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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 397 records · Page 22Linked to original sources
PubMed1989

Structure and function of the Saccharomyces cerevisiae CDC2 gene encoding the large subunit of DNA polymerase III.

Saccharomyces cerevisiae cdc2 mutants arrest in the S-phase of the cell cycle when grown at the non-permissive temperature, implicating this gene product as essential for DNA synthesis. The CDC2 gene has been cloned from a yeast genomic library in vector YEp13 by complementation of a cdc2 mutation. An open reading frame coding for a 1093 amino acid long protein with a calculated mol. wt of 124,518 was determined from the sequence. This putative protein shows significant homology with a class of eukaryotic DNA polymerases exemplified by human DNA polymerase alpha and herpes simplex virus DNA polymerase. Fractionation of extracts from cdc2 strains showed that these mutants lacked both the polymerase and proofreading 3'-5' exonuclease activity of DNA polymerase III, the yeast analog of mammalian DNA polymerase delta. These studies indicate that DNA polymerase III is an essential component of the DNA replication machinery.

Amino Acid Sequence↗
PubMed1989

Ferritin H gene polymorphism in idiopathic hemochromatosis.

The authors studied the H ferritin restriction polymorphism in 83 hemochromatosis patients and 84 controls as well as in 19 nuclear families. No significant difference was found with the ten restriction enzymes used (HindIII, EcoRI, EcoRV, PvuII, BamHI, PstI, Bg/I, Bg/II, HincII, and TaqI). Hence, the genomic abnormality responsible for idiopathic hemochromatosis is not a major deletion of an H ferritin gene. A higher frequency of one HindIII fragment, although nonsignificant when the number of comparisons made is taken into account, was observed in the patients. This HindIII fragment hybridizes with the H ferritin probe and with a 28 S ribosomal probe, and its segregation with HLA haplotypes (hence its assignment to chromosome 6) is uncertain. Its possible meaning in the expression of the disease is discussed.

Chromosome Mapping↗
PubMed1989

Mitochondrial introns aI1 and/or aI2 are needed for the in vivo deletion of intervening sequences.

Some pet- (or mit-) mutations impeding the splicing of one or several intron(s) of the yeast mitochondrial pre-mRNA(s) are suppressed in vivo by the DNA deletion of these introns. We have genetically demonstrated that introns aI1 and/or aI2 of the cytochrome c oxidase subunit 1 gene are necessary for this deletion process. The facts that adjacent introns are simultaneously deleted and that, in the pet- (or mit-) mutants which easily revert by intron deletion, the splicing of the introns they affect is only partially blocked, suggest that the intron encoded proteins aI1 and/or aI2 could intervene by means of their putative reverse transcriptase activity.

Chromosome Deletion↗
PubMed1989

Anion channels in a leaky epithelium. A patch-clamp study of choroid plexus.

We have used the patch-clamp technique to characterize three anion channels in the ventricular membrane of the choroid plexus epithelium from Necturus. The most frequently occurring channel had a nonlinear IV-curve. The conductance in excised patches with 112 mM chloride at both sides was 28 pS at 0 mV, increasing towards positive membrane potentials. The selectivity ratios were PNa:PCl less than or equal to 0.1 and PNO3:PCl:PHCO3 = 1.6:1:0.43. SITS and furosemide (1 mM) on the inside reduces chloride flux to 0.15 and 0.37 times the control value. In attached patches, the most commonly observed channel had a conductance of 7.5 pS. The single-channel current for this channel reversed direction at 15 mV hyperpolarization, indicating accumulation of chloride to a factor of 1.8 above equilibrium. External stimulation of the tissue by theophylline, IBMX and dbcAMP, or by hypotonic shock did not increase the activity of this channel. In very few excised patches, we have observed a chloride channel with a conductance of 7 pS with 112 mM chloride at both sides. The 7 pS channel appears to be identical to a 2 pS channel found in attached patches. The 2 pS channel was not normally active in attached patches but was activated in 28% of the patches by external stimulation. Finally, in few excised patches we have found a 375 pS channel which inactivates within seconds when membrane potential is stepped from 0 mV to a value that differs more than 10-20 mV from zero. The channel did not conduct gluconate but PNO3:PCl = 1.08 and PNa:PCl less than or equal to 0.1. Internal SITS and furosemide (1 mM) reduced chloride flux to 0.3 and 0.5 times the control value. The channel was never seen in attached patches. The current carried through these channels can not account for the transepithelial steady state Cl- -flux measured by microelectrodes. KCl exit from the cell is suggested to be carried by KCl-cotransport or by channels that are too small to be seen in patch-clamp experiments.

