Database: MEDLINE <: biomedical, nursing & dental literature, 1966 - Nov 2000.> Search Strategy (You Saved Citations 1-122 From Set 74): ----------------------------------------------------------------------------- 1 ("IgA" or "IgM" or "IgG").mp. 132944 2 exp Antibodies/ 484000 3 exp T-lymphocytes/ 132035 4 ("T" adj cell$1).mp. 120230 5 exp B-lymphocytes/ 51338 6 ("B" adj cell$1).mp. 55065 7 exp Macrophages/ 66982 8 exp Complement/ 36669 9 complement.mp. 68491 10 im.fs. 736370 11 9 and 10 39268 12 or/1-8,11 707573 13 exp Tooth demineralization/ 22684 14 demineralization.mp. 1629 15 caries.mp. 15334 16 caires.mp. 1 17 craies.mp. 0 18 careis.mp. 4 19 carise.mp. 0 20 (teeth adj3 cavit:).mp. 422 21 (tooth adj3 cavit:).mp. 217 22 (dental adj3 cavit:).mp. 276 23 (dentin adj3 cavit:).mp. 256 24 (enamel adj3 cavit:).mp. 183 25 (teeth adj3 decay:).mp. 379 26 (tooth adj3 decay:).mp. 325 27 (dental adj3 decay:).mp. 251 28 (dentin adj3 decay:).mp. 12 29 (enamel adj3 decay:).mp. 20 30 (active adj decay).mp. 9 31 (rampant adj3 decay:).mp. 14 32 (recurrent adj3 decay:).mp. 30 33 (white adj spot:).mp. 513 34 carious.mp. 2083 35 cariology.ti,ab. 56 36 (non-cavitated adj3 lesion:).mp. 15 37 (noncavitated adj3 lesion:).mp. 2 38 Tooth remineralization/ 479 39 (dental adj3 fissure:).mp. 99 40 (tooth adj3 fissure:).mp. 50 41 (teeth adj3 fissure:).mp. 98 42 caries-free.mp. 606 43 cariesfree.mp. 17 44 Cariogenic agents/ 729 45 precavit:.mp. 8 46 (filled adj3 teeth).mp. 513 47 (filled adj3 tooth).mp. 117 48 (oral adj fissure:).mp. 6 49 (tooth adj3 remineraliz:).mp. 28 50 (teeth adj3 remineraliz:).mp. 24 51 dft.mp. 415 52 dfs.mp. 1266 53 dmf:.mp. 6412 54 cariogeni:.mp. 1789 55 or/13-54 32343 56 12 and 55 714 57 limit 56 to english language 589 58 exp Genetics/ 1206180 59 (cn or ge).fs. 901090 60 gene$1.mp. 443661 61 genetic:.mp. 259943 62 genom:.mp. 99495 63 genotyp:.mp. 48882 64 chromosom:.mp. 199850 65 congenit:.mp. 84285 66 familial.mp. 37802 67 heritab:.mp. 5915 68 inherit:.mp. 33803 69 twin$1.mp. 19323 70 Diseases in twins/ 8030 71 exp Multiple birth offspring/ 12476 72 consanguin:.mp. 6420 73 or/58-72 1589028 74 57 and 73 122 75 from 74 keep 1-122 122 *************************** <1> UI - 20373071 AU - Simmonds RS AU - Tompkins GR AU - George RJ IN - Department of Microbiology, University of Otago, Dunedin. TI - Dental caries and the microbial ecology of dental plaque: a review of recent advances. [Review] [68 refs] SO - New Zealand Dental Journal 2000 Jun;96(424):44-9 AB - Our understanding of the microbial ecology of dental plaque has rapidly grown with recent developments in the techniques of molecular biology. In particular, knowledge of the mechanisms underlying the acquisition, establishment, pathogenicity, and evolution of the group of organisms responsible for dental caries--the mutans streptococci--has expanded to the point that we can now contemplate new opportunities for caries prevention. These advances reinforce developing concepts of dental plaque as an interdependent, interacting community of specialised organisms with an ability to rapidly adapt conferred by gene structures that facilitate the expeditious modular rearrangement of protein components. [References: 68] <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 - 20228595 AU - Ma JK IN - Department of Oral Medicine and Pathology, Guy's Hospital, London. TI - The caries vaccine: a growing prospect. SO - Dental Update 1999 Nov;26(9):374-80 AB - A vaccine against dental caries, for so long a subject of purely academic research, is currently undergoing phase II clinical trials and could be available commercially within 5 to 6 years. The approach, which is safe, effective, and provides long-term protection for up to a year, is based on a topical application and does not require any injections. The development of this vaccine has been made possible by recent advances in molecular biology and genetic engineering. Perhaps one of the most intriguing aspects has been the use of green plants to produce the vaccine. This article describes a topical vaccine against Streptococcus mutans, which is the main cause of dental caries. <6> UI - 20152089 AU - Wynn RL AU - Meiller TF AU - Crossley HL IN - Department of Oral Medicine and Diagnostic Sciences, Dental School, University of Maryland at Baltimore, USA. TI - Tobacco "plantibodies" for caries prevention. [Review] [25 refs] SO - General Dentistry 1999 Sep-Oct;47(5):450-4 <7> UI - 20090585 AU - Weiss IM AU - Kaufmann S AU - Mann K AU - Fritz M IN - Physik Department der TU-Munchen, Institut fur Biophysik, E22, James-Franck-Strasse, Garching, 85747, Germany. TI - Purification and characterization of perlucin and perlustrin, two new proteins from the shell of the mollusc Haliotis laevigata. SO - Biochemical & Biophysical Research Communications 2000 Jan 7;267(1):17-21 AB - Two new proteins, named perlucin and perlustrin, with M(r) 17,000 and 13,000, respectively, were isolated from the shell of the mollusc Halotis laevigata (abalone) by ion-exchange chromatography and reversed-phase HPLC after demineralization of the shell in 10% acetic acid. The sequence of the first 32 amino acids of perlucin indicated that this protein belonged to a heterogeneous group of proteins consisting of a single C-type lectin domain. Perlucin increased the precipitation of CaCO(3) from a saturated solution, indicating that it may promote the nucleation and/or the growth of CaCO(3) crystals. With pancreatic stone protein (lithostathine) and the eggshell protein ovocleidin 17, this is the third C-type lectin domain protein isolated from CaCO(3) biominerals. This indicates that this type of protein performs an important but at present unrecognized function in biomineralization. Perlustrin was a minor component of the protein mixture and the sequence of the first 33 amino acids indicated a certain similarity to part of the much larger nacre protein lustrin A. Copyright 2000 Academic Press. <8> 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. <9> UI - 20021679 AU - Freedman AS AU - Neuberg D AU - Mauch P AU - Soiffer RJ AU - Anderson KC AU - Fisher DC AU - Schlossman R AU - Alyea EP AU - Takvorian T AU - Jallow H AU - Kuhlman C AU - Ritz J AU - Nadler LM AU - Gribben JG IN - Department of Adult Oncology and Biostatistics, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. TI - Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. SO - Blood 1999 Nov 15;94(10):3325-33 AB - We report the results of high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT. At BM harvest, only 30% of patients were in complete remission, and overt BM infiltration was present in 47%. The disease-free survival (DFS) and overall survival (OS) are estimated to be 42% and 66% at 8 years, respectively. Patients whose BM was negative by polymerase chain reaction (PCR) for bcl2/IgH rearrangement after purging experienced longer freedom from recurrence than those whose BM remained PCR positive (P <.0001). