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Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 55 records · Page 3Linked to original sources
PubMed1998

A nationwide prospective surveillance study in Israel to document pediatric invasive infections, with an emphasis on Haemophilus influenzae type b infections. Israeli Pediatric Bacteremia and Meningitis Group.

BACKGROUND AND METHODS: An ongoing nationwide prospective surveillance study was initiated in Israel in October, 1988, to document childhood invasive infections caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. This study enabled us to document the effect on childhood invasive Hib disease of the introduction of conjugate Hib vaccines to Israel. RESULTS: The incidence of invasive Hib disease before the age of 5 years dropped from 34 per 100000 before initiation of immunization to < 5 per 100000 in 1995 and is projected to be <4 in 1996. After <2 years, when various conjugate vaccines had been available in the private sector alone and had achieved partial coverage only, the Israeli Ministry of Health decided to add Hib conjugate vaccine to the regular infant immunization program, free of charge, effective for all infants born after January 1, 1994. The vaccine chosen was Hib polysaccharide linked to outer membrane protein complex of N. meningitidis B. Vaccine coverage has exceeded 90% of all infants born since January 1, 1994. Efficacy and effectiveness during the first 34 months of the program (January 1, 1994, to October 31, 1996) were 95.4 and 99.7%, respectively, for all invasive Hib disease and 97 and 99.4%, respectively, for Hib meningitis. CONCLUSION: The described ongoing surveillance program showed the existence and extent of Hib problems in Israel and documented the success of the immunization program in essentially eliminating the disease in Israel.

Child, Preschool↗
PubMed1998

Lymphocyte subsets in human tonsils: the effect of age and infection.

The aim of the present study was to determine the effect of repeated tonsillitis on the development of lymphocyte subsets in the tonsils and among peripheral blood lymphocytes (PBL) of children. Subsets of T- and B cells were analyzed in the tonsils and in PBL of patients undergoing tonsillectomy for idiopathic tonsillar hypertrophy, recurrent tonsillitis, or tonsillar hypertrophy and tonsillitis. The majority of the CD4+ cells in the tonsils displayed the CD45RO+ phenotype, while the majority of those in the PBL displayed the CD45RA+ phenotype. Likewise, the proportion of CD45RO+CD8+ cells was higher in the tonsils than among PBL. The proportion of CD4 cells expressing the CD45RO marker increased with age among PBL, but not in the tonsils. B cells, detected by their CD19, CD20, and CD21 markers, were three times more abundant in the tonsils than in the PBL. The proportion of CD38+ cells showed a negative correlation with age, both in the tonsils and among PBL. Among PBL a striking age-related reduction was seen in the proportion of CD19+, CD21+ and CD38+CD21+ B cells. In contrast, in the tonsils age-related changes could be detected only in the proportion of CD21+CD38+ cells. No difference among patients with various clinical diagnoses was detectable in any of the T- and B cell subsets in the tonsils and PBL. Thus, lymphocyte subsets evolve independently in the tonsils and peripheral blood, with the repeated antigenic challenge of tonsillar lymphocytes not influencing circulating memory cells.

ADP-ribosyl Cyclase↗
PubMed1998

Aspects of leukocyte function and the complement system following aerobic exercise in young female gymnasts.

