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Biomedical subjects

M Simon

Publications and source records attributed to M Simon.

At least 325 records · Page 18Linked to original sources
PubMed1992

Analysis of the MSS51 region on chromosome XII of Saccharomyces cerevisiae.

We have localized gene MSS51 on chromosome XII of Saccharomyces cerevisiae between the RDN1 and CDC42 loci. 'Head to head' with MSS51 is another gene, QRI5, the function of which is unknown. However, the proximity of these genes, the structure of the intergenic region and the presence of an ABF1 binding site right in the middle of this region suggest that the MSS51 and QRI5 expressions are submitted to a common regulatory process.

Amino Acid Sequence↗
PubMed1992

The California Maternal Serum alpha-Fetoprotein Screening Program: the role of ultrasonography in the detection of spina bifida.

Between January 1988 and June 1990, 161 cases of open spina bifida were identified by the California Maternal Serum alpha-Fetoprotein Screening Program. Eight percent of these cases were not diagnosed by an initial ultrasonographic evaluation. Three defects were not recognized until birth. Ultrasonography is inadequate to identify all cases of open spina bifida.

California↗
PubMed1992

Distribution of 125I-endothelin-1,-2,-3 binding sites in mammalian kidneys.

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.

Animals↗
PubMed1992

cDNA sequence of human p11 calpactin I light chain.

The cDNA encoding full-length human p11 calpactin I light chain has been cloned and subjected to DNA sequencing. The open reading frame specifies a 97-amino-acid residue protein that surprisingly is identical to the p11 sequences of two mammalian ungulate species, cow and pig. However, the previously reported p11 polypeptide sequences of mouse and rat exhibited 8-9% nonidentity to human p11. These mammalian sequence comparison results are unexpected in view of current molecular cladistic theories that suggest a closer relationship between primates and rodents, rather than primates and ungulates. The mouse p11 gene has been previously mapped to chromosome 3 at a position syntenic with a centromeric-proximal region on human chromosome 1, and the human p11 cDNA clone is likely to be useful in physical mapping on chromosome 1.

Amino Acid Sequence↗
PubMed1992

Demonstration of Epstein-Barr viral DNA in paraffin-embedded specimens of lymphoproliferative syndrome. Evidence for a productive infection comparable to lymphoblastoid cell lines.

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.

Adult↗
PubMed1992

Characterisation of eight monoclonal antibodies to involucrin.

Involucrin is a precursor of the insoluble protein envelope that is assembled in the outermost layers of the epidermis. The coding sequence of the protein contains a number of short tandem repeats that have been greatly altered during mammalian evolution. We have characterised eight mouse monoclonal antibodies raised against human involucrin, all of which bind to the protein in immunoprecipitation, immunoblot and immunohistochemical preparations. Each antibody was screened for cross-reactivity with gorilla, owl monkey, dog and pig involucrin and with a fragment of the human protein, expressed in lambda gt 11, that includes the entire early region of the modern segment of repeats. Three antibodies recognised involucrin in all of these assays. Four antibodies recognised primate involucrins and the lambda gt 11 fragment. One antibody, which showed cross-reactivity with lower molecular weight proteins, only recognised primate involucrins and therefore bound outside the early region of the modern segment. Since the antibodies can be used to detect involucrin both biochemically and histologically, in a range of species, they will have applications in further studies of the expression, function and evolution of the protein.

Amino Acid Sequence↗
PubMed1992

Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer.

Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma.

Antineoplastic Agents↗
PubMed1992

Changes in peripheral sympathetic outflow of pithed spontaneously hypertensive rats after bradykinin and DesArg-bradykinin infusions: influence of converting-enzyme inhibition.

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.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Excretion of anthranilate and 3-hydroxyanthranilate by Saccharomyces cerevisiae: relationship to iron metabolism.

Resting suspensions of cells of Saccharomyces cerevisiae grown in iron-rich or iron-deficient conditions were studied by following the fluorescence emission changes (lambda em. 400-460 nm, lambda exc. 300-340 nm) occurring in these suspensions upon addition of glucose and ferric iron. The results show that, in addition to NAD(P)H, metabolites of the aromatic amino acid pathway interfere with the fluorescence measurements, and that they could be involved in ferric iron reduction. Wild-type strains of S. cerevisiae are known to excreted anthranilic acid and 3-hydroxyanthranilic acid in response to glucose. The major fluorescing compound excreted by a chorismate-mutase-deficient mutant strain of S. cerevisiae was identified as anthranilic acid. The excretion of anthranilic and 3-hydroxyanthranilic acids was correlated with the ferric-reducing capacity of the extracellular medium. Excretion during growth was much greater by cells cultured in iron-rich medium than by cells grown in iron-deficient medium. The possibility was examined that a link could exist between the biosynthesis of aromatics and the ferri-reductase activity of the cells, via chorismate synthase and its putative diaphorase-associated activity. Two ferri-reductase-deficient mutants excreted much less 3-hydroxyanthranilate than did the parental wild-type strains. However, the ferri-reductase activity of a chorismate-synthase-deficient mutant was comparable to that of the parental strain.

3-Hydroxyanthranilic Acid↗
PubMed1992

Comparison of the N-linked oligosaccharide structures of the two major human myelin glycoproteins MAG and P0: assessment and relative occurrence of oligosaccharide structures by serial lectin affinity chromatography of 14C-glycopeptides.

