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Biomedical subjects

A Schmid

Publications and source records attributed to A Schmid.

At least 253 records · Page 14Linked to original sources

Altered transcription of a defective measles virus genome derived from a diseased human brain.

Measles virus (MV) is a negative strand RNA virus which usually causes acute disease, but in rare cases its persistence in the human brain induces the lethal disease subacute sclerosing panencephalitis (SSPE). The transcription of MV and of a defective MV derived from autopsy material of a SSPE case was studied in cultured cells. In the lytic infection the levels of the MV mRNAs decreased progressively with the distance of the six cognate genes from the 3' end of the genome, reflecting transcriptional attenuation at every gene junction. Transcripts covering two or three adjacent genes accounted for up to 20% of single gene transcripts; incidentally the MV intergenic transcription signals were found to be less conserved than the analogous signals of other negative strand RNA viruses. Although the analysed SSPE-derived defective MV showed a localized transcription defect at the phosphoprotein--matrix gene junction (substitution of the mRNAs by readthrough transcripts), the corresponding intergenic 'consensus' sequence and the surrounding nucleotides were not altered. This implies that factor(s) involved in the transcription of this defective SSPE virus fail to recognize this particular signal sequence, a constellation which in this and other cases might be causally related to the development of MV persistence.

Base Sequence↗

Investigation on the metabolic degradation of the side chain of furazolidone.

The investigation was aimed at providing insight into the side chain metabolism of furazolidone in mice. The agents used in the experiments were furazolidone, 3-amino-2-oxazolidinone, oxazolidinone, nitrofurantoin, 3-aminohydantoin and hydantoin, administered intraperitoneally at five equimolar doses ranging from 0.178 to 0.888 mmol/kg. The parameters investigated included ethane and ethylene expiration, formation of malondialdehyde and total glutathione content in the liver. Ethylene expiration was found to be strongly enhanced by aminooxazolidinone and slightly increased by furazolidone. Ethane expiration was increased after aminooxazolidinone administration. Malondialdehyde formation was not affected by any of the agents used. Total glutathione was decreased by furazolidone and nitrofurantoin. The above findings indicate that, in vivo, the azomethine linkage of the side chain of furazolidone hydrolyses to form 3-amino-2-oxazolidinone, subsequently cleaved to ethylene.

Animals↗

Intracerebral Nocardia brasiliensis infection.

Case report about cerebral infection with the species Nocardia Brasiliensis in a not immunocompromised host. Diagnosis, treatment and neuroradiological findings are shown and compared with current studies.

Anti-Bacterial Agents↗

Mechanism of sugar transport through the sugar-specific LamB channel of Escherichia coli outer membrane.

Lipid bilayer experiments were performed with the sugar-specific LamB (maltoporin) channel of Escherichia coli outer membrane. Single-channel analysis of the conductance steps caused by LamB showed that there was a linear relationship between the salt concentration in the aqueous phase and the channel conductance, indicating only small or no binding between the ions and the channel interior. The total or the partial blockage of the ion movement through the LamB channel was not dependent on the ion concentration in the aqueous phase. Both results allowed the investigation of the sugar binding in more detail, and the stability constants of the binding of a large variety of sugars to the binding site inside the channel were calculated from titration experiments of the membrane conductance with the sugars. The channel was highly cation selective, both in the presence and absence of sugars, which may be explained by the existence of carbonyl groups inside the channel. These carbonyl groups may also be involved in the sugar binding via hydrogen bonds. The kinetics of the sugar transport through the LamB channel were estimated relative to maltose by assuming a simple one-site, two-barrier model from the relative rates of permeation taken from M. Luckey and H. Nikaido (Proc. Natl. Acad. Sci. USA 77:165-171 (1980a)) and the stability constants for the sugar binding given in this study.

Bacterial Outer Membrane Proteins↗

Improved model for the induction of proestrus-like gonadotropin surges in long-term ovariectomized rats.

In long-term (greater than 4 wk) ovariectomized rats the positive response of the gonadotropin release apparatus to a priming dose of estradiol is moderate as compared with that of proestrous rats exposed to endogenous estradiol. In the present study, high sensitivity to estrogen was restored in long-term ovariectomized rats by pretreatment with estradiol benzoate (EB, 20 micrograms, day 0) and progesterone (P, 2.5 mg, day 3). Estradiol benzoate (20 micrograms) given on day 5 induced proestrus-like surges of LH and FSH in the afternoon on day 6. Additional administration of P (2.5 mg at noon on day 6) had a facilitatory effect. Stimulation of LH release could be evoked in rats by the described regimen 1, 6 or 50 wk after ovariectomy. The long-term ovariectomized rat injected with EB and P as described might provide a useful model for neuroendocrinological investigations on the gonadotropin surge mechanism.

Animals↗

Morphometric investigations of terminal villi of diabetic placentas in relation to the White classification of diabetes mellitus.

In this morphometric study, terminal villi of 22 placentas of maternal diabetes mellitus were compared with the results in terminal villi of 22 normal placentas. The results demonstrate that there is a distinct retardation in maturation, statistically significant with bigger cross sectional surfaces of the terminal villi, particularly, when classified in 3000 mu2-steps, the number of the villous vessels and number of epithelial plates. Only slightly decreased in diabetic placentas is the villous vessels cross sectional surface as well as the degree of vascularization. The correlation between the degree of histometric changes and the severity and duration of the disease was separately investigated (classification was done according to White). It could be shown, that the degree of morphologic changes in the terminal villi does not run strictly parallel to the severity and duration of diabetes. The retardation in maturation of the terminal villi increases from White group A to C. In White group D, which is the most severe stage of diabetes mellitus which we investigated, the values of measured parameters are close to the normal placentas. This observation is interpreted as a compensatory reaction of the fetal organ placenta to the reduction in utero placental blood flow in diabetes caused by the diabetic angiopathy