Database: EMBASE <: international biomedical and pharmaceutical literature, 1988 - Aug 2000. [Trial access until 3/2001. Feedback welcome to medical.library@umich.edu] Search Strategy (You Saved Citations 1-119 From Set 73): ----------------------------------------------------------------------------- 1 exp Tooth demineralization/ 7753 2 demineralization.mp. 907 3 caries.mp. 1846 4 caires.mp. 0 5 craies.mp. 0 6 careis.mp. 1 7 carise.mp. 0 8 (teeth adj3 cavit:).mp. 32 9 (tooth adj3 cavit:).mp. 31 10 (dental adj3 cavit:).mp. 55 11 (dentin adj3 cavit:).mp. 14 12 (enamel adj3 cavit:).mp. 6 13 (teeth adj3 decay:).mp. 60 14 (tooth adj3 decay:).mp. 59 15 (dental adj3 decay:).mp. 48 16 (dentin adj3 decay:).mp. 0 17 (enamel adj3 decay:).mp. 1 18 (active adj decay).mp. 5 19 (rampant adj3 decay:).mp. 4 20 (recurrent adj3 decay:).mp. 3 21 (white adj spot:).mp. 229 22 carious.mp. 114 23 cariology.ti,ab. 2 24 (non-cavitated adj3 lesion:).mp. 0 25 (noncavitated adj3 lesion:).mp. 1 26 Tooth remineralization/ 819 27 (dental adj3 fissure:).mp. 7 28 (tooth adj3 fissure:).mp. 3 29 (teeth adj3 fissure:).mp. 1 30 caries-free.mp. 30 31 cariesfree.mp. 0 32 Cariogenic agents/ 3 33 precavit:.mp. 2 34 (filled adj3 teeth).mp. 47 35 (filled adj3 tooth).mp. 9 36 (oral adj fissure:).mp. 4 37 (tooth adj3 remineraliz:).mp. 1 38 (teeth adj3 remineraliz:).mp. 4 39 dft.mp. 583 40 dfs.mp. 1015 41 dmf:.mp. 1290 42 cariogeni:.mp. 169 43 or/1-42 12701 44 exp Genetics/ 10525 45 (cn or ge).fs. 87348 46 gene$1.mp. 441975 47 genetic:.mp. 235931 48 genom:.mp. 69641 49 genotyp:.mp. 27632 50 chromosom:.mp. 104283 51 congenit:.mp. 48604 52 familial.mp. 25779 53 heritab:.mp. 3554 54 inherit:.mp. 27009 55 twin$1.mp. 9553 56 Diseases in twins/ 2748 57 exp Multiple birth offspring/ 3143 58 consanguin:.mp. 2251 59 or/44-58 680672 60 ("IgA" or "IgM" or "IgG").mp. 46850 61 exp Antibody/ 148283 62 exp t lymphocyte/ 73689 63 ("T" adj cell$1).mp. 84898 64 exp b lymphocyte/ 24155 65 ("B" adj cell$1).mp. 36046 66 exp macrophage/ 32547 67 exp Complement/ 9969 68 complement.mp. 29322 69 exp immunology/ 5386 70 68 and 69 170 71 or/60-67,70 317658 72 43 and 59 and 71 123 73 limit 72 to english language 119 74 from 73 keep 1-119 119 *************************** <1> UI - 2000272322 AU - Stollerman GH TI - Vaccines from transgenic plants. SO - Hospital Practice 15 JUL 1998Vol 33(7) (pp 41-42), 1998. <2> UI - 2000262933 AU - Bartova J AU - Kratka-Opatrna Z AU - Prochazkova J AU - Krejsa O AU - Duskova J AU - Mrklas L AU - Tlaskalova H AU - Cukrowska B IN - J. Bartova, Institute of Dental Research, Vinohradska 48, 12060 Prague 2; Czech Republic. E-Mail: jirina.bartova@post.cz. TI - Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings. SO - Mediators of Inflammation Vol 9(2) (pp 115-120), 2000. AB - Early onset periodontitis (EOP) is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a.), a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC) were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL-4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL-4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL-4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour's hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes. [References: 31] <3> UI - 2000227702 AU - Ochs RL AU - Muro Y AU - Si Y AU - Ge H AU - Chan EKL AU - Tan EM IN - Dr. E.M. Tan, Autoimmune Disease Center, Scripps Research Institute, 10550 N Torrey Pines Rd, San Diego, CA 92037; United States. TI - Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. SO - Journal of Allergy & Clinical Immunology Vol 105(6 I) (pp 1211-1220), 2000. AB - Background: Sera of patients with atopic dermatitis (AD) were found to have autoantibodies that reacted with tissue culture cell substrates in immunohistochemistry to display a characteristic pattern of nuclear distribution of dense fine speckles. The sera also recognized a 70-kd protein on Western immunoblots, and the antigen was termed dense fine speckles 70 kd (DSF70). Objective: Because spontaneously occurring autoantibodies could be immune responses to proteins that might be participating in the disease process, it was of interest to identify the antigens driving the autoimmune antibody response. Methods: A serum containing high-titer antibodies to DFS70 was used to immunoscreen a complementary (c)DNA expression library to isolate cDNA encoding the antigen. After the cDNA was isolated, this was used to express recombinant protein to determine the prevalence of antibody in AD and other conditions. Results: Thirty percent of patients with AD were found to have antibody to recombinant DFS70 in Western immunoblots. Sixteen percent of patients with asthma and 9% of patients with interstitial cystitis had antibodies of the same specificities. The cDNA encoding DFS70 was identical to a transcription coactivator called p75, which had been shown to be required for RNA polymerase II-dependent transcription. Another important finding was that IgE antibodies to DFS70 were also present in AD sera. Conclusion: It is suggested that a common basis for the presence of autoantibodies to DFS70 might be related to AD in asthma, interstitial cystitis, and other conditions. A possible role of this antigen-antibody system in pathogenesis remains to be demonstrated, but it appears to be a marker for a subset of patients with AD. [References: 33] <4> UI - 2000220530 AU - Korzenik JR AU - Dieckgraefe BK IN - Dr. J.R. Korzenik, Division of Gastroenterology, Department of Internal Medicine, Washington Univ. School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110; United States. TI - Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease. SO - Digestive Diseases & Sciences Vol 45(6) (pp 1121-1129), 2000. AB - The current hypothesis for the etiology of Crohn's disease proposes an excessive immune response, largely T-cell driven, possibly against endogenous bacteria. Standard therapy is therefore directed towards suppression of this immune response. An alternative theory of pathogenesis accounts for epidemiologic and pathophysiologic observations that have been hitherto underemphasized, namely, (1) genetic disorders with deficiencies in neutrophil function can give rise to a clinical and pathologic syndrome indistinguishable from Crohn's; (2) abnormal neutrophil function is well described in Crohn's disease; (3) a group of bacteria implicated in other chronic inflammatory disorders causes impairment of neutrophil function; and (4) 20th century environmental risk factors for Crohn's disease may directly suppress neutrophil function and may have led to a shift in the dominant gut flora with similar effects. We propose that some cases of Crohn's disease result from the interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in failure to effectively clear intramucosal microbes effectively. While encompassing existing data, this hypothesis proposes a proximate defect in the mucosal immune response. If this paradigm were correct, new therapeutic approaches might involve strategies to alter intestinal flora and stimulate neutrophil function. [References: 97] <5> UI - 2000205613 AU - Anonymous IN - M. Bhargava, Department of Haematology, All India Institute Medical Sciences, AIIMS, New Delhi 110029. E-Mail: manorama@medinst.ernet.in. TI - Pattern of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements in childhood acute lymphoblastic leukemia in India. SO - Leukemia Research Vol 24(7) (pp 575-582), 2000. AB - In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x109/l vs. 103.7x109/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x109/l vs. 63.4x109/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region. Copyright (C) 2000 Elsevier Science Ltd. [References: 28] <6> UI - 2000175631 AU - Tabeta K AU - Yamazaki K AU - Hotokezaka H AU - Yoshie H AU - Hara K IN - Dr. K. Yamazaki, Department of Periodontology, Faculty of Dentistry, Niigata University, 5274, Gakkocho-Dori, 2-ban-cho, Niigata 951-8514; Japan. E-Mail: kaz@dent.niigata-u.ac.jp. TI - Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients. SO - Clinical & Experimental Immunology Vol 120(2) (pp 285-293), 2000. AB - The presence of antibodies to the 60-kD human and Porphyromonas gingivalis GroEL hsp60 in the sera and inflamed gingival tissues of periodontitiS patients was examined. In order to obtain the antigens, recombinant plasmids carrying human hsp60 and P. gingivalis GroEL genes were constructed and expressed as histidine-tagged recombinant proteins. Immunoreactivities of these proteins were confirmed by MoAbs specific to mammalian hsp60 and cross-reactive with both mammalian and bacterial hsp60. Western blot analysis clearly demonstrated that the number of periodontitis patients showing a positive response to P. gingivalis GroEL was higher than the number of periodontally healthy subjects. Furthermore, anti-P. gingivalis GroEL antibody was detected in all samples of gingival tissue extracts. For human hsp60, a higher frequency of seropositivity was found in the periodontitis patients than in the healthy subjects. In addition, the periodontitis patients demonstrated stronger reactivity compared with the healthy subjects. Quantitative analysis of serum antibodies by ELISA also demonstrated that the levels of antibodies in the sera of patients were significantly higher than those of control subjects. In the gingival tissue extracts, seven out of 10 patients demonstrated a positive response to human hsp60 and tso of these demonstrated strong positivity. Affinity-purified serum antibodies to human hsp60 and P. gingivalis GroEL from selected patients reacted with P. gingivalis GroEL and human hsp60, respectively, suggesting cross-reactivity of antibodies. These results suggest that molecular mimicry between GroEL of the periodontopathic bacterium P. gingivalis and autologous human hsp60 may play some role in immune mechanisms in periodontitis. [References: 28] <7> UI - 2000166930 AU - O'Brien-Simpson NM AU - Black CL AU - Bhogal PS AU - Cleal SM AU - Slakeski N AU - Higgins TJ AU - Reynolds EC IN - E.C. Reynolds, Oral Health Sciences Unit, School of Dental Science, University of Melbourne, 711 Elizabeth St., Melbourne, Vic. 3000; Australia. E-Mail: e.reynolds@dent.unimelb.edu.au. TI - Serum immunoglobulin G (IgG) and IgG subclass responses to the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis in adult periodontitis. SO - Infection & Immunity Vol 68(5) (pp 2704-2712), 2000. AB - Serum immunoglobulin G (IgG), IgM, and IgG subclass responses to the RgpA-Kgp proteinase-adhesin complex of Porphyromonas gingivalis were examined by enzyme-linked immunosorbent assay using adult periodontitis patients and age- and sex-matched controls. Twenty-five sera from subjects with adult periodontitis (diseased group) and 25 sera from healthy subjects (control group) were used for the study. Sera and subgingival plaque samples from 10 sites were collected from each patient at the time of clinical examination. The level of P. gingivalis in the plaque samples was determined using a DNA probe. Highly significant positive associations between the percentage of sites positive for P. gingivalis and measures of disease severity (mean pocket depth, mean attachment loss, and percentage of sites that bled on probing) were found. The diseased group had significantly higher specific IgG responses to the RgpA-Kgp