Hereditary complement deficiencies in Israel.
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Complement Activation↗
Biomedical subjects
M Schlesinger
Publications and source records attributed to M Schlesinger.
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↗
[The immune system in uremic adults and children--laboratory and clinical aspects].
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Adult↗
State purchase of mental health care: models and motivations for maintaining accountability.
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Contract Services↗
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↗
Factors affecting the availability and use of hemodialysis facilities.
This article describes factors related to the geographic distribution of hemodialysis facilities and the relationship between availability and use. Such facilities tend to be concentrated in the same types of areas as other medical resources, and the number of medical specialists in an area is related to the rate of treatment for renal diseases. The proportion of treatment stations in an area owned by for-profit organizations is not related to the total treatment rate, but the market share of for-profit facilities is positively related to in-center treatment and negatively related to home treatment.
Ambulatory Care Facilities↗
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↗
Unitary-group approach to spin-dependent operators.
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Journal Article↗
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↗
A clinical and immunologic study of colchicine in asthma.
A double-blind, randomized, crossover chronic study was done to determine the efficacy of colchicine in 10 atopic patients with asthma. A constant dose of sustained-release theophylline and albuterol by inhalation, as needed, was administered. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced the mean (+/- SEM) daily clinical score from 2.18 +/- 0.34 to 1.64 +/- 0.32 (p less than 0.05), and the daily number of inhalations of albuterol from 5.89 +/- 1.48 to 4.01 +/- 1.26 (p less than 0.02). Colchicine significantly (p less than 0.05) increased the concanavalin A-induced suppressor cell function from 16.2 +/- 4.6% to 39.0 +/- 10.7%, which was similar to healthy volunteers (41.1 +/- 3.5%). Furthermore, colchicine significantly (p less than 0.05) decreased serum IgE from 248 +/- 63 to 188 +/- 46 IU/ml. Colchicine had no significant effect on pulmonary function tests, the early phase reaction of antigen-induced bronchial inhalation challenge, and immediate skin test responses. Thus, colchicine has immunomodulatory effects that may perhaps have a mild benefit in the treatment of asthma.
Adolescent↗
The potential to express or suppress human interleukin-2 and interferon-gamma genes is not restricted to distinct cell subsets.
Cell surface markers CD4, CD8, Leu8 and Leu15 (CD11) were used to separate human lymphoid cell subsets with monoclonal antibody-coated immunomagnetic beads. We show that each of these subsets is able to suppress the induction of IL-2 and IFN-gamma genes effectively. This is manifested by a pronounced superinduction of IL-2 and IFN-gamma mRNA, as well as IFN-gamma protein, in cell populations depleted of one of these subsets. Co-culture of cell subsets with total cell populations or depleted ones, on the other hand, leads to severe inhibition of expression of these genes. In these experiments, cells in suppressor subsets exhibit little, if any, expression of IL-2 and IFN-gamma genes. By contrast, depending on donor and lymphoid tissue examined (tonsils or peripheral blood mononuclear cells), CD4, CD8, Leu8, and Leu15 cell subsets are also able to express IL-2 or IFN-gamma genes to high levels. Moreover, in Leu8+ cells that do not express the IFN-gamma gene, extensive expression of both mRNA and protein can be elicited by inhibiting the activation of suppressor cells with gamma-irradiation before induction. These results support the concept that the potential to express or suppress human IL-2 and IFN-gamma genes is not restricted to distinct cell subsets. Suppression or expression can be elicited in cells carrying a given surface marker, depending on the state of the immune system in a lymphoid tissue.
Antigens, CD↗
Serum amyloid A and P protein genes in familial Mediterranean fever.
Two recent studies have suggested the involvement of serum amyloid A (SAA) and P (APCS) genes in familial Mediterranean fever (MEF). To test the role of SAA and APCS in MEF and MEF-amyloidosis, we studied 17 informative families (15 Armenians, 2 non-Ashkenazi Jews) and 8 MEF patients with amyloidosis using a candidate gene approach. No evidence for any MEF-associated polymorphism was found in any of the 41 Armenian and Jewish MEF patients tested. Our family studies allowed us to rule out tight linkage between SAA and MEF (lod score = -2.16, theta less than or equal to 0.06). For APCS we found that the allele frequency in the MEF-amyloidosis patients was similar to that in 18 unrelated MEF patients without amyloidosis and their 33 healthy parents. Finally, we excluded close genetic linkage between APCS and MEF at 8.5 cM or less (lod score = -2.2).
Alleles↗
Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.
High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.
Adolescent↗
The failure of prenatal care policy for the poor.
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Health Policy↗
Changes in the level of soluble CD-2 molecules in the serum of HIV-infected individuals.
It has been shown previously that the level of soluble CD-2 determinants (E-receptors) is elevated in the serum of patients with various immunodeficiency states. The aim of the present preliminary study was to determine the level of soluble CD-2 in the sera of individuals infected with human immunodeficiency virus (HIV), in order to assess the contribution of soluble CD-2 molecules to the immunological deterioration of these patients. The serum CD-2 concentration was determined by an enzyme-linked immunosorbent assay, using a monoclonal CD-2 antibody. Considerable levels of CD-2 were detected in the sera of 15.9% of 63 normal controls tested, with a mean absorbance at 492 nm of 0.154 +/- 0.033. In contrast, in none of the 13 asymptomatic HIV-infected individuals tested could soluble CD-2 be detected (mean absorbance of 0.00093 +/- 0.0048). Elevated concentrations of CD-2 were found in the sera of 3 of 12 patients tested who were suffering from acquired immunodeficiency syndrome (AIDS). Thus, following HIV infection there is an initial phase of reduction of soluble CD-2, probably reflecting diminished T-cell activation. Thereafter, in some AIDS patients episodes of T-cell destruction seem to be correlated with the release of CD-2 molecules into the serum.
AIDS-Related Complex↗