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued complete remission (CR). The 12-year survival from diagnosis for these 153 patients is 69%. Considering that the median survival from diagnosis and first recurrence of patients with advanced follicular lymphoma are 8 and 5 years, respectively, our results provide evidence that myeloablative therapy and ABMT may prolong overall survival. <10> UI - 99396570 AU - Huang GT AU - Potente AP AU - Kim JW AU - Chugal N AU - Zhang X IN - Section of Oral Biology and Dental Research Institute, UCLA School of Dentistry, Los Angeles, CA 90095-1668. USA. TI - Increased interleukin-8 expression in inflamed human dental pulps. SO - Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, & Endodontics 1999 Aug;88(2):214-20 AB - OBJECTIVE: Elevated levels of interleukin-8, a potent chemoattractant and activator of neutrophils, are associated with infectious and inflammatory diseases. However, little is known about interleukin-8 expression in human dental pulp. The purpose of this study was to determine whether tissue levels of interleukin-8 are elevated in irreversibly inflamed human pulps. STUDY DESIGN: Experimental samples were from teeth clinically diagnosed with irreversible pulpitis (diseased pulps). Controls were from freshly extracted, caries-free third molars (normal pulps). Samples were subjected to enzyme-linked immunosorbent assay and/or immunohistochemical analysis with specific antibodies to interleukin-8. RESULTS: The enzyme-linked immunosorbent assay studies showed elevated levels of interleukin-8 in diseased pulps (mean, 1.82+/-0.79 pg/mL/microg protein), as compared to detectable interleukin-8 levels in samples from normal pulps (mean, 0.08+/-0.04 pg/mL/microg protein; P<.05). Immunohistochemical analyses demonstrated that diseased samples exhibited a higher density of localized interleukin-8 staining in areas with heavy infiltration of inflammatory cells. In contrast, normal pulps showed negative or weak interleukin-8 staining. CONCLUSIONS: Interleukin-8 concentration was higher in pulps diagnosed with irreversible pulpitis; only negligible amounts of interleukin-8 were present in normal pulps. <11> UI - 99409667 AU - Tetu B AU - Brisson J AU - Lapointe H AU - Wang CS AU - Bernard P AU - Blanchette C IN - Department of Pathology, Universite Laval, Quebec, Canada. Bernard.Tetu@crhdq.ulaval.ca TI - Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases. SO - Breast Cancer Research & Treatment 1999 May;55(2):137-47 AB - This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node-positive (NPBC) and node-negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin-3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer. <12> 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. <13> UI - 99272438 AU - Czuczman MS AU - Dodge RK AU - Stewart CC AU - Frankel SR AU - Davey FR AU - Powell BL AU - Szatrowski TP AU - Schiffer CA AU - Larson RA AU - Bloomfield CD IN - Roswell Park Cancer Institute, Buffalo, NY, USA. TI - Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: cancer and leukemia Group B study 8364. SO - Blood 1999 Jun 1;93(11):3931-9 AB - The prognostic value of immunophenotype in adult acute lymphoblastic leukemia (ALL) has varied based on the methods used, surface markers studied, and therapy administered. From April 1991 to September 1996, samples of leukemic marrow or blood from 259 eligible and evaluable adult ALL patients entering dose-intensive Cancer and Leukemia Group B (CALGB) front-line treatment protocols were prospectively studied for immunophenotypic classification by multiparameter flow cytometry (MFC) in a central laboratory. A B-lineage (B-LIN) phenotype was expressed in 79% of cases, with one third coexpressing myeloid antigens. A T-lineage (T-LIN) phenotype was expressed in 17% of cases, with one quarter coexpressing myeloid antigens. Since the advent of more intensive CALGB therapy which incorporated cyclophosphamide and the early use of L-asparaginase into the backbone of daunorubicin, vincristine and prednisone, together with central nervous system prophylaxis for adult ALL, no significant differences in response rates, remission duration, or survival have been seen in those patients coexpressing myeloid antigens. The T-LIN phenotype was associated with younger age (P =.01), a higher male to female ratio (P =.01), higher white blood cell count (P =.001) and hemoglobin (P <.001) levels, presence of a mediastinal mass (P <. 001), and longer survival (P =.01) and disease-free survival (DFS) (P =.01) when compared to patients with a B-LIN phenotype. The 3-year probability of survival and DFS (95% confidence interval [CI]) of T-LIN adult ALL was 0.62 (0.46 to 0.76) and 0.62 (0.44 to 0. 77), respectively. Comparatively, the 3-year probability of survival and DFS (95% CI) of B-LIN adult ALL was 0.42 (0.35 to 0.50) and 0.39 (0.31 to 0.47), respectively. The number of T markers expressed in T-LIN ALL cases was shown to have prognostic significance. In particular, patients expressing six or more markers compared with patients expressing three or fewer markers had longer DFS (P =.003) and survival (P =.004). The presence of the Philadelphia chromosome was significantly associated with B-LIN ALL cases which coexpressed CD19(+), CD34(+), and CD10(+) (49%; P =.003), whereas the majority of t(4;11) cases were CD19(+), CD34(+) but CD10(-). The knowledge gained from this study of MFC of a large number of patients will permit a reduction in the number of antigens to be evaluated in future studies. Overall, this should lead to cost savings without loss of valuable information. A rational approach for future studies would be to use four-color flow cytometry (instead of the current three-color) to help further streamline the study of immunophenotype of adult ALL by MFC. <14> 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. <15> UI - 99116995 AU - Kelly CG AU - Younson JS AU - Hikmat BY AU - Todryk SM AU - Czisch M AU - Haris PI AU - Flindall IR AU - Newby C AU - Mallet AI AU - Ma JK AU - Lehner T IN - Department of Immunology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, UK. c.kelly@umds.ac.uk