Search PubMedSearch

Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 19 recordsLinked to original sources

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

Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone marrow transplanted mice.

We studied the efficacy of in vivo and in vitro treatments with IL-1, IL-2, IL-3, and GM-CSF in the protection against bacterial (Salmonella typhimurium), fungal (Candida albicans) and viral (influenza virus A/PR8) infections, of normal, sublethally irradiated and lethally irradiated, bone marrow (BM) reconstituted mice. In parallel, the cytokines were tested for their ability to potentiate hematopoietic activity in vitro and in vivo. We demonstrate that, under the experimental conditions employed, IL-1 had the best protective activity against the three micro-organisms in both normal and immunocompromised mice when administered in vivo. Administration of IL-2 led to increased resistance in normal but not in immunodeficient mice, whereas GM-CSF had no beneficial effects. In contrast, preincubation of BM cells in these cytokines, singly or combined, prior to transplantation to lethally irradiated mice, did not confer protection against subsequent infection, although it increased the number of BM derived CFU-GM in culture (except in the case of IL-2). Administration of IL-1 or GM-CSF to BM transplanted mice facilitated WBC recovery, whereas IL-2 delayed it. Collectively, the data suggest that IL-1, alone or combined with other cytokines, may be beneficial in the prevention or treatment of microbial infections in immunocompromised and BM transplanted patients. It can also be concluded that enhanced hematopoietic recovery may not always coincide with the development of resistance to micro-organisms.

Animals

Urinary albumin excretion in patients with familial Mediterranean fever: a pilot study.

Amyloidosis of the kidney is the most threatening complication in familial Mediterranean fever (FMF), and colchicine has been shown to reduce its occurrence. In the preclinical stage of kidney amyloidosis, no proteinuria is observed by the standard Albustix method. However, whether these patients have normal or increased urinary albumin excretion is not known. The purpose of this study was to evaluate albumin excretion in FMF patients treated with colchicine and to compare these values to those of a normal control group. Twenty-two subjects with FMF were compared with 16 normal subjects matched with regard to age and body surface area. The two groups did not differ with regard to female/male ratio and arterial pressure. Urine samples were collected overnight while patients were recumbent and in the daytime while they were ambulant. After measuring albumin concentration (Ua) by radio-immunoassay and creatinine concentration through the standard method, the urinary albumin excretion rate (UaV) and urinary albumin creatinine ratio (Ua/c) were calculated. In the FMF group, three patients had microalbuminuria--defined as an albumin excretion rate higher than 20 micrograms/min. Two of them had this condition only in the early morning collection. These three patients were characterized by a longer duration of symptoms (18 vs. 9 years). No patient in the control group had microalbuminuria. The mean UaV in the FMF group did not differ significantly from that of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Contracting between public agencies and private psychiatric inpatient facilities.

Purchasing human services through contracts with private providers has become an increasingly common practice over the past 20 years. Using data from a national survey of psychiatric inpatient facilities, this paper examines the extent to which psychiatric units in privately controlled general hospitals and private psychiatric specialty hospitals (N = 611) participate in contractual arrangements to provide services to governmental bodies. It also examines how the likelihood of such a practice is affected by hospital characteristics (general or specialty, for profit or nonprofit) and features of hospitals' environments, including the competitiveness of the market for psychiatric inpatient care and the population's need for services in the hospital's county. The findings indicate that nonprofit psychiatric specialty hospitals were more likely than other types of hospitals to enter into such contracts, and that forces such as local competition and need for services were not predictors of such involvement. Contracting was shown to have a significant impact on the level of referrals a hospital accepted, but these levels were also affected by competition and need. Among hospitals with public contracts, referral acceptance from public agencies was unaffected by these factors, but they did have a significant effect on referral acceptance by hospitals without public contracts. These data suggest that public agencies contracting for services with private hospitals may represent a means by which "public sector" patients may gain access to private providers. Further, this mechanism may impose sufficient structure and regulation on the acceptance of such patients that many concerns of hospital administrators regarding patients who are costly and difficult to treat and discharge can be allayed.

Contract Services

A national study of psychiatric hospital care.

