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Biomedical subjects

Y Levy

Publications and source records attributed to Y Levy.

At least 199 records · Page 11Linked to original sources
PubMed1996

Immune network and autoimmunity.

The concept of autoimmunity is regarded as the inability of the immune system to distinguish between self and non-self. This oversimplification of the concept is far from explaining the complex and perplexing mechanisms that are postulated to lead to its development. The transition from autoimmune state, in which no corresponding clinical manifestation exist, to an autoimmune disease, is further complicated by the evidence of multiple factors that participate in the evolution of the disease state. This article is written in a stepwise manner, initially reviewing the basic elements of the immune system, which are essential to understanding the fundamental processes underlying the occurrence of autoimmunity. Subsequently, a description of the factors involved in the etiopathogenesis and the presumed triggering events leading to the emergence of autoimmune diseases are described, with special emphasis on the important role of the idiotypic network, either in the maintenance of the normal immune response, or in the breakdown of self-tolerance eventuating in the autoimmune disease.

Animals↗
PubMed1996

Effects of interferon-alpha and -gamma on B cell differentiation in macroglobulinemia.

We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells via an IL-6 autocrine pathway. Here we investigate whether interferon-alpha or -gamma would interfere with B cell differentiation either in patients with IgM gammopathy of undetermined significance (IgM-MGUS) or Waldenström's macroglobulinemia (WM). A 65% inhibition of in vitro B cell differentiation was noted in 8 of 10 patients in the presence of either interferon-alpha or -gamma. Cells from 4 patients (3 IgM-MGUS and 1 WM) were susceptible to both types of interferon while B cell differentiation from 4 patients (3 IgM-MGUS and 1 WM) was inhibited only by one type of interferon. During in vitro culture, IL6 synthesis was unaffected by the presence of interferon alpha or gamma in the 8 cases studied. Likewise, no modulation of the constitutive B cell IL6-R expression from 6 patients studied (4 WM and 2 IgM-MGUS) was observed. These data indicate that interferons did not modify the differentiation of B cells in macroglobulinemia via modulation of the IL6-IL6-R pathway. This is in contrast with the mode of action of interferons in other lymphoid malignancies such as multiple myeloma or chronic lymphocytic leukemia where they directly modulate IL6-production and/or IL6-R expression.

Antineoplastic Agents↗
PubMed1996

Comparison of clinical and laboratory parameters for systemic lupus erythematosus activity in Israelis versus Europeans.

The clinical activity of systemic lupus erythematosus (SLE) may be influenced by ethnic and environmental factors. The Consensus group on Activity Criteria for SLE attempted in a multicenter study to determine well-accepted criteria for disease activity. Of the 704 randomly assigned patients, 41 (5.8%) were from Israel. A detailed history including epidemiological, clinical and laboratory data was recorded. Significant differences were found between Israeli and European patients in the occurrence of Raynaud's phenomenon [12 (30%) vs. 358 (51%), respectively (P < 0.05)] and skin vasculitis [6 (15%) vs. 216 (34%), respectively (P < 0.05)]. In addition to those clinical differences, significant differences were also found in the occurrence of VDRL, low complement levels and lupus anticoagulant. Additional differences were found in some laboratory data, indicating differences in the sensitivity of the various laboratories. We conclude that the differences between the Israeli and European groups in the clinical data can be attributed mainly to environmental factors (weather, viruses), and in the laboratory data to ethnic differences (e.g., HLA) and to the different diagnostic methods used.

Adult↗
PubMed1996

Low dose aspirin in patients with ischemic heart disease may precipitate secondary myocardial infarction.

We conducted a retrospective case-control study to compare the frequency of myocardial infarction (MI) or unstable angina (UA) precipitated by aspirin-induced upper gastrointestinal (GI) bleeding among patients with and without ischemic heart disease(IHD), and to determine whether the risk of MI or UA is related to the hemoglobin level on admission. Of the 51 patients admitted to the hospital between 1987 and 1994 because of aspirin-induced upper GI bleeding, 33 had ischemic heart disease. The prevalence of MI and UA inpatients with IHD and aspirin-induced upper GI bleeding was significantly higher than in patients without IHD (42% vs. 5.5% respectively) (P < 0.005). Of the patients with upper GI bleeding and a hemoglobin concentration of 5-8 g/dl, 75% had either MI or UA in comparison to 50% and 18% of the patients with hemoglobin concentrations of 8-10 and 10-14 g/dl respectively. We conclude that low dose aspirin therapy may precipitate MI or UA, especially in patients with IHD, by inducing upper GI bleeding. Patients with IHD who use low dose aspirin to prevent MI should be instructed how to identify emerging symptoms of peptic ulcer as well as the initial signs of upper GI bleeding. Early diagnosis and treatment of these patients might prevent the induction of secondary MI or UA.

