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S Yatziv

Publications and source records attributed to S Yatziv.

At least 19 recordsLinked to original sources
PubMed2001

Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children.

Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.

Adolescent↗
PubMed1999

Cytokines in Gaucher's disease.

Gaucher's disease (GD) is characterized by hepatosplenomegaly, bone marrow infiltration, osteonecrosis, which may all be associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. Levels of serum cytokines, which are soluble products of mononuclear phagocytes (MNP), were evaluated in 24 GD patients. Levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble interleukin-2 receptor (sIL-2R) in GD patients were significantly higher than in normal controls. We attempted to correlate cytokine levels with disease severity. Type I GD patients with more severe clinical manifestations had significantly higher levels of IL-1beta, IL-1Ra and IL-6, relative to type I patients with milder disease. Three patients homozygous for the 1448C mutation with neuropathic type III disease, had significantly higher levels of sIL-2R than type I patients or controls. We speculate that cytokine over-expression may relate to the pathophysiology of some of the clinical manifestations of GD. Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients.

Chemotaxis, Leukocyte↗
PubMed1998

Effect of natural beta-carotene supplementation in children exposed to radiation from the Chernobyl accident.

Attempts were made to evaluate 709 children (324 boys and 385 girls) who had been exposed long-term to different doses of radiation during and after the Chernobyl accident and had moved to Israel between 1990 and 1994. Upon arrival, all of them underwent a check-up for most common clinical disorders and were then divided into three groups according to their residences (distance from the reactor) and the level of irradiation exposure: no radiation, <5 Ci/m2, and >5 Ci/m2, respectively. Blood serum analyses for total carotenoids, retinol, alpha-tocopherol and oxidized conjugated dienes in 262 of the children showed increased HPLC levels of conjugated dienes, indicating increased levels of oxidation of in vivo blood lipids in children from the contaminated areas. The levels were higher in girls than in boys. Some 57 boys and 42 girls were given a basal diet with a diurnal supplementation of 40 mg natural 9-cis and all-trans equal isomer mixture beta-carotene in a capsulated powder form of the alga Dunaliella bardawil, for a period of 3 months. Blood serum analyses were regularly conducted before supplementation to determine the baseline effect of radiation exposure to the children, after 1 and 3 months of natural beta-carotene supplementation. After supplementation, the levels of the oxidized conjugated dienes decreased in the children's sera without any significant changes in the level of total carotenoids, retinol or alpha-tocopherol. Other common blood biochemicals were within the normal range for all tests and no statistical differences before or after supplementation of beta-carotene were noted. High pressure liquid chromatography (HPLC) analyses for carotenoids in the blood detected mainly oxycarotenoids, and to a lesser extent, all-trans beta-carotene, alpha-carotene, but not 9-cis beta-carotene. The results suggest that irradiation increases the susceptibility of lipids to oxidation in the Chernobyl children and that natural beta-carotene may act as an in vivo lipophilic antioxidant or radioprotector.

Adolescent↗
PubMed1990

Glycosidase activities of mycoplasmas.

The activities of alpha- and beta-glucosidase, beta-galactosidase and beta-N acetylglucosaminidase were assessed at acidic pH by fluorimetry using the appropriate 4-methylumbelliferyl substrate in four Mycoplasma species (M. pneumoniae, M. gallisepticum, M. hominis and M. capricolum) and in Acholeplasma laidlawii. The glycosidase activities were in a low range (0.1-4.2 nmole per h per mg protein) with the exception of higher activities of beta-N-acetylglucosaminidase in A. laidlawii. The enzyme levels of a virulent and a nonvirulent strain of M. pneumoniae were comparable. Despite the very sensitive assay, neuraminidase activity was not detected in M. pneumoniae and M. gallisepticum. No induction of alpha-glucosidase could be demonstrated for M. pneumoniae or A. laidlawii. At least part of the glycosidase activities was localized in the membrane fraction of all mycoplasmas studied. This may support the hypothesis that pathogenic mycoplasmas, being membrane parasites, may modify, by their glycosidases, some host cell glycoconjugates. However, our study did not distinguish the pathogenic mycoplasmas to possess a characteristic glycosidase profile.

Acetylglucosaminidase↗
PubMed1990

Turnover of proteoglycans in skin fibroblast cultures derived from patients with mucopolysaccharidoses.