TI - A synthetic peptide adhesion epitope as a novel antimicrobial agent [see comments]. CM - Comment in: Nat Biotechnol 1999 Jan;17(1):20 SO - Nature Biotechnology 1999 Jan;17(1):42-7 AB - The earliest step in microbial infection is adherence by specific microbial adhesins to the mucosa of the oro-intestinal, nasorespiratory, or genitourinary tract. We inhibited binding of a cell surface adhesin of Streptococcus mutans to salivary receptors in vitro, as measured by surface plasmon resonance, using a synthetic peptide (p1025) corresponding to residues 1025-1044 of the adhesin. Two residues within p1025 that contribute to binding (Q1025, E1037) were identified by site-directed mutagenesis. In an in vivo human streptococcal adhesion model, direct application of p1025 to the teeth prevented recolonization of S. mutans but not Actinomyces, as compared with a control peptide or saline. This novel antimicrobial strategy, applying competitive peptide inhibitors of adhesion, may be used against other microorganisms in which adhesins mediate colonization of mucosal surfaces. <16> 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. <17> 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] <18> 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. <19> UI - 99068997 AU - Ockenfels HM AU - Schultewolter T AU - Ockenfels G AU - Funk R AU - Goos M IN - Department of Dermatology, University of Essen, 45122 Essen, Germany. TI - The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network. SO - British Journal of Dermatology 1998 Sep;139(3):390-5 AB - Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric acid derivatives (FAEs) has been reported to be effective in the treatment of psoriasis, but the mode of action is still unknown. To clarify this phenomenon, keratinocytes from psoriatic patients as well as from healthy volunteers were mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the cytokine concentrations were then measured in the culture supernatants. Furthermore, mRNA expression was determined in epidermal growth factor (EGF) -activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78 T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in the psoriatic cocultures. However, it did not have this effect on cocultures from control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all cultures but stimulated the IL-10 secretion. This immunomodulation away from the TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells by Northern blot analysis. An increased number of eosinophils is a known side-effect in patients treated with this drug, suggesting a clinical relevance of this immunomodulation in vivo. This immunomodulation and the suppression of cytokines from the psoriatic cytokine network could be responsible for the beneficial effect of DMF in the treatment of a hyperproliferative and TH1 cytokine-mediated skin disease. <20> UI - 99069290 AU - Senpuku H AU - Yanagi K AU - Nisizawa T IN - Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan. TI - Identification of Streptococcus mutans PAc peptide motif binding with human MHC class II molecules (DRB1*0802, *1101, *1401 and *1405). SO - Immunology 1998 Nov;95(3):322-30 AB - A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of this PAc molecule, has been noted as a possible target in research for an effective dental caries vaccine. To identify the antigenic peptide binding to major histocompatibility complex (MHC) class II (HLA-DR) molecules in the A-region, we prepared a panel of overlapping synthetic peptides in the second unit of the A-region, and established that a simple enzyme-linked immunosorbent assay (ELISA) binding assay could be achieved by incubating the DR-crude. Binding to DR molecules of these peptides from nine donors was investigated by using the ELISA binding assay. It was revealed that the PAc(316-334) peptide bound more strongly to the HLA-DR molecule in seven out of nine subjects. In particular, DR8 (DRB1*0802), DR5 (DRB1*1101) and DR6 (DRB1*1402 and *1405), which bound strongly to PAc(316-334) peptide, were identified. Moreover, we synthesized glycine-substituted peptide analogues of the peptide and examined the binding motif of the binding region. As a result, the multiple binding motif in DR8, DR5 and DR6 was found in L-RV-K-A. It is suggested that a peptide vaccine for dental caries that is more effective for humans, with fewer adverse side-effects, could be designed by combining the multiple binding motif with the B-cell epitope to produce only the inhibiting antibody against dental caries. The peptide could therefore be useful for peptide vaccine development in the general human population. <21> 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] <22> 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] <23> UI - 99109545 AU - Niederacher D AU - An HX AU - Camrath S AU - Dominik SI AU - Gohring UJ AU - Oertel A AU - Grass M AU - Hantschmann P AU - Lordnejad MR AU - Beckmann MW IN - Department of Gynaecology and Obstetrics, Heinrich-Heine-Universitat, Dusseldorf, Germany. TI - Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. SO - European Journal of Cancer 1998 Oct;34(11):1770-6 AB - Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer. <24> 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 <25> 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. <26> 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. <27> 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. <28> 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. <29> UI - 98244620 AU - Arakawa T AU - Langridge WH TI - Plants are not just passive creatures: [news; comment]. CM - Comment on: Nat Med 1998 May;4(5):601-9 SO - Nature Medicine 1998 May;4(5):550-1 <30> UI - 98244634 AU - Ma JK AU - Hikmat BY AU - Wycoff K AU - Vine ND AU - Chargelegue D AU - Yu L AU - Hein MB AU - Lehner T IN - Department of Immunology, United Medical and Dental Schools, Guy's Hospital, London, UK. j.ma@umds.ac.uk TI - Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans [see comments]. CM - Comment in: Nat Med 1998 May;4(5):535, Comment in: Nat Med 1998 May;4(5):550-1 SO - Nature Medicine 1998 May;4(5):601-6 AB - A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody.The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure. In the human oral cavity, the secretory antibody survived for up to three days, compared with one day for the IgG antibody. The plant secretory antibody afforded specific protection in humans against oral streptococcal