1-Methyl-3-isobutylxanthine↗
PubMed1989

The role of lipoproteins in EBV early antigen induction in Raji cells.

Synthesis of the Epstein-Barr virus (EBV) associated early antigen (EA) can be induced by a variety of agents in Raji cells, a latently EBV-infected Burkitt lymphoma line. We investigated the role of lipoproteins in this EA induction system. Cell growth was not affected by lipoprotein-deficiency, but EA induction by most combinations of the inducers TPA (tetradecanoyl-phorbol-acetate), IdU (iododeoxyuridine), n-BA (n-butyric acid), anti-IgM and EA inducing factor (EIF), was greatly reduced. Only the inducer combination TPA/n-BA was completely independent of the presence of lipoproteins, indicating a different induction pathway. Removing the lipid moieties of the culturing serum did not result in reduced EA induction. Thus, the lowered EA inducibility in lipoprotein-deficiency is due to the absence of the protein moiety (apolipoprotein). Addition of HDL or VLDL partially reconstituted the original EA inducibility, whereas LDL had no effect. Lipoproteins were particularly important during the first 4 hours of induction, the phase where inducers may act on cell membrane structures (e.g., receptors). But lipoproteins were also required throughout the incubation period, even in a late and inducer independent phase.

Antigens, Viral↗
PubMed1989

Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis.

The aim of the present study was to evaluate the effectiveness of single-energy computed tomography in determining iron overload in idiopathic hemochromatosis, with special reference to slightly overloaded cases. Liver attenuation was determined in 100 patients (46 cases of idiopathic hemochromatosis, 32 cases of chronic liver disease, and 22 normal controls). The iron load was determined for the first two groups by biochemical determination of liver iron concentration (performed in all but 12 subjects in the chronic liver disease group) and hepatic histologic grading. The main results for liver attenuation (upper normal limit, 72 Hounsfield units) showed that despite a high specificity (0.96), this parameter was of low sensitivity (0.63). Although mean liver attenuation in idiopathic hemochromatosis (77 +/- 14) was significantly higher than in chronic liver diseases (53 +/- 17; p less than 10(-4) and normal controls (66 +/- 3; p less than 10(-3], and despite an overall good correlation between liver attenuation and liver iron concentration (r = 0.72; p less than 10(-3], liver attenuation was unable to detect moderate iron overload. Fourteen of 18 patients with a liver iron concentration of less than 150 mumol/g dry liver wt had liver attenuation values of less than 72. Moreover, 3 of 18 subjects with a liver iron concentration of greater than 150 had a liver attenuation of less than 72. Of these 17 false-negatives, only 7 could be attributed to associated steatosis. On the whole, single-energy computed tomography, when used on a routine basis for diagnosing iron overload, is of limited clinical value in idiopathic hemochromatosis due to its poor sensitivity. Hepatic histologic examination together with biochemical determination remains the most accurate means to assess liver iron.

Fatty Liver, Alcoholic↗
PubMed1989

Perianal findings in prepubertal children selected for nonabuse: a descriptive study.