Aged↗
PubMed1996

Effect of dietary supplementation of beta-carotene on human monocyte-macrophage-mediated oxidation of low density lipoprotein.

Oxidative modification of low density lipoprotein (LDL), a key step in early atherosclerosis, is protected by the lipoprotein-associated antioxidants. The present study analyzes the effect of beta-carotene in plasma, in LDL and in monocyte-macrophages, on macrophage-mediated oxidation of LDL. We investigated the effect of dietary supplementation of beta-carotene on plasma lipid peroxidation [induced by AAPH (2,2-Azobis-2-amidinopropane hydrochloride)] and on cell-free and cell-mediated oxidation of LDL by human monocyte-derived macrophages (HMDM) in the presence of CuSO4. Significant enrichment with beta-carotene was noted in plasma (twofold), in LDL (2.6-fold) and in HMDM (1.6-fold) 2 weeks after dietary supplementation with 180 mg/day of beta-carotene. Plasma lipid peroxidation analyzed by conjugated dienes generation decreased by 22% (P < 0.01) and LDL susceptibility to oxidation analyzed by malondialdehyde generation decreased by 40% (P < 0.01). After beta-carotene supplementation, beta-carotene-enrichment of HMDM capacity to oxidize native LDL, whereas beta-carotene enrichment of LDL significantly reduced LDL oxidation. In conclusion, then, our results suggest that beta-carotene content of LDL, but not that of the macrophages, is responsible for the inhibition of oxidation of LDL.

Administration, Oral↗
PubMed1996

Penetration of clindamycin and metronidazole into inflamed appendiceal tissue.

OBJECTIVE: To calculate the penetration of clindamycin and metronidazole into inflamed appendiceal tissue. DESIGN: Prospective study. SETTING: Teaching hospital, Israel. SUBJECTS: 20 Consecutive men and women operated on for acute appendicitis. INTERVENTIONS: Appendicectomy. Each patient was given three intravenous injections of gentamicin 80 mg combined with either clindamycin 600 mg or metronidazole 500 mg immediately before operation over a period of 15 minutes. MAIN OUTCOME MEASURES: Serum and tissue concentrations of the antibiotics. RESULTS: There was no significant difference between the mean serum concentrations of the drugs (clindamycin 17.86 micrograms/ml and metronidazole 9.75 micrograms/ml) but the mean tissue concentrations of clindamycin (10.41 micrograms/g in the base and 9.86 micrograms/g in the tip of the appendix) were significantly higher than those of metronidazole (5.65 micrograms/g in the base and 5.89 micrograms/g in the tip; p = 0.02 and p = 0.05, respectively). Tissue concentrations of clindamycin and serum concentration of both drugs were more than twice their MIC90. The tissue concentrations of metronidazole were close to its MIC90. CONCLUSIONS: Clinical trials are necessary before any conclusion about therapeutic superiority of one or other agent can be drawn.

Adult↗
PubMed1996

Do some antiphospholipid antibodies target endothelial cells?

Anti-endothelial cell activity is partly due to antiphospholipid antibodies (aPLA) because: a) the two types of antibodies are present in patients with connective tissue diseases and cardiolipin-binding monoclonal antibodies recognize endothelial cells (EC); b) anionic phospholipids are detectable on the outer face of the EC membrane lipid bilayer and an anti-beta 2-glycoprotein I (beta 2-GPI) monoclonal antibody binds to EC; c) the binding of aPLA to EC and the functional affinity of this binding are dependent on the presence of beta 2-GPI; d) anti-EC antibodies trigger the expression of anionic phospholipids on the outer leaflet of the EC membrane.

Antibodies, Antiphospholipid↗
PubMed1996

Membranous nephropathy in primary antiphospholipid syndrome: description of a case and induction of renal injury in SCID mice.

