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Biomedical subjects

Y Levy

Publications and source records attributed to Y Levy.

At least 253 records · Page 14Linked to original sources
PubMed1991

High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

IL6 and lymphoproliferative disorders.

Interleukin 6 has pleiotropic effects on cells from various lineages. Several data indicate that it may play a critical role in the development of multiple myeloma by an autocrine or parcrine stimulation pathway. For instance, we showed that oligodeoxynucleotides antisens of IL6 mRNA were capable to decrease the proliferation of two different myeloma cell lines. In Waldenström's macroglobulinemia, at the initial stage of the disease, there is an autocrine differentiation pathway which is dependent of the secretion of IL6 by tumor cells. IL6 may also be implicated in the pathogenesis of some other lymphoid malignancies such as follicular lymphomas or large cell lymphomas. Its role in the systemic symptoms of Castleman disease has been clearly established.

Castleman Disease↗
PubMed1991

The pupillary effects of retrobulbar injection of botulinum toxin A (oculinum) in albino rats.

Botulinum toxin (BoTx) has been clinically used in the treatment of localized dystonic states such as blepharospasm, as well as in strabismus. Reported side effects have included primary excessive weakness of neighboring extraocular muscles. To evaluate possible involvement of the iris, we injected BoTx into the retrobular space of albino rats. Ipsilateral mydriasis with cholinomimetic supersensitivity developed in the treated animals. There was no apparent optic nerve dysfunction. The authors observed these effects using BoTx doses insufficient to cause clinical weakness or electrophysiological evidence of generalized neuromuscular dysfunction. The mydriasis disappeared spontaneously within 2-3 weeks. Higher BoTx doses resulted in severe neuromuscular paralysis and death. These findings were consistent with clinical botulism, which may include autonomic paralysis. The site of BoTx action could be the ciliary ganglion or cholinergic terminals in the iris. The authors concluded that side effects of BoTx were not necessarily limited to striated muscle weakness.

Animals↗
PubMed1991

Phenotype and immunoglobulin gene configuration of blood B cells from patients with multiple myeloma.

We have studied the phenotype and the immunoglobulin gene configuration of blood B cells from 15 patients with stage III multiple myeloma (MM) at diagnosis. Highly purified B cells (greater than 90% CD20 positive cells) were obtained after L-leucine methyl ester monocyte depletion and elimination of T cells by rosetting. The percentage of B cells with surface immunoglobulin (sIg) featuring the same light and heavy chain isotype as the serum monoclonal immunoglobulin was very low, except in one patient, in whom 25-30% of B cells displayed surface and cytoplasmic immunoglobulin (cIg) sharing idiotypic determinants with the serum monoclonal IgG kappa. In all cases but one the percentage of circulating plasma cells accounted for less than 2% of the enriched B cell preparations. In one patient purified B cell population contained 30% of plasma cells and the immunoglobulin gene study revealed a rearranged JH hybridizing fragment identical in bone marrow and blood B cell DNA samples. In the other 14 cases no rearranged fragment was detected although we used a technique allowing the detection of at least 2% clonal cells. The absence of clonal cells in the patient whose B cells contained a high percentage of cells featuring surface IgG molecules was confirmed on purified sIgG-positive cells. In addition CD20-positive cells from this patient did not contain gamma mRNA. Therefore the IgG molecules were clearly extrinsic. Although the existence of clonal B lymphocytes or of myeloma idiotype related B cells cannot be ruled out, they escape detection by sensitive genetic studies of immunoglobulin genes.

B-Lymphocytes↗
PubMed1991

Effect of urine and urine components on the chemiluminescent response of bacteria-stimulated polymorphonuclear leukocytes.

