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Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 109 records · Page 6Linked to original sources

Hereditary properdin deficiency in three families of Tunisian Jews.

Hereditary properdin deficiency is a rare genetic disorder of the complement system. Three propositi and six additional family members with properdin deficiency have been found following analysis of the hemolytic activity of the classical (CH50) and the alternative (AP50) complement pathways in the sera of 101 survivors of meningococcal infections and 59 survivors of severe pneumococcal and Haemophilus influenza infections. All the properdin-deficient individuals had undetectable levels of properdin by radial immunodiffusion and by Western blotting. They belonged to three non-related families of Tunisian Jews who came from different parts of Tunisia. Two patients had a meningococcal infection at 15 and 16 years of age, respectively, and one had Haemophilus influenza meningitis at 1.5 years of age. In contrast to the fulminant and fatal course of meningococcal infection which was previously described in some properdin-deficient patients, our patients had a relatively mild disease. Properdin deficiency may not be as rare as previously thought. Analysis of AP50, in addition to CH50, in sera of patients who had meningococcal infection, will probably disclose many more cases of hereditary properdin deficiency. In addition, our findings indicate that, as in other complement abnormalities, hereditary properdin deficiency may also be associated with the ethnic origin of the patient.

Adolescent↗

Carrier detection in families with properdin deficiency by microsatellite haplotyping.

Human properdin deficiency is an X-linked disorder strongly predisposing to meningococcal disease which has been recorded in over 50 cases of various ethnic origins. Immunochemically, total deficiency (type I), partial deficiency (type II), and deficiency due to a dysfunctional molecule (type III) can be differentiated. It is therefore most likely that the causative molecular defects will show considerable genetic heterogeneity. Analysis of the properdin locus at Xp11.3-Xp11.23 has led to the characterization of two polymorphic (dC-dA)n.(dG-dT)n repeats located approximately 15 kb downstream from the structural gene. Three families (two Scottish Caucasoid, one Tunisian Sephardic) with seven deficient individuals were investigated immunochemically and using a nonradioisotopic polymerase chain reaction-based method for microsatellite detection. Probable and definite carriers frequently showed properdin levels which were in the normal range. No recombinants between the microsatellite loci and properdin deficiency were detected, thus allowing identification of the defective allele through the generations in all three pedigrees. Haplotyping for these highly polymorphic microsatellites in close physical linkage to the properdin gene can provide rapid and nonradioactive detection of carrier status and prenatal diagnosis without extensive sequencing analysis.

Base Sequence↗

Peripheral blood lymphocyte subsets in infants with diarrhea with and without Giardia lamblia infection.

The aim of the present study was to define the cellular immune response during gastrointestinal Giardia lamblia infection in young children. The level of lymphocyte subsets was determined in the peripheral blood of infants with G. lamblia-associated diarrhea or acute gastroenteritis and from control infants without diarrhea. The proportion of peripheral blood lymphocytes (PBL) expressing the CD8 marker (suppressor cytotoxic T cells) and the CD57 marker (natural killer cells and subset of CD8+ T cells) was highest in infants with acute gastroenteritis, lower in infants without diarrhea, and lowest among those with G. lamblia-associated diarrhea. The level of CD4+ PBL (helper T cells) did not differ significantly among the three groups of children tested. The level of memory, or helper-inducer, CD4+CD29+ PBL was increased markedly in acute gastroenteritis as compared with their level among the other two groups, whereas naive or virgin CD4+CD45RA+ PBL had the reciprocal distribution among the three groups of infants. In contrast to acute gastroenteritis from other causes, G. lamblia-associated diarrhea did not elicit changes in lymphocyte subsets.

Antibodies, Monoclonal↗

Is health care different? Popular support of federal health and social policies.