Primary antiphospholipid syndrome (PAPS) is a recently recognized clinical entity encompassing the combination of thromboembolic phenomena, thrombocytopenia and recurrent abortions in the presence of antiphospholipid antibodies. We present a patient with PAPS accompanied by renal involvement, manifested as membranous nephropathy, as proven by a renal biopsy. To investigate further the possible association between PAPS and the renal lesions we attempted to induce similar renal manifestations by transferring peripheral blood lymphocytes (PBL) from this patient to severe combined immunodeficiency (SCID) mice. The mice transfused with PBL from the affected patient exemplified antiphospholipid antibodies (aPL) following which a renal lesion consistent with the human membranous nephropathy lesion was precipitated. This study substantiates the role of aPL as possible inducers of renal damage.

Adult↗
PubMed1996

[Neuronal apoptosis in the course of human immunodeficiency virus infection].

Apart from the unique changes characteristic of "HIV encephalitis", the productive infection of central nervous system by HIV, which involves predominantly the white matter and basal ganglia, evidence is accumulating that the cerebral cortex may also be affected in AIDS patients. Neuronal loss, suspected at microscopical examination, has been demonstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In an attempt to look for an apoptotic process at the origin of neuronal loss in AIDS, we examined samples of frontal cortex, temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 HIV-positive asymptomatic cases using in situ end labelling to demonstrate characteristic DNA fragmentation. These were compared with 5 seronegative asymptomatic controls, and 2 seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in all the AIDS cases and in the Alzheimer's cases. Positive in situ end labelling was usually associated with morphological changes suggestive of neuronal apoptosis. Semiquantitative appreciation of the density of apoptotic neurons showed that neuronal apoptosis was more severe in atrophic brains. In contrast, no correlation was found between the density of apoptotic neurons and the presence of HIV encephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV-positive case. Apoptosis was never observed in asymptomatic seronegative cases. Experimental studies tend to support our in vivo findings. Infection by HIV of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was identified in non infected control cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Conjunctival oculosporidiosis in east Africa caused by Rhinosporidium seeberi.

BACKGROUND AND OBJECTIVE: Conjunctival rhinosporidiosis is an infectious disease rarely recorded outside the Indian subcontinent. The disease is caused by Rhinosporidium seeberi, an endosporulating microorganism of uncertain taxonomic classification. We report a series of cases manifesting this infection. MATERIAL AND METHODS: The demographic, clinical, and histopathologic data of 14 cases of conjunctival rhinosporidiosis on record at our Ophthalmic Pathology Laboratory were reviewed. RESULTS: All cases were from East Africa; 10 were from Malawi and 4 from Kenya. Ten specimens were from males and three from females. Their age ranged from 7 to 20 years. All patients were treated by surgical excision, and no recurrence was recorded. None of the cases was diagnosed clinically as rhinosporidiosis. Histologically, all stages of the organism's life cycle could be found in the excised tissue, from small trophocytes to large sporangia-containing sporoblasts. There were changes in histochemical stainings with growth and maturation. In general, the inflammation was of chronic nongranulomatous type. CONCLUSIONS: Conjunctival rhinosporidiosis is a rare infectious disease that typically appears in young males in rural regions, and that can be treated by surgical excision. It typically causes chronic nongranulomatous inflammation. Various stages of the R seeberi life cycle can be seen in the affected tissue.

Adolescent↗
PubMed1995

Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.

Adult↗
PubMed1995

Granulocyte growth factors: achieving a consensus.

A consensus meeting held under the auspices of the European School of Oncology concluded that the use of granulocyte growth factors is definitely indicated, or acceptable given existing evidence, in the following circumstances: to alleviate congenital neutropenia; in the mobilisation of peripheral blood progenitor cells for autotransfusion; to encourage engraftment following bone marrow transplantation and in cases of failed engraftment; to support continuation of ganciclovir anti-CMV therapy in certain patients with AIDS, where the switch to foscarnet is contraindicated or where toxicity to foscarnet develops. It was also agreed that there is an overwhelming need for carefully controlled clinical trials in a wide range of indications in which growth factor use may improve outcome. In the majority of tumours, the possible benefit of dose optimisation and intensification, and therefore the role of growth factors in support of such measures has still to be defined. Extramedullary toxicities may in these instances become dose limiting.

AIDS-Related Opportunistic Infections↗
PubMed1995

Neuronal apoptosis in HIV infection in adults.