Recent studies have reported reduced immunity in trained athletes. Scant information exists on changes in the immune function among trained children. The purpose of this study was to assess the effect of aerobic exercise on the phagocytic process of neutrophils and the complement system in young athletes. Subjects included prepubertal elite female gymnasts (n = 7) and untrained girls (n = 6) aged 10-12 years. Venous blood was withdrawn before, immediately post and 24 h following a 20-min run at a heart rate of 170-180 beats.min-1. Neutrophil random migration, chemotactic activity, bactericidal function and PMA/FMLP-stimulated superoxide anion release as well as various complement components were assessed. Net chemotaxis was found reduced (P < 0.05) 24 h following exercise (58 +/- 11 vs. 36 +/- 11 cells/field in gymnasts and 47 +/- 7 vs. 42 +/- 8 cells/field in untrained girls pre- and 24 h post-exercise, respectively). The basal values, as well as post-exercise values of bactericidal activity were lower (P < 0.05) in gymnasts as compared with the control group (0.8 +/- 0.3, 0.8 +/- 0.2 and 0.8 +/- 0.1 log decrease of colonies in gymnasts at pre-, immediately post-, and 24 h post-exercise, respectively and 1.1 +/- 0.1, 1.1 +/- 0.1 and 1.0 +/- 0.2 log decrease of colonies in controls, respectively). No significant effect on the bactericidal activity was observed in either group following exercise. The addition of homologous sera did not correct the bactericidal activity. PMA-stimulated superoxide anion release decreased (P < 0.05) among gymnasts immediately following exercise (5.7 +/- 0.4 vs. 4.4 +/- 1.0 mmol O2/10(6) PMN.min) and remained low 24 h later. The same trend was observed in FMLP-stimulated neutrophils but the data were not significant. Significantly decreased levels (P < 0.05) of the early complement components (C1Q, C1R) were also found following exercise (1.34 +/- 0.64 vs. 1.27 +/- 0.28 and 1.09 +/- 0.07 vs. 1.02 +/- 0.06 pre- and post-exercise in gymnasts and untrained, respectively). Furthermore, consistently lower C2 and C3 were observed in gymnasts compared with controls. Neutrophil dysfunction as well as impairment of the complement system seem to occur following exercise.

Analysis of Variance↗
PubMed1998

Hereditary CD4+ T lymphocytopenia.

Two siblings suffering from mental retardation, progressive bronchiectasis, extensive warts, and persistent hepatitis B are described. The propositus also had an unusual physiognomy and non-specific colitis. Both patients had a marked decrease in the population of CD4+ helper T cells.

Adolescent↗
PubMed1998

Antibodies to cytomegalo and Epstein-Barr viruses in human saliva and gingival fluid.

The prevalence of antibodies to EBV and CMV was studied in 34 samples of whole saliva and gingival crevicular fluids (GCF) obtained from clinically healthy volunteers and compared to the corresponding antibodies present in the serum of each individual. Higher prevalence of serum antibodies was found to EBV (85.2%) than to CMV (64.7%) (P < 0.04). The percentage of saliva samples containing IgG and/or IgA antibodies was not significantly different for the two viruses (79.4% for EBV and 58.8% for CMV). However, in the GCF the percentage to EBV was lower-32.3% as compared to 70.5% for CMV (P < 0.002). The prevalence of CMV in serum saliva and GCF was similar. However, while in the saliva similar levels of IgG and IgA were found, in the GCF IgA prevails. The picture for EBV is different: a similar percentage of antibodies was noticed in serum and saliva, but it was significantly lower in the GCF. However, antibodies to EBV were mostly IgA both in the saliva and the GCF. Although a similar number of samples were positive to both viruses in the saliva, the IgA response to EBV was higher than to CMV (P < 0.05), while in GCF IgA response was higher to CMV (P < 0.05). Passive transudation rather than active transport of plasma-derived Ig is probably responsible for the presence of IgG, while the IgA found in saliva and GCF is derived from local synthesis by plasma cells rather than from selective transport from blood.

Adult↗
PubMed1998

Enhanced lymphoid cell recovery after bone marrow transplantation: correlation with the presence of costimulatory antibodies in serum.

We describe a patient with T cell deficiency who underwent bone marrow transplantation (BMT) from an HLA-identical brother. The patient's white blood cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes from both peaks displayed a phenotype of mature T cells together with characteristics of a constitutively activated state; that is, they 1) exhibited high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2) spontaneously secreted IL-2, 3) expressed activation specific cell surface markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts in both peaks correlated with the presence of anti-lymphocytic antibodies in the patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from the donor and from unrelated individuals. These antibodies were present before BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the appearance of the second WBC peak during that period. The patient's anti-lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro proliferation of normal T cells suboptimally activated via the TCR. The unique characteristics of these antibodies could explain the enhanced T cell recovery observed post-BMT as well as the constitutive activation state of these cells. Furthermore, such antibodies may eventually facilitate development of a therapeutic method for inducing enhanced post-BMT recovery.

Adolescent↗
PubMed1997

Molecular bases of C7 deficiency: three different defects.

