Biomedical subjects
Publications and source records attributed to M Simon.
Ninety two patients suffering from porphyria cutanea tarda were examined ophthalmologically in a paired case-control study. The incidence of pinguecula and that of pterygium were 8 times and 2 times higher, respectively, in PCT patients that in the control group. The photodamage of the conjunctiva is presumed to be a result of the photoactivity of uroporphyrin in the tissues.
The Saccharomyces cerevisiae ADR1 gene has recently been demonstrated to control transcription of several genes encoding peroxisomal proteins or proteins necessary for peroxisome formation. Therefore, the effect of two other genes (SNF1 (CAT1, CCR1) and SNF4 (CAT3)) known to control derepression of glucose-repressible genes was studied. Levels of transcripts of genes encoding catalase A, fatty acid beta-oxidation enzymes and of the PAS1 gene are reduced in snf1 and snf4 mutants on ethanol as well as on oleic acid medium. By immunogold labelling with an antibody directed against peroxisomal thiolase, clusters of peroxisomes were detected in wild-type cells, whereas smaller single peroxisomes were observed in adr1 mutant cells. Results of immunofluorescence experiments are consistent with these observations. No peroxisomes were detected in snf1 and snf4 mutants by immunogold labelling as well as by immunofluorescence.
1. Binding sites for 125I-labeled endothelin (ET) isopeptides ET-1, ET-2 and ET-3 were visualized by autoradiography in the kidneys of man, baboon, rhesus monkey, tree shrew, pig and rat. 2. Highest levels of binding for the three isoforms were observed in the glomeruli, cortical and medullary vessels of baboon, rhesus monkey, pig and rat, whereas there was no noticeable labeling of glomeruli in human and tree shrew kidneys. 3. The enrichment of binding sites depended on the species and peptide investigated, suggesting different affinities and/or densities of a heterogenous population of renal ET receptors.
B-cell lymphoproliferative syndromes (LPS) occurring in immunodeficient subjects are frequently associated with EBV infections. Histology as well as EBV-related serology are not diagnostic, but demonstration of EBV DNA in LPS suspected lesions might be useful for diagnosis. We studied four autopsied cases of LPS that developed in the setting of bone marrow transplantation, with proliferations ranging from poly- to monoclonal. Our protocol of DNA extraction allowed detection of EBV DNA in formalin-fixed, paraffin-embedded tissue specimens of all four cases. In dot blot hybridization the sensitivity in these specimens was 10% as compared to fresh frozen material, but still sufficient for a biotinylated probe. Southern blotting with the former DNA was not successful due to extensive degradation. In situ hybridization resulted in positive signals in all cases, using either 35S or 3H labeled probes. The labeling pattern suggested virus replication in B cells of LPS. By this, LPS resembles productively infected lymphoblastoid cell lines rather than latently EBV-infected Burkitt's lymphoma (BL). These findings strengthen the concept of LPS as a distinct clinicopathologic entity, differing from monoclonal, latently EBV-infected BL, as well as from polyclonal infectious mononucleosis, and the more common EBV-negative Non-Hodgkin lymphomas of the immunocompetent host.
Because converting enzyme and kininase II are identical enzymes and probably influence both the biosynthesis of angiotensin II and the metabolism of bradykinin, we investigated the effects of bradykinin and desArg-bradykinin on the sympathetic outflow of pithed spontaneously hypertensive rats (SHRs) before and after acute or chronic inhibition of the converting enzyme by ramipril. Sympathetic outflow was induced by preganglionic electrical stimulation of the spinal cord and measured as circulating, stimulation dependent norepinephrine and epinephrine by high-performance liquid chromatography (HPLC) and electrochemical detection. Bradykinin increased dose-dependently norepinephrine and epinephrine release, particularly when converting enzyme was inhibited. DesArg-bradykinin did not influence norepinephrine outflow but caused a dose-dependent increase in epinephrine release only after converting-enzyme inhibition. It is suggested that both bradykinin and desArg-bradykinin could compensate for the lack of effect of angiotensin II on sympathetic outflow.
The effects of misonidazole (MISO) and two other nitroimidazoles (5-NO2 and 4,5-NO2) on the bioelectric parameters of ion transport (potential difference and short circuit current) across frog skin as a membrane model, were studied in vitro. The nitroimidazoles investigated caused structure dependent effects on the sodium transport function of the membrane. MISO induced a biphasic action following administration on the external side of the membrane: after an initial enhancement, the potential difference and short circuit current signals both decreased. The other imidazole derivatives, 5-NO2 and 4,5-NO2, showed only one phase, whether administered on the external or internal membrane surface. All the nitroimidazoles investigated decreased sodium transport after internal or external surface administration. It was found that the 4,5-NO2 imidazole derivative irreversibly decreased the bioelectric membrane parameters.
Chemotaxis, phagocytic and intracellular killing activities of polymorphonuclear leukocytes (PMNL) were investigated in vitro in 7 patients suffering from the acute phase of Sweet's syndrome. A moderate but consistent impairment of neutrophilic chemotactic activity (NCA) was revealed in all patients. Intracellular killing of blastospores of Candida albicans was diminished in 5/7 patients. Phagocytosis and oxidase activities were within normal levels. These results point to an alteration of some PMNL functions in the acute phase of Sweet's syndrome.
