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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 451 records · Page 25Linked to original sources
PubMed1987

Association of three chicken proteins with the 34 kD target of Rous sarcoma virus tyrosine kinase.

Transformation of chicken embryo fibroblasts by avian retroviruses induces the tyrosine phosphorylation of a 34-39 kD cellular protein (p34). In vitro, p34 isolated from intestine interacts with F-actin in a Ca2+-dependent manner. We report here that, in the absence of Ca2+ chelators, three proteins co-purified with p34 extracted from a cytosolic or membrane fraction of chicken embryo fibroblasts; these two fractions account respectively for 10-20% and 50% of the total cellular p34. Isolated from the cytosoluble fraction of fibroblasts by sucrose gradient centrifugation and hydrophobic chromatography, p34 and the other proteins behaved as a homogeneous species upon non-denaturing gel electrophoresis, gel filtration, and CsCl density gradient centrifugation, thus indicating a strong association. Moreover, an analysis by electron microscopy following uranyl acetate staining revealed particles with a raspberry-like shape. This association was always disrupted by the calcium-chelating agent, EGTA.

Animals↗
PubMed1987

Construction of a yeast strain devoid of mitochondrial introns and its use to screen nuclear genes involved in mitochondrial splicing.

We have constructed a respiring yeast strain devoid of mitochondrial introns to screen nuclear pet- mutants for those that play a direct role in mitochondrial intron excision. Intron-less mitochondria are introduced by cytoduction into pet- strains that have been made rho0; cytoductants therefrom recover respiratory competency if the original pet- mutation is required only for mitochondrial splicing. By this means, we have identified 11 complementation groups of such genes. Their total number may be estimated as about 18.

Cell Nucleus↗
PubMed1987

Pharmacokinetics and renal elimination of desferrioxamine and ferrioxamine in healthy subjects and patients with haemochromatosis.

1 Desferrioxamine mesylate (DM) (10 mg kg-1 = 15.24 mumol kg-1) was given by intramuscular injection to five healthy subjects and to six patients with haemochromatosis, after informed consent. 2 Desferrioxamine (DFA), ferrioxamine (FeA), aluminoxamine (AlA), aluminium (Al) and iron (Fe) were measured in plasma, before and 10, 20, 30, 60 min and 2, 4, 6, 8, 12 h after DM injection and in urine collected over a 6 h period the day before and the day of administration. 3 The predominant form in plasma from control subjects was DFA whereas FeA predominated in plasma from patients. In controls, rapid and slow phases of decline in plasma DFA concentrations were found, with half-lives of 1.0 h and 6.1 h, respectively. In the patients, only a single phase of decline was observed, with a half-life of 5.6 h. Total clearances of DFA were 296 ml h-1 kg-1 in controls and 239 ml h-1 kg-1 in patients. 4 The amount of FeA eliminated in urine during 6 h was significantly lower in controls (8.0 +/- 4.6 mumol) than in patients (129.2 +/- 40.0 mumol), with respective renal clearances estimated over 6 h of 516 ml h-1 kg-1 and 1,716 ml h-1 kg-1. DFA elimination was similar in both groups and its renal clearance estimated over 6 h was 91 ml h-1 kg-1 in controls and 85 ml h-1 kg-1 in patients. 5 Since there was no overlap in the 1 h DFA/FeA plasma ratio between controls and patients, this might be useful as an index of iron overload.

Adult↗
PubMed1987

The fate of intravenously administered hepatic ferritin in normal, phenylhydrazine-treated and scorbutic guinea-pigs.

When highly purified hepatic 59Fe-ferritin was injected intravenously into normal guinea-pigs more than half of it was taken up by red cell precursors and the iron was used for haem formation. This was studied in more detail in animals in which a reticulocytosis had been induced either by phenylhydrazine or by repeated venescetions. 55% of the injected ferritin iron was found in reticulocytes at 1 h. Experiments using ferritin doubly labelled with 59Fe and 125I indicated that the whole molecule was taken up, with two-thirds of the radioactivity being associated with the membrane at 1 h and one third being already within the cell. There was a progressive loss of 125I activity over the ensuing hours, while most of the 59Fe was slowly internalized and incorporated into haem between 1 and 24 h. In contrast, 90% of the activity taken up by red cell precursors from 59Fe-transferrin was present as haem at all times. The liver and spleen were the two other major sites of 59Fe-ferritin uptake in phenylhydrazine treated animals. While there was an early uptake of 59Fe into haem in these organs, some redistribution occurred with time, since most of the 59Fe was in a non-haem fraction by 24 h. In a final experiment the distribution and fate of 59Fe-ferritin was studied in scorbutic animals treated with phenylhydrazine. The findings were similar to those in normals similarly treated, which suggests that ferritin iron was being effectively mobilized for haem formation despite the ascorbic acid depletion.

Animals↗
PubMed1987

Chronic and subacute myelomonocytic leukaemia in the adult: a report of 60 cases with special reference to prognostic factors.

We report 60 cases of chronic and subacute myelomonocytic leukaemias (CMML and SMML) in the adult, using the FAB group criteria. The M/F sex ratio was 3.3 and the mean age 67.5 years. Splenomegaly was found in 32% of cases, hyperleucocytosis in 52% of cases and mean blood monocytosis was 4.3 X 10(9)/l. Marrow smears showed an excess of blasts in 57% of patients, a moderate increase in monocytes in most cases and frequent myelodysplastic features. An increase in serum lysozyme and polyclonal hypergammaglobulinaemia were usual and clonal cytogenetic anomalies found in about half of the patients tested. Treatment was usually palliative and the median survival was 28 months, a blastic transformation being responsible for a third of the deaths. Prognostic factors at diagnosis were analysed retrospectively in the 46 patients who had sufficient follow up. Percentage of marrow blasts haemoglobin level and blood monocytosis at diagnosis, were subject to multivariate analysis, resulting in a discriminant 'score'. This allowed assignment of each patient into one of two prognostic subgroups (10.9% probability of error): a poor prognosis one, with a life expectancy of less than 1 year and a high risk of acute transformation (subgroup termed SMML) and a better prognosis subgroup (termed CMML), with some CMML patients surviving over 5 years.

