Subpopulations of lymphocytes and autoimmunity.
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Autoimmunity↗
Biomedical subjects
M Schlesinger
Publications and source records attributed to M Schlesinger.
Compound heterozygous complement C3 deficiency.
Complete deficiency of the third component of the complement system is a result of defects in the two alleles of the C3 gene. In this study a family with C3 deficiency is reported; the parents expressed a distinct abnormality of the C3 gene and their two children had compound heterozygous C3 deficiency. These are the first reported cases of compound heterozygous complement deficiency. Our results indicate that the maternal abnormality leads to synthesis of an abnormal proC3 protein which is not secreted from the cells. The paternal abnormality results in ablation of synthesis of the proC3 protein.
Autoradiography↗
Management of mental health and substance abuse services: state of the art and early results.
Managed care (MC) refers to capitated practice (HMOs), utilization management (UM), and programs of case management for persons with mental illness and problems of substance abuse. These approaches differ substantially, and within each type are variations. Management of mental health and substance abuse services is increasingly prevalent, often sharply reducing costs. Savings result from reducing inpatient hospitalization and, sometimes, by substituting less expensive services for more costly ones. Most studies of managed care, however, measure costs narrowly, neglecting shifts in costs to patients, professionals, families, and the larger community. Strategies typical of HMOs and UM may result in lower-quality care for persons with serious mental illness and problems of substance abuse. Studies on this topic are reviewed, an analytic frame of reference is presented, and research needs are defined.
Cost Allocation↗
Inherited complement C3 deficiency: a defect in C3 secretion.
The molecular basis of inherited complement C3 deficiency in a 20-year-old newly diagnosed male patient was studied. Using an enzyme-linked immunosorbent assay, the patient's C3 serum level was found to be approximately 7 micrograms/ml, which is less than 1% of normal. In contrast, Northern analysis indicated that the patient's C3 mRNA was of normal size and quantity. Peripheral blood monocytes (PBM) and skin fibroblast cultures (F) from the patient and from healthy donors were labeled for 2 h with [35S] methionine. Analysis of cell lysates and supernatants by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated normal levels of C3 in lysates of patient's PBM and F. However, C3 secretion in the patient's cells was extremely reduced, with pulse-chase experiments demonstrating a long delay in the disappearance of intracellular C3. Secretion of C1r and factor B by the patient's cells was normal. Lipopolysaccharide and interleukin-1 increased C3 synthesis in the patient's PBM and F, but had no effect on the secretion. SDS-PAGE analysis of trypsin-cleaved intracellular C3 revealed an aberrant cleavage profile for the patient's C3. Collectively, these data indicate that C3 deficiency in this patient is due to a defect in the C3 secretion, probably as the result of abnormality in the proC3 structure.
Adolescent↗
A distinctive form of soluble CD8 is secreted by stimulated CD8+ cells in HIV-1-infected and high-risk individuals.
The aim of the present study was to investigate the biochemical structure and pathogenic significance of the soluble CD8 (sCD8) present in the serum of HIV-1-infected individuals. In a longitudinal study of a cohort of HIV-infected homosexuals and the amount of sCD8 detected in the plasma was correlated with changes in lymphocyte subsets and with the clinical course of HIV infection. The level of sCD8 in the plasma, the percentage, and the absolute number of CD8+CD38+ cells were increased in HIV-seronegative, high-risk homosexuals and in seropositive HIV+ individuals. The plasma concentration of serum sCD8 showed a significant correlation with the absolute number of CD8+ and CD8+CD38+ cells in HIV+ homosexuals. In addition to a molecule with a molecular weight (m.w.) of 30 kDa, sCD8 isolated from the plasma of HIV-1-infected individuals and of healthy controls was found to consist of two molecules, one with a m.w. of 57 to 62 kDa and another with a m.w. of 66 to 70 kDa. The former was the predominant molecule in normal individuals, while the latter was the predominant molecule in HIV-negative high-risk homosexuals and in HIV-infected individuals. The latter molecule, secreted by chronically stimulated CD8+ cells, seems to be present in the circulation as a dimer. While it was previously shown that CD8 can be shed from the cell membrane in vitro, the present study indicates that in vivo-stimulated CD8+ cells release a distinctive form of soluble CD8.
Acquired Immunodeficiency Syndrome↗
Killing of meningococci by neutrophils: effect of vaccination on patients with complement deficiency.
To evaluate the in vitro effect of meningococcal vaccination, 3 C7-deficient (C7-D) siblings and 2 normal controls were studied before and 6 weeks after vaccination with treatment meningococcal vaccine (serogroups A, C, Y, and W). Serobactericidal activity was not detected in the C7-D subjects and was low in the controls. Neither group was affected by vaccination. However, opsonized phagocytic killing increased significantly following vaccination in C7-D subjects and normal controls, despite only a modest increase in antimeningococcal titers. Heat inactivation of sera added to neutrophils resulted in low killing activity, which did not increase after vaccination. Thus, tetravalent meningococcal vaccine appears to enhance the phagocytic killing of meningococci in both normal and C7-deficient persons and should be given to all persons with C7 deficiencies.