complex than did the control group, and the responses were significantly associated with mean probing depths and percentage of sites positive for P. gingivalis. Analysis of the IgG subclass responses to the RgpA-Kgp complex revealed that the subclass distribution for both the diseased and control groups was IgG4 > IgG2 > IgG3 = IgG1. The IgG2 response to the complex was positively correlated with mean probing depth, whereas the IgG4 response was negatively correlated with this measure of disease severity. Immunoblot analysis of the RgpA-Kgp complex showed that sera from healthy subjects and those with low levels of disease, with high IgG4 and low IgG2 responses, reacted with the RgpA27, Kgp39, and RgpA44 adhesins; however, sera from diseased subjects with low IgG4 and high IgG2 responses reacted only with the RgpA44 and/or Kgp44 adhesins. Epitope mapping of the RgpA27 adhesin localized a major epitope recognized by IgG4 antibodies in sera from subjects with high IgG4 and low IgG2 responses to the RgpA-Kgp complex which was not recognized by sera from diseased subjects with low IgG4 and high IgG2 responses. [References: 61] <8> UI - 2000167955 AU - Cole BOI AU - Welbury RR AU - Bond E AU - Abinun M IN - B.O.I. Cole, Dept. of Child Dental Health, Dental Hospital and School, Richardson Road, Newcastle upon Tyne NE2 4AZ; United Kingdom. TI - Dental manifestations in severe combined immunodeficiency following bone marrow transplantation. SO - Bone Marrow Transplantation Vol 25(9) (pp 1007-1009), 2000. AB - Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency disorder with an estimated overall frequency of 1 in 75,000 live births. Bone marrow transplantation is the only curative treatment available. Using T cell-depleted HLA non-identical bone marrow requires preconditioning with a short course of cytotoxic chemotherapy. We report severe dental developmental anomalies in three such patients under longterm follow up. [References: 12] <9> UI - 2000147972 AU - Carlander D AU - Kollberg H AU - Wejaker P-E AU - Larsson A IN - A. Larsson, Department of Medical Sciences, University Hospital, S-751 85 Uppsala; Sweden. E-Mail: anders.larsson@klinkem.uas.lul.se. TI - Peroral immunotheraphy with yolk antibodies for the prevention and treatment of enteric infections. SO - Immunologic Research Vol 21(1) (pp 1-6), 2000. AB - Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are very good producers of specific antibodies. After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified. A laying hen produces more than 20 g of yolk antibodies (IgY) per year. These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent bacterial and viral infections. [References: 25] <10> UI - 2000096276 AU - Taylor DO IN - Dr. D.O. Taylor, Department of Medicine, Division of Cardiology 4A-100, University Utah Health Sciences Ctr., 50 N. Medical Drive, Salt Lake City, UT 84132; United States. TI - Immunosuppressive therapies after heart transplantation: Best, better, and beyond. SO - Current Opinion in Cardiology Vol 15(2) (pp 108-114), 2000. AB - Despite the significant advances in transplantation immunology and immunosuppressive therapies over the past 30 years, current immunosuppressive regimens are still inadequate in the majority of cardiac transplant recipients. Although short- and long-term survival rates have improved significantly, only 50% will survive 10 years and very few will survive 20 years. Complications of overimmunosuppression and underimmunosuppression account for the majority of these deaths. Only true 'immunologic' tolerance can provide the outcome we pursue, namely, prolonged allograft function and otherwise normal immune function without chronic immunosuppressive therapy and its risks. Until a successful tolerance-inducing protocol is developed, we must use the current and upcoming immunosuppressive agents and techniques. (C) 2000 Lippincott Williams and Wilkins, Inc. [References: 35] <11> UI - 2000067731 AU - Talwar GP AU - Diwan M AU - Razvi F AU - Malhotra R IN - G.P. Talwar, Talwar Research Foundation, New Delhi; India. TI - The impact of new technologies on vaccines. SO - National Medical Journal of India Vol 12(6) (pp 274-280), 1999. AB - Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by accellular purified fractions devoid of side-effects. Non- pathogenic but immunogenic mutants of tetanus and diphtheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophillus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti- inflammatory experimental vaccines against multiple sclerosis and insulin- dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual. [References: 75] <12> UI - 2000020183 AU - Dickinson CJ IN - Dr. C.J. Dickinson, Wolfson Inst. Preventive Medicine, Charterhouse Square, London EC1M 6BQ; United Kingdom. E-Mail: c.j.dickinson@mds.qmw.ac.uk. TI - The possible role of osteoclastogenic oral bacterial products in etiology of Paget's disease. SO - Bone Vol 26(2) (pp 101-102), 2000. <13> UI - 1999426538 AU - Anonymous TI - Oral defense with cathepsin C. SO - Nature Medicine Vol 5(12) (pp 1358), 1999. <14> UI - 1999425809 AU - Nuckolls GH AU - Slavkin HC IN - G.H. Nuckolls, Craniofacial Development Section, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD 20892; United States. E-Mail: gnuckolls@nih.gov. TI - Paths of glorious proteases. SO - Nature Genetics Vol 23(4) (pp 378-379), 1999. <15> UI - 1999402742 AU - Rice HE AU - Chuang E IN - Dr. H.E. Rice, Division of Pediatric Surgery, Box 3815, Duke University Medical Center, Durham, NC 27710; United States. TI - Current management of pediatric inflammatory bowel disease. SO - Seminars in Pediatric Surgery Vol 8(4) (pp 221-228), 1999. AB - Inflammatory bowel disease (IBD) is a relatively rare condition of childhood, although the wide range of presenting complaints, scope of complications, and choices of therapy for this condition make it particularly difficult to treat in children. Novel approaches to the management of Crohn's disease and ulcerative colitis have gained recent favor. This report summarizes the current medical and surgical management of IBD, recent advancements in clinical therapies, and particular aspects of IBD care for children. [References: 36] <16> UI - 1999390860 AU - Takahashi K AU - Macdonald DG AU - Murayama Y AU - Kinane DF IN - Prof. D.F. Kinane, Periodontology Unit, Glasgow Dental Hospital and School, 378 Sauchiehall Street, Glasgow G2 3JZ; United Kingdom. TI - Cell synthesis, proliferation and apoptosis in human dental periapical lesions analysed by In situ hybridisation and immunohistochemistry. SO - Oral Diseases Vol 5(4) (pp 313-320), 1999. AB - OBJECTIVE: The role of structural and host defensive cells in periapical lesions has been assessed previously by morphometric and immunohistochemical studies. The aim of this study was to investigate the function of periapical cells by employing molecular techniques to estimate the cell synthetic activity, proliferation and apoptosis in these lesions. We specifically sought answers to the following questions. Which cells of the periapical lesions are quiescent or actively synthesising proteins? Do immune cells proliferate in this region in the same way as epithelial cells proliferate? Furthermore do cells in periapical lesions undergo apoptosis, and if so which cells exhibit this programmed cell death? MATERIALS: Twenty-five periapical tissue samples (15 granulomas and 10 radicular cysts) were assessed. Polyadenosine (poly (A)) RNA and ribosomal RNA (rRNA) bearing cells in formalin-fixed/paraffin-embedded periapical tissues were analysed by in situ hybridization (ISH) using digoxigenin-labelled oligo d (T) and 28S rRNA probes respectively in order to estimate cell synthetic activity. Furthermore, S-phase proliferating and cycling cells were examined by ISH using a histone probe and Ki67 immunostaining so as to assess cellular proliferation. Mononuclear cells were further differentiated by immunohistochemistry (IHC) as T cells, B cells and macrophages. Apoptotic cells were determined by in situ endlabelling methodology for detecting fragmented DNA. RESULTS: Poly (A) RNA (mostly messenger RNA) and 28S rRNA- expressing cells were detected in all samples. Plasma cells exhibited strongest staining for the two probes, with slight to moderate staining found in the epithelium, fibroblasts, macrophages, endothelial cells and lymphocytes, whereas almost all polymorphonuclear leucocytes (PMN) were negative for these probes. A few histone mRNA-expressing cells were detected in basal and suprabasal epithelial cells and mononuclear cells in 15/25 cases but their reactivity was weak. Ki-67 positive cells were found in all samples and their numbers were generally higher than histone mRNA positive cells. Apoptotic cells were detected in 23/25 cases and the majority of apoptotic cells were PMN which were engulfed by large cytophagocytic macrophages. CONCLUSION: This study indicates that in dental periapical lesions, apoptosis occurs predominantly in PMN. It is evident that most cells apart from PMN are exhibiting synthetic activity but only epithelial cells undergo proliferation which implies that immune cells must proliferate at distant lymph nodes and travel to the periapical lesion rather than proliferating within the lesion. These results suggest considerable advantages in estimating gene expression within cells in addition to the immunohistochemical detection of cells to determine cell activity at inflamed sites. Clearly, functional cell synthetic activity, resolution and clearance systems operate in peri- apical cystic and granuloma lesions. [References: 36] <17> UI - 1999359773 AU - Price P AU - Calder DM AU - Witt CS AU - Allcock RJN AU - Christiansen FT AU - Davies GR AU - Cameron PU AU - Rogers M AU - Baluchova K AU - Moore CB AU - French MA IN - Dr. P. Price, Dept. of Clinical Immunology, Royal Perth Hospital, Perth, 6001; Australia. E-Mail: pprice@cyllene.uwa.edu.au. TI - Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3). SO - Tissue Antigens Vol 54(4) (pp 391-399), 1999. AB - Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.xm. [References: 35] <18> UI - 1999348013 AU - Hale GA AU - Heslop HE AU - Bowman LC AU - Rochester RA AU - Pui C-H AU - Brenner MK AU - Krance RA IN - Dr. H.E. Heslop, Center for Cell and Gene Therapy, Baylor College of Medicine, 1102 Bates St., Houston, TX 77030; United States. TI - Bone marrow transplantation for therapy-induced acute myeloid leukemia in children with previous lymphoid malignancies. SO - Bone Marrow Transplantation Vol 24(7) (pp 735-739), 1999. AB - Twenty-one children who developed therapy-related acute myeloid leukemia after treatment for acute lymphoblastic leukemia received allogeneic bone marrow transplants between January 1990 and June 1997. All had previously received epipodophyllotoxin-containing regimens and 11 had cytogenetic abnormalities involving 11q23. Induction chemotherapy was given to 13 patients and eight patients went directly to BMT. Eleven received marrow from matched siblings, eight from matched unrelated donors and two from haploidentical family members. Conditioning regimens included cyclophosphamide (CY), cytarabine, and total body irradiation. Four patients are alive disease-free between 1118 and 1825 days post-BMT resulting in a 3-year DFS of 19%. Ten patients relapsed at a median of 