The results of the perianal portion of a project designed to collect normative data of the anogenital anatomy from a representative sample of prepubertal children is presented. A total of 318 children were examined by three physicians from a child sexual abuse evaluation program. After screening for the onset of puberty and the possibility of undetected abuse, 267 subjects remained. The sample included 161 girls and 106 boys ranging in age from 2 months to 11 years. The perianal findings that were encountered with the greatest frequency included erythema (41%), increased pigmentation (30%), and venous engorgement (52%) after two minutes in the knee-chest position. Wedge-shaped smooth areas in the midline, with or without depressions, were found both anterior and posterior to the anus in 26% of the children. Anal skin tags/folds were discovered anterior to the anus in 11%. In 49% of the children there was some dilatation of the anus which opened and closed intermittently in 62%. Flattening of the anal verge and rugae occurred during dilatation by the midpoint of the examination in 44% and 34%, respectively. Perianal findings that were found infrequently in all subgroups included skin tags/folds (0%) and scars (1%) outside the midline, anal dilatation greater than 20 mm without the presence of stool in the rectal ampulla (1.2%), irregularity of the anal orifice after complete dilatation (3%), and prominence of the anal verge (3%). No abrasions, hematomas, fissures, or hemorrhoids were encountered. Less commonly detected findings within specific subgroups included perianal erythema in girls (32%) as compared to boys (57%), pigmentation in the lighter skinned white children (22%) when compared to black (53%) and Hispanic (58%) children, and venous congestion at the beginning of the examination (7%) when compared to the same findings after four minutes in the knee-chest position (73%). There were no perianal skin tags/folds found in the boys. The relatively high incidence of perianal soft tissue changes that were found in this study, when compared to the frequency of similar observations in children suspected of having been sexually abused, reemphasizes the caution medical examiners must exercise in rendering an opinion as to the significance of medical findings.

Anal Canal↗
PubMed1989

Thyroid inclusion in the lung. Metastasis of an occult papillary carcinoma or ectopia?

The incidental autopsy finding of a thyroid inclusion in the lung of a 26-year-old man, accompanied by an occult papillary carcinoma (OPC) in the thyroid gland, raises the question about the possibility of true thyroid ectopia in the lung vs. metastasis of an OPC. Based on the embryonic development of the thyroid gland and the known thyroid ectopias, as well as on statistical figures on OPCs and their metastases, both possibilities are discussed. The histological pattern of the thyroid inclusion and the lack of regional nodal metastases argue in favour of ectopia, even though a definitive conclusion cannot be drawn.

Adult↗
PubMed1989

Effect of cycloheximide upon maturation of bovine oocytes.

Germinal vesicle breakdown (GVBD) of bovine oocytes was completely blocked by cycloheximide added to culture medium at concentrations of 1-20 micrograms/ml. Nevertheless, under such conditions a certain degree of chromatin condensation inside the germinal vesicle was observed. The inhibitory effect was not influenced by the presence or absence of cumulus cells and was fully reversible; but the process of GVBD was then significantly accelerated. The critical period in which the proteins necessary for GVBD are synthesized lasts approximately the first 5 h of culture. When germinal vesicle-arrested oocytes are fused to maturing bovine oocytes containing condensed chromosomes, GVBD of immature oocytes occurs within 3 h, even in the presence of cycloheximide. In the mouse, GVBD cannot be inhibited by protein synthesis inhibitors. When immature mouse oocytes are fused with immature bovine oocytes and the giant cells are then cultured in cycloheximide-supplemented medium, both GVs are observed, or only mouse GVBD occurs in common cytoplasm after 8 h of culture. We conclude that protein synthesis is necessary for GVBD of bovine oocytes. Our results also suggest that maturation-promoting factor (MPF) is not autocatalytically amplified in mammalian oocytes.

Animals↗
PubMed1989

Changes in the concentration and composition of biliary and serum bile acids in the young domestic fowl.

1. Concentrations of biliary and serum bile acids, their molecular compositions and serum cholesterol concentrations were determined in chicks at 2, 3, 4 and 6 weeks of age. 2. The concentration of biliary bile acid was maximal at 3 to 4 weeks, decreasing by 6 weeks of age. 3. The serum concentration of bile acid was maximal at three weeks of age. 4. Serum total cholesterol increased from two weeks and was maximal at 6 weeks of age. 5. Chenodeoxycholic acid was the predominant biliary unconjugated bile acid. 6. Tauro-chenodeoxycholic acid and tauro-cholic acid were the dominant molecular species of biliary and serum conjugated bile acid.

Age Factors↗
PubMed1989

Involucrin in the epidermal cells of subprimates.