colonization for at least four months. We demonstrate that transgenic plants can be used to produce high affinity, monoclonal secretory antibodies that can prevent specific microbial colonization in humans. These findings could be extended to the immunotherapeutic prevention of other mucosal infections in humans and animals. <31> UI - 98118226 AU - Papadopoulos EB AU - Carabasi MH AU - Castro-Malaspina H AU - Childs BH AU - Mackinnon S AU - Boulad F AU - Gillio AP AU - Kernan NA AU - Small TN AU - Szabolcs P AU - Taylor J AU - Yahalom J AU - Collins NH AU - Bleau SA AU - Black PM AU - Heller G AU - O'Reilly RJ AU - Young JW IN - Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY, USA. TI - T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease. SO - Blood 1998 Feb 1;91(3):1083-90 AB - Thirty-one consecutive patients with acute myelogenous leukemia (AML) in first complete remission and 8 with AML in second complete remission received T cell-depleted allogeneic bone marrow transplants from HLA-identical sibling donors. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide. Those patients at risk for immune-mediated graft rejection received additional immune suppression with antithymocyte globulin and methylprednisolone in the early peritransplant period. Patients with AML who underwent allogeneic T-cell-depleted bone marrow transplantations (BMT) in first or second remission have achieved respective disease-free survival (DFS) probabilities of 77% (median follow-up at approximately 56 months) and 50% (median follow-up at approximately 48 months). Ten of 31 patients transplanted in first remission were > or = 40 years old and have attained a DFS at 4 years of 70%. For patients with AML transplanted in first or second remission, the respective cause-specific probabilities of relapse were 3.2% or 12.5%, and those of nonleukemic mortality were 19.4% or 37.5%. There were no cases of immune-mediated graft rejection and no cases of grade II to IV acute graft-versus-host disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS) of 100%, except 2 patients with KPS of 80% to 90%. T-cell-depleted allogeneic BMT can provide durable DFS together with an excellent performance status in the majority of patients with de novo AML. In addition, GVHD is not an obligatory correlate of the graft-versus-leukemia benefit or freedom from relapse afforded by allogeneic BMT administered as postremission therapy for AML. This study provides a basis for prospective comparison with other postremission therapies considered standard in the management of patients with this disease. <32> UI - 98101667 AU - Freedman AS AU - Neuberg D AU - Gribben JG AU - Mauch P AU - Soiffer RJ AU - Fisher DC AU - Anderson KC AU - Andersen N AU - Schlossman R AU - Kroon M AU - Ritz J AU - Aster J AU - Nadler LM IN - Division of Hematologic Malignancies and Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA. arney-freedman@dfci.harvard.edu TI - High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission [see comments]. CM - Comment in: J Clin Oncol 1998 Jan;16(1):3-5 SO - Journal of Clinical Oncology 1998 Jan;16(1):13-8 AB - PURPOSE: The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. PATIENTS AND METHODS: Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. RESULTS: Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration was present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months (range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. CONCLUSION: ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT. <33> 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. <34> UI - 98069848 AU - Clark GM AU - Allred DC AU - Hilsenbeck SG AU - Chamness GC AU - Osborne CK AU - Jones D AU - Lee WH IN - Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center, San Antonio 78284, USA. gary@oncology.uthscsa.edu TI - Mitosin (a new proliferation marker) correlates with clinical outcome in node-negative breast cancer. SO - Cancer Research 1997 Dec 15;57(24):5505-8 AB - Tumor proliferation rate is an important prognostic factor in breast cancer, and S-phase fraction (SPF), as measured by flow cytometry, is the most clinically validated of several methods for measuring it. However, flow cytometry is not well suited to evaluating the formalin-fixed, paraffin-embedded tumors that are routinely available or to the increasing number of small breast cancers. These and other limitations have motivated research into alternative methods for measuring proliferation, including immunohistochemistry (IHC) against cell cycle-related antigens, which are better suited for the evaluation of small archival tissue samples. Mitosin is a recently described 350 kD nuclear phosphoprotein that is expressed in the late G1, S, G2, and M phases of the cell cycle but not in G0. Using a new monoclonal antibody (14C10), this pilot study evaluated mitosin expression by IHC in a series of 386 node-negative, formalin-fixed, archival breast cancers and correlated the results with several prognostic factors and clinical outcome (median follow-up, 78 months; range 3-214 months). The median and range of mitosin positive cells were 7% and 1-47%, respectively. There was a strong positive correlation between mitosin and SPF (r = 0.57; P = 0.0001), and there were significant negative correlations with estrogen receptor, progesterone receptor, and patient age. Mitosin was not related to overall survival in this pilot study. However, in a univariate cutpoint analysis of disease-free survival (DFS), patients with high levels of mitosin (>9% positive cells) had significantly worse DFS than did patients with lower levels (68% versus 84% at 5 years, respectively). In a multivariate analysis of DFS, large tumor size (>2 cm) and high mitosin were the only independently significant predictors of recurrence (relative risks = 2.47 and 1.72, respectively) in a model containing the additional factors estrogen receptor, progesterone receptor, patient age, and SPF. These preliminary results suggest that mitosin as assessed by IHC may be superior to SPF as a prognostic factor in node-negative breast cancer, but additional studies are necessary to validate these promising findings. <35> 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. <36> UI - 98025885 AU - Kapur R AU - Everett ET AU - Uffman J AU - McAndrews-Hill M AU - Cooper R AU - Ryder J AU - Vik T AU - Williams DA IN - Department of Pediatrics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, USA. TI - Overexpression of human stem cell factor impairs