Adult↗
PubMed1987

The treatment of adult idiopathic thrombocytopenic purpura. Infusion of vinblastine in ITP.

16 adult idiopathic thrombocytopenic purpura (ITP) patients, with mean age 51 years, were treated by 5 weekly slow intravenous infusions of vinblastine (0.1 mg/kg). When a complete or partial response (CR or PR) was obtained, slow infusions were repeated at 2-weekly then monthly intervals, as maintenance therapy. In 4 cases with ITP of recent onset, but presenting contraindication or failure to prednisone and high dose intravenous immunoglobulins, CR was obtained in all patients after 4 to 15 days (mean 9.5). Only one of these patients relapsed. In 12 cases of refractory chronic ITP (of whom 10 had been splenectomized), there were 2 CR, 6 PR and 4 failures. The 8 responding patients had a mean interval to response of 20 days. The 6 PR were short and did not exceed 15 days. Our results do not support a superiority of this treatment compared to other modes of administration of vinca alkaloids in ITP (intravenous bolus, vinca loaded platelets).

Adult↗
PubMed1987

Expression of OKM5 antigen on human keratinocytes in positive intracutaneous tests for delayed-type hypersensitivity.

Antigenic characteristics of human keratinocytes (HK) were studied in positive intracutaneous tests for delayed-type hypersensitivity in vivo using murine monoclonal antibodies against human OKM5, OKM1, OKT6, Leu-7 and HLA-DR antigens and compared with those of negative skin reactions. By contrast to negative intracutaneous tests, keratinocytes displayed both OKM5 and HLA-DR antigens in all positive skin reactions above the dermal inflammatory infiltrate. OKM5 recognizes an 88-kilodalton cell surface determinant of monocytes, which could also be induced in vitro in keratinocytes upon incubation with gamma-interferon. We demonstrate here for the first time that the expression of this macrophage marker can also be induced in vivo in the HK.

Animals↗
PubMed1987

[Anomalies of cellular immunity in Graves' disease treated by synthetic antithyroid drugs: effects on prognosis].

The involvement of humoral immunity mechanism in etiology of Graves' disease was observed for the first time in 1956. Twenty years later cellular auto-immune dysfunction was also described. To day, there is evidence for suppressor T cell deficiency and decrease in T suppressor lymphocytes in Graves' disease and cell mediated immunity might be one of the most important point in the pathogenesis of Graves disease. For the future, cellular auto-immune dysfunction might be used to predict the evolution of the disease and to choice the best therapeutic scheme.

Antithyroid Agents↗
PubMed1987

A study of 609 HLA haplotypes marking for the hemochromatosis gene: (1) mapping of the gene near the HLA-A locus and characters required to define a heterozygous population and (2) hypothesis concerning the underlying cause of hemochromatosis-HLA association.

We compared 609 haplotypes carrying the idiopathic hemochromatosis allele with 475 control haplotypes. Four haplotypes were more frequent in hemochromatosis: A3, B7 (actually A3, CW., B7, Bfs, DR2); A3, B14 (actually A3, CW., B14, BfF, DRW6); A11, B35; and A11, B5. The linkage disequilibrium for A3, B7 and A3, B14 (and probably also for A11, B5) was undeniably stronger in hemochromatosis than in controls. Two haplotypes--A3, B12 and A3, B15--were more frequent in hemochromatosis, without linkage disequilibrium. Four haplotypes in linkage disequilibrium in hemochromatosis--i.e., A2, B12; A1, B8; A9, B7; and A29, B12--were also found to have the same frequency and strength of linkage in controls. The dual observation (1) that haplotypes carrying A3 without either B7 or B14 were highly significantly more frequent in hemochromatosis than in controls and (2) that haplotypes carrying B7 or B14 but not A3 had the same frequency in hemochromatosis and controls led to the formal conclusion that only A3 is an independent marker for the hemochromatosis allele, B7 and B14 being involved only owing to the haplotypic mode of marking; the hemochromatosis allele can thus be mapped closer to locus A than to locus B. Our findings fit well with the hypothesis that the hemochromatosis mutation was a rare if not unique event that produced an ancestral HLA marking that was subsequently modified by recombinations and geographical scattering due to migrations.

Alleles↗
PubMed1986

[HLA pattern in patients with lichenoid drug exanthem].

27 patients suffering from lichenoid drug eruption have been studied with special reference to histocompatibility standardisation. In comparison with a control group (n = 54), our patients revealed high and statistically significant levels of HLA-A1, HLA-B8, and HLA-DR3 (p less than 0.05). These results are discussed with particular regard to HLA patterns previously obtained in lichen planus.

Drug Eruptions↗
PubMed1986

[Evaluation of micro- and macrophage function in splenectomized patients--possible dermatologic consequences].

Various micro- and macrophage functions were studied in vitro in 15 patients having previously undergone posttraumatic splenectomy as well as in 100 healthy persons. We found reduced capacity of intracellular inactivation of microorganisms by microphages (7/15) and slight impairment of chemotactic activity in both systems (8/15; 9/13). Possible dermatological consequences are discussed.

Adult↗