Adult↗
Spin-dependent operators in the unitary-group approach.
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Journal Article↗
Kinetics of the pleiotropic effect of interleukin 4 on the surface properties of human B-lymphoma cells.
Striking antigenic changes were elicited by interleukin 4 (IL-4) in the Farage human B-cell lymphoma line. After 2 days of incubation with IL-4 the expression of CD23, CD54 (ICAM-1), CD58 (LFA-3) was increased while the levels of CD21, CD22, CD38 were diminished. Prolonged incubation of Farage cells with IL-4 for 6-8 days led to increased expression of CD11a (LFA-1) CD39, CD40, and to disappearance of CD21 and CD38. The modulation of antigenic properties of Farage cells was associated with enhancement of their homotypic adhesiveness and the formation of giant clumps of cells. The recovery of Farage cells which had been exposed to IL-4 for six days was not complete and eleven days after withdrawal of the cytokine, these cells still displayed a lower level of CD21 and of CD38 than control cells. Cycling and non-cycling cells did not appear to differ in their antigenic properties, indicating that modification of the antigenic profile did not result from cell selection or cell arrest. These results showed that the pleiotropic effect of IL-4 on various cell surface structures on malignant human B cells proceeds at different rates suggesting that distinct metabolic pathways may regulate their expression.
Antigens, Neoplasm↗
Verifying the future of electronic eligibility verification.
Many vendors and potential users of eligibility verification systems know the obstacles that deter the widespread acceptance and implementation of the technology. On the following pages, executives of firms representing the payor, provider and clearinghouse communities express their perceptions regarding the status and need for online eligibility verification and its cost advantages.
Eligibility Determination↗
Further mapping of the properdin deficiency gene in a Tunisian Jewish family--evidence for genetic homogeneity.
The properdin deficiency gene has been localized to Xp21.1-Xcen; however, it is not clear whether the mutation responsible for the disease co-maps exactly with the structural properdin gene. Based on a recent study on a total of six families, the gene was found linked to DXS255 (theta = 0.00). As only a few families have been studied, it is not known whether the same gene is responsible for the disease in all families. In order to better localize the disease gene in Israel, we studied a Tunisian Jewish family with properdin deficiency for linkage with various X-markers. A maximum lod score of 1.93 at theta = 0.00 was calculated with the DXS7 probe while there was one recombination with DXS255. This study helps to better localize the properdin deficiency gene to Xp11.3-p21.1 proximal to DXS255 locus and confirms that there is no indication of genetic heterogeneity. Whether the properdin structural gene (PFC) and properdin deficiency locus are one and the same await demonstration of mutations in the structural gene in patients with properdin deficiency.
Chromosome Mapping↗
Prevalence of viral antibodies in gingival crevicular fluid.
The prevalence of antibodies to CMV, Mumps and Coxsackie virus strains 1, 3 and 4 was studied in 39 samples of gingival crevicular fluids (GCF) obtained from clinical healthy patients and compared to the corresponding antibodies present in the serum of each individual. In spite of the high prevalence of humoral antibodies to CMV (75%), only 24% of the gingival crevicular fluid samples exhibited IgG or IgA antibodies to this virus. The differences in the prevalence of antibodies against Mumps virus in the sera and GCF were even greater: whereas 87% of the patients exhibited serum antibodies, not even a single gingival fluid sample was found to be positive. Antibodies to Coxsackie B strains 1, 3 and 4 were found in 72%, 63% and 52% of the sera and in 25%, 19% and 33% of the gingival fluid samples (IgG only). The presence of the antibodies and their profile in GCF and serum is different. The mechanism of possible permeation is not clear but it seems that viral antibodies in this milieu are not derived from the serum solely by passive transudation, and that the antibodies are produced locally at least in some of the GCF specimens.
Adolescent↗
Rapid Il-2-induced adherence of human natural killer cells. Expression of mRNA for cytokines and IL-2 receptors in adherent NK cells.
Natural killer (NK) cells selected by IL-2-induced rapid adherence to plastic and called A-NK cells represent a phenotypically and functionally distinct subset of mature peripheral blood NK cells. To further characterize this subset of NK cells functionally, their potential to express mRNA for the IL-2R and various cytokines after IL-2 activation was examined. Highly purified normal human peripheral blood resting NK (R-NK) cells were obtained by negative immunoselection using OKT3 mAb and magnetic beads coated with goat anti-mouse Ig. By two-color flow cytometry, > 90% of these R-NK cells were either CD3-CD56+CD16+ or - or CD3-CD56-CD16+. R-NK cells were activated in the presence of 6000 IU/ml (22 nM) of IL-2 for different periods of time. After 1, 3, 5, or 24 h, plastic-adherent (A) and nonadherent (NA) NK cells were separated and compared for the expression of the IL-2R or cytokine mRNA by in situ hybridization, using 35[S]-cDNA probes. Only low proportions of R-NK cells expressed genes for IL-2Rp55 (16%) or cytokines IL-2 (20%), IFN-gamma (18%), TNF-alpha (16%), and TGF-beta (7%). Thus, the genes for the IL-2Rp55 and these cytokines were not constitutively expressed by most human R-NK cells, and there was no indication that the NK cells used in these experiments were activated in vivo or during the purification procedure. However, larger proportions of R-NK cells showed expression of mRNA for IL-1-beta (35%) and IL-6 (40%), which indicates that genes for these cytokines may be constitutively expressed in a substantial proportion of normal human circulating NK cells. When R-NK cells were incubated in the presence of 22 nM of IL-2 for 1 to 24 h and separated into A-NK cells and NA-NK cells, a large proportion of A-NK cells became positive for IL-2R and cytokine gene expression. In contrast, the proportion of mRNA-positive NA-NK cells was similar or lower than that observed for R-NK cells, with the exception of an increase in TGF-beta.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell Adhesion↗
Psychosocial stress and NK cells among members of a communal settlement.