Over the past several years there has been a striking increase in policymakers' attention to health care reform. This paper explores whether there has been a corresponding shift in popular attitudes and identifies factors that may have changed these attitudes. The first part of the analysis relies on survey data collected between 1975 and 1989 to estimate a set of regression models, relating support for federal involvement in health care, antipoverty programs, and general domestic policies to a set of sociodemographic characteristics. Relative to other federal policies, support for health initiatives grew over this period. During the same period, long-standing differences in support between rich and poor, old and young, educated and uneducated, all narrowed for health care, though they did not for other types of federal policies. The second part of this study explores motivations that might account for these patterns. We identify a half dozen ways in which health care may be viewed as "different," that is, more or less appropriate for federal action. Analysis of survey data from 1987 suggests that there are relatively small differences in the attitudes and perceptions that motivate support for federal health initiatives, relative to federal domestic policies in general. However, there are more striking differences between health programs and more overtly redistributive policies. Compared to redistributive federal programs, support for federal health initiatives are (a) less identified with racial minorities or economically disadvantaged groups, (b) less constrained by notions of individual responsibility, (c) more closely associated with concerns about equal opportunity in American society, and (d) somewhat more constrained by choices between federal and local government. These patterns persist whether or not respondents are politically active and whether they report themselves to be liberal or conservative. We suggest that the growing support for federal intervention in health care, relative to other social policies, is in part an inadvertent by-product of ideological positions popularized during the Reagan and Bush administrations. We draw from these results some predictions about the course of the ongoing debate over federal health policies.

Adult↗

Myelomonocytic antigens are rarely expressed on B-lymphocytic leukemia cells.

In the light of recent observations reporting that B-lymphocytic leukemia (B-CLL) cells may express a variety of myelomonocytic antigens, 28 patients with B-CLL and B-leukemic lymphocytic lymphoma were studied for the presence of these antigens using monoclonal antibodies to detect CD13, CD33, CD15 and CD14. Analysis of immunofluorescence (IF) was carried out by two procedures; one which employed the standard conventional method of gating used in our laboratory for flow cytometry, while the other procedure increased the sensitivity of the analysis, by moving the marker for IF to the left, so as to widen the gate to include more cells with low IF. Using the conventional methodology, the mean proportion of cells considered positive was less than 3% for any of the 4 markers studied. In only a few patients were 5% or more of the B-CLL cells positive for some of the markers studied (3 patients with 6.2-11.3% CD13+; 2 with 6.0-9.6% CD14+, and one with 11.8% CD15+ cells). No case had more than 2.5% + CD33+ cells. The second procedure with a wider gate to enhance sensitivity for less positive cells, increased the number of positive cells for any of the markers in only 4 patients. These results are contradictory to others reported recently, and some of the possible causes for this discrepancy are discussed. It is suggested that more useful data may be obtained if the level of staining intensity and patterns of positive staining are documented in the future.

Antibodies, Monoclonal↗

Complement profile in primary biliary cirrhosis.

PBC is a chronic progressive liver disease of unknown etiology. Several abnormalities found in PBC support the hypothesis that it may be considered an autoimmune disease. Despite the complex and interesting relationship that exists between autoimmune disorders and the complement system, very few reports on the level of the serum complement component in PBC have been published, and most of these comprised only a few patients or analyzed only a scant number of the complement components. In the present study, sera of 73 PBC patients were analyzed for the levels of 10 complement components. It was found that the levels of most of the serum complement components, including C1q, C2, C3, C5, C7, properdin and factor B were significantly elevated in patients with PBC in comparison to healthy controls. The level of C4 was slightly lower than that of the normal controls (p = 0.019), while the levels of C6 and C8 were within the normal range. The number of PBC patients with serum levels of C4 and C6 < 60% of normal pooled serum was higher than in the respective control groups (6/69 compared with 0/26 and 4/71 compared with 0/27, respectively). However, the difference was not statistically significant. Thus, our study shows alterations in the levels of most complement components in PBC, the reasons for which are discussed.

Autoimmune Diseases↗

Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response.

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.

Adolescent↗

Accessory nipples: any relationship to urinary tract malformation?