150 days (range 30-664 days) post-BMT and all eventually died of disease. Seven patients died of regimen-related toxicity. The outlook for patients with therapy-related AML/MDS remains poor and more effective therapy is needed. [References: 22] <19> UI - 1999321134 AU - Thurnheer T AU - Guggenheim B AU - Gruica B AU - Gmur R IN - R. Gmur, Inst. Oral Microbiol. Gen. Immunol., University of Zurich, Plattenstrasse 11, CH-8028 Zurich; Switzerland. E-Mail: gmuer@zzmk.unizh.ch. TI - Infinite serovar and ribotype heterogeneity among oral Fusobacterium nucleatum strains?. SO - Anaerobe Vol 5(2) (pp 79-92), 1999. AB - Fusobacterium nucleatum is part of the residential human microbiota and is associated with various infections. It is characterised by broad genetic heterogeneity, but reliable phenotypic markers are lacking. The purpose of the present study was to generate antibodies for the detection of F. nucleatum, to characterise expression patterns of the detected surface antigens on oral isolates, to investigate the prevalence of distinguishable subtypes in clinical samples from the oral cavity, and to compare antigenic with ribotype heterogeneity. Thirty-seven monoclonal antibodies (mAbs) were generated and characterised using strains from 52 taxa. Antibody-binding bacteria were monitored in 35 samples of supra- and subgingival plaque from healthy sites and sites affected by gingivitis or periodontitis. Results indicated broad but structured antigenic heterogeneity. Detecting at least 28 different epitopes, the mAbs defined 19 serovars. Epitopes were expressed on periodate-sensitive polysaccharide chains. Ribotyping of 40 oral F. nucleatum strains (PvuII digestion) resulted in the detection of similarly broad genetic heterogeneity, which rarely corresponded to the observed phenotypic diversity. Clinical samples were generally positive for multiple (up to eight) serovars of which some colonised supra- and subgingival plaques from both healthy and diseased sites, whereas others were restricted to inflamed sites. The majority of the studied isolates could not be grouped with reference strains of the five established subspecies of F. nucleatum, corroborating doubts about the usefulness of the current classification scheme. Although, as a whole the described monoclonal antibodies can only recognise a part of the overwhelming heterogeneity of this 'species', they should prove of value to investigations of the importance, the antigenic stability and the origin of positive subtypes of F. nucleatum from human infections. [References: 48] <20> UI - 1999299550 AU - Stashenko P AU - Teles R AU - D'Souza R IN - P. Stashenko, Department of Cytokine Biology, Forsyth Dental Center, 140 The Fenway, Boston, MA; United States. TI - Periapical inflammatory responses and their modulation. SO - Critical Reviews in Oral Biology & Medicine Vol 9(4) (pp 498-521), 1998. AB - Periapical inflammatory responses occur as a consequence of bacterial infection of the dental pulp, as a result of caries, trauma, or iatrogenic insult. Periapical inflammation stimulates the formation of granulomas and cysts, with the destruction of bone. These inflammatory responses are complex and consist of diverse elements. Immediate-type responses - including vasodilatation, increased vascular permeability, and leukocyte extravasation - are mediated by endogenous mediators, including prostanoids, kinins, and neuropeptides. Non-specific immune responses - including polymorphonuclear leukocyte and monocyte migration and activation, and cytokine production - are elicited in response to bacteria and their products. Interleukin-I and prostaglandins in particular have been implicated as central mediators of periapical bone resorption. Chronic periapical inflammation further involves specific T- and B-cell-mediated anti-bacterial responses, and activates a network of regulatory cytokines which are produced by Th1- and Th2-type T-lymphocytes. Various naturally occurring and genetically engineered models of immunodeficiency are beginning to help elucidate those components of the immune system which protect the pulpal/periapical complex. Both specific and non-specific responses interface with and are regulated by the neural system. The modulation of these responses by immune response modifiers, cytokine antagonists, and other novel therapeutic agents is discussed. As an experimental model, periapical inflammation has many advantages which permit it to be used in studies of microbial ecology and pathogenesis, host response, neuroimmunology, and bone resorption and regeneration. [References: 272] <21> UI - 1999298483 AU - Katz J AU - Black KP AU - Michalek SM IN - J. Katz, Department of Oral Biology, University of Alabama, 845 South 19th St., Birmingham, AL 35294-2170; United States. TI - Host responses to recombinant hemagglutinin B of Porphyromonas gingivalis in an experimental rat model. SO - Infection & Immunity Vol 67(9) (pp 4352-4359), 1999. AB - Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Several hemagglutinin genes have been identified, cloned, and expressed in Escherichia coli. The purpose of this study was to characterize host responses to purified recombinant hemagglutinin B (rHag B), using the conventional Fischer rat as the experimental animal model. The effectiveness of immunization with rHag B on protection against experimental periodontal bone loss following infection with P. gingivalis was also evaluated. Groups of rats were immunized by the subcutaneous route with rHag B in complete Freund's adjuvant, immunized with rHag B and orally infected with P. gingivalis, nonimmunized and noninfected, or orally infected with P. gingivalis only. Serum and saliva samples were collected throughout the experiment and evaluated for serum immunoglobulin G (IgG) and IgM and salivary IgA antibody activity by enzyme-linked immunosorbent assay. No salivary IgA anti-Hag B activity was detected in the various groups of rats. A slight serum IgM response similar to that seen in preimmune samples was observed. Serum IgG antibody activity to Hag B was detected only in samples from rats immunized with rHag B. This response was primarily of the IgG1 and IgG2a subclasses, followed by IgG2b and low levels of IgG2c. Supernatants from rHag B-stimulated splenic lymphoid cell cultures from immunized rats contained high levels of gamma interferon, followed by interleukin-2 (IL-2), IL-10, and then IL-4. These results are consistent with the induction of T helper type 1 (Th1)- and Th2-like responses. Western blot analysis of sera derived from rHag B-immunized rats reacted with trichloroacetic acid (TCA) precipitates of P. gingivalis 33277, 381, A7A1-28, and W50, revealing a 50-kDa band reflective of Hag B. However, sera derived from rats immunized with P. gingivalis whole cells or from rats infected with P. gingivalis only did not react with rHag B but did react with TCA precipitates of P. gingivalis strains. Finally, radiographic measurements of periodontal bone loss indicated that rats immunized with rHag B had less bone loss than those infected with P. gingivalis only. These results demonstrate the effectiveness of purified rHag B in inducing a protective immune response and support the potential usefulness of this component of P. gingivalis in the development of a vaccine against adult periodontitis. [References: 47] <22> UI - 1999257164 AU - Sugita N AU - Yamamoto K AU - Kobayashi T AU - Van Der Pol WL AU - Horigome T AU - Yoshie H AU - Van De Winkel JGJ AU - Hara K IN - Dr. H. Yoshie, Department of Periodontology, Niigata Univ. School of Dentistry, Gakko-cho 2-5274, Niigata 951-8514; Japan. E-Mail: psugita@dent.niigata-u.ac.jp. TI - Relevance of FcgammaRIIIa-158V-F polymorphism to recurrence of adult periodontitis in Japanese patients. SO - Clinical & Experimental Immunology Vol 117(2) (pp 350-354), 1999. AB - The immunoglobulin receptor FcgammaRIIIa (CD 16) is distributed on natural killer (NK) cells, macrophages, and gammadelta T cells, and is polymorphic. FcgammaRIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined FgammaRIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over- representation of FcgammaRIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making FcgammaRIIIA a candidate gene for recurrence risk of adult periodontitis. [References: 37] <23> UI - 1999226853 AU - Cassatella MA IN - M.A. Cassatella, Department of Pathology, Faculty of Medicine, University of Verana, 37134 Verona; Italy. TI - Neutrophil-derived proteins: Selling cytokines by the pound. SO - Advances in Immunology Vol 73 (pp 369-509), 1999. <24> UI - 1999161421 AU - Rosales F AU - Peylan-Ramu N AU - Cividalli G AU - Varadi G AU - Or R AU - Naparstek E AU - Slavin S AU - Nagler A IN - Dr. A. Nagler, Bone Marrow Transplantation Dept., Hadassah University Hospital, POB 12000, Jerusalem 91120; Israel. TI - The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases. SO - Bone Marrow Transplantation Vol 23(9) (pp 861-865), 1999. AB - Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC > 1.0 x 109/l at day +19 (10-33), ANC > 0.5 x 109/l at day +22 (10-56) and platelets > 25 x 109/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions. [References: 39] <25> UI - 1999131538 AU - Nguyen Dinh Khoa AU - Hasunuma T AU - Kobata T AU - Kato T AU - Nishioka K IN - Dr. K. Nishioka, Rheumatol., Immunol.,/Genet. Program, Institute of Medical Science, St. Marianna Univ. Sch. of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512; Japan. TI - Expression of murine HOXD9 during embryonic joint patterning and in human T lymphotropic virus type I tax transgenic mice with arthropathy resembling rheumatoid arthritis. SO - Arthritis & Rheumatism Vol 42(4) (pp 686-696), 1999. AB - Objective. To characterize the expression of murine HOXD9 during normal joint development and in arthritic joints of human T lymphotropic virus type I (HTLV-I) tax transgenic mice and the role of HTLV-I tax in HOXD9 expression. Methods. Expression of HOXD9, HOXD10, HOXD11, HOXD12, and HOXD13 genes in joint tissues at the ankle/foot regions of mouse embryos at day 10 to day 18 of gestation (E10-E18) and neonates within 10 days after birth was determined by reverse transcriptase-polymerase chain reaction and in situ reverse transcription methods. Adult synovial tissues from 5 HTLV-I tax transgenic mice with chronic polyarthritis and 4 nontransgenic (normal) mice were also examined for expression of these HOXD genes. The effect of HTLV-I on HOXD9 expression in cultured synoviocytes was studied by in vitro infection and transfection experiments. Results. Expression of HOXD9 was detected in embryonic joints, preferentially on articular cartilage, only during the early stages of joint development (up to E15), whereas other HOXD genes were expressed throughout the embryonic and neonatal stages. In adult mice, transcripts of HOXD9 were specifically detected in synovial tissues from 4 of 5 arthritic mice, especially in the lining and sublining synovial cells, but not in synovial tissues of normal mice. Activation of HOXD9 was observed in cultured synoviocytes infected with HTLV-I in vitro as well as in those transfected with HTLV-I tax. Conclusion. Our findings suggest that HOXD9 is involved not only in the early stages of normal joint development, but may also be involved in the pathologic process of arthritis. HTLV-I