The role of polymorphonuclear leukocytes (PMN) found in urine during infectious episodes is still unknown. Opsonophagocytosis of Escherichia coli by normal blood PMN in the presence of urine was measured using a chemiluminescence (CL) assay. PMN were challenged by a type I fimbriated E. coli strain shown to elicit a CL response through attachment to the mannose-containing receptors on the leukocytes. In the presence of urine the CL response decreased significantly. Urine osmolality due to inorganic salts partially caused this decrease. A higher inhibitory effect was elicited by urea. Under otherwise similar conditions, the presence of an additional CL-inhibiting factor, most probably a protein, was detected in urine; however, its identity has not yet been defined. In vitro and in vivo urine dilution improved PMN function. No difference in effect on CL response was found between urine obtained from 25 children with recurrent urinary tract infections and urine from 15 age-matched controls.

Adolescent↗
PubMed1990

Differential effects of low and high concentrations of interleukin 6 on human B cells.

In this report we have studied the functional effects of a wide range of interleukin 6 concentrations on human B cells. B cells purified from tonsils and from five of six spleens proliferated directly in a dose-dependent manner in the presence of low concentrations (1-100 pg/ml) of IL 6 whereas B cells from the sixth spleen proliferated only after in vitro anti-mu antibodies activation. Only large B cells (presumably in vivo activated B cells) were responsive to IL 6. High concentrations of IL 6 (1-10 ng/ml) did not trigger B cell proliferation but were able to up-regulate the expression of the B5 activation antigen on B cells, whereas the expression of two other B cell antigens (CD20 and CD23) was unchanged. At all concentrations of IL 6 tested (0.01-10 ng/ml) no B cell differentiation occurred after 7 days culture. Depletion before culture of B5+ cells from the B cell-enriched spleen cell preparation abolished both the proliferative effect and up-regulation of B5 antigen induced by IL 6, indicating that this lymphokine acted primarily on activated B cells. This differential effect of "low" and "high" concentrations of IL 6 on activated B cells may solve controversy on the role of IL 6 as an early or late agent in B cell maturation.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1990

Intralipid infusion in patients with familial hypercholesterolemia. Effect of serum and plasma lipoproteins on platelet aggregation and on macrophage cholesterol metabolism.

Intralipid infusion into normal volunteers was recently shown to possess anti-atherogenic properties. We studied the effect of intralipid infusion in patients with severe Familial Hypercholesterolemia (FH) refractory to conventional therapy. FH patients and normal subjects, who served as controls, were given an intravenous infusion of intralipid for 6 h. Serum samples taken from both groups before, during and after intralipid infusion were studied for their ability to inhibit cellular cholesterol accumulation by macrophages. A significantly lower rate of cellular cholesterol esterification (of 46%, P less than 0.005 and 44%, P less than 0.005 in patients and normals, respectively) was demonstrated in macrophages incubated with serum obtained during intralipid infusion compared to those incubated with preinfusion serum. The maximal effect was demonstrated with serum samples taken at the end of the infusion, but the inhibitory effect persisted even at 24 h post-infusion. It was found that chylomicron like particles could induce the above-mentioned effects on macrophage cholesterol esterification. A significant decrement of 50% (P less than 0.005) in aggregation of platelets isolated from plasma samples taken during and after intralipid infusion from both groups was demonstrated, when compared to platelets isolated in the preinfusion state. This effect persisted 18 h subsequent to infusion. We conclude that intralipid infusion abolishes serum ability to stimulate cholesterol esterification in cultured macrophages, and exhibits inhibitory effects upon platelet aggregation. If similar events occur in the arterial wall, intralipid might inhibit foam cell formation.

Adolescent↗
PubMed1990

Interleukin 6 dependence of spontaneous in vitro differentiation of B cells from patients with IgM gammapathy.