melanocyte, mast cell, and thymocyte development: a role for receptor tyrosine kinase-mediated mitogen activated protein kinase activation in cell differentiation. SO - Blood 1997 Oct 15;90(8):3018-26 AB - Stem cell factor (SCF) is synthesized as both soluble (S) and membrane-associated (MA) proteins. Indirect insight into the function of MA and S isoforms of SCF has come from studies performed in Steel (Sl) mutant mice. However, the physiologic role(s) of these two isoforms remain unknown. In an attempt to better understand the in vivo role of c-kit/SCF interactions on various cell lineages, transgenic mice were generated that overexpress MA isoform of human SCF (hSCF). In murine cells, hSCF behaves as an antagonist to normal SCF function, due to interference with the interaction between endogenous murine SCF and its receptor, c-kit, encoded by the dominant white spotting (W) gene. Mice expressing the hSCF transgene display a variety of phenotypic abnormalities, which are accentuated when combined with W alleles. Here we show that mice homozygous for the hSCF transgene demonstrate a coat color deficiency seen in some mice homozygous for mild W alleles. Specifically, homozygous hSCF transgenic mice (hSCF220) display a pronounced forehead blaze, with additional white spots over the cervical region, as well as a very large belly spot. Doubly heterozygous animals that carry both a mutated W allele and the hSCF transgene also display an unusual pigment defect and a dramatic reduction in the number of dermal mast cells. Furthermore, overexpression of MA hSCF in the thymus results in abnormal thymocyte differentiation and proliferation, which is associated with reduced mitogen activated protein (MAP) kinase activation. Thus, MAP kinase activation by a receptor tyrosine kinase, such as c-kit, may be critical for the differentiation of thymocytes in vivo. <37> UI - 97279796 AU - Mattijssen V AU - Schattenberg A AU - Schaap N AU - Preijers F AU - De Witte T IN - Division of Haematology, University Hospital Nijmegen, The Netherlands. TI - Outcome of allogeneic bone marrow transplantation with lymphocyte-depleted marrow grafts in adult patients with myelodysplastic syndromes. SO - Bone Marrow Transplantation 1997 Apr;19(8):791-4 AB - Thirty-five patients with myelodysplastic syndromes (MDS) were treated with BMT between 1986 and 1994. Their median age was 41 years (range 23-60). Thirteen patients had transfusion-dependent refractory anaemia (RA). Twenty-two patients suffered from more advanced stages of MDS, 15 being in complete remission (CR) after chemotherapy. In 31 recipients, pretransplant conditioning consisted of cyclophosphamide and TBI with or without the addition of idarubucin; four patients were conditioned with other schedules. Donors were genotypically HLA-identical and MLC-negative siblings in 32, and others in three cases. All patients received a graft depleted of 98% of T lymphocytes using counterflow centrifugation. Fourteen patients are alive and in continuous remission with a median follow-up of 20 months (range 15-113) after BMT. Seven patients relapsed between 3 and 18 months after BMT and subsequently died. Fourteen transplantation-related deaths occurred. Outcome in patients under and over 40 years old was comparable. The probability of disease-free survival (DFS) at 2 years after BMT was 39% (95% confidence interval (CI), 22-56%). Considering patients with HLA-identical and MLC-negative sibling donors transplanted for RA (n = 11) or more advanced stages of MDS in CR (n = 14), the probabilities of DFS were 73% (95% CI, 47-99%) and 42% (95% CI, 15-69%), respectively. This indicates that BMT with lymphocyte-depleted grafts can cure a substantial number of relatively old patients with MDS, especially when grafts from HLA-identical and MLC-negative siblings are used and patients are suffering from RA. <38> 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. <39> UI - 97313162 AU - Yu H AU - Nakano Y AU - Yamashita Y AU - Oho T AU - Koga T IN - Department of Preventive Dentistry, Kyushu University, Faculty of Dentistry, Higashi-ku, Fukuoka, Japan. TI - Effects of antibodies against cell surface protein antigen PAc-glucosyltransferase fusion proteins on glucan synthesis and cell adhesion of Streptococcus mutans. SO - Infection & Immunity 1997 Jun;65(6):2292-8 AB - Cell surface protein antigen (PAc) and glucosyltransferases (GTFs) produced by Streptococcus mutans are considered to be major colonization factors of the organism, and the inhibition of these two factors is predicted to provide protection against dental caries. In this study, we have constructed fusion protein PAcA-GB, a fusion of the saliva-binding alanine-rich region (PAcA) of PAc with the glucan binding (GB) domain of GTF-I, an enzyme catalyzing the synthesis of water-insoluble glucan from sucrose, and fusion protein PAcA-SB, a fusion of PAcA with the sucrose binding (SB) domain of GTF-I. The recombinant fusion proteins were purified from cell extracts of Escherichia coli harboring the fusion genes, and rabbit antibodies against these fusion proteins were prepared. Water-insoluble glucan synthesis by cell-associated and cell-free GTF preparations from S. mutans as well as total glucan synthesis by GTF-I was markedly inhibited by anti-PAcA-GB immunoglobulin G (IgG) antibodies but not by anti-PAcA-SB IgG antibodies. Significant inhibition of the sucrose-independent and sucrose-dependent adhesion of S. mutans to saliva-coated hydroxyapatite beads was observed when anti-PAcA-GB antibodies were added to the reaction mixture. Anti-PAcA-SB antibodies inhibited the adhesion of S. mutans to the beads in the absence of sucrose but not in the presence of sucrose. Immunization with the fusion protein PAcA-GB may be useful for controlling the colonization of teeth by S. mutans. <40> UI - 97190174 AU - Chia JS AU - Lin SW AU - Yang CS AU - Chen JY IN - Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Republic of China. chiajs@ntumc1.mc.ntu.edu.tw TI - Antigenicity of a synthetic peptide from glucosyltransferases of Streptococcus mutans in humans. SO - Infection & Immunity 1997 Mar;65(3):1126-30 AB - Human salivary immunoglobulin A (IgA) and serum IgG antibodies to the Streptococcus mutans glucosyltransferases (Gtfs) and to a synthetic peptide of 19 amino acids from a conserved region in the Gtfs (residues 435 to 453) were determined in young adults by enzyme-linked immunosorbent assay. Varying levels of antibody to Gtfs were detected in saliva or serum, with significantly higher