One hundred two infants and children age 3 days to 16.5 years, found to have accessory nipples (AN), were enrolled in this study. They were categorized by ethnic origin, sex, positive family history of AN, and number, site, and shape of AN, to determine factors for increased risk of anomalies of the urinary tract. Physical and ultrasound examinations of the abdomen did not reveal evidence of urinary tract malformation in any of the children. The results of this survey support the contentions that AN are not associated with urinary tract malformations, and that no further investigation is required in children with solitary AN.

Abnormalities, Multiple↗

Antigenic differences between subsets of peripheral blood lymphocytes differing in their right angle light scatter in flow cytometric analysis.

The expression of various cell surface markers on peripheral blood lymphocytes (PBL) of young children and of adults was determined by flow cytometry among cells with either high or low light side scatter (SSC). In adults and in children, CD4+ lymphocytes (helper T cells) were more abundant among PBL with low SSC than among PBL with high SSC. The proportion of CD57+ (Leu-7+) cells (NK cells and a subset of CD8+ T cells) was significantly elevated among high SSC PBL, while that of CD8+ PBL (cytotoxic suppressor T cells) was only slightly elevated. CD4+ and CD8+ lymphocytes which coexpressed the CD29 marker, characteristic for activated or memory T cells, were significantly more abundant among lymphocytes with high SSC. In adults, the proportion of CD4+ CD45RA+ lymphocytes, naive T cells, was significantly higher among low SSC cells. The present study indicates that determination of the SSC of lymphocyte subsets by flow cytometry can improve the discrimination among lymphocyte subpopulations and contribute to assessment of their state of activation.

Adolescent↗

The role of general hospitals in the privatization of inpatient treatment for serious mental illness.

For almost three decades, many have regarded general hospital psychiatric units as the most appropriate setting for acute treatment of persons with serious mental illness who were once treated mostly in state hospitals. The extent to which this transfer has taken place and the differences between public and private general hospitals have been unclear. Using data from the 1988 National Mental Health Facilities Study and published data from the 1970s, the authors found that nearly half of all general hospitals providing psychiatric services treat persons with serious mental illness. Significant differences in case and payer mix were observed between public and private general hospitals, although these differences were smaller than in the 1970s. The findings suggest increased involvement by private general hospitals in treating patients reimbursed by public payers, but the findings also indicate that persons with serious mental illness and those using Medicaid are still more prevalent in public general hospitals than in private ones.

Community Mental Health Services↗

Changes in lymphocyte subsets in myasthenia gravis: correlation with level of antibodies to acetylcholine receptor and age of patient.

We report a detailed analysis of the subsets of lymphocytes in patients with myasthenia gravis (MG). There was a slight, nonsignificant increase in the level of CD5+ B lymphocytes among MG patients as compared with normal controls. The proportion of CD5+ T cells in MG was similar to that in controls. However, whereas age had no effect on the level of these cells in normal individuals, a significant age-related decrease of these cells was present in MG patients. The proportion of double-positive CD4+CD8+ T cells was significantly increased in MG. The level of the CD29+CD4+ (helper-inducer) subset was significantly higher in MG patients than in controls. There was no correlation between the titer of autoantibodies to acetylcholine receptor and the level of either CD29+CD4+ T cells or CD5+ B cells among MG patients. The only T-cell subset that correlated with the autoantibody titer was the CD45RA+CD4+ (suppressor-inducer) subset of CD4+ T cells.

Adolescent↗

The complement system and primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic liver disease of unknown etiology. Several immunological abnormalities found in PBC support the hypothesis that autoimmune mechanisms are involved in its pathogenesis. The complement system being an important constituent of the immune system had not been extensively studied regarding its relationship with PBC. However, some workers reported abnormally high serum levels of some complement components with the exception of C4 that was found to be low. Here we review the literature and analyze the possible roles played by the complement system in PBC.

Antigen-Antibody Complex↗