The molecular basis of C7 deficiency has been investigated in two Irish families and a number of Israeli families of Moroccan Sephardic Jewish origin. Exon PCR and sequencing revealed a heterozygous point mutation at the 3' splice acceptor site of intron 1 in one Irish family. In the other Irish family, exons 7 and 8 failed to amplify and they were shown to be deleted. Marker haplotype studies of the C6 and C7 gene region and Southern blots show that the Irish family with the splice defect also segregate for the deletion, which is not easily detected in heterozygotes. The Israeli C7-deficient cases all share a C7 haplotype and are homozygous for a mis-sense mutation in exon 9. However, one individual is heterozygous for markers at adjacent C6 loci, showing that there has been an intergenic recombination and suggesting that the deficiency mutation is of appreciable antiquity.

Amino Acid Sequence↗
PubMed1997

[Pediatric flexible bronchoscopy].

Between 1993-1996, 200 pediatric flexible bronchoscopies were performed. Indications were: chronic cough (158 children), persistent pulmonary infiltrates (89), recurrent stridor (28), suspected tracheobronchial foreign body (20), suspected tuberculosis (17) and hemoptysis (3). Some children had more than 1 indication. 124 patients were boys (mean 4.18 +/- 2.86 years; range 1 month-15 years) and 76 were girls (mean 4.39 +/- 2.7 years; range 4 months-15 years). The procedure included direct vision recorded by video-camera and bronchoalveolar lavage; the lavage fluid was sent for culture, Gram and Ziehl-Nielsen strains and for cytology. There were a few minor side effects: mild stridor which resolved within a few hours (10 children) and transient fever (3). This simple, flexible instrument was effective and helpful in the diagnosis and treatment of children with respiratory symptoms in a secondary hospital facility.

Adolescent↗
PubMed1997

The appearance of the CD4+CD8+ phenotype on activated T cells: possible role of antigen transfer.

Stimulation of peripheral blood lymphocytes (PBL) with phytohemagglutinin (PHA) strikingly increased the proportion of CD4+CD8+ cells. Highly purified CD4+ and CD8+ lymphocyte populations cultured in the presence of PHA consistently failed to coexpress the CD8 and CD4 markers. Similarly, exposure of highly purified CD4+ cells to PHA and recombinant interleukin-2 resulted in augmented expression of CD25 but failed to induce the expression of CD8. When purified preparations of either CD4+ or CD8+ cells were activated separately for 3 days and incubated together for an additional 5 h, a considerable proportion of CD4+CD8+ cells was found in the mixture. Cycloheximide treatment did not prevent the appearance of the CD8 marker on CD4 cells. CD4+CD8+ cells isolated from PBL exposed for 3 days to PHA lost their CD8 antigenicity within 24-48 h in the absence of PHA. Increased levels of soluble CD4 and CD8 antigens were found in supernatant fluids of PHA-stimulated cells. T cells failed, however, to bind soluble markers even after prolonged incubation in the presence of supernatant fluids. Our studies show that activation of CD4+ cells per se does not elicit the CD4+CD8+ phenotype and that soluble T cell markers do not bind to T cells. Rather, it seems that direct cell-cell contact is required for the transfer of CD8 molecules from CD8+ cells to the membrane of CD4+ cells.

Biological Transport↗
PubMed1997

Concentrations of soluble CD95 and CD8 antigens in the plasma and levels of CD8+CD95+, CD8+CD38+, and CD4+CD95+ T cells are markers for HIV-1 infection and clinical status.

Apoptosis mediated via the CD95 (FAS/APO-1) receptor is thought to play a role in the depletion of CD4+ T cells in HIV infection. In the present study expression of the CD95 antigen on lymphocyte subsets and the plasma level of soluble CD95 (sCD95) were determined in HIV-1-infected adults. The expression of CD95 was increased on CD8 cells in all groups of HIV+ individuals, while increased expression of CD95+ cells on CD4 cells was limited to individuals with CD4 counts of < 200 mm3. The proportion of CD4+ that expressed CD95 was inversely correlated with the percentage of CD4+ PBL. The concentration of sCD95 was significantly higher in the plasma of HIV-infected individuals than in normal controls. The level of sCD95 in HIV-infected subjects showed no correlation with the percentage of PBL expressing CD95, indicating that the increased level of sCD95 did not reflect release from CD95+ PBL. The plasma sCD95 concentration was significantly correlated with the percentage of CD8+ cells and, particularly, with CD8+ CD38- cells. A striking inverse correlation was found between the sCD95 plasma concentration and the proportion of CD4+ CD95+ cells out of the total CD4+ population. There was no correlation between the serum level of sCD95 and that of soluble CD8 (sCD8), both of which were increased in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals was correlated with the percentage of CD95+ and CD8+ CD38+ cells. The present study indicates that plasma sCD95 may be one of the factors that regulate apoptotic death of lymphocytes in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

DNA haplotypes of the complement C6 and C7 genes associated with deficiencies of the seventh component; and a new DNA polymorphism in C7 exon 13.

