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Biomedical subjects

L Shapira

Publications and source records attributed to L Shapira.

At least 55 records · Page 3Linked to original sources
PubMed1994

Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes.

Bacterial LPS stimulates human monocytes to secrete inflammatory cytokines, which are involved in several disease processes. However, the mechanism of LPS activation of cytokine expression and secretion is not completely understood. In this study, we investigated the signal transduction pathways involved in LPS-stimulated TNF-alpha and IL-1 beta secretion. TNF-alpha and IL-1 beta secretion were completely blocked by protein kinase C (PKC) and cyclic nucleotide-dependent protein kinase inhibitor, H-7, but were not affected by H-89, a specific cyclic nucleotide-dependent protein kinase inhibitor. In addition, LPS was found to induce activation of PKC, reaching maximal activity at 30 min and returning to unstimulated levels after 60 min. LPS stimulation only slightly increased intracellular levels of diacylglycerol, the natural activator of PKC, and pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did not affect LPS-stimulated TNF-alpha secretion. LPS-induced PKC activation was found not to be affected by blocking of the LPS receptor, CD14, with mAb or by inhibition of protein tyrosine kinase with herbimycin A. However, these agents suppressed LPS-induced TNF-alpha secretion and TNF-alpha mRNA accumulation. The results suggest that TNF-alpha and IL-1 beta secretion after LPS stimulation of human monocytes requires the activation of protein tyrosine kinase and PKC, upstream to the activation of gene transcription. The activation of PKC by LPS is probably mediated by a diacylglycerol-independent pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

HLA polymorphism in Moroccan Jewry.

The Moroccan Jewish community living in Israel shows a relatively large genetic distance from other North African Jewish communities. In this work the polymorphism of HLA class I and class II determinants, as defined by serology and oligotyping, is analyzed in 113 healthy unrelated Jews of Moroccan stock. The class I antigens HLA-A1, -B44, and -Cw7 showed the highest frequency, while the most prevalent class II variants were DRB1*0701 and *1104, DQA1*0501, and DQB1*0201 and *0301. HLA A1-B13-DR7, A2-B51-DR10, and A1-B44-DR13 were the most typical three-locus haplotypes. Although the antigen frequency distribution of the Moroccan Jews falls within the Caucasian diversity range, this community has a unique pattern in terms of antigen, gene, and haplotype frequencies. Thus, in the Moroccan Jews DRB1*1305, an allele believed to be the result of a recombination event between DRB1*1301-1302 and DRB1*1101, is represented to a much larger extent than in all the other population groups studied at the 11th IHWS. This allele may therefore be a typical Jewish variant. A particular finding was the high frequencies of HLA-B13, B52, and DR10, alleles common among some Oriental populations. The answer to this enigmatic phenomenon probably must be sought in the tortuous history of this community.

Alleles↗
PubMed1994

Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor.

The purpose of this study was to investigate factors influencing the ability of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis to elicit secretion of tumor necrosis factor-alpha (TNF alpha) from human monocytes (adherent mononuclear cells). The results indicate that P. gingivalis LPS stimulation of TNF alpha from monocytes is comparable to LPS from Escherichia coli. Both LPS, although structurally different, increased TNF alpha secretion in a dose-dependent manner. In serum-free conditions, TNF alpha secretion was relatively low, but it dramatically increased at human serum concentrations as low as 1%. Maximal secretion was observed in the presence of 10% serum, with a slight decrease at higher serum concentrations. The CD14 molecule is a putative monocyte LPS receptor. When cells were pre-incubated with a blocking monoclonal antibody (My4) to CD14, TNF alpha-mRNA accumulation and TNF alpha secretion were reduced to control levels at LPS concentrations of up to 10 ng/ml. At higher LPS concentrations, the blocking effect was only partial, in spite of 50-fold excess antibody concentration. The blocking effect was observed only in the presence of serum. The effect of the CD14 antibody was dose-dependent with saturation at 2.5 micrograms/ml. The results suggest that CD14 is one of the major receptors for P. gingivalis LPS but highlight the necessity to investigate other cell-surface receptors mediating P. gingivalis-LPS interactions. These interactions are believed to be important in the pathogenesis of periodontal destruction.

Antibodies, Monoclonal↗
PubMed1994

Priming effect of Porphyromonas gingivalis lipopolysaccharide on superoxide production by neutrophils from healthy and rapidly progressive periodontitis subjects.

Pre-incubation of neutrophils from rapidly progressive periodontitis (RPP) patients with lipopolysaccharide (LPS) extracted from Porphyromonas gingivalis was found to prime the neutrophils for enhanced FMLP-stimulated superoxide production in a dose-dependent manner. The priming effect of P. gingivalis LPS on neutrophils from control subjects was scanty or without effect at all. Inclusion of human serum in the experimental priming conditions increased the control and RPP neutrophil response by 2 to 3 fold. Blocking of the CD14 receptor on the neutrophil surface with monoclonal antibody eliminated the priming effect. Furthermore, incubation of control neutrophils with P. gingivalis LPS in the presence of serum from RPP patients generated a higher response as compared to incubation with control serum. The data suggest that neutrophil priming described in RPP patients is dependent on a serum factor which alters the neutrophil response to priming agents such as LPS.