levels of antibody to GtfD than to GtfB/C or GtfC. Anti-Gtf IgA levels in saliva did not correlate with those of IgG in serum. Caries-free (CF) volunteers exhibited significantly higher salivary IgA antibody levels to the peptide and to GtfB/C or GtfC than did the caries-active (CA) subjects. Preincubation of CF saliva and serum with the peptide inhibited the antibodies to the Gtfs in a dose-dependent manner, whereas preincubation of the samples from the CA group resulted in only partial inhibition. Our results indicated that this 19-amino-acid peptide includes one of the major B-cell epitopes of Gtfs and that CF individuals have higher titers of antibodies than CA subjects. <41> UI - 97180044 AU - Senpuku H AU - Iizima T AU - Koga T AU - Nisizawa T IN - Department of Oral Science, National Institute of Health, Tokyo, Japan. TI - Identification of human antigenic epitopes in an alanine-rich repeating region using sera from hu-PBL-SCID mice immunized with a surface protein antigen of Streptococcus mutans. SO - Oral Microbiology & Immunology 1996 Oct;11(5):343-9 AB - A 190-kDa surface protein antigen (PAc) of Streptococcus mutans is considered to play an important role in dental caries. To identify antigenic epitopes of the PAc in humans, we immunized severe combined immunodeficient (SCID) mice with recombinant PAc that was transplanted with human peripheral blood mononuclear cells (PBMC). The reactivities of the sera from the immunized hu-PBL-SCID mice to the recombinant PAc and 24 19-mer synthetic peptides covering the alanine-rich repeating region (A-region) presented in the PAc molecule were then examined. The results showed that the immunized mice produced a significant recombinant PAc-specific human antibody, and among 24 19-mer peptides, 6 19-mer peptides showed a strong reaction with the antibodies. In addition, 4 19-mer peptides containing human antigenic epitope in a donor were identified with enzyme-linked immunosorbent assay (ELISA) inhibition assays using the recombinant PAc protein. In this study, the SCID mouse was useful in identifying human antigenic epitopes. <42> UI - 97013198 AU - Kobayashi I AU - Izumi T AU - Okamura K AU - Matsuo K AU - Ishibashi Y AU - Sakai H IN - Department of Oral Pathology, Faculty of Dentistry, Kyushu University, Japan. TI - Biological behavior of human dental pulp cells in response to carious stimuli analyzed by PCNA immunostaining and AgNOR staining. SO - Caries Research 1996;30(3):225-30 AB - The change in proliferative and metabolic activities of human dental pulp cells responding to carious stimuli was studied by means of immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and silver-binding nucleolar organizer region (AgNOR) staining. We classified the pulp tissues into five groups according to the progression of dental caries, ranging from grade 0 (the pulp of noncarious teeth) to grade 4 (the pulp of perforated carious teeth). PCNA-positive pulp cells were detected only in advanced dental caries (grades 3 and 4), and the difference in immuno-positive rate was significant between the two grades (p <0.001). However, the mean number of AgNORs per nucleus increased even in the early phase of dental caries, significant differences being detected between grades 1 and 2 (p<0.005), 2 and 3 (p<0.005), and 3 and 4 (p<0.001). Our data suggested that the metabolic activity of dental pulp cells was enhanced in the early phase of dental caries. However, proliferation of pulp cells occurred later in small degrees during fully developed caries such as grades 3 and 4. The slow and weak response in cellular proliferation might contribute to the usual fragility of the pulp to various assaults including caries or pulpitis. <43> 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. <44> UI - 97051061 AU - Wang Q AU - Singh S AU - Taylor KG AU - Doyle RJ IN - Department of Microbiology and Immunology, University of Louisville, Kentucky 40292, USA. TI - Anti-adhesins of Streptococcus sobrinus. [Review] [48 refs] SO - Advances in Experimental Medicine & Biology 1996;408:249-62 <45> 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. <46> UI - 96437060 AU - Freedman AS AU - Gribben JG AU - Neuberg D AU - Mauch P AU - Soiffer RJ AU - Anderson KC AU - Pandite L AU - Robertson MJ AU - Kroon M AU - Ritz J AU - Nadler LM IN - Division of Hematologic Malignancies and Biostatistics, Dana-Farber Cancer Institute, Boston, MA. TI - High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission. SO - Blood 1996 Oct 1;88(7):2780-6 AB - We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival. <47> UI - 96379381 AU - Franco E AU - Saunders CP AU - Roberts GJ AU - Suwanprasit A IN - Royal Children's Hospital, Victoria, Australia. TI - Dental disease, caries related microflora and salivary IgA of children with severe congenital cardiac disease: an epidemiological and oral microbial survey. SO - Pediatric Dentistry 1996 May-Jun;18(3):228-35 AB - The objectives were to determine levels of dental caries, plaque accumulation, gingival inflammation, knowledge of dental health practices, and oral bacterial loading of S. mutans, Lactobacillus sp., Candida sp., and salivary IgA in the mouths of children afflicted with severe congenital heart disease. A total of 60 children from the cardiac units of the Hospital for Sick Children and Guys Hospital Paediatric Department were compared with 60 case-matched control children from the Department of Orthodontics and Paediatric Dentistry, UMDS (Guys Dental School), London. Using the methodology of the World Health Organization, the decayed, missing and filled surfaces and teeth of primary (dmft) and permanent (DMFT) were compared. There were similar levels of caries in the cardiac (dmft 3.9 and DMFT 2.7) and the control (dmft 3.7 and DMFT 2.0). A significant difference was the proportion of untreated carious lesions in the cardiac group (52%) compared to the control group (32%; P < 0.001). Standard oral microbiological techniques were used to isolate S. mutans, Lactobacillus sp., Candida sp., and conventional methods for estimating salivary IgA. There was no difference between the cardiac and the control group. Children with severe congenital cardiac disease have moderately high levels of dental caries with a significantly greater amount of untreated disease. The high bacterial loading associated with high levels of bacterial dental plaque and gingivitis may put cardiac patients at unnecessary risk of developing bacterial endocarditis. <48> 