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Biomedical subjects

M Margalit

Publications and source records attributed to M Margalit.

At least 19 recordsLinked to original sources

Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders.

BACKGROUND: beta-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes. AIM: To determine whether beta-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells. METHODS: The immunological effect of beta-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression. RESULTS: Administration of beta-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in beta-glucosylceramide-treated mice solely in the HCC model. The effect of beta-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon gamma levels in the colitis model, whereas an opposite effect was noted in the HCC model. CONCLUSIONS: beta-glucosylceramide alleviates immunologically incongruous disorders and may be associated with "fine tuning" of immune responses, by changes in plasticity of NKT lymphocytes.

Animals↗

Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping.

The aim of this study was to determine the effect of adoptive transfer of regulatory natural killer T (NKT) lymphocytes on the metabolic disorder in leptin-deficient ob/ob mice, which feature depletion and defective function of NKT and CD4 lymphocytes. Leptin-deficient ob/ob mice were subjected to transplantation of 1 x 10(6) of either ob/ob or wild-type-derived NKT lymphocytes, or to transplantation of either ob/ob or wild-type-derived splenocytes. The effect on hepatic fat content was measured by magnetic resonance imaging (signal intensity index) and histology, using the steatohepatitis grading scale. The degree of glucose intolerance was measured by an oral glucose tolerance test (GTT). Adoptive transfer of wild-type or ob/ob-derived regulatory NKT cells led to a 12% decrease in hepatic fat content. A significant histological shift from macrosteatosis to microsteatosis was observed. Marked improvement in the GTT was noted in wild-type or ob/ob-derived NKT recipients. Metabolic effects were associated with a significant decrease in peripheral and intrahepatic CD4/CD8 lymphocyte ratios. Intrahepatic CD8 trapping was observed in all responders. Serum interleukin 10 levels decreased significantly. In conclusion, adoptive transfer of a relatively small number of regulatory NKT lymphocytes into ob/ob mice results in a significant reduction in hepatic fat content, a shift from macro to microsteatosis, and significant improvement in glucose intolerance. These effects were associated with decreased peripheral and intrahepatic CD4/CD8 ratios and decreased interleukin 10 levels. The results further support a role for regulatory NKT lymphocytes in the pathogenesis of non-alcoholic steatohepatitis in the leptin-deficient murine model.

Adoptive Transfer↗

Adoptive transfer of small numbers of DX5+ cells alleviates graft-versus-host disease in a murine model of semiallogeneic bone marrow transplantation: a potential role for NKT lymphocytes.

Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 x 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 x Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 x 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 x 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNgamma/IL-10, and IFNgamma/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.

Adoptive Transfer↗

[Cholangiocarcinoma in primary sclerosing cholangitis: "chronicle of a death foretold"?].

Primary sclerosing cholangitis (PSC), a condition usually associated with inflammatory bowel disease, is a chronic inflammatory state of the biliary tract characterized by fibrotic strictures of intrahepatic and extrahepatic bile ducts. Between 5-15% of patients with PSC will develop cholangiocarcinoma. The diagnosis of cholangiocarcinoma in patients with PSC is difficult, as it is often impossible to distinguish benign PSC-related strictures from lesions associated with cholangiocarcinoma. Consequently, most patients are diagnosed with advanced disease and have a dismal prognosis at the time of diagnosis. The importance of characterizing patients with PSC who have an increased risk of developing cholangiocarcinoma and of developing means for early detection of this disease cannot be over-emphasized. Detection of cholangiocarcinoma in asymptomatic patients is additionally important, as this condition is considered a contraindication for liver transplantation. We describe a patient with longstanding Crohn's disease and PSC who developed cholangiocarcinoma, and review the literature regarding risk factors for cholangiocarcinoma, early detection of cholangiocarcinoma and the significance of existing cholangiocarcinoma in the context of liver transplantation.

Adult↗

Enzyme replacement therapy in the management of longstanding skeletal and soft tissue salmonella infection in a patient with Gaucher's disease.

A splenectomised patient with Gaucher's disease who developed multiple foci of osteomyelitis and soft tissue abcesses, after a severe episode of group C salmonella sepsis, is described. Aggressive antibiotic treatment and surgical drainage had little effect and the patient's condition continued to deteriorate. With initiation of enzyme replacement therapy (ERT) in addition to specific antibiotic treatment, defervescence and gradual healing occurred. Complete resolution of the infection was seen after 15 months. The possible role of ERT in healing bacterial infections in Gaucher's disease is discussed.

Adult↗

Effect of ozone on neutrophil function in vitro.

The application of ozone is widely practised as a form of alternative medicine, particularly in Germany and Eastern Europe. Ozone major autohemotherapy (the return of a small amount of a patient's blood to the circulation after ex vivo exposure to ozone) has been reported to have a therapeutic effect in various pathological conditions, including ischemic, infectious, autoimmune and neoplastic disorders. Ozone has an effect on the expression of cytokines, adhesion molecules and acute phase reactants, which are responsible in part for the respiratory inflammatory response observed after exposure to this gas. The purpose of the present study was to investigate the effect of ozone administration ex vivo, at a concentration commonly used in major autohemotherapy, on peripheral blood neutrophil function in vitro. Blood drawn from healthy volunteers was studied for neutrophil adhesion, chemotaxis and O-2 production before and after exposure to 30 microg/ml ozone. There was no significant difference in adhesion and chemotaxis of neutrophils exposed to ozone versus unexposed cells. O-2 production was minimally decreased (20.3 +/- 5.0 vs. 22.1 +/- 5.5 nmol/106 cells/10 min, respectively; P=0.01), a reduction of no clinical significance. This study confirms that major autohemotherapy with ozone is safe as far as neutrophil function is concerned. Combined with previous data, it seems that well-designed clinical trials to assess the efficacy of major autohemotherapy would pose no danger to blood cell populations, and should be encouraged.