The turnover of proteoglycans in the extracellular matrix was studied in fibroblasts cultures derived from patients with mucopolysaccharidosis (MPS) and healthy donors. The cells were labelled with 35S-sulfate and 14C-glucosamine and it was found that in MPS-fibroblasts the rate of extracellular matrix turnover was hardly affected, where as the intracellular turnover was severely inhibited. Similar results were obtained with normal fibroblasts treated with 20 mM ammonia. Autoradiography revealed that MPS fibroblasts have a preferential accumulation of 35S-sulfate labelled material in the nuclear area, indicating that the nucleus may also be affected in MPS pathology. It is suggested that, although lysosomal enzymes are an important factor in intracellular proteoglycan turnover, they do not play a crucial role in the turnover of extracellular matrix proteoglycans.

Autoradiography↗
PubMed1989

Propionic acidemia--biochemical studies.

The first documented case of propionic acidemia in Israel is described. Diagnosis was based on three independent methods: analysis of urinary organic acids by gas chromatography/mass spectrometry, assay of propionyl CoA carboxylase activity and oxidation of 1-14C-propionate by cultured skin fibroblasts. The use of more than one method for confirmation of the diagnosis is considered to be of importance in providing an additional margin of safety in cases where genetic counseling and prenatal diagnosis in future pregnancies are indicated.

Ammonia↗
PubMed1988

Macrophages exposed in vitro to conduritol B epoxide resemble Gaucher cells.

In Gaucher disease the genetic lack of acid beta-glucosidase activity causes glucocerebroside to accumulate in the lysosomes of macrophage-derived cells, producing large characteristic Gaucher cells. The formation of Gaucher cells seems to be central to the pathobiology of this lysosomal storage disease. To develop a model simulating this process, cultured murine peritoneal macrophages were treated with conduritol B epoxide, a specific irreversible inhibitor of acid beta-glucosidase, for 6, 15, and 24 days. The conduritol B epoxide-treated macrophages accumulated glucocerebroside as a function of time, progressing to a fivefold elevation over control values after 24 days of treatment. Electron microscopy of the cells treated for 24 days reveals characteristics of Gaucher cells, including striations consisting of oriented fibrils. With conventional staining techniques, these fibrils have an appearance considered highly characteristic of Gaucher disease. Thus, macrophages treated with conduritol B epoxide are a useful model for studying the metabolic consequences and morphologic features associated with glucocerebroside accumulation in Gaucher cells.

Animals↗
PubMed1988

Gaucher-like changes in human blood-derived macrophages induced by beta-glucocerebrosidase inhibition.

Human blood-derived macrophages were cultured in the presence of conduritol-B-epoxide, a specific inhibitor of beta-glucosidase, to induce changes resembling those occurring in the cells of patients with Gaucher's disease. After 24 hours of incubation, only 5% of the original beta-glucosidase activity remained; on removal of the inhibitor, the enzyme activity recovered almost fully to control levels after 5 days. After 30 days of incubation with conduritol-B-epoxide, the macrophages contained almost 10 times as much glucocerebroside as the untreated controls, and the cells displayed morphologic changes reminiscent of Gaucher's cells. This in vitro system may enable detailed studies on the pathogenetic mechanisms associated with glucocerebroside accumulation in human macrophages as well as on the turnover of the accumulated substrate and reversal of the morphologic abnormalities on removal of the inhibitor.

Blood Cells↗
PubMed1986

beta-Glucosidase inhibition in murine peritoneal macrophages by conduritol-B-epoxide: an in vitro model of the Gaucher cell.

Murine peritoneal macrophages were cultured in the presence of conduritol-B-epoxide, a specific covalent inhibitor of beta-glucosidase. The inhibition was found to be dose and time dependent. Upon removal of the inhibitor from the culture medium, beta-glucosidase activity recovered to half maximum by 2.2 days. Treatment of macrophages with this inhibitor for 15 days did not affect cell viability, lysosomal enzyme release to the medium, or levels of intracellular lysosomal enzymes, other than beta-glucosidase activity. This inhibition results in the accumulation of glucocerebroside. In vitro studies on the pathobiology of such macrophages whose beta-glucosidase activity has been reduced may be useful toward understanding the pathogenesis of Gaucher disease.

Animals↗
PubMed1986

Parameters affecting the in vitro maturation of human monocytes to macrophages.