Integrins are cell surface molecules of importance in a wide variety of cellular functions, including morphogenesis, cell migration and cell matrix interactions. The beta-2 (B2) integrin (leukocyte integrin, CD11/CD18) subfamily comprising three members, each consisting of a shared beta subunit (CD18) non-covalently associated with unique alpha subunits (CD11a, CD11b, CD11c). In the present study, we have analysed the expression pattern of B2 integrins on the surface of human keratinocytes (HKs) in biopsies obtained from healthy volunteers, from positive tuberculin skin tests and from patients with acute urticaria (AU), lichen planus (LP), psoriasis vulgaris (PV), mycosis fungoides (MF) or purpura pigmentosa chronica (PPC). In biopsies obtained from positive tuberculin tests and from the clinically involved skin of patients with LP, PV, MF or PPC, a multifocally occurring, suprabasal peroxidase-positive reaction was observed on the membranes of the HKs when the monoclonal antibodies (MABs) Dako CD11a, Dako-p150, 95 or Dako CD18 were used. In contrast, no specific staining of the HKs was observed with the same MABs in biopsies from healthy volunteers, from patients with AU and in the uninvolved skin specimens obtained from the other patients. The HKs from PV, LP, MF, PPC and AU patients and those from the healthy subjects failed to give a positive reaction when the MAB against CD11b (OKM1) was used. Our present findings provide further evidence that HKs may be actively involved in cell adhesion processes.
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To determine whether a correlation exists between the biochemical expression of hemochromatosis and the HLA genotype, we studied 174 family members of 32 persons with the disease. Persons who shared both HLA haplotypes with the proband (and presumably having two hemochromatosis alleles) differed significantly from those who shared only one haplotype (and presumably having one hemochromatosis allele) in terms of serum iron (P less than 0.001 for both sexes), unsaturated iron-binding capacity (P less than 0.01 for female and P less than 0.0001 for male subjects) and serum ferritin (P less than 0.0001 for female and P less than 0.00001 for male subjects). The only significant difference between relatives having one hemochromatosis allele and age and sex-matched controls was related to serum ferritin values in male subjects (P less than 0.05, despite considerable overlap). In our hands, serum ferritin was the best indicator of disordered iron metabolism and was elevated among most homozygous but among few heterozygous family members.
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Inflammation is characterized by the combined reaction of living tissue of the target organ and various types of white blood cells recruited from the circulation and platelets, which tend to eliminate the injurious agent and to repair the damaged tissue. Much of the current knowledge of the functions and characteristics of human white blood cells has been derived from studies of lymphoid cells from patients with various diseases. The results of recent studies (17, 19, 28) have pointed to the diagnostic importance of the immunocompetent cells. The various characteristics of cells involved in immune mediated reactions of various organs and in circulation in man may lead to a better understanding of immune reactions and finally to effective therapeutic modalities.
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The basic disorder of iron metabolism in idiopathic haemochromatosis finds expression on at least two levels: the intestinal mucosa (increased iron absorption) and the liver. Its exact nature, however, remains obscure. The role of iron overload in the pathogenesis of the disorder seems clear. Lysosome disruption has recently been proposed as a possible pathogenic factor. Phenotypic family studies have lent considerable weight to the hypothesis of a recessive transmission of idiopathic haemochromatosis. Demonstration of a close link between the disease and the HLA antigen A3 and haplotype A3, B14 has made it possible: to remove all doubt as to the hereditary nature of the disease; identify the underlying gene as located on chromosome 6 near the A locus of the HLA system; demonstrate a recessive mode of transmission; and achieve the early detection of individuals at risk in the family of a patient with the disease. Thanks to this possibility of early detection, the feasability of preventive measures is greatly enhanced.
Over the last few years the study of idiopathic haemochromatosis has not brought to light any basic change in the overall pattern of organic and metabolic damage produced by the disease and comprising altered skin pigmentation, liver disease, diabete mellitus, heart disease, endocrine dysfunction, bone and joint disease. Nevertheless, certain facets of the clinical picture have been described and progress has been made in understanding the signs of the disease. Although the desferrioxamine test is no without merit, especially if performed after vitamin C administration, for measuring the extent of iron overload, two methods seem better equipped: serum ferritin radioimmunoassay and measurement of iron concentration in a liver biopsy specimen. The HLA antigen A3 and, more especially, haplotype A3, B14, are markers for the genetic basis of the disease. Repeated phlebotomy therapy generally brings about symptomatic improvement and a significant increase in survival.
We studied iron overloading and HLA genotype in two families with overt forms of idiopathic haemochromatosis in two successive generations. In each family the spouse of the patient with overt haemochromatosis in the first generation had clinical and laboratory signs of moderate iron overload and a HLA haplotype A3, B14 and A3, B7 respectively--which is frequently associated with the haemochromatosis gene. This specific HLA haplotype had been transmitted to the second generation patient with overt disease, which thus could be considered as having received a haemochromatosis gene from each parent. Although the finding of cases of overt disease in successive generation firstly suggests a dominant transmission the genetical analysis of these families lead to further strong argument in favour of recessive inheritance of idiopathic haemochromatosis.