Aggressive Periodontitis↗
PubMed1994

The secretion of PGE2, IL-1 beta, IL-6, and TNF alpha by adherent mononuclear cells from early onset periodontitis patients.

The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) by adherent mononuclear cells (AMNC) from 28 patients with early-onset periodontitis was studied. The early onset-periodontitis patients consisted of 12 patients with localized juvenile periodontitis (LJP) and 16 patients with severe generalized periodontitis (SGP). The AMNC responses to different concentrations of lipopolysaccharide (LPS) (E. coli) were determined in these 28 patients and compared to 14 healthy controls. Mediator levels in the supernatant were measured using radioimmunoassays for PGE2, IL-1 beta, and IL-6 determination and an enzyme linked immunosorbent assay for TNF alpha levels. The mean age of the patients was 19.9 years for the LJP group, 30.4 years for SGP, and 28.0 years for the controls. The mean number of teeth per patient with attachment loss of > 6 mm was 4.75 in the LJP patients and 17.3 in the SGP group. In the absence of LPS, LJP AMNC secreted significantly more PGE2 than unstimulated control or SGP AMNC, while similar baseline amounts of IL-1 beta, IL-6, and TNF alpha were secreted by AMNC from the 3 patient groups. LPS stimulation resulted in the dose-dependent secretion of significantly higher levels of PGE2 by LJP AMNC compared to SGP AMNC which in turn secreted significantly more than controls. TNF alpha secretion by LJP monocytes was significantly greater than the SGP and the control groups while IL-1 beta secretion by the SGP AMNC was depressed compared to the other two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

HLA A9 and B15 are associated with the generalized form, but not the localized form, of early-onset periodontal diseases.

HLA proteins are genetically determined, and account in part for individual immune response. Several studies have been performed seeking an association between HLA antigens and various forms of periodontitis with no conclusive results. The aim of the present study was to determine the frequency of HLA antigens of patients suffering from the localized (LJP) and the generalized (SGP) forms of early-onset periodontitis (EOP). Twenty-six EOP patients from the same ethnic group were studied in comparison to 113 race-matched controls. The EOP group included 11 LJP and 15 SGP patients. HLA-A9 and B15 antigens were found to be significantly elevated in the patient group. These differences were found to be due to the high frequency of A9 and B15 antigens in the SGP patients, with the LJP patient group showing no significant difference from the control group. The results are in agreement with previous studies in which A9 and B15 were found to be associated with EOP. However, previous studies did not differentiate between the localized and the generalized form of EOP. These results support the hypothesis that the generalized and the localized forms of EOP are under different genetic control.

Adolescent↗
PubMed1994

Neutrophil defects as risk factors for periodontal diseases.

There are several hypotheses proposed for the etiologic mechanisms causing periodontal diseases. These include a paradigm in which all individuals are equally susceptible to one or several pathogenic bacteria; a second paradigm that holds that all bacteria are equally virulent and that host susceptibility determines onset of disease; or a combination of the above. In this review, we analyze the role of neutrophil dysfunction as a risk factor for the onset of periodontitis. Both intrinsic or genetically inherited abnormalities of neutrophils and acquired neutrophil abnormalities are considered. While a large body of data implicates neutrophil dysfunction, either intrinsic or acquired (bacterially or extrinsically induced), as a significant risk factor for the periodontal diseases, clear, prospective, longitudinal epidemiologic studies to evaluate this association remain to be performed.

Bacterial Physiological Phenomena↗
PubMed1994

Sequential manifestation of different forms of early-onset periodontitis. A case report.

Pathogenic bacteria constitute the primary extrinsic agent in the etiology of early onset periodontitis. However, the risk of developing periodontal disease is not equal for all individuals, suggesting host factors are involved in determining an individual's disease susceptibility. In this report, a case of an otherwise healthy female, who exhibited prepubertal periodontitis (PPP) at age 10, juvenile periodontitis (JP) at age 13, and rapidly progressive periodontitis (RPP) at age 29 years, is presented. Microbial, immunological, and genetic features of the case are presented. PPP, JP, and RPP are considered distinct disease entities, albeit with similar pathology and pathogenesis, yet all were manifest sequentially in the same individual. This report presents the idea that certain individuals are predisposed to early-onset periodontal diseases and the early identification of risk factors is important in the management of these individuals.

Adolescent↗
PubMed1994

Subgingival irrigation with amine fluoride-stannous fluoride gel in treated periodontal pockets.