The N-linked oligosaccharide structures of human myelin-associated glycoprotein (MAG) and P0 have been characterized by serial lectin affinity chromatography (SLAC) of 14C-glycopeptides. 14C-Glycopeptides were prepared from purified MAG derivative and P0 by extensive proteolytic digestion and N-14C-acetylation. Assuming that all the 14C-glycopeptides were radiolabelled to the same specific radioactivity, the relative occurrence of the oligosaccharide structures was correlated to the amount of incorporated radioactivity. Sixteen and 15 fractions were generated by SLAC of MAG and P0 14C-glycopeptides, respectively. Despite this tremendous structural heterogeneity, the oligosaccharide "fingerprints" of MAG and P0 obtained by SLAC displayed similarities: (a) of the three types of N-linked oligosaccharides, the complex type accounted for 80.4% and 94.9% of MAG and P0 radioactivity, respectively; (b) biantennary complex oligosaccharides were the major structures present on MAG and P0; (c) approximately 60% of MAG and P0 oligosaccharides possessed a bisecting N-acetylglucosamine residue; and (d) large amounts of oligosaccharides with an alpha(1-6)fucose residue were found in both MAG and P0 and, noticeably, approximately 25% of the tri- and/or tetraantennary and approximately 90% of the bisected biantennary oligosaccharides of both glycoproteins contained alpha(1-6)fucose residues in the core. This study demonstrates that MAG and P0, both belonging to the immunoglobulin superfamily, display structural similarities in their N-linked oligosaccharide contents.

Carbon Radioisotopes↗
PubMed1992

Comparison of the N-linked oligosaccharide structures of the two major human myelin glycoproteins MAG and P0: assessment of the structures bearing the epitope for HNK-1 and human monoclonal immunoglobulin M found in demyelinating neuropathy.

The epitope for HNK-1 and patient's monoclonal autoantibodies in demyelinating polyneuropathy associated with immunoglobulin M gammopathy is borne by different types of N-linked oligosaccharide structures in human P0 and myelin-associated glycoprotein (MAG). Fourteen glycopeptide fractions bearing different oligosaccharide structures were obtained from either MAG or P0 glycopeptides by serial lectin affinity chromatography on concanavalin A-Sepharose, Phaseolus vulgaris erythrophytohemagglutinin-agarose, Pisum sativum agglutinin-agarose, and Phaseolus vulgaris leucophytohemagglutinin-agarose. As shown by dot-TLC plate immunostaining, the same MAG and P0 glycopeptide fractions were recognized by HNK-1 and patient's immunoglobulin M, confirming that these antibodies display similar specificities. The antigenic carbohydrate was present in glycopeptide fractions that either interact with Pisum sativum agglutinin-agarose or were bound by Aleuria aurantia agglutinin-digoxigenin, indicating that these structures contained alpha(1-6)fucose residues. This study demonstrates that the L2/HNK-1 epitope is borne mainly or even exclusively by N-linked oligosaccharide structures alpha(1-6)fucosylated in the core.

Antibodies, Monoclonal↗
PubMed1992

Comparative study of nitroimidazoles on the bioelectric properties of frog skin as a membrane model.

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.

Animals↗
PubMed1992

Autoradiographic characterization of angiotensin receptor subtypes in fetal and adult human kidney.

To better understand the action of angiotensin II (ANG II) and angiotensin receptor antagonists (ARA) in human kidney, ANG II receptors were characterized by in vitro autoradiography in fetal and adult human renal tissue using 125I-[Sar1-Ile8]ANG II (125I-ANG II), a potent ANG II antagonist. Binding was inhibited with the ARAs DuP 753 and PD 123177, respectively. In adult kidneys (n = 5), binding of 125I-ANG II showed the following characteristics: arterial vessels had dissociation constant (Kd) = 387.6 +/- 29.1 (SD) pM and maximal binding (Bmax) = 41.4 +/- 3.6 fmol/mg tissue equivalent (TE); glomeruli had Kd = 885.7 +/- 217.1 pM and Bmax = 35.5 +/- 8.1 fmol/mg TE; and outer medulla had Kd = 142.1 +/- 52.5 pM and Bmax = 7.7 +/- 2.3 fmol/mg TE. PD 123177 effectively displaced 125I-ANG II only in large preglomerular vessels [half-maximal inhibitory concentration (IC50) = 0.22 +/- 0.1 nM, type 2 receptor (AT2)], whereas DuP 753 displaced only the labeled ligand in glomeruli (IC50 = 0.28 +/- 0.11 nM) and outer medulla (IC50 = 0.39 +/- 0.11 nM, AT1). In fetal kidneys (n = 4), a diffuse 125I-ANG II binding was demonstrated in the medulla (Kd = 36.6 +/- 7.1 pM; Bmax = 25 +/- 3.8 fmol/mg TE) and in the cortex (Kd = 19.5 +/- 8 pM; Bmax = 7.2 +/- 2.2 fmol/mg TE). Both cortical (IC50 = 0.039 +/- 0.019 nM) and medullary binding (IC50 = 0.076 +/- 0.039 nM) could only be displaced by PD 123177.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The Simon nitinol filter: evaluation by MR and ultrasound.

In this prospective blinded study of inferior vena caval (IVC) patency, 18 patients underwent 25 duplex ultrasound (US) and magnetic resonance (MR) angiography examinations over an eight-month period following Simon nitinol filter placement. Clinical examination for lower extremity venous stasis and plain abdominal radiography were also performed. Twenty-three of 24 MR examinations and 11 of 24 US examinations were judged technically adequate by the blinded observers. One technically adequate US exam was false positive for intraluminal caval thrombus. Thirteen technically inadequate US examinations missed 3 complete caval occlusions and 2 partial occlusions. MR identified all patients with complete or partial caval occlusion. The authors conclude that duplex US reliably confirms IVC patency only when strict criteria for technical adequacy and interpretation are met (good visualization of filter and IVC above and below filter). MR, although expensive, more reliably identifies nonoccluding intraluminal thrombus and caval occlusion. It should be the noninvasive study of choice in symptomatic patients with venous stasis and patients with recurrent pulmonary emboli.

Adult↗