BACKGROUND: The delivery system for psychiatric inpatient services in the United States has changed dramatically over the past 30 years, undergoing a marked privatization. METHOD: To assess the effect of changes in ownership and types of inpatient settings on the structure of the mental health services system, the authors surveyed a national sample of nonfederal mental health facilities in 1988. RESULTS: Comparing their data to those of earlier surveys, they found that a decline in the number of patients per staff occurred in most settings over the last decade, suggesting that this aspect of quality of care may have improved. They observed important ownership-related differences in 1988 in diagnostic mix (e.g., more schizophrenia treated in public facilities than in private ones) and in payer source (e.g., more third-party revenues in public facilities than occurred in the past). CONCLUSIONS: There was a significant interaction between ownership form and type of facility, suggesting that the type of inpatient setting, ownership, and the relation between the two should be considered in assessing the impact of privatization on the accessibility of health care available for the mentally ill. The authors found that the increase in private psychiatric hospitals has widened the availability and choice of treatment facilities for those with private funding sources (especially children and adolescents) but has not had a similar effect in increasing sources of care for the seriously mentally ill dependent upon public financing.

Adolescent

The effect of heating on the expression and function of CD-2 molecules on human T-lymphocytes.

CD-2 molecules on the surface of human T-lymphocytes endow these cells with the capacity of binding sheep (SRBC) and human red blood cells (HRBC). It has recently become clear that they play an important role in the regulation of T-cell functions. The aim of the present study was to analyze the effect of heating at 45 degrees C for 1 hour on the capacity of human T-lymphocytes to bind SRBC and HRBC and to stain with CD-2 monoclonal antibody. Heating of human peripheral blood lymphocytes (PBL), thymus cells, or cells of the HD-MAR T-cell line drastically reduced their capacity of forming rosettes with SRBC. Heating of human thymus and HD-MAR cells also abrogated the formation of rosettes with HRBC. In contrast, the proportion of cells stained by high concentrations of CD-2 MoAb was reduced by only about 10-15%. Using radioiodine-labeled CD-2 MoAb, heating was found to reduce the number of cell surface E-receptors by 42% on PBL and by 27% on HD-MAR cells. The molecular weight of CD-2 molecules present on heated T-cells was identical with that of E-receptors on unheated cells. Heating was found to abolish antibody-induced capping of CD-2 molecules. Thus, heat treatment of human T-cells resulted in a moderate reduction in the number of cell-surface CD-2 molecules and in impaired mobility of CD-2 molecules in the membrane. It remains possible that in addition heating may affect the functional integrity of E-receptors or induce metabolic alterations detrimental for rosette formation.

Antibodies, Monoclonal

The effect of in vitro T lymphocyte depletion on generation of IL2-activated cytotoxic cells.

The effect of immunocompetent lymphocyte depletion on precursors and effector cells of IL2 activated non-MHC restricted cytotoxic cells (LAK) generated from bone marrow (BM) or peripheral blood was investigated. Lymphocyte depletion was carried out by using Campath-1, a monoclonal rat anti-human lymphocyte antibody recognizing CDW52, that binds human complement and is used routinely in clinical bone marrow transplantation (BMT). The results indicate that LAK precursors derived from BM cells are sensitive to Campath-1 treatment, while a variable degree of sensitivity was demonstrated in LAK precursor cells derived from peripheral blood. In contrast, effector LAK cells generated in vitro were shown to be resistant to treatment with Campath-1 and complement. We hypothesize that if indeed IL2-dependent non-MHC restricted cytotoxic cells play a role in vivo in the immediate post-BMT period, a T lymphocyte depletion procedure such as the Campath-1 may have the capacity to reduce, at least temporarily, the graft-versus leukemia effects mediated by such anti-tumor effector mechanisms.

Animals

Absence of natural killer cells in a child with pure red blood cell aplasia.

A 16-year old boy was known to suffer from red blood cell (RBC) aplasia from the age of 4 years. Peripheral blood lymphocytes (PBL) from the patient were found to lack natural killer (NK) cytotoxic activity, even after stimulation with alpha-interferon. His PBL also lacked Leu-7+ and Leu-11+ cells, although his granulocytes showed normal expression of the Leu-11 marker. The lack of NK cells did not seem to result from the various immunosuppressive treatments he received, since the NK deficiency was noted 2 years after he stopped receiving such treatment. The possibility is discussed that lack of NK cells may lead to the development of RBS aplasia if NK cells play a role in promoting the production of RBC.

Antigens, Surface