The protein involucrin is a precursor of the cross-linked envelope that forms during terminal differentiation of the keratinocyte. Most of the human involucrin molecule consists of a segment of homologous repeats of a sequence of 10 amino acids. A similar segment is present in the involucrin of other higher primates, but not in lower animals. We show here that the older part of the involucrin molecule (the ancestral segment) is present in the epidermal cells of subprimates. This has been demonstrated with antisera prepared against different peptides of the ancestral segment of the human protein. No single antiserum detects involucrin of all subprimate species, but probably all involucrins can be detected using antiserum against some sequence in the ancestral segment. Although the involucrin gene has been extensively remodeled in higher primates, its origins extend lower in the animal kingdom.

Amino Acids↗
PubMed1989

Absence of BoLA class I antigens on bovine spermatozoa.

Forty AI bulls were tested for BoLA class I antigens by means of eight specific polyclonal reagents. By means of immobilization and sperm penetration tests these antigens were not detected on sperm cells. Isoimmunization studies with the use of sperm as antigenic stimuli and insemination of frozen spermatozoa diluted in specific reagents did not prove the presence of BoLA class I antigens on bovine spermatozoa. The cytotoxic tests used in this investigation were not reliable.

Animals↗
PubMed1989

The proteins associated with the soluble form of p36, the main target of the src oncogene product in chicken fibroblasts, are glycolytic enzymes.

One of the main targets of pp60v-src tyrosine kinase is a 34 to 39-kilodalton protein of chicken embryo fibroblasts called p36 or calpactin I. We have previously reported an association of the cytoplasmic fraction of p36 (10-20% of the total cellular p36) with three chicken polypeptides named p32, p48, and p54. We have now raised and affinity-purified antibodies against each of these proteins. This has allowed their identification: p32 is lactate dehydrogenase, p48 is enolase, and p54 is phosphoglucose isomerase. An association between p36 and two other known substrates of pp60v-src, the glycolytic enzymes enolase and lactate dehydrogenase, suggests a cellular organization of the various targets of the oncogene tyrosine kinases. Furthermore, a possible relationship between p36 and glycolysis is questioned.

Animals↗
PubMed1989

Simon nitinol inferior vena cava filter: initial clinical experience. Work in progress.

The Simon nitinol filter for percutaneous interruption of the vena cava to prevent pulmonary embolism is currently undergoing a multicenter clinical trial. Preliminary clinical results are reported as work in progress. The results in 44 patients at two centers are analyzed in detail, and major events are reported from 103 patients in 17 centers in the United States during a 10-month period. The filter was successfully inserted via the femoral or jugular route in all patients through a 9-F catheter. The placement procedure was easy and without significant complications. Follow-up studies included plain radiography, ultrasonography, magnetic resonance (MR) imaging, and clinical evaluation. No filter migration or perforation occurred among the 103 patients. Symptomatic occlusions occurred in 7%-9%, comparable to other series, and some asymptomatic occlusions were detected with MR imaging only. The implications of occlusion of the filter are discussed.

Adult↗
PubMed1989

Basic and interleukin-2-augmented natural killer cell activity in lichen planus.

Natural killer cell (NK) activity of peripheral blood lymphocytes against K 562 cells was investigated in lichen planus (LP). 38 LP patients with cutaneous or oral mucosal involvement and 20 healthy controls participated in the study. A statistically significant decrease in the NK response in LP patients with extensive erosive oral mucosal involvement (p less than 0.02) and in generalized acute eruptive LP (p less than 0.01) was noted compared to those with nonerosive LP of the oral mucosa or healthy controls. Interleukin 2 failed to restore completely the reduced NK activities in our patients with LP.

Acute Disease↗
PubMed1989

Immunopathological investigations in purpura pigmentosa chronica.

We studied the cell infiltrates and antigenic characteristics of keratinocytes in biopsies from purpura pigmentosa chronica (PPC), with eleven monoclonal antibodies against several cell surface markers of effector and/or accessory cells of the immune system and compared the reactivity patterns with those in biopsies from uninvolved skin. Immunohistochemical staining revealed a predominance of activated helper T lymphocytes in the cutaneous inflammatory infiltrate. In contrast to uninvolved skin, lesional keratinocytes were found to express HLA-DR, OKM5, Leu-8 and Leu-11b (CD16) antigens in all biopsies from the involved skin. We demonstrate here for the first time the in vivo expression of several effector and/or accessory cell markers on lesional keratinocytes and infiltrate cells in PPC.

Adolescent↗