tax appeared as an activator of this HOX gene in cultured synoviocytes. [References: 30] <26> UI - 1999115392 AU - Denton MD AU - Magee CC AU - Sayegh MH IN - Dr. M.H. Sayegh, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; United States. E-Mail: msayegh@rics.bwh.harvard.edu. TI - Immunosuppressive strategies in transplantation. SO - Lancet 27 MAR 1999Vol 353(9158) (pp 1083-1091), 1999. <27> UI - 1999101494 AU - Barry JM IN - Dr. J.M. Barry, Div. Urology Renal Transplantation, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201; United States. TI - Renal transplantation. SO - Current Opinion in Urology Vol 9(2) (pp 121-127), 1999. AB - There has been an increase in the transplantation of kidneys from living, genetically unrelated donors and from extended criteria cadaver donors. The past policies about paid renal donors are being reconsidered. Techniques have been developed to reduce morbidity for the living renal donor. The variety of immunosuppressants allows individuation of therapy. Guidelines for conception and pregnancy have been established. [References: 37] <28> UI - 1999024166 AU - Sims TJ AU - Mancl LA AU - Braham PH AU - Page RC IN - R.C. Page, Research Center in Oral Biology, Box 357480, University of Washington, Seattle, WA 98195; United States. E-Mail: rcobiol@u.washing ton.edu. TI - Antigenic variation in Bacteroides forsythus detected by a checkerboard enzyme-linked immunosorbent assay. SO - Clinical & Diagnostic Laboratory Immunology Vol 5(5) (pp 725-731), 1998. AB - Evidence indicating that multiple serotypes of Bacteroides forsythus participate in rapidly progressing periodontal infections has not been reported previously. Our aim was to develop an assay for detecting subsets of B. forsythus clinical isolates which differ in serogroup membership and subsets of patients with immunoglobulin G (IgG) responses which differ in serogroup recognition. A checkerboard enzyme-linked immunosorbent assay (ELISA) was used to assess variation in the IgG binding profiles of 22 clinical isolates in sera from 28 patients with early-onset rapidly progressive periodontitis. To accommodate the maximum number of isolates and sera in a given assay run, a multiplate assay grid with standard 96-well microtest plates was established. Single dilutions of individual sera were placed in rows crossing columns of isolate-coated wells, and antigenspecific IgG immobilized in the wells was measured as ELISA absorbance. Pooled sera and isolates were assayed in parallel to serve as negative controls for variation in IgG binding profiles. Correlation and hierarchical cluster analysis of the absorbance data matrix showed that the isolates could be sorted into at least four clusters based on variations in their IgG binding profiles across different sera. Furthermore, at least two patient clusters were defined by variations in their serum IgG antigen recognition profiles across different isolates. We conclude that multiple serogroups of B. forsythus exist and that different serogroups are dominant in the antibody response of different patients. The method applied here could be used to serologically classify clinical isolates of other species which evoke a serum antibody response in patients. [References: 12] <29> UI - 1998398292 AU - Murakami Y AU - Hanazawa S AU - Tanaka S AU - Iwahashi H AU - Kitano S AU - Fujisawa S IN - S. Hanazawa, Department of Oral Microbiology, Meikai University School Dentistry, 1-1 Keyakidai, Sakado City, Saitama 350-0283; Japan. TI - Fibronectin in saliva inhibits Porphyromonas gingivalis fimbria-induced expression of inflammatory cytokine gene in mouse macrophages. SO - FEMS Immunology & Medical Microbiology Vol 22(3) (pp 257-262), 1998. AB - The aim of this study was to examine whether fibronectin in saliva plays a regulatory role in Porphyromonas gingivalis fimbria-mediated pathogenesis in adult periodontal disease. Our previous study demonstrated that fibronectin is one of the binding proteins of P. gingivalis fimbrillin. In the present study, we observed that fibronectin in saliva binds specifically to the fimbrillin. The fibronectin content in saliva of adult periodontal patients was significantly lower than that of healthy subject. In addition, the inhibitory action of salivary fibronectin from adult periodontal patients toward P. gingivalis fimbria-induced expression of the neutrophil chemoattractant KC gene in mouse macrophages was clearly weak compared with that of the fibronectin from healthy subjects. These results suggest that fibronectin in saliva plays an important role as a regulator in the pathogenesis of P. gingivalis fimbriae in adult periodontal disease. Copyright (C) 1998 Federation of European Microbiological Societies. [References: 20] <30> UI - 1998396280 AU - Ohguchi M AU - Ishisaki A AU - Okahashi N AU - Koide M AU - Koseki T AU - Yamato K AU - Noguchi T AU - Nishihara T IN - T. Nishihara, Department of Oral Science, Natl. Inst. of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640; Japan. E-Mail: tatsujin@nih.go.jp. TI - Actinobacillus actinomycetemcomitans toxin induces both cell cycle arrest in the G2/M phase and apoptosis. SO - Infection & Immunity Vol 66(12) (pp 5980-5987), 1998. AB - We found that the culture supernatant of the periodontopathic bacterium Actinobacillus actinomycetemcomitans had a cytotoxic effect on several cell lines. In this study, we purified the toxin from the culture supernatant of A. actinomycetemcomitans Y4 by a four-step procedure: ammonium sulfate precipitation, POROS HQ/M column chromatography, polymyxin B matrix column chromatography, and Mono-Q column chromatography. The purified toxin gave two major bands of protein with molecular masses of 80 and 85 kDa upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The mechanism of cell death of the B-cell hybridoma cell line HS-72 was examined by observing changes in nuclear morphology, an increase in the proportion of fragmented DNA, and the typical ladder pattern of degraded chromosomal DNA, indicating the induction of apoptosis. Overexpression of human Bcl-2 suppressed apoptosis in HS-72 cells, indicating that the toxin from A. actinomycetemcomitans induces apoptosis by a Bcl-2-inhibitable mechanism. Flow cytometric analysis revealed that the toxin caused cell cycle arrest in the G2/M phase and apoptosis in HS-72 cells. In addition, aurintricarboxylic acid, a DNA endonuclease inhibitor, markedly decreased the percentage of apoptotic cells but had no effect on cell cycle arrest in the G2/M phase. Taken together, these findings suggest that the toxin from A. actinomycetemcomitans could mediate the development of periodontal diseases through cell cycle arrest in the G2/M phase and apoptosis in B lymphocytes of periodontal tissue. [References: 43] <31> UI - 1998418358 AU - Yoshiba N AU - Yoshiba K AU - Iwaku M AU - Ozawa H IN - Dr. N. Yoshiba, Dept. of Operative Dent./Endodontics, Niigata Univ. School of Dentistry, Gakkocho-dori-2, Niigata 951-8514; Japan. E-Mail: yoshiba@dent.niigata-u.ac.jp. TI - Immunohistochemical localizations of class II antigens and nerve fibers in human carious teeth: HLA-DR immunoreactivity in Schwann cells. SO - Archives of Histology & Cytology Vol 61(4) (pp 343-352), 1998. AB - Nerve fibers and class II major histocompatibility complex (MHC) antigen-expressing dendritic cells have been known to gather in the dental pulp beneath carious lesions. Significant functional interactions presumably occur between the neural and immune elements. The present study analyzed the morphological relationship between class II-expressing cells and nerve fibers in fuman carious teeth, visualized by a HLA-DR monoclonal antibody and a protein gene product 9.5 (PGP 9.5) polyclonal antibody; a confocal laser scanning microscope (CLSM) and an electron microscope were used. In pulps affected by early caries, HLA-DR-positive dendritic cells aggregated mainly in the cell-free zone associated with bundles of PGP 9.5-immunoreactive nerve fibers. In pulps affected by advanced caries, the accumulated HLA-DR-positive cells and PGP 9.5-immunoreactive nerve fibers showed close association with each other especially beneath the odontoblast layer: the cells even embraced the nerve fibers. Intriguingly, class II molecules were recognized not only in dendritic cells but also in the Schwann cells of non-myelinated nerves in the pulp. Using immunoelectron microscopy, class II molecules were localized on the surface of the non-myelinating Schwann cells and also within some vesicles, whereas myelinating Schwann cells lacked this immunoreactivity. PGP 9.5-immunoreactive nerve fibers were also observed densely in the odontoblast layer, and CLSM revealed an intimate association of the nerve fibers and dendritic cells. The immunoreactivity for HLA-DR in Schwann cells depended upon the severity of the carious lesion. Class II-expressing Schwann cells are suggested to function as antigen-presenting cells in addition to dendritic cells. [References: 40] <32> UI - 1998364269 AU - Kramer MHH AU - Hermans J AU - Wijburg E AU - Philippo K AU - Geelen E AU - Van Krieken JHJM AU - De Jong D AU - Maartense E AU - Schuuring E AU - Kluin PM IN - Dr. P.M. Kluin, Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden; Netherlands. TI - Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. SO - Blood 01 NOV 1998Vol 92(9) (pp 3152-3162), 1998. 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. [References: 54] <33> UI - 1998295679 AU - Takeshita A AU - Murakami Y AU - Yamashita Y AU - Ishida M AU - Fujisawa S AU - Kitano S AU - Hanazawa S IN - S. Hanazawa, Department of Oral Microbiology, Meikai Univ. School of Dentistry, Keyakidai, Sakado City, Saitama 350-0283; Japan. E-Mail: hanazawa@dent.meikai.ac.jp. TI - Porphyromonas gingivalis fimbriae use beta2 integrin (CD11/CD18) on mouse peritoneal macrophages as a cellular receptor, and the CD18 beta chain plays a functional role in fimbrial signaling. SO - Infection & Immunity Vol 66(9) (pp 4056-4060), 1998. AB - In this study, we demonstrate that Porphyromonas gingivalis fimbriae use molecules of beta2 integrin (CD11/CD18) on mouse peritoneal macrophages as cellular receptors and also show that the beta chain (CD18) may play a functional role in signalling for the fimbria-induced expression of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) genes in the cells. Using a binding assay with 125I-labeled fimbriae, we observed that fimbrial binding to the macrophages was inhibited by treatment with CD11a, CD11b, CD11c, or CD18 antibody but not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of beta2 integriu (CD11/CD18) on the macrophages. Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1beta and TNF-alpha genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment. Interestingly, intracellular adhesion molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial binding to the cells in a dose-dependent manner. In addition, ICAM-1 clearly inhibited the fimbria-induced expression of IL-1beta and TNF-alpha genes in the cells. However, such inhibitory action was not observed with laminin treatment. These results suggest the importance of beta2 integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease. [References: 36] <34> UI - 1998286231 AU - Herzberg GZ AU - Rossi AF AU - Courtney M AU - Lansman SL AU - Gelb BD AU - Parness IA AU - Lai WW IN - Dr. G.Z. Herzberg, Sound Shore Medical Center, 16 Guion Place, New Rochelle, NY 10802; United States. TI - Usefulness of tacrolimus versus cyclosporine after pediatric heart transplantation. SO - American Journal of Cardiology Vol 82(4) (pp 541-543), 1998. AB - This study compared the early clinical course of 9 pediatric heart transplantation recipients treated with cyclosporine A-based immunosuppression with 10 similarly aged recipients treated with tacrolimus- based therapy. One-year follow-up after transplantation revealed that tacrolimus-treated children had similar left ventricular function, experienced fewer episodes of severe rejection, were more rapidly weaned from corticosteroids, and had relatively few side effects from immunosuppression compared with cyclosporine A-treated children. [References: 11] <35> UI - 1998257061 AU - Higashiyama M AU - Kodama K AU - Yokouchi H AU - Takami K AU - Adachi M AU - Taki T AU - Ishiguro S AU - Nakamori S AU - Yoshie O AU - Miyake M IN - Dr. M. Higashiyama, Department of Thoracic Surgery, Osaka Can./Cardiovas. Dis. Med. Ctr., Nakamichi 1-3-3, Higashinariku, Osaka 537; Japan. TI - KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: An immunohistochemical analysis. SO - Cancer 01 AUG 1998Vol 83(3) (pp 466-474), 1998. AB - BACKGROUND. The KAI1/CD82 gene, the product of which is a member of the transmembrane-4 superfamily, is a suppressor of metastasis; as a result, it is inversely associated with tumor progression and is a favorable prognostic factor in some tumors. This study was performed to determine the prognostic value of KAI1/CD82 protein levels in nonsmall cell lung carcinoma (NSCLC). In addition, levels of KAI1/CD82 expression in metastatic lesions were determined and compared with those in primary NSCLC lesions. METHODS. KAI1/CD82 expression in 200 NSCLC patients who underwent potentially curative surgery was immunohistochemically detected with C33, an anti-KAI1/CD82 monoclonal antibody. According to the degree of KAI1/CD82 positive cancer cells within the tumor tissue, each sample was classified as KAI1/CD82 positive, KAI1/CD82 reduced, or KAI1/CD82 negative. RESULTS. Sixty-five samples (32.5%) were KAI1/CD82 positive, 31 (15.5%) were reduced, and 104 (52%) were negative. There was no significant association between KAI1/CD82 expression and clinicopathologic factors, but patients who were positive for KAI1/CD82 expression had significantly favorable prognoses for overall survival (P = 0.0026) and disease free survival (DFS; P = 0.0007) compared with the other groups. In particular, among patients with adenocarcinoma, similar results were even more significant. In multivariate analysis, immunohistochemical KAI1/CD82 expression in patients with NSCLC was an independent prognostic factor for overall survival and DFS; in those with adenocarcinoma, it was an even more valuable factor. In some patients with NSCLC, especially those with adenocarcinoma, KAI1/CD82 expression levels in metastatic lesions were diminished compared with levels of expression in the primary lung lesions. CONCLUSIONS. The immunohistochemically determined level of KAI1/CD82 expression in NSCLC cells within tumor tissue appears to be a favorable prognostic factor for overall survival as well as DFS. The results of this study suggest that decreased KAI1/CD82 expression may be associated with tumor progression and enhanced metastatic potential in some patients with this disease. [References: 27] <36> UI - 1998228403 AU - Comandini UV AU - Tossini G AU - Longo MA AU - Ferri F AU - Cuzzi G AU - Noto P AU - Zaccarelli M AU - Visco G IN - Dr. U.V. Comandini, Via Flaminia 195, I-00196, Rome; Italy. TI - Sporadic Hepatitis C virus infection: A case-control study of transmission routes in a selected hospital sample of the general population in Italy. SO - Scandinavian Journal of Infectious Diseases Vol 30(1) (pp 11-15), 1998. AB - A case-control study was performed on 9,175 Italian adult outpatients in 5 hospitals in Rome. The study was carried out to clarify the role of some less investigated risk factors (RF) in the spread of hepatitis C virus (HCV) infection. All subjects were contacted by interviewers, who completed a questionnaire. Their sera were stored and subsequently tested for both HCV and hepatitis B virus core (HBc) antibodies. 365 subjects, positive for anti-HCV and anti-HBc-negative, and who had denied intravenous drug use (IDU) (cases) were compared with an equal number of suitable random controls negative for anti-HCV and anti-HBc. Gender, age and region of birth and residence mere matched. The prevalence of 13 RFs were statistically compared by univariate and multivariate analysis. A positive anti-HCV test was significantly associated, by multivariate analysis with intravenous treatments and minor surgical procedures (both before 1975) (p < 0.001), blood transfusions (before 1991) (p < 0.01), diabetes (p < 0.01), and deliveries in hospital (p < 0.05) (both before 1975). After 1975 (1991 for transfusions), all associations lost their significance. Intra-familial (sexual and non sexual), occupational RFs and dental care were not significantly associated with the presence of anti-HCV. We suggest that non-disposable syringes, commonly used until 1975 in Italy for i.v. treatments, have been the major route for HCV transmission in Italy among non-IDU subjects. [References: 32] <37> UI - 1998203496 AU - Thomas X AU - Thiebaut A AU - Olteanu N AU - Danaila C AU - Charrin C AU - Archimbaud E AU - Fiere D IN - X. Thomas, Service d'Hematologie, Lab. Ctr. Hematol. de Cytogenetique, Hopital Edouard Herriot, F-69437 Lyon Cedex 03; France. TI - Philadelphia chromosome positive adult acute lymphoblastic leukemia: Characteristics, prognostic factors and treatment outcome. SO - Hematology & Cell Therapy Vol 40(3) (pp 119-128), 1998. 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 109/1 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 diseasefree 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. [References: 52] <38> UI - 1998173015 AU - Anonymous TI - Fields of pharmaceuticals. SO - Nature Medicine Vol 4(5) (pp 535), 1998. <39> UI - 1998171469 AU - Sanchez E AU - Chacon I AU - Plaza MM AU - Munoz E AU - Cruz MA AU - Martinez B AU - Lopez L AU - Martinez-Montero JC AU - Orradre JL AU - Saez AI AU - Garcia JF AU - Piris MA IN - Dr. M.A. Piris, Dept. of Pathology, Hospital 'V. de la Salud', Av/ Barber 30, 45004 Toledo; Spain. E-Mail: mpiris@cht.es. TI - Clinical outcome in diffuse large B-cell lymphoma is dependent on the relationship between different cell-cycle regulator proteins. SO - Journal of Clinical Oncology Vol 16(5) (pp 1931-1939), 1998. AB - Purpose: The goal of this work was to perform a comprehensive exploration of the relationship between the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and the expression of a panel of tumor suppressor and oncogenic proteins, which includes some cell-cycle regulator proteins involved in the p53 pathway. Patients and Methods: To this end, we collected the clinical data of 141 patients with DLBCL and immunohistochemically analyzed diagnostic tumoral tissue from each patient for the presence of Ki67 (MIB1, Immunotech, Marseille, France), bcl2, p53, p21/WAF1, MDM2, and retinoblastoma (Rb) proteins. Results: The results show that several proteins are associated with some of the clinical traits analyzed. Multivariate analysis showed that an extended overall survival (OS) time was associated with low growth fraction, high Rb protein, and low MDM2 expression, as well as with known clinical parameters. The probability of inducing a complete remission (CR) was only associated with clinical parameters, although univariate study showed that a low growth fraction was associated with a higher probability of inducing a CR, Univariate study of disease-free survival (DFS) showed that tumors with high bcl2 expression and nodal origin have a shorter DFS time, although multivariate study only confirmed the adverse effect of bcl2 expression. Conclusion: Taking all these results into consideration, it seems that although the overall outcome for patients with DLBCL is decided by a combination of different clinical and biologic variables, the expression of some of these cell-cycle regulator proteins appears to be specifically associated with the different clinical features of tumors. [References: 44] <40> UI - 1998170880 AU - Sugita N AU - Kumura A AU - Matsuki Y AU - Yamamoto T AU - Yoshie H AU - Hara K TI - Activation of transcription factors and IL-8 expression in neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis. SO - Inflammation Vol 22(3) (pp 253-267), 1998. AB - DNA binding activity of NF-kappaB and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappaB activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-kappaB and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF. [References: 43] <41> UI - 1998120770 AU - Iwasaki Y AU - Hara Y AU - Koji T AU - Shibata Y AU - Nakane PK AU - Kato I IN - Y. Iwasaki, Department of Periodontology, Nagasaki Univ. School of Dentistry, 1-7-1 Sakamoto, Nagasaki 852; Japan. TI - Differential expression of IFN-gamma, IL-4, IL-10, and IL-1beta mRNAs in decalcified tissue sections of mouse lipopolysaccharide-induced periodontitis mandibles assessed by in situ hybridization. SO - Histochemistry & Cell Biology Vol 109(4) (pp 339-347), 1998. AB - To examine the role of T cell subgroups, Th1 and Th2, in the development of periodontitis, the expression of various cytokines was investigated in a mouse model of alveolar bone resorption using in situ hybridization (ISH) with digoxigenin-labeled oligonucleotides. When mice received repetitive injections with Escherichia coli lipopolysaccharide into the gingiva every 48 h, alveolar bone resorption was detectable after the fourth injection, reaching a maximum after the 13th injection. For the best performance of ISH, we first had to choose a decalcification protocol. Among various decalcification protocols, 10% EDTA (4 [degree] C, 5-6 days) was the best for 28S rRNA staining. Positive cells for transcripts of interferon-gamma (Th1 product) were detected after the fourth injection, reaching a maximum after the tenth injection. A similar pattern was obtained for interleukin (IL)-10 mRNA (Th2 product) and IL-1beta, while the positive cell number reached a maximum after the 13th and 10th injections, respectively. The number of IL-4 mRNA (Th2 product)-positive cells remained low till the tenth injection, but increased thereafter. Consequently, we found that the population change from Th1 to Th2 in the inflammation site correlated with the transition from gingivitis to periodontitis, indicating differential roles of T cell subgroups in the development of periodontitis. [References: 41] <42> UI - 1998089299 AU - Barbour SE AU - Nakashima K AU - Zhang J-B AU - Tangada S AU - Hahn C-L AU - Schenkein HA AU - Tew JG IN - H.A. Schenkein, School of Dentistry, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0566; United States. TI - Tobacco and smoking: Environmental factors modify the host response (immune system) and have an impact on periodontal health. SO - Critical Reviews in Oral Biology & Medicine Vol 8(4) (pp 437-460), 1997. AB - This review summarizes the current data on the effects of smoking and tobacco on the