Adult↗

Social skills and classroom behavior among adolescents with mild mental retardation.

Relations among self-reported social skills, teacher ratings of classroom behavior, and direct observations of social interactions among 87 adolescents with mild mental retardation were investigated and variables predicting the students' task orientation identified. Three information sources were employed. Results demonstrated that the four domains of social skills were related to the students' task orientation. The regression analysis revealed that students who were characterized by better social skills and fewer occurrences of hyperactivity and behavioral difficulties were viewed by teachers as evidencing more compliant and task-oriented behavior, implying their better ability to benefit from the special curriculum. The three sources of information validated one another and added information to the conceptualization and appraisal of social and academic competence among students with mental retardation.

Achievement↗

The family system of moderately mentally retarded children.

Families of 39 moderately mentally retarded children (behaviourally disordered and non-behaviourally disordered) were classified according to the Reiss Card-Sort procedure. Thirty-four out of the 39 families were found to have a faulty family system according to Reiss' typology, distant sensitive or consensus sensitive. Though behaviour disorders in the moderately mentally retarded child were not found to be related to the type of faulty family, parental perceptions of their child's behavioural disorder were different in the distant sensitive and consensus sensitive types. Results are discussed in the context of the interface between the family system and the adaptation of the mentally retarded child.

Adolescent↗

Classification and validation of family climate subtypes in kibbutz fathers of disabled and nondisabled children.

The aim of the study was to investigate the impact of disabled children on their fathers. Perceptions of family climate, sense of coherence, and satisfaction from family life were measured among 66 fathers of disabled children and among 74 fathers with nondisabled children in an Israeli kibbutz. The fathers of disabled children showed lower sense of coherence, derived less satisfaction from family life, and viewed their families as less encouraging of personal growth among family members. Four subtypes of family climate patterns, perceived by fathers of disabled children, were identified by cluster analysis and validated by the sense of coherence and global family satisfaction measures. Cluster analysis for the fathers of nondisabled children replicated the subtypes identified. The four subtypes were conceptualized as families with a (a) personal growth orientation, (b) conflict orientation, (c) conflict avoidance orientation, and (d) recreation avoidance orientation. Significant differences were found between the subtypes with regard to the family climate variables and satisfaction and coherence measures. Results demonstrated that different patterns of family climate characterized the two groups of fathers: In almost every cluster the measures of personal growth were lower for the fathers of disabled children.

Adaptation, Psychological↗

Behavior disorders and mental retardation: the family system perspective.

The aim of this study was to investigate feelings of stress among parents of mentally retarded children who demonstrate behavior disorders. The interrelations of the children's pathology and family climate variables with the levels of parental stress were studied. The sample consisted of 39 families with moderately mentally retarded children divided into two groups: Children demonstrating disruptive behavior (n = 17), and children who did not demonstrate behavior disorders (n = 22). The instruments included the Child Behavior Checklist, the Classroom Behavior Inventory, the Family Environment Scale, and the Questionnaire on Resources and Stress. Significant differences between the children's levels of pathology validated the two groups' division. The children with disruptive behavior were described by their parents as more hyperactive and aggressive, and were described by their teachers as more distractable and dependent on adults. No significant differences were found between the profiles of family climate among the two groups of parents. However, levels of children's pathology and aspects of family climate predicted the parental stress, pinpointing different patterns of variables for fathers and mothers. Further studies should be addressed to the interrelations between children's pathology, family climate, and parental feelings of stress.

Adaptation, Psychological↗

Academic competence and social adjustment of boys with learning disabilities and boys with behavior disorders.

The aim of the present study was to compare academic competence and social adjustment of students with learning disabilities and two groups of students with behavior disorders. The sample consisted of 31 boys with learning disabilities and 52 boys with behavior disorders divided into two subgroups: (a) boys displaying hyperactive behavior (BDH) and (b) boys not demonstrating such behavior (BDNH). Significant differences were found among the three groups using the Classroom Behavior Inventory, and three measures contributed to the significant difference: Hostility versus Consideration, Extroversion versus Introversion, and Independence versus Dependence. The results highlighted teachers' needs for differential approach in their interventional planning.

Achievement↗

Mothers' perceptions of anxiety of their diabetic children.

Within the theoretical framework of family dynamics, the anxiety levels expressed by 20 diabetic children, the level of anxiety ascribed to them by their mothers, and the anxiety levels of 20 healthy children were studied. The diabetic children did not form an emotionally deviant group in terms of their expressed anxiety, although their mothers viewed them as significantly more anxious than they judged themselves. The mothers' own anxiety was the best predictor of their perceptions of their children's anxiety. The results are discussed in terms of their effects on communication and coping in the families.

Adaptation, Psychological↗

Suicidal behavior at school: a systemic perspective.

This article delineates the interpersonal function of suicidal behavior in children. Children's suicidal attempts have a major impact on their immediate surroundings and can be perceived as a mode of controlling the family or school. In order to highlight this approach, a case of epidemic suicidal attempts in a special education high school is presented. A systemic mode of intervention, consisting of an adolescents' group and a teachers' group within the school system, is described. The importance of implementing systemic modes in preventing suicide is outlined.

Adolescent↗