantation. BGMT Group. SO - Blood 1995 Aug 15;86(4):1619-28 AB - A prospective, randomized trial was initiated in adult acute lymphoblastic leukemia (ALL) to compare (1) disease-free survival (DFS) after allogeneic or autologous bone marrow transplantation (BMT) and (2) the relapse rate of patients treated with or without interleukin-2 (IL-2) after autologous BMT. A total of 135 previously untreated patients, aged under 55 years, received the Berlin-Frankfurt-Muster (BFM) induction regimen: 126 patients (93%), of which 120 were HLA-typed, achieved complete remission (CR). According to this genetic randomization, patients with (n = 43) or without an HLA-identical sibling (n = 77) were to receive allogeneic or autologous BMT, respectively. The 3-year post-CR probability of DFS was significantly higher in the HLA-identical sibling group than in the non-HLA-identical sibling group (68% v 26%; P < .001). Eligible patients were randomized to receive (n = 30) or not to receive (n = 30) IL-2 after autologous BMT: the 3-year post-BMT probability of continuous CR was similar in both groups (29% v 27%, respectively). We conclude that, in ALL, early allogeneic BMT after the BFM induction regimen is an effective consolidation treatment and that IL-2 does not decrease the high relapse rate observed after autologous BMT. <56> UI - 95347827 AU - Taubman MA AU - Holmberg CJ AU - Smith DJ IN - Department of Immunology, Forsyth Dental Center, Boston, Massachusetts 02115, USA. TI - Immunization of rats with synthetic peptide constructs from the glucan-binding or catalytic region of mutans streptococcal glucosyltransferase protects against dental caries. SO - Infection & Immunity 1995 Aug;63(8):3088-93 AB - Previously, we have described peptide constructs from two regions of glucosyltransferase (GTF) of mutans streptococci. A putative catalytic site in the amino-terminal half of the molecule and a repeated glucan-binding site in the carboxyl-terminal half of GTF were the regions upon which sequences were based. The present study explored the effects of immunization with these peptide constructs (called CAT or GLU) and with streptococcal GTFs from Streptococcus sobrinus and S. mutans on immunological, microbiological, and disease parameters. Groups of immunized Sprague-Dawley rats were infected with either 10(8) S. sobrinus 6715 or 10(8) S. mutans SJ32 organisms. Serum immunoglobulin G antibody levels, determined by enzyme-linked immunosorbent assay, to the respective peptide constructs and to the appropriate streptococcal GTF were significantly increased (after immunization) prior to infection and at the end of the experiment. Also, serum antibody from CAT-, GLU-, and S. sobrinus GTF-immunized rats inhibited S. sobrinus GTF-mediated insoluble glucan synthesis (all) and S. mutans GTF-mediated soluble glucan synthesis (all except anti-GLU) from sucrose. Immunization with the CAT or GLU peptide construct resulted in significantly reduced smooth surface and sulcal caries after infection with S. sobrinus. Sulcal dental caries after infection with S. mutans SJ32 were also significantly reduced in CAT- and GLU-immunized rats. Thus, immunization with peptides whose sequences are based on putative functional domains of mutans streptococcal GTF are protective toward a cariogenic S. sobrinus or S. mutans infection. <57> UI - 95369929 AU - Kelly CG AU - Todryk S AU - Kendal HL AU - Munro GH AU - Lehner T IN - Department of Immunology, United Medical School at Guy's Hospital, London, United Kingdom. TI - T-cell, adhesion, and B-cell epitopes of the cell surface Streptococcus mutans protein antigen I/II. SO - Infection & Immunity 1995 Sep;63(9):3649-58 AB - The T-cell and antibody responses to a cell surface streptococcal antigen (SA I/II) were investigated in naturally sensitized humans. Serum antibody responses were directed predominantly to the N-terminal (residues 39 to 481) and central (residues 816 to 1213) regions of SA I/II which may be involved in bacterial adhesion to salivary receptors. T-cell responses were also directed predominantly towards the central region. The linear peptide relationship of the immunodominant and minor T- and B-cell as well as adhesion epitopes was mapped within residues 816 to 1213. Immunodominant T-cell and B-cell epitopes were identified within residues 803 to 853, which were separated in linear sequence from the adhesion epitopes (residues 1005 to 1044). Adhesion epitopes overlapped with minor B- and T-cell epitopes (residues 1005 to 1054 and 1085 to 1134). An immunodominant promiscuous T-cell epitope (residues 985 to 1004) was adjacent to an adhesion epitope (residues 1005 to 1024). The limited B-cell response to adhesion epitopes is consistent with the success of Streptococcus mutans in colonizing the oral cavity. The strategy of T-cell, adhesion, and B-cell epitope mapping has revealed a general approach for identifying components of subunit vaccines which may focus responses to critical functional determinants. Such epitopes of SA I/II may constitute the components of a subunit vaccine against dental caries. <58> UI - 95319180 AU - Slovak ML AU - Kopecky KJ AU - Wolman SR AU - Henslee-Downey JP AU - Appelbaum FR AU - Forman SJ AU - Blume KG IN - Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA, USA. TI - Cytogenetic correlation with disease status and treatment outcome in advanced stage leukemia post bone marrow transplantation: a Southwest Oncology Group study (SWOG-8612). SO - Leukemia Research 1995 Jun;19(6):381-8 AB - A retrospective cytogenetic study was performed to determine whether non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic studies were available for 90 (78%