immune system and its potential impact on periodontal health. Smokers are 2.5-6 times more likely to develop periodontal disease than non- smokers, and there is evidence for a direct correlation between the number of cigarettes smoked and the risk of developing disease. Tobacco users also tend to exhibit increased severity of periodontal disease. Direct correlations between tobacco use and increased attachment loss and pocket depth and reduced bone crest height have been reported. Although the correlation between tobacco use and periodontal disease is quite strong, the role of tobacco in the pathogenesis of periodontal disease is uncertain. Recent studies indicate that one potential mechanism is that tobacco use exacerbates periodontal disease because it alters the immune response to periodontal pathogens. Indeed, smokers exhibit increased numbers of peripheral blood mononuclear phagocytes which appear to be functionally compromised. Inadequate phagocyte activity could reduce the clearance of pathogens from the oral cavity and thereby facilitate the development of periodontal disease. Tobacco-exposed B- and T-lymphocytes exhibit reduced proliferative capacities which could limit the production of protective immunoglobulins against oral pathogens. The risk factors for periodontal disease can be broadly classified as genetic, environmental, host-response factors, and host-related factors such as age. Tobacco, an environmental factor, undermines the host response and may facilitate the development and progression of periodontal disease. This review highlights the inter- relatedness of two of the risk factors associated with periodontal disease. [References: 159] <43> UI - 1998031974 AU - Kesavalu L AU - Holt SC AU - Ebersole IN - J.L. Ebersole, Department Periodontics, School of Dentistry, University Texas Hlth Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284; United States. TI - Porphyromonas gingivalis virulence in a murine lesion model: Effects of immune alterations. SO - Microbial Pathogenesis Vol 23(6) (pp 317-326), 1997. AB - This study utilized various mouse strains with documented alterations in immune system components to assess their contribution to modify the virulence of Porphyromonas gingivalis. P. gingivalis W50 was cultivated on blood agar plates, harvested and used to challenge mice by subcutaneous injection on the dorsolateral surface of the back. Soft tissue lesion development was estimated by measuring the area of the spreading lesion formed by this microorganism over a period of 15 days. Challenge of various normal inbred and outbred mouse strains including: BALB/cN, BALB/cJ, BALB/c nu/+, ICR, B1O.A(4R), B1O.MBR, A/J, C57BL/6J, CBA/CaH, C.B-17/ Icv TacfDF and C3H/HeN with 2 x 1010 bacteria showed similar lesion size among these strains ( [similar] 400 mm2). Genetically deficient mouse strains [C.B-17/lcr Tac (SCID); DBA/2 (C5 deficient); BALB/ c nu/nu (T cell deficient); CBA/CaHN-XID/J (B cell deficient) and C3H/HeJ (LPS hyporesponsive)] demonstrated a lesion size which was similar to normal animals. C57BL/6J-BgJ (NK cell deficient) mice exhibited a significantly more severe lesion than the other strains tested. Following healing of the lesions, we initiated a secondary infection of the surviving animals to estimate the acquisition of protective immunity following recovery from the primary infection. Normal mice demonstrated a delayed onset and decrease in lesion size of 15 to 30% compared with the primary infection. In contrast, each of the immunodeficient strains appeared unable to develop immune protection to the secondary challenge. The findings suggest that protection against primary infections with P. gingivalis are mediated by innate immune mechanisms (PMN. NK cells). Additionally, it appears that T-cell-dependent humoral responses are critical to developing immunity to subsequent P. gingivalis infection. [References: 57] <44> UI - 1998028199 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 - Dr. A.S. Freedman, Division of Hematologic Malignancies, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115; United States. E-Mail: 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. SO - Journal of Clinical Oncology Vol 16(1) (pp 13-18), 1998. 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-close 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 R/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. [References: 43] <45> UI - 1998015827 AU - Cascavilla N AU - Musto P AU - D'Arena G AU - Ladogana S AU - Matera R AU - Carotenuto M IN - Dr. N. Cascavilla, Divisione di Ematologia, IRCCS, Ospedale 'Casa Sollievo Sofferenza', viale Cappuccini, 71013 San Giovanni Rotondo; Italy. TI - Adult and childhood acute lymphoblastic leukemia: Clinico-biological differences based on CD34 antigen expression. SO - Haematologica Vol 82(1) (pp 31-37), 1997. AB - Background and Objective. The prognostic significance of CD34 antigen expression n acute lymphoblastic leukemias (ALL), especially in adult patients, is still not well established. In the present report we analyzed a series of biological and clinical findings from 128 ALL patients in order to evaluate the possible clinical significance of this marker. Methods. The clinical and biological significance of CD34 expression, an early marker of hemopoietic cells, was analyzed by flow cytometry in a series of 128 patients affected by ALL, including 78 adults and 50 children under 15 years old. Results. Overall, 68.7% of patients showed significant (> 10%) CD34 expression. There was no difference between CD34+ and CD34- ALL with respect to age, sex, FAB morphology, hepatosplenomegaly, Plt count, Hb level, DNA index, P-170 expression. CD34+ ALL displayed a significantly lower frequency of extramedullary involvement, a lower LDH level and lower WBC count, lower proliferative activity (as evaluated by the Ki67 monoclonal antibody) than CD34- ALL. CD34 expression was also associated with early phenotypes in both B- and T-ALL, co-expression of myeloid antigens, and the presence of the Ph1 chromosome. Due to a different distribution oF prognostic factors investigated, DFS and OS were both significantly better in CD34+ than in CD34- childhood ALL, whereas no statistical difference was found in adults. Multivariate analyses confirmed these data in children. Interpretation and Conclusions. Expression of the CD54 antigen is a positive prognostic factor in childhood ALL. In adult ALL the presence oF this marker on leukemic cell does not seem to influence the clinical outcome of these patients. [References: 50] <46> UI - 1997351352 AU - Gunduz K AU - Gunalp I AU - Erden I IN - K. Gunduz, GMK Bulvari 116-3, Maltepe 06570, Ankara; Turkey. TI - Focal dermal hypoplasia (Goltz's syndrome). SO - Ophthalmic Genetics Vol 18(3) (pp 143-149), 1997. AB - A 17-year-old female with Goltz's syndrome was examined because of visual acuity loss in her right eye. Ocular examination revealed microcornea, iris, choroid and optic disc coloboma in the right eye. There were several erthematous and hyperpigmented areas on the body. Magnetic resonance (MR) imaging of the orbits and brain demonstrated right optic nerve hypoplasia and diffuse cortical and cerebellar atrophy. Skeletal manifestations were short stature, scoliosis, syndactyly, clinodactyly, and osteopathia striata. Dental defects included hypodontia, developmental defects, and malocclusion. There were multiple papillomatous lesions on the lids and perioral skin and the nose was asymmetric. Her mental development was apparently normal. She had left bifid ureter and renal pelvis, scant hair on the pubic and genital region, and poor breast development. Histopathologic examination of the biopsy taken from a characteristic skin lesion revealed attenuated epidermis, hypoplastic dermis, and subcutaneous fat close to epidermis. Immunofluorescence staining was negative for IgG, IgM, IgA, C3, C4, fibrin, and albumin. Ultrastructural examination showed that no viral particles were present. Prometaphase chromosome analysis revealed a normal 46, XX female karyotype. Cortical and cerebellar atrophy can occur in a patient with Goltz's syndrome. [References: 19] <47> UI - 1997338428 AU - Kelly CG AU - Booth V AU - Kendal H AU - Slaney JM AU - Curtis MA AU - Lehner T IN - C.G. Kelly, Department of Immunology, Guy's Tower, Guy's Hospital, London Bridge, London SE1 9RT; United Kingdom. TI - The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis. SO - Clinical & Experimental Immunology Vol 110(2) (pp 285-291), 1997. AB - Passive immunization with the monoclonal antibody 61BG1.3 selectively prevents colonization by Porphyromonas gingivalis in humans (Booth V, Ashley FP, Lehner T. Infect Immun 1996; 64:422-7). The protective MoAb recognizes the beta component of the RI protease of P. gingivalis which is formed by proteolytic processing of a polyprotein precursor termed PrpR1. This subunit is both a haemagglutinin and an antigen which is recognized by sera from patients with periodontitis. In this study the relationship was investigated between a colonization epitope which is recognized by the MoAb 61BG1.3, a haemagglutinating and B cell epitope which are recognized by sera from patients with periodontitis. B cell epitopes were mapped by Western blotting with a series of truncated recombinant polypeptides spanning the adhesion domain within residues 784-1130 of PrpR1 and by ELISA using a panel of synthetic peptides spanning the same sequence. The epitope which is recognized by the protective MoAb was mapped within residues 907-931 of PrpR1, while serum responses of patients were directed predominantly to the adjacent carboxy-terminal sequence within residues 934-1042. The haemagglutinating epitope was mapped to residues 1073-1112. In view of our previous findings that the MoAb 61BG1.3 prevents colonization of P. gingivalis in vivo and inhibits haemagglutination, these two epitopes may be in proximity in the native protein. Active or passive immunization strategies which target the protective or haemagglutinating epitopes of the adhesion domain of PrpR1 may provide a means of preventing infection with P. gingivalis. [References: 27] <48> UI - 1997318460 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 - Dr. D.A. Williams, H.B. Wells Ctr. for Pediatric Res., Howard Hughes Medical Institute, Cancer Research Bldg, 1044 W Walnut, Indianapolis, IN 46202-5225; United States. 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 Vol 90(8) (pp 3018-3026), 1997. 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. [References: 30] <49> UI - 1997293526 AU - Klebanoff SJ AU - Mehlin C AU - Headley CM IN - S.J. Klebanoff, Department of Medicine, Box 357185, University of Washington, Seattle, WA 98195-7185; United States. TI - Activation of the HIV type 1 long terminal repeat and viral replication by dimethylsulfoxide and related solvents. SO - AIDS Research & Human Retroviruses Vol 13(14) (pp 1221-1227), 1997. AB - The HIV-1 long terminal repeat (LTR) introduced into the macrophage cell line THP-1 and the T lymphocyte cell line Jurkat in association with the luciferase reporter gene is activated by the polar, aprotic solvents dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), and dimethylformamide (DMF). These solvents also greatly potentiated the activation of the LTR in THP-1 cells by phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), H2O2, and a Staphylococcus epidermidis product. Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at 1 mug/ml had no effect on the LTR in THP-1 cells unless the solvents were added. The aprotic solvents also greatly potentiated the activation of the LTR in Jurkat cells by PMA, TNF-alpha, and H2O2, whereas LPS, LTA, or the S. epidermidis product had no effect in the presence or absence of the solvents. DMSO, DMAC, and DMF also increased the production of intact virions by latently HIV-1-infected ACH-2, J1.1, U1, and OM10.1 cells under some experimental conditions. The use of the polar aprotic solvents DMSO, DMAC, and DMF, by amplification, may allow the better detection of a weak activator of the LTR and facilitate studies of the mechanism of activation. [References: 28] <50> UI - 1997286652 AU - Abiko Y AU - Ogura N AU - Matsuda U AU - Yanagi K AU - Takiguchi H IN - Y. Abiko, Department of Biochemistry, Nihon Univ. School of Dentistry, 2-870-1 Sakaecho-nishi, Matsudo, Chiba 271; Japan. E-Mail: yabiko@mascat.nihon-u.ac.jp. TI - A human monoclonal antibody which inhibits the coaggregation activity of Porphyromonas gingivalis. SO - Infection & Immunity Vol 65(9) (pp 3966-3969), 1997. AB - A B-cell line producing a human monoclonal antibody (HuMAb) against a recombinant 40-kDa outer membrane protein (OMP) of Porphyromonas gingivalis was constructed by in vivo immunization of a severe combined immunodeficiency C.B.-17/Icr mouse, which had been injected with human peripheral blood lymphocytes, with recombinant 40-kDa OMP and subsequent Epstein-Barr virus immortalization of B cells isolated from the spleen of the mouse. This HuMAb inhibited coaggregation between P. gingivalis vesicles and Actinomyces naeslundii cells. [References: 28] <51> UI - 1997286624 AU - Nakashima K AU - Schenkein HA AU - Califano JV AU - Tew JG IN - J.G. Tew, Dept. of Microbiology/Immunology, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980678, Richmond, VA 23298-0678; United States. TI - Heterogeneity of antibodies reactive with the dominant antigen of Actinobacillus actinomycetemcomitans. SO - Infection & Immunity Vol 65(9) (pp 3794-3798), 1997. AB - The serotype b-specific carbohydrate antigen (SbAg) of Actinobacillus actinomycetemcomitans Y4 is reported to be the O antigen of lipopolysaccharide, and the highest titers of serum antibody reactive with A. actinomycetemcomitans in early-onset periodontitis (EOP) patients bind SbAg. These high titers of serum antibody reactive with SbAg are associated with a lesser extent and severity of periodontal disease. The aim of this study was to determine if a limited number of genes code for anti-SbAg antibodies as has been shown for immunoglobulin G (IgG) reactive with the type b polysaccharide from Haemophilus influenzae. Serum IgG reactive with the SbAg was prepared from 20 high-titer EOP patients by affinity chromatography. The IgG subclass concentrations were determined, and heterogeneity was analyzed by isoelectric focusing (IEF). IgG2 was the dominant subclass (83% of total IgG) in the anti-SbAg IgG fraction and represented an average of 1.33% of total serum IgG2. The IgG2 reactive with SbAg was isolated from the affinity-purified IgG fraction by affinity chromatography with protein A and subclass-specific monoclonal antibodies. On IEF gels, only 4 to 20 bands were observed in the anti-SbAg IgG fractions, indicating limited heterogeneity. N- terminal amino acid sequence analysis of eight representative anti- SbAg IgG2 preparations indicated that variable heavy and light chains consisted largely of V(H)III and V(K)II, respectively. However, a significant fraction of anti-SbAg may use V(H) and V(k) genes with blocked N termini. In short, these findings indicate that IgG reactive with SbAg is very much like the antibody reactive with H. influenzae type b polysaccharide. Similarities include IgG2 dominance, limited bands on IEF gels, supporting an oligoclonal response, and use of genes from V(H)III and V(k)II regions. [References: 31] <52> UI - 1997268399 AU - Yamamoto T IN - Dr. T. Yamamoto, Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh City, Osaka 562; Japan. TI - Diagnosis of X-linked hypophosphatemic vitamin D resistant rickets. SO - Acta Paediatrica Japonica Vol 39(4) (pp 499-502), 1997. AB - Recent advances in the pathophysiology and diagnosis of X-linked hypophosphatemic rickets (XLH) are reviewed. The recent discovery of the gene that is responsible for XLH especially enables us to understand the mechanism of hypophosphatemia in XLH. Laboratory and radiological findings are important for the diagnosis. However, dental abnormalities such as spontaneous dental abscess and a defect of dentin maturation are also notable findings. [References: 29] <53> UI - 1997265340 AU - Honma K AU - Ishii N AU - Kato T AU - Ishihara K AU - Okuda K AU - Okuda K IN - Dr. K. Honma, Oral Health Science Center, Department of Microbiology, Tokyo Dental College, 1-2-2 Masago Mihama-ku, Chiba 261; Japan. TI - Genetic control of immune responses to a synthetic fimbrial antigen of Actinobacillus actinomycetemcomitans. SO - Microbiology & Immunology Vol 41(8) (pp 609-614), 1997. AB - The incidence of infection by Actinobacillus actinomycetemcomitans, one of the important pathogens in human periodontal diseases, has been reported to be associated with racial background and genetic factors. We attempted to determine the genetic regulation of immune responses to A. actinomycetemcomitans fimbriae, an attachment factor, using various inbred strains of mice. For this purpose, we synthesized an oligopeptide antigen using the amino acid sequence of the fimbriae and conjugated this antigen to branched lysine polymer resin beads. After immunization with the synthetic A. actinomycetemcomitans fimbrial antigen, serum antibody levels and the delayed-type hypersensitivity (DTH) reaction to the antigen were measured by enzyme-linked immunosorbent assay (ELISA) and footpad swelling responses, respectively. The strains of mice found to be high-IgG responders to the antigen were B10.HTT, B10.RIII, B10.A (5R) and B10.S (9R). These results indicate that mice with E(beta)(s):E(alpha)(k), E(beta)(r):E(alpha)(r) and E(beta)(b):Ealpha(k) respond strongly to the synthetic peptide. All of the high- IgG responders showed a high DTH response. A cell transfer experiment confirmed that CD4 T cells mediated with a DTH response to the synthetic peptide. Thus, the results of this study demonstrate that the immune responses to A. actinomycetemcomitans fimbriae are genetically controlled. [References: 17] <54> UI - 1997196377 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 - Dr. R.D. Gascoyne, FRCPC, Department of Pathology, B.C. Cancer Agency, 600 W 10th Ave, Vancouver, BC V5Z 4E6; Canada. TI - Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. SO - Blood Vol 90(1) (pp 244-251), 1997. 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. [References: 61] <55> UI - 1997168456 AU - Yu H AU - Nakano Y AU - Yamashita Y AU - Oho T AU - Koga T IN - T. Koga, Department of Preventive Dentistry, Kyushu Univ. Faculty of Dentistry, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82; 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 Vol 65(6) (pp 2292-2298), 1997. 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. [References: 37] <56> UI - 1997158270 AU - Suzuki T AU - Tai H AU - Yoshie H AU - Jeannel D AU - Fournier S AU - DuPont B AU - De The G AU - Hara K IN - Dr. K. Hara, Department of Periodontology, Niigata Univ. School of Dentistry, 2-5274 Gakko-cho, Niigata 951; Japan. TI - Characterization of HIV-related periodontitis in AIDS patients: HIV- infected macrophage exudate in gingival crevicular fluid as a hallmark of distinctive etiology. SO - Clinical & Experimental Immunology Vol 108(2) (pp 254-259), 1997. AB - In an attempt to clarify the immunobiological events featuring periodontitis lesions of AIDS patients in the late stage of the disease, peripheral blood (PB) and gingival crevicular fluid (GCF) leucocytes from periodontitis lesions of 23 late-stage AIDS patients were analysed by three- colour flow cytometry for detection and identification of intracytoplasmic p24+ cell fractions. The cells were reacted with CD14 and CD68 for mononuclear phagocytes or with CD4 and CD14 for Th cells, then with anti-p24 MoAb. To detect HIV proviral sequences and intracellular p24 RNA sequences, genomic DNA and cellular RNA from leucocytes were extracted for semi-nested polymerase chain reaction (PCR) amplification. CD68+/p24+ and CD14+/p24+ fractions were larger in GCF than in PB (P < 0.0001; P < 0.003). CD14+/p24+ fraction was lower in GCF than in PB (P < 0.05). The fluorescence intensities (FI) for intracellular p24 in CD68+ and CD14+/CD68+ cells were higher in GCF than in PB (P < 0.003; P < 0.02), whereas those of CD14+ macrophages did not differ. The p24 FI of CD68+ macrophages in GCF correlated with CD4+ lymphocyte counts in PB (P < 0.005). p24 FI levels of CD14+ monocytes in GCF and PB significantly correlated (P < 0.02), whereas that of CD68+ macrophages did not. PCR and reverse transcriptase (RT)-PCR of cellular DNA and RNA yielded positive signals, demonstrating viral integration and production in GCF leucocytes. These results show that periodontitis lesions in AIDS patients can be characterized by a rapid macrophage turnover, and these HIV-infected macrophage exudates in GCF may be considered as a within- mouth source of virus. [References: 23] <57> UI - 1997147349 AU - Mattijssen V AU - Schattenberg A AU - Schaap N AU - Preijers F AU - De Witte T IN - Dr. V. Mattijssen, Division of Haematology, University Hospital Nijmegen, Geert Grooteplein 8, 6500 HB Nijmegen; Netherlands. TI - Outcome of allogeneic bone marrow transplantation with lymphocyte-depleted marrow grafts in adult patients with myelodysplastic syndromes. SO - Bone Marrow Transplantation Vol 19(8) (pp 791-794), 1997. 