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. <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 - 96125030 AU - Hermine O AU - Haioun C AU - Lepage E AU - d'Agay MF AU - Briere J AU - Lavignac C AU - Fillet G AU - Salles G AU - Marolleau JP AU - Diebold J AU - Reyas F AU - Gaulard P IN - Departement de Pathologie, Hopital Henri Mondor, Creteil, France. TI - Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA). SO - Blood 1996 Jan 1;87(1):265-72 AB - Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups. <53> UI - 96159468 AU - Yamamoto T AU - Katayama I AU - Nishioka K IN - Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan. TI - Involvement of basic fibroblast growth factor in fibroblast-stimulatory serum activity of a patient with systemic lupus erythematosus and multiple dermatofibromas. SO - Dermatology 1995;191(4):281-5 AB - BACKGROUND: Multiple dermatofibromas (DFs) are often associated with systemic lupus erythematosus (SLE). An increased number of mast cells is observed in the upper portion or over the lesion of DF. OBJECTIVE: To investigate the role of the serum of a patient with multiple DFs, we examined its growth effects on fibroblasts. METHOD: 3H-Thymidine incorporation was used to examine the effects of the serum of an SLE patient with multiple DFs on fibroblasts derived from DF and normal skin. RESULTS: The serum of the SLE patient with multiple DFs exhibited a stronger growth-stimulatory activity on normal and DF-derived fibroblasts in a dose-dependent manner, compared to that of SLE without DFs or normal sera. The growth effects were inhibited in 40% by antiplatelet-derived-growth-factor antibody and almost completely inhibited by antibody against basic fibroblast growth factor. Cultured fibroblasts derived from the upper portion of the DF lesion, which included most of the numerous mast cells, demonstrated a higher level of 3H-thymidine uptake after stimulation of autologous serum compared to that from the mid and lower portions of DF. CONCLUSION: These results suggested the existence of various fibroblast growth factors derived from the mast cells in SLE patients with multiple DFs. <54> UI - 96107101 AU - Borke JL AU - Zaki AE AU - Eisenmann DR AU - Ashrafi SH AU - Sharawy MM AU - Rahman SS IN - Dept. Oral Biology, Physiology, Medical College of Georgia, School of Dentistry, Augusta 30912-1129, USA. TI - In situ hybridization and monoclonal antibody analysis of plasma membrane Ca-pump mRNA and protein in submandibular glands of rabbit, rat and man. SO - Scanning Microscopy 1995 Sep;9(3):817-23; discussion 723-4 AB - The degree of supersaturation of saliva with calcium (Ca) is related to the mineral phase of enamel in erupted teeth, the incidence of caries, and the formation of calculus. The mechanisms for regulating salivary Ca concentration are therefore of relevance to dentistry. Sections of rabbit, rat and human submandibular gland (SMG) were processed for immuno-histochemistry with a specific anti-plasma membrane Ca-pump antibody, 5F10. Western blots confirm that the molecular weight of the proteins identified by our antibody (135 kDa) is consistent with an appropriate molecular weight for PMCA antigen (135-150 kDa). Tissue sections were also processed for in situ hybridization to study the distribution of the PMCA mRNA isoforms. In mammals, the PMCA1 gene is reported to code for a PMCA protein with a role in maintaining the intracellular Ca levels in both epithelial and non-epithelial cells. Other genes including the PMCA2 and PMCA4 genes may code for PMCA proteins specific to Ca transporting tissues. Our studies demonstrate cytoplasmic labeling of PMCA mRNA with hPMCA-1 and hPMCA-4 specific cDNA probes in humans, and rPMCA-1 and rPMCA-2 specific oligonucleotide probes in rats. Labeling of PMCA protein and all mRNA isoforms was found in the cytoplasm of the interlobular and intralobular ducts (except for intercalated ducts). The demonstrated presence of PMCA in SMGs of rabbit, rat, and man, may suggest a role for PMCA in the regulation of intracellular Ca and in a mechanism for regulating and maintaining the high concentration of Ca in salvia. <55> UI - 96100290 AU - Nagao Y AU - Sata M AU - Tanikawa K AU - Itoh K AU - Kameyama T IN - Department of Oral Surgery, Kurume University School of Medicine, Fukuoka, Japan. TI - High prevalence of hepatitis C virus antibody and RNA in patients with oral cancer. SO - Journal of Oral Pathology & Medicine 1995 Sep;24(8):354-60 AB - We have investigated the correlation between the prevalence of hepatitis C virus (HCV), which is detectable in saliva, and oral cancer and other digestive tract cancers in the Northern Kyushu region of Japan. Anti-HCV antibodies were detected in sera from 24 of the 100 patients with oral cancer (24%, p < 0.05 vs the control group, p < 0.01 vs the stomach cancer group), in 11 of 104 patients with non-malignant diseases receiving dental treatment (the control group, 10.6%), and in 12 of 113 patients with stomach cancer (10.6%). HCV-RNA was detected in sera from 17 of 100 oral cancer patients (17%, p < 0.05 vs the control group) and 4 of 104 patients of the control group (3.9%). These results indicate a high prevalence of HCV infection in oral cancer patients, which warrants a systematic study of etiological associations between oral cancer and HCV. <56> 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. <57> 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. <58> 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. <59> UI - 95325894 AU - Greer JP AU - Macon WR AU - Lamar RE AU - Wolff SN AU - Stein RS AU - Flexner JM AU - Collins RD AU - Cousar JB IN - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6305, USA. TI - T-cell-rich B-cell lymphomas: diagnosis and response to therapy of 44 patients. SO - Journal of Clinical Oncology 1995 Jul;13(7):1742-50 AB - PURPOSE: Clinicopathologic features of 44 patients with well-documented T-cell-rich B-cell lymphomas (TCRBCLs) were reviewed to determine if there were distinguishing clinical characteristics and to evaluate the responsiveness to therapy. PATIENTS AND METHODS: Forty-one patients had de novo TCRBCL, while three patients had a prior diagnosis of diffuse large B-cell lymphoma. Seventeen TCRBCLs were identified from a retrospective analysis of 176 lymphomas diagnosed before 1988 as peripheral T-cell lymphoma (PTCLs). The initial pathologic diagnosis was incorrect in 36 of 44 cases (82%), usually due to the absence of adequate immunophenotypic and/or genotypic studies at the initial study. RESULTS: The median