In vitro maturation of human monocytes to macrophages was characterized by morphological criteria, cell size and lysosomal enzymes activity. Purified populations of monocytes were maintained in culture at either adherent or nonadherent conditions and their maturation to macrophages was observed in both cases. The addition of external factors such as hydrocortisone and vitamin D3 inhibited monocyte maturation. In the absence of external factors, nonadherent monocytes were inhibited in their maturation for up to 10 days when plated at crowded cell concentrations. In addition, the presence of human serum in the culture media had a higher inhibitory activity than similar concentrations of fetal calf serum. Supernates from crowded macrophages were also inhibitory for monocyte maturation. We suggest the possibility that cell crowding, as well as soluble factors found in the serum and probably secreted by macrophages, participate in the regulation of monocyte development by inhibiting their maturation. Once released from this inhibitory signal or environment, the monocytes mature to macrophages.

Adolescent↗
PubMed1986

Calcification of intervertebral disks in I-cell disease.

I-cell disease (ICD) is associated with skeletal dysplasia. However, changes of the intervertebral disks had not been previously reported. We describe a child with clinical and laboratory evidence of ICD who had multiple intervertebral disk calcifications. Since an excessive degeneration of the cartilage had previously been found in ICD, we propose that this process may give rise to calcification of the intervertebral disks in patients with ICD.

Calcinosis↗
PubMed1986

Protective effects of the glutathione redox cycle and vitamin E on cultured fibroblasts infected by Mycoplasma pneumoniae.

The role of the glutathione (GSH) redox cycle and vitamin E as antioxidant defense systems was studied in normal human cultured skin fibroblasts infected by virulent Mycoplasma pneumoniae. In cells infected for 20 h, catalase activity was inhibited by 75% and the intracellular GSH decreased to 32% of its normal values. GSH peroxidase and oxidized glutathione (reductase activities in the infected cells were unaffected.) GSSG glutathione in the medium of the infected cells rose in accordance with the intracellular GSH decrease. The observed elevation in GSSG/GSH ratio was attributed to the increase in intracellular H2O2 content in M. pneumoniae-infected cells due to the marked inhibition in their catalase activity. The protective effect of the GSH redox cycle in infected cells was studied by depletion of cellular GSH, prior to their infection with M. pneumoniae, using buthionine sulfoximine (BSO), a selective inhibitor of gamma-glutamyl cysteine synthetase. After 16 h of incubation with BSO, the GSH levels were reduced to 38% of their normal value and recovered to 55% during 24 h after removal of the inhibitor. BSO had no effect on GSH peroxidase and catalase activities in either infected or noninfected cells. The level of malonyldialdehyde (an indicator of membrane lipid peroxidation) in BSO-treated cells infected by M. pneumoniae was 1.8 times higher than in infected controls. Cells enriched with 0.25 and 2.25 micrograms of vitamin E per mg of protein prior to their infection by M. pneumoniae revealed the following: a lesser degree of catalase inhibition, 46 and 30%, respectively, versus 64% in infected control cells that were not supplemented with vitamin E; lower levels of malonyldialdehyde, 55 and 20% increments, respectively, versus a 140% increment in infected controls; higher residual activity of lactate dehydrogenase, 76 and 96%, respectively, versus 58% in infected controls. Our data indicate that the oxidative damage induced in M. pneumoniae-infected cells due to the increase in intracellular levels of H2O2 and O2- is limited by the host cell GSH redox cycle and by supplementation with vitamin E.

Buthionine Sulfoximine↗
PubMed1986

Lysosomal hydrolases in blood-derived macrophages of patients with I-cell disease.

Three lysosomal hydrolases, beta-galactosidase, beta-glucuronidase, and beta-N-acetylglucosaminidase, were examined in blood-derived macrophages and media of two patients with I-cell disease. The activities of the three enzymes were lower in I-cell macrophages than in normal controls. However, the media collected from these cells possessed higher activities than control media. beta-N-acetylglucosaminidase derived from media of I-cell macrophages was not endocytosed by fibroblasts from patients with Sandhoff's disease and was only partially endocytosed by I-cell macrophages. These findings indicate that blood-derived macrophages of patients with I-cell disease are affected. In addition, the data presented suggest the presence of two types of receptors in human blood-derived macrophages: mannose and mannose-6-phosphate.

Acetylglucosaminidase↗