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. [References: 19] <58> UI - 1997070343 AU - Iacopino AM AU - Doxey D AU - Cutler CW AU - Nares S AU - Stoever K AU - Fojt J AU - Gonzales A AU - Dill RE IN - Dr. A.M. Iacopino, Department of Biomedical Sciences, Baylor College of Dentistry, P.O. Box 660677, Dallas, TX 75266-0677; United States. TI - Phenytoin and cyclosporin A specifically regulate macrophage phenotype and expression of platelet-derived growth factor and interleukin-1 in vitro and in vivo: Possible molecular mechanism of drug-induced gingival hyperplasia. SO - Journal of Periodontology Vol 68(1) (pp 73-83), 1997. AB - Phenytoin (PHT) is an anticonvulsant drug commonly used for the prevention of seizures. A common side effect of PHT therapy is gingival hyperplasia, occasionally so severe that it requires surgical intervention. Cyclosporine A (CSA) is a drug widely used for the control of rejection phenomena following solid organ and bone marrow transplantation. A frequent side effect of CSA administration is gingival overgrowth. As yet, the molecular mechanisms of drug-induced gingival hyperplasia are unknown although it has been postulated that certain drugs increase fibroblastic activity through alterations in levels of various growth factors and cytokines. The purpose of this study was to: 1) evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and interleukin (IL)-1beta production in vitro after exposure to CSA; 2) determine the levels of PDGF-B and IL-1beta gene expression in minimally inflamed gingival tissues of control patients and PHT-treated patients exhibiting gingival overgrowth as well as patients with severe gingival inflammation; and 3) combine characterization of macrophage phenotype with clinical presentation and expression of PDGF-B and IL-1beta in gingival tissues from the control and PHT-treated patients. For the in vitro studies, commercial ELISA kits were used to measure PDGF-A/PDGF-B and IL-1beta levels in conditioned media from rat and human monocyte/macrophage cell cultures. CSA caused a significant elevation of PDGF but did not cause any changes in IL-1beta levels. For the in vivo studies, quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B and IL-1beta mRNA levels in experimental groups. PHT-treated patients exhibiting gingival overgrowth demonstrated a significant increase in PDGF-B mRNA compared with minimally inflamed controls. Patients with severe gingival inflammation also demonstrated a significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is approximately 6 times larger than PDGF-B upregulation produced by inflammation alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no significant increase in IL-1beta mRNA; however, IL-1beta mRNA levels in the severely inflamed gingival samples demonstrated a significant increase. Additionally, for the clinical samples, macrophage phenotype was characterized immunohistochemically in adjacent sections using specific monoclonal antibodies for inflammatory and reparative/proliferative phenotypes. There were no significant differences in the numbers of either macrophage phenotype in minimally inflamed gingival tissues; however, in the severely inflammed tissue, there was a significant increase in the inflammatory macrophage phenotype and in the hyperplastic gingival tissue, there was a significant increase in the reparative/proliferative macrophage phenotype. The results of this investigation indicate that the clinical presentation of inflamed and hyperplastic gingival tissues is associated with specific macrophage phenotypes which express the pro-inflammatory cytokine IL-1beta in inflamed tissues or the essential polypeptide growth factor PDGF-B in PHT-induced hyperplastic tissues. [References: 63] <59> UI - 1996359786 AU - Declich P AU - Isimbaldi G AU - Sironi M AU - Galli C AU - Ferrara A AU - Caruso S AU - Baldacci MP AU - Stioui S AU - Privitera O AU - Boccazzi G AU - Federici S IN - Department of Pathology, Legnano General Hospital, Via Candiani n.2,I-20025 Legnano; Italy. TI - Sporadic fundic gland polyps: An immunohistochemical study of their antigenic profile. SO - Pathology, Research & Practice Vol 192(8) (pp 808-815), 1996. AB - Fundic Gland Polyps (FGPs) are small sessile (2-5 mm), usually multiple polyps arising in the gastric, acid-secreting mucosa of disputed histogenesis. They have been described in a sporadic form, prevalently in middle aged females, or associated with familial adenomatosis coli-Gardner's syndrome. We performed an immunohistochemical study on 24 sporadic FGPs, using monoclonal antibodies (MAbs) against differentiation markers, class II MHC antigens (HLA-DR), oncofetal and proliferation antigens, aimed to characterize the antigenic profile of the polyps. A preliminary cytogenetic study on five polyps was also done, using an in situ culture method after collagenase treatment. Cytokeratins 8-18 (CAM 5.2 MAb) and 20 (IT-Ks 20.8 MAb), Epithelial Membrane Antigen (EMA) and Chromogranin A were normally expressed by FGPs. FGPs did not express HLA II DR. FGPs did not react with an anti-CEA MAb (F6), but they were frequently positive (22/24, 91.6%) with B72.3 MAb (reacting with the cancer-associated mucin epitope sialyl-Tn). The PC10 MAb (against PCNA or cyclin) showed enhanced expression in the deep glandular-cystic compartment of FGPs; the PCNA index of FGPs was significantly higher than in normal fundic mucosa. The cytogenetic study on the 5 cases analysed, revealed a normal karyotype. We have demonstrated that FGPs express in the paranuclear zone the sialyl-Tn epitope, a side-chain sugar normally masqued in adult gastric mucins, thus revealing an alteration in mucin synthesis; FGPs' higher proliferation index as compared with normal fundic mucosa supports the hypothesis of their hyperproliferative nature. <60> UI - 1996328790 AU - Yamazaki K AU - Nakajima T AU - Gemmell E AU - Kjeldsen M AU - Seymour GJ AU - Hara K IN - Department of Periodontology, Niigata Univ. School of Dentistry, Gakkocho-Dori, 2-5274,Niigata 951; Japan. TI - Biased expression of T cell receptor Vbeta genes in periodontitis patients. SO - Clinical & Experimental Immunology Vol 106(2) (pp 329-335), 1996. AB - The aim of the present study was to investigate the hypothesis that there is selective activation and expansion of a limited repertoire of T cell receptor (TCR)-bearing T cells in periodontitis tissue. We studied TCR Vbeta gene expression in gingival tissues of periodontitis lesions and compared these with peripheral blood mononuclear cells (PBMC) from the same patients using polymerase chain reaction (PCR) amplification with 22 Vbeta-specific sense primers in combination with a common antisense Cbeta-specific primer. After initial therapy, gingival tissue specimens were obtained from 14 periodontitis patients at the time of periodontal surgery, and PBMC were also obtained from the same patients by density gradient centrifugation. Total RNA was extracted and analysed by reverse transcription PCR. The PCR products were electrophoresed on a 2% agarose gel and stained with ethidium bromide. For each product, gingival tissue and the respective peripheral blood were compared. The TCR repertoire identified in the PBMC in general overlapped with that of the gingival tissue. However, Vbeta6 appeared to be over-expressed in the gingival tissues compared with the PBMC, but Vbeta16 appeared to be under-expressed in the gingival tissues. Although it is not known whether this is due to antigen-specific activation or superantigen activation, the data suggest that there may be as yet uncharacterized T cell subsets in periodontal disease tissue. <61> UI - 1996307168 AU - Yuwono M AU - Rossi TM AU - Fisher JE AU - Tjota A IN - Department of Pediatrics, Children's Hospital of Buffalo, 219 Bryant Street,Buffalo, NY 14222; United States. TI - Oncogene expression in patients with familial polyposis coli/Gardner's syndrome. SO - International Archives of Allergy & Immunology Vol 111(1) (pp 89-95), 1996. AB - We evaluated whether c-myc and ras P-21 oncogene expression could identify familial polyposis coli/Gardner's syndrome patients at risk for colon cancer. Monoclonal antibodies recognizing c-myc and ras P-21 proteins were used in immunohistochemistry to stain 26 paraffin-embedded tissue specimens collected over 12 years from 5 familial polyposis coli/Gardner's syndrome patients at various stages of their disease. Differences in staining intensity between specimens were noted with each of the two tissues markers; however, c-myc showed also a distinct cellular staining pattern in patients with advanced histologic features. The c-myc oncogene exhibited strong homogeneous cytoplasmic staining in all adenocarcinoma specimens; weak cytoplasmic staining was found in normal biopsies and in 5/10 familial polyposis coli/Gardner's syndrome specimens in the early stage of disease. In contrast, a heterogenous staining pattern with a strong supranuclear and weak nuclear and cytoplasmic staining was demonstrated in specimens with advanced histologic features of familial polyposis coli/Gardner's syndrome and also in postoperative ileal specimens. Anti-ras P-21 antibody, on the other hand, demonstrated a homogeneous cytoplasmic staining pattern in all specimens. We feel that the c-myc oncogene expression, in distinction to that of ras P-21, has potential as a genetic tissue marker to distinguish early from more progressive disease. <62> UI - 1996291353 AU - Kato T AU - Kimizuka R AU - Okuda K IN - Department of Microbiology, Tokyo Dental College, 1-2-2 Masago,Mihama-ku, Chiba 261; Japan. TI - Isolation and characterization of hemolytic genes from Actinobacillus actinomycetemcomitans. SO - FEMS Microbiology Letters Vol 143(2-3) (pp 217-221), 1996. AB - Periodontopathic Actinobacillus actinomycetemcomitans produces hemolysin and other leukotoxins. In the present study, two distinct clones which lysed horse erythrocytes were isolated by screening genomic DNA libraries of A. actinomycetemcomitans ATCC 43718 on blood agar plates. DNA hybridization analysis indicates that there were two distinct hemolytic genes present. Sonicated extracts from both Escherichia coli clones possessed hemolytic activities on horse, sheep and human erythrocytes, but not those of rabbit. Rabbit antiserum to A. actinomycetemcomitans ATCC 43718 whoIe cells inhibited the hemolytic activities of these clones. <63> UI - 1996286796 AU - Nimgaonkar M AU - Kemp A AU - Lancia J AU - Ball ED IN - Division of Hematology, Univ. of Pittsburgh Medical Center, 200 Lothrop Street,Pittsburgh, PA 15213; United States. 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 Vol 5(1) (pp 39-48), 1996. 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. <64> UI - 1996285586 AU - Wittstock M AU - Flemmig TF AU - Schmidt H AU - Mutters R AU - Karch H IN - Inst. fur Hygiene und Mikrobiologie, Universitat Wurzburg, Josef-Schneider-Str. 2,97080 Wurzburg; Germany. TI - Serodiagnosis of Porphyromonas gingivalis infection by immunoblot analysis with recombinant collagenase. SO - Journal of Clinical Microbiology Vol 34(10) (pp 2411-2413), 1996. AB - The Porphyromonas gingivalis collagenase-specific serum immunoglobulin A (IgA), IgM, and IgG responses from 20 patients with early-onset periodontitis (EOP), 20 patients with adult periodontitis (AP), and 20 age- and sex- matched healthy controls were examined by immunoblot analysis. A recombinant collagenase antigen used for the immunoblot analysis was produced by using the plasmid pGEX-2T, which allows the fusion between the collagenase and glutathione S-transferase. There was no significant difference in collagenase-specific IgG antibody detection between samples from the EOP, AP, and control groups. In contrast, 85% of AP and EOP sera had collagenase- specific IgA antibodies, whereas only 20% of control sera showed collagenase- specific IgA reactivity. Plaque samples from all groups were assessed by PCR with primers complementary to the collagenase-encoding gene prtC. The results indicated that 90% of AP and EOP plaque samples and 10% of control samples were positive for P. gingivalis. All patients with collagenase-specific IgA antibodies were PCR positive. The results of the study indicate a nearly complete concordance (k = 0.856) between the presence of collagenase-specific IgA antibodies and PCR detection of P. gingivalis. By using PCR as the 'gold standard,' the sensitivity and specificity of the IgA immunoblot test were 94.7 and 90.9%, respectively. Therefore, the recombinant collagenase is a potential candidate for use in the serodiagnosis of periodontitis. <65> UI - 1996217160 AU - Choi B-K AU - Wyss C AU - Gobel UB IN - Inst. fur Mikrobiologie und Hygiene, Universitatsklinikum Charite,