The aim of the present study was to assess the effect of daily psychosocial stress on the human immune system. We tested 38 couples living in a communal settlement (kibbutz) under similar economic and social conditions, sharing similar housing, nutrition and health care. They were tested repeatedly over a two year period for a number of psychosocial parameters including demoralization, social support, family cohesion, adaptational hardiness and hostility. In parallel, the natural killer "NK" cell system was analysed for distinctive markers and for cytotoxic activity. The proportion of CD16+ lymphocytes was found to correlate with cytotoxic NK activity in both men and women. In contrast, the proportion of CD57+ cells correlated with that of CD16+ cells only in women while in men only the CD57+CD8-lymphocytes subset correlated with CD16+ cells. For each individual tested, the values of NK activity and NK markers obtained in tests carried out more than a year apart showed a striking correlation. In males, NK cytotoxicity correlated with hostility but was negatively correlated with family cohesion, adaptability and hardiness. The level of CD16+ and CD57+ cells correlated positively with demoralization in males only. Changes in the level of NK activity and in the level of CD16+ cells occurring in husbands during the observation period correlated positively with changes in demoralization and negatively with changes in family cohesion and adaptability. The results indicate that daily psychological stress and low family function may enhance the NK system, and that this response may differ between the sexes.
Adult↗
The complement system and systemic sclerosis.
Serum concentrations of the various complement components including the classical and the alternative pathways were determined in 58 control healthy subjects and 80 patients with systemic sclerosis (SSC). The mean concentrations of C1q, C2, C5, C6, C7, C9, and factor B were significantly increased in the SSC patients in comparison to controls, while the increases were not significant for C3 and C8. C4 was an exception in that the mean levels were found to be decreased, with 18 patients having levels < 65% of the mean normal value. Properdin was also found to be decreased, but not significantly. We found a similarity between the pattern of serum complement component concentrations in SSC patients and patients with primary biliary cirrhosis, two disorders frequently associated in the same patients. The significance of complement component patterns in these diseases is discussed.
Complement Activation↗
The effect of IL-4 on the phenotype of a human B-cell lymphoma line (Farage) lacking immunoglobulin expression.
Farage cells do not express surface immunoglobulins (sIg) but display a high level of CD19, CD21, CD22, CD23, CD39, CD40 B-cell antigens, and various adhesion proteins, such as CD11a (LFA-1), CD29 (VLA-4), CD44, CD54 (ICAM-1), and CD58 (LFA-3). The phenotype of Farage resembled that of EBV-LCL but differed from the phenotype of Burkitt's lymphoma lines, which were CD39- CD44-, expressed a high level of CD38, and either lacked CD21 or were weakly positive. Exposure to IL-4 augmented the concentrations of CD23 and of adhesion proteins on the surface of Farage cells but diminished the expression of CD21, CD22, and CD38. IL-4 did not induce the expression of sIg on Farage cells and failed to affect the level of HLA-DR. IL-2 and TPA did not alter the level of CD21 and adhesion proteins on Farage cells. Although IL-4 induced unique changes of the antigenic pattern in Farage, no significant effect on the phenotype of Burkitt's lymphoma lines was detected after IL-4 treatment. The present study indicates that the responsiveness of B cells to IL-4 is not determined by the expression of sIg but rather is associated with the antigenic profile characteristic for non-germinal center B lymphocytes.
Antibodies, Monoclonal↗
Project Safety Net: a health screening outreach and assessment program.
Although comprehensive geriatric assessment (CGA) has been conducted in many settings, its use in community-based outreach programs has been limited. We have developed Project Safety Net, a program that identifies low-income urban-dwelling frail elderly persons and provides CGA and appropriate referral. The program uses validated screening instruments and makes extensive use of a custom-designed computer program to provide information to the interdisciplinary team and for research purposes. During an 8 month period, 814 older persons were screened including high proportions who were widowed (51%) and who lived alone (66%). The effectiveness of this program remains to be determined in a randomized clinical trial.
Aged↗
Application of unitary-group methods to composite systems.
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Journal Article↗