age of patients was 53 years (range, 17 to 92), and the male-to-female ratio was 1.4:1. B symptoms were present in 22 of 41 patients (54%); splenomegaly was detected in 11 patients (25%). Clinical stage at diagnosis was as follows: I (n = 8), II (n = 6), III (n = 15), IV (n = 14), and unstaged (n = 1). Although therapy was heterogeneous, the disease-free survival (DFS) and overall survival (OS) rates at 3 years for patients with de novo TCRBCL were 29% and 46%, respectively. A complete response (CR) to combination chemotherapy for intermediate-grade lymphomas was observed in 16 of 26 patients (62%); 11 of these patients (42%) had a continuous CR, compared with one of 14 patients (7%) who received radiation therapy or therapy for low-grade lymphoma or Hodgkin's disease (HD) (P < .05). However, there was no difference in OS between patients who received chemotherapy for intermediate-grade lymphoma versus other therapies (49% v 48%) due to a high response rate to salvage therapies, including seven patients without disease after marrow transplantation. CONCLUSION: TCRBCLs are difficult to recognize without immunoperoxidase studies. Patients with TCRBCL have clinical features similar to patients with other large B-cell lymphomas, except they may have more splenomegaly and advanced-stage disease; they should receive combination chemotherapy directed at large-cell lymphomas. <60> UI - 95302098 AU - Maeda T AU - Takamori K AU - Shima M AU - Kurihara Y IN - Department of Pedodontics, Nihon University School of Dentistry at Matsudo, Chiba, Japan. TI - Effects of salivary immune response to Streptococcus mutans on caries occurrence and caries development in mice with autoimmune disease. SO - Journal of Nihon University School of Dentistry 1995 Mar;37(1):41-6 AB - MRL/l strain mice, which possess a lymphoproliferative gene inducing swelling of systemic lymph nodes, develop a SLE (systemic lupus erythematosus)-like syndrome at around 8 w of age. MRL/n mice, which carry 99.6% of the genes of MRL/l mice, lack the gene for lymphoproliferation and exhibit only a slight degree of lymph node swelling late in life. This study investigated whether the salivary immune response caused by Streptococcus mutans(S. mutans) infection prevented dental caries in MRL/l and MRL/n mice after 8 w of age. A total of 10 MRL/l mice and 10 MRL/n mice were fed a commercial pellet diet without sucrose until 74 d of age, and then fed Diet 2000 containing 56% sucrose ad libitum from 75 to 130 d of age. On d 75, both strains of mice were inoculated with S. mutans JC-2 for 7 d. At 130 d of age, saliva samples were collected and caries scores were assessed. The results obtained suggested that the salivary immune response was one of the most important factors regulating caries occurrence. <61> UI - 95247294 AU - Redman TK AU - Harmon CC AU - Lallone RL AU - Michalek SM IN - Department of Microbiology, University of Alabama at Birmingham 35294, USA. TI - Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A of Streptococcus sobrinus: dose response and induction of protective humoral responses in rats. SO - Infection & Immunity 1995 May;63(5):2004-11 AB - An attenuated, recombinant Salmonella typhimurium mutant, chi 4072(pYA2905), expressing the surface protein antigen A (SpaA) of Streptococcus sobrinus was investigated for its effectiveness in inducing protective immune responses against S. sobrinus-induced dental caries in an experimental caries model. Fischer rats were orally immunized with either 10(8) or 10(9) CFU of S. typhimurium chi 4072(pYA2905). Persistence of salmonellae in Peyer's patches and spleens and the induction of immune responses were determined. Maximum numbers of salmonellae were recovered from Peyer's patches of rats within the first week of immunization, with higher numbers recovered from rats given 10(9) CFU than from those given 10(8) CFU. Serum anti-Salmonella and anti-SpaA responses increased more rapidly in rats given 10(9) CFU than in rats given 10(8) CFU. The salivary antibody response to SpaA increased with time, but the response varied in the two groups. In a separate study, rats were orally immunized with the recombinant Salmonella mutant and then challenged with cariogenic S. sobrinus 6715. The levels of serum and salivary antibody and caries activity were assessed at the termination of the experiment. Higher levels of salivary immunoglobulin A antibody to SpaA and Salmonella carrier were detected in rats given 10(9) CFU than in those given 10(8) CFU, and these responses were higher than those in nonimmunized controls. Mandibular molars from immunized rats had lower numbers of recoverable streptococci and less extensive carious lesions than those from nonimmunized, control rats. These data indicate that oral immunization with an attenuated recombinant S. typhimurium expressing SpaA of S. sobrinus induces the production of antigen-specific mucosal antibody and confers protection against dental caries. <62> UI - 95048782 AU - Smith DJ AU - Taubman MA AU - King WF AU - Eida S AU - Powell JR AU - Eastcott J IN - Department of Immunology, Forsyth Dental Center, Boston, Massachusetts 02115. TI - Immunological characteristics of a synthetic peptide associated with a catalytic domain of mutans streptococcal glucosyltransferase. SO - Infection & Immunity 1994 Dec;62(12):5470-6 AB - The immunogenicity of a multiple antigenic peptide construct consisting of four copies of the synthetic 21-mer peptide DANFDSIRVDAVDNVDADLLQ was measured. The composition of this peptide was derived from a sequence in the N-terminal region of mutans streptococcal glucosyltransferases (GTFs) containing an aspartic acid implicated in catalysis. The peptide (CAT) construct was synthesized as a tetramer on a lysine backbone and subcutaneously injected into Sprague-Dawley rats for polyclonal antibody formation or intraperitoneally injected into BALB/c mice, and then spleen cell fused with Sp2/0Ag14 murine myeloma cells for monoclonal antibody formation. The resulting rat antisera and mouse monoclonal antibodies reacted with CAT and with native GTF isozymes from Streptococcus sobrinus and Streptococcus mutans (in enzyme-linked immunosorbent assay and Western blot [immunoblot] analyses). Functional inhibition of the water-insoluble glucan synthetic activity of S. sobrinus GTF-I was demonstrated with an immunoglobulin M anti-CAT monoclonal antibody (> 80% inhibited) and with rat sera (approximately 17% inhibited). The monoclonal antibody preparation also modestly inhibited the water-solub