Productive infection of the central nervous system by HIV predominantly involves the white matter and basal ganglia. Involvement of the cerebral cortex with neuronal loss is also described in AIDS patients but not in asymptomatic HIV-positive patients. The mechanism of neuronal damage is unknown. To enquire whether neuronal loss in AIDS may be due to an apoptotic process, we examined the cerebral cortex from 12 patients who died from AIDS using two different methods: in situ end labelling and gel electrophoresis of DNA to demonstrate DNA fragmentation. None of the patients had cerebral opportunistic infection or tumour. Four patients had no significant neuropathological changes, eight patients had variable cerebral atrophy and four of them also had productive HIV infection of the brain. These patients were compared with four HIV-positive asymptomatic patients, five seronegative asymptomatic controls, and two seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in the cortex in all AIDS patients, as well as in the Alzheimer's patients. Apoptosis was not observed in the asymptomatic cases whether seropositive or seronegative. Neuronal apoptosis was more severe in atrophic brains, and did not directly correlate with productive HIV infection, suggesting an indirect mechanism of neuronal damage is most likely.

Adult↗
PubMed1995

Autoimmune aspects of primary pulmonary hypertension.

Although primary pulmonary hypertension (PPH) is considered to be an idiopathic condition, it has been postulated that autoimmunity may play a role in the pathogenesis of the disease. This argument has been based on frequent coexisting clinical and serological rheumatic findings. Moreover, approximately in a third of the patients with PPH, and antinuclear factor can be detected. Pulmonary hypertension may appear as a secondary complication to various autoimmune conditions. In light of these findings we examined sera derived from 40 patients diagnosed as having PPH for the presence of 18 different autoantibodies by the ELISA and immunofluorescent techniques. Of the 40 patients, 62.4% had circulating autoantibodies and 47.5% presented with multiantibody responses. Autoantibodies most commonly observed were antinuclear (42.5%), anti-ssDNA (25%) and antithyroglobulin (30%) antibodies. These results may imply that in a subgroup of patients with PPH the disease may be ascribed to an immune dysregulation or alternatively that autoantibodies accompany the disease progression as an epiphenomenon.

Antibodies, Antinuclear↗
PubMed1995

The occurrence of thromboembolic events following airplane flights--'the economy class syndrome'.

The occurrence of thromboembolic phenomena following long-distant airplane flights is well characterized in the literature. However, it seems that despite being repeatedly described, the recognition of its implications by the medical services at the airports is still insufficient. We describe two cases: the first presented with a clinical picture consistent with the diagnosis of pulmonary embolus validated by a lung perfusion-ventilation scan, and the second, with deep vein thrombosis in his left femoral vein. Both patients were diagnosed several days after a prolonged airway flight. The purpose of this article is to draw attention to the thromboembolic phenomena known to be associated with airplane flights, provide possible mechanisms to account for their envolvement, and emphasize the measures that should be taken to prevent their occurrence.

Aged↗
PubMed1994

Modulation of spontaneous B-cell differentiation in macroglobulinemia by retinoic acid.

We previously showed that clonal blood B cells from patients with macroglobulinemia spontaneously differentiate in vitro to plasma cells. This process is dependent on an interleukin (IL)-6 autocrine pathway. We investigate here whether all-trans-retinoic acid (RA) interferes with B-cell differentiation either in patients with IgM gammapathy of undetermined significance (MGUS) or Waldenström's macroglobulinemia (WM). RA at a concentration of 10(-5) to 10(-8) mol/L inhibited by 50% to 80% the in vitro differentiation of purified B cells from four of five patients with MGUS and from one of five patients with WM as assessed by the IgM content of day 7 culture supernatants. We next determined whether this effect could be related to an inhibition of IL-6 secretion by cultured B cells and/or a downregulation of the IL-6 receptor (IL-6R), which was constitutively expressed on patients' blood B cells. A 50% to 100% (mean, 80%) inhibition of IL-6 production was found in seven of 10 patients (five with MGUS and two with WM). The IL-6R was no more detectable on cells from patients with MGUS after 2 days of treatment with RA and slightly downregulated in patients with WM. It was of interest that B cells susceptible to the action of RA belonged mostly to patients with IgM MGUS, which reinforces our previous data showing distinct requirements for IL-6-dependent differentiation of blood B cells from patients with VM or IgM MGUS.

B-Lymphocytes↗