Eight common DNA polymorphisms have been described for the linked C6 and C7 genes. We now describe a ninth polymorphism in C7 exon 13 which is located in a tight cluster with two previously reported markers. We have used all these markers to investigate the heterogeneity of C7 deficiency. Five of the nine C7 deficient probands (resident in Ireland, South Africa, Russia and Israel) are heterozygous for C6/C7 haplotypes. Seven different C7 deficient haplotypes were found for C7 markers alone, but all the four Israelis share one and three out of four Irish haplotypes share another. The markers appear to be a good guide to the heterogeneity of C7 deficiency and have been useful in choosing homozygous subjects for the investigation of molecular defects.

Child↗
PubMed1997

Competition, ownership, and access to hospital services. Evidence from psychiatric hospitals.

OBJECTIVES: This article examines the impact of increasing competition among hospitals on access to inpatient services and preexisting differences in access between nonprofit and for-profit facilities. It tests theoretical propositions that suggest that nonprofit and for-profit hospitals will respond in different ways and to differing degrees to changing competitive pressures. METHODS: Drawing data from a 1987-88 national survey of psychiatric hospitals, the authors measured access in terms of the availability of different types of services and the provision of uncompensated care. The impact of hospital ownership, competition as well as the interaction of ownership and competition was assessed through a set of regression models, controlling for other characteristics of the hospital markets and local service system. RESULTS: Nonprofit psychiatric hospitals provide greater access than their for-profit counterparts under conditions of limited competition. Increased competition reduces the ownership-related differences in uncompensated care, but increases the differences for marginally profitable services. The market share of for-profit hospitals had an independent negative effect on access, holding constant the intensity of competition. CONCLUSIONS: The interaction of ownership and competition explains some seemingly inconsistent finding in the literature and points to the complexity of relying on ownership-based policies to protect access in an increasingly competitive health-care system.

Diagnosis-Related Groups↗
PubMed1997

Countervailing agency: a strategy of principaled regulation under managed competition.

Despite the failure of recent attempts to reform health care, strategies of managed competition remain the dominant prescription for government oversight of managed care. A number of assumptions and prescriptions in the conventional managed competition model are challenged. More specifically, externalities in the costs and benefits associated with health care and asymmetric information between providers and patients make it unlikely that a managed care system designed to be responsive to consumers will, in practice, produce socially desirable outcomes. An alternative approach for the regulation of managed care more explicitly protects the role of health care professionals as agents for their patients while defining the appropriate role of managed care as the agent for broader societal interests. This strategy of "countervailing agency-" acknowledges that oversight of managed care inevitably involves value-laden choices. It is based on institutional arrangements and regulatory strategies that are intended to balance competing interests and values.

Capitation Fee↗
PubMed1997

Possible autosomal-dominant inheritance of prepubertal periodontitis in an extended kindred.

This study presents the clinical findings and the distribution of prepubertal periodontitis in an extended family with high prevalence of this entity. The expression of surface markers and adhesion molecules on peripheral lymphocytes were also studied. Approximately 50% of the children in this family suffered from prepubertal periodontitis. All the affected children were otherwise healthy. 2 identical twins were similarly, but not identically, affected. Detailed laboratory tests and analysis of lymphocyte surface marker expression, including CD18, were all within the normal levels. Both localized and generalized forms of prepubertal periodontitis were found. The high prevalence of prepubertal periodontitis in the 2 branches of this family, and the fact that identical twins were similarly affected, suggest a strong genetic predisposition for prepubertal periodontitis. The family pedigree is consistent with an autosomal-dominant mode of transmission. The coexistence of localized and generalized forms of the disease in sibs suggests the same genetic etiology for both entities with variability in disease expression. This variability in disease expression is further supported by the fact that 2 identical twins were not identically affected.