PURPOSE: To evaluate the long-term effect of subgingival irrigations with amine fluoride mixed with stannous fluoride on the repopulation of bacteria in deep periodontal pockets (> 5 mm) following the active phase of non-surgical mechanical treatment. MATERIALS AND METHODS: A split-mouth design was utilized in eight periodontal patients and the effect of the treatment was evaluated by microbiological culturing and clinical parameters. RESULTS: Slight reduction in total anaerobe counts were detected in both treated and control sides, up to the first 5 weeks, followed by an increase in the counts reaching a plateau after 30 weeks. In contrast, black-pigmented bacteroides species (BPB) were significantly suppressed in the treated sides as compared to the control sides over the whole study period. The difference between the clinical parameters and between the tested and control sides, although in some points were found to be statistically significant, seem to have no clinical significance. The use of amine fluoride-stannous fluoride gel for irrigations of deep periodontal pockets as an adjunctive to conventional treatment, can prevent the repopulation of the pockets by BPB, which are considered to be a major group of periodontal pathogens.

Amines↗
PubMed1993

Rapid fluorometric quantification of monocyte attachment in tissue culture wells.

A simple fluorometric assay that permits rapid quantification of attachment of monocytes or macrophages in tissue culture wells is described. Using 4,6-diamidino-2-phenylindole (DAPI) as a specific fluorochrome marker for DNA, we observed a dose-dependent increase with strong linear correlation in fluorescent emission over a broad range of DNA concentrations. Measurements of the DNA content of the human monocytic cell line THP-1 demonstrated a linear correlation between fluorescence intensity and cell number from 5 x 10(4) to 1 x 10(6) cells, with an estimated average DNA content of 7.5 pg DNA per cell. While untreated THP-1 cells were not detectably adherent, PMA induction for 24 h results in 57-76% adherence to plastic surface. This method was found to be useful for measuring the number of peripheral blood monocytes separated from lymphocytes by attachment. 16 subjects were sampled and the standard deviation of each individual did not exceed 10%. The number of attached cells was between 10-16% of the total mononuclear cells. Fluorescence measurement of DNA with DAPI permits rapid and accurate determination of cell numbers and appears useful in the quantification of adherent populations such as myelocytic cells and cell lines.

Cell Adhesion↗
PubMed1993

Cloning and characterization of human TNF alpha promoter region.

We report the sequence of a 1.2-kb human tumor necrosis factor alpha (TNF alpha) promoter region, which was cloned using PCR. The sequence has several variations from two previous reports and exhibits many potential DNA-binding sites specific to mammalian gene regulatory proteins inducible by lipopolysaccharides.

Base Sequence↗
PubMed1993

The role of the host response in periodontal disease progression: implications for future treatment strategies.

In this paper, we review the relevant aspects of host responses in periodontal diseases as we understand them today. Discussion will focus on neutrophil function, lymphocytes and the immune response, macrophage function, cytokines and complement, fibroblasts and growth factors, and regeneration. Recent literature and concepts will be presented with an emphasis on future directions and application to treatment regimens.

Forecasting↗
PubMed1992

A localized absence of interleukin-4 triggers periodontal disease activity: a novel hypothesis.

Pathogenic bacteria constitute the primary extrinsic agent in the etiology of Adult periodontitis. In addition to direct toxic effects, bacteria induce destructive immunologic and other inflammatory reactions in the host, leading to the observed pathologic alteration in the tissue. The risk to develop periodontal disease is not equal for all individuals, suggesting host factors are important in determining an individuals disease susceptibility. Regulation of immune response is important in maintaining the equilibrium between periodontal health and disease. We hypothesize that, in the case of Adult periodontitis, a localized lack of the regulatory cytokine interleukin-4 (IL-4) in the gingival tissues predisposes susceptible individuals to progress from gingivitis to periodontitis.

Adult↗
PubMed1992

Effect of hard cheese exposure, with and without fluoride prerinse, on the rehardening of softened human enamel.

The in situ rehardening effect was compared between Cheddar cheese consumption and saliva secretion with and without a fluoride pretreatment on softened human enamel. Ten volunteers wearing prostheses which held slices of human enamel participated in this study. Average microhardness of enamel was determined on the surface at baseline, after exposing to an acidic beverage, after exposing to saliva and mastication of cheese, with and without a mouth F prerinse (10 ml Meridol containing 0.025% F). The rehardening was increased in the groups consuming cheese compared to the saliva controls. The effect was increased by an F prerinse; the initial hardness of the intact enamel surface, however, was not reached.

Amines↗
PubMed1991

Tooth enamel softening with a cola type drink and rehardening with hard cheese or stimulated saliva in situ.

The in-situ remineralization effect of hard cheese was compared with that of saliva on tooth enamel in man. The intra-oral test of softening enamel surfaces by a cola type drink followed by rehardening by chewing hard cheese and/or parafilm was assessed by microhardness and SEM measurements. Cheese consumption significantly increased the enamel hardness, whereas stimulated saliva did not have this effect. The remineralizing effects are presumably due to uptake of calcium and phosphate salts by the surface enamel. Morphologically, the enamel surfaces did not return to their original state.

Carbonated Beverages↗