Blood B cells from eight patients with clonal lymphoid disorders characterized by monoclonal IgM secretion (four with malignant plasmacytic proliferation typical of Waldenström macroglobulinemia and four without overt lymphoid neoplasia) were found to spontaneously differentiate in vitro into plasma cells. In all instances, monoclonal plasma cells (8-45% of the cells) were generated from extensively purified B cells or T-cell-depleted peripheral blood mononuclear cells after a 7-day culture period, with a corresponding high rate of IgM secretion into the culture medium. This differentiation occurred in the absence of any cell proliferation process as measured by [3H]thymidine uptake at day 2 or 4. Normal B cells did not differentiate under the same experimental conditions. Detection of interleukin 6 (IL-6) bioactivity in all patients' B-cell culture supernatants as well as of IL-6 mRNA in freshly prepared, uncultured B cells in the two cases studied by in situ hybridization suggested that IL-6 secretion by B cells may play a role in this process. Moreover, in the four patients without overt lymphoid proliferation, B-cell differentiation was significantly inhibited (60-80%) in the presence of anti-IL-6 antibodies. In contrast, anti-IL-6 antibodies did not preclude the differentiation into plasma cells of B cells from the four patients with bona fide Waldenström macroglobulinemia. These results suggest a two-step pathogenesis for such human lymphoplasmacytic clonal proliferations, the initial stage being characterized by an IL-6-dependent autocrine differentiation pathway.

Antibodies, Monoclonal↗
PubMed1990

Riboflavin deficiency and the function and fluidity of rat erythrocyte membranes.

The effect of riboflavin deficiency on the fluidity and function of the red blood cell (RBC) membrane and on the activity of some enzymes involved in antioxidant defense mechanisms was studied. Growing male rats were fed an experimental (riboflavin-deficient) or a control (riboflavin-supplemented) diet. Following 7 wk of feeding, RBC from riboflavin-deficient rats contained higher levels of peroxidation products, most likely due to decreased glutathione reductase activity. An elevation in glutathione peroxidase activity was also observed whereas the activity of catalase and superoxide dismutase was not affected. Membrane fluidity was studied by fluorescence polarization, using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. The fluidity of RBC membranes isolated from riboflavin-deficient rats was significantly lower than that of the controls. This decreased fluidity was accompanied by an increase in the activity of the membrane-bound enzyme acetylcholinesterase. This study demonstrated that a decrease in cells' ability to cope with peroxidative damage as a result of riboflavin deficiency may lead to changes in the fluidity and function of membranes.

Acetylcholinesterase↗
PubMed1990

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↗
PubMed1990

Chlamydia trachomatis and inflammatory bowel disease--a coincidence?

Serological tests of 35 patients suffering from inflammatory bowel disease were compared to those of 35 healthy controls. The tests were performed using the indirect immunoperoxidase assay. Ninety-three per cent of 15 patients with Crohn's disease had IgG antibodies against Chlamydia, compared to 26% in the control group. In the 20 patients with ulcerative colitis, 45% had IgG antibodies against Chlamydia, compared to 10% in the control group. High serum titres of IgG antibodies were found in most of the patients with inflammatory bowel disease, mainly with Crohn's disease, while weak reactions appeared in most of the controls in which antibodies were detected. These results suggest a high incidence of Chlamydia infection in the studied patients with inflammatory bowel disease, especially in those with Crohn's disease. The possible association between Chlamydia trachomatis and inflammatory bowel disease is discussed.

Antibodies, Bacterial↗
PubMed1990

Neurosarcoidosis: signs, course and treatment in 35 confirmed cases.

Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted.

Adolescent↗
PubMed1989

[Massive pericardial effusion following minoxidil].

Minoxidil is a potent antihypertensive which is reserved for severe cases. A 58-year-old man admitted for evaluation of progressive dyspnea and peripheral edema had been taking Minoxidil, Normiten and Lasix for severe hypertension. Echocardiography disclosed a massive pericardial effusion but there were no signs of tamponade. Discontinuation of Minoxidil resulted in complete clearance of the pericardial fluid within 3 months. Awareness of this potentially fatal side-effect of Minoxidil is mandatory.

Echocardiography↗
PubMed1989

Recurrent ascites in an infant with perinatally acquired cytomegalovirus infection.

We describe an infant with symptomatic perinatally-acquired cytomegalovirus (CMV) infection manifested by fever, anaemia, thrombocytopenia and hepatosplenomegaly. This infant developed recurrent episodes of severe ascites during which the virus was isolated from his urine. This rare hepatic manifestation of neonatal CMV infection has, to the best of our knowledge, only been reported twice in aborted fetuses with intrauterine systemic CMV infection.

Ascites↗