Adult↗
PubMed1997

The development of the complement system after 28 weeks' gestation.

OBJECTIVE: To assess the levels and development of the various complement components in preterm infants, particularly among those born before 34 weeks' gestation. SUBJECTS AND METHODS: We measured the complement system's activities (CH50 and AP50) as well as its various components (C1q,r,s, C2-C9, Factor B, and properdin) in 25 preterm infants [gestational age (GA) 28-33 weeks], 35 preterm infants (GA 34-36 weeks), 50 full-term newborn infants (GA 37-42 weeks), and 49 healthy adults as control subjects. RESULTS AND CONCLUSIONS: The results of these studies are: (i) complement levels and activity were significantly reduced in preterm and full-term neonates when compared with adult levels, with the exception of C7 which was within the normal range in most infants. C8 and C9 were the most markedly reduced at all gestational ages. (ii) Complement levels correlated significantly with gestational age, but not with birth-weight, type of delivery, or gender. (iii) Between 28 and 33 weeks' gestation, there appeared to be almost no development of the complement system.

Adult↗
PubMed1997

Paradigms lost: the persisting search for community in U.S. health policy.

Local communities have long played an important role in health and social policy in the United States. But the concept of community was strangely absent from the federal debate on health care reform in 1993 and 1994. I attribute this absence to the paradoxical nature of community as a frame for guiding policy making. The concept of community has broad appeal across the ideological spectrum, but this breadth masks a set of long-standing and powerful tensions that determine when communities are seen as appropriately given responsibility for addressing societal problems. This article reviews the historical evolution of the role of community in health policy, highlighting the ways in which various tensions emerged. It applies these perspectives to an analysis of the attitudes of the U.S. public and congressional staff in 1995. Data from two surveys demonstrate that support for community-based reforms is much lower for medical care than for other social needs, including some health-related concerns such as long-term care and the treatment of substance abuse. Statistical analyses suggest several possible explanations for the lower support for community-based medical care. The article concludes with a discussion of the implications for future communitarian strategies designed to improve U.S. medicine or social policy.

Attitude to Health↗
PubMed1997

Pathways controlling the expression of surface CD21 (CR2) and CD23 (Fc(epsilon)IIR) proteins in human malignant B cells.

The aim of the present study was to analyze the pathways regulating the expression of CD21 and CD23 B-cell differentiation antigens on human malignant B cells. Exposure of Farage cells, derived from a human B-cell lymphoma, to phorbol 12-myristate 13-acetate (PMA) down-regulated CD21 and CD23 expression, while interleukin 4 (IL4) inhibited the expression of CD21 but augmented CD23 expression. When Farage cells were stained with either anti-CD21 or anti-CD23 monoclonal antibodies (mAb), subsequent exposure to IL4 failed to change the staining of the cells, indicating that IL4 did not affect the turnover of CD21 and CD23 molecules. Inhibition of protein synthesis with cycloheximide (CXM) had no effect on the expression of CD21 molecules, but abrogated their down-regulation by IL4, suggesting that IL4 induced the synthesis of proteins which modify the processing of CD21 molecules. The inhibitory effect of IL4 on the expression of CD21 and its augmentary effect on the expression of CD23 was abrogated by H7 (1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine), an inhibitor of serine protein kinase. Staurosporine, an additional inhibitor of serine kinases also abrogated the effect of IL4 on CD23 expression. H8 (N-(2-[Methylamino]ethyl)-5-isoquinolinesulfonamide), a preferential inhibitor of protein kinases A and G, and genistein, an inhibitor of tyrosine kinases had no effect on IL4-induced modulation of CD21 and CD23 in Farage cells. The exposure of B-chronic lymphocytic leukemia (CLL) cells to PMA reduced the expression of CD21, but increased the expression of CD23. IL4 had no effect on the expression of CD21 on CLL-cells but strongly enhanced the level of CD23. H7, H8 and genistein each abrogated to a different extent the effect of IL4 on the expression of CD23 by CLL-cells. These data indicate that activation of serine/threonine kinases in malignant B cells inhibited the production of CD21 proteins, while different protein kinases appeared to be involved in up- and down-regulation of CD23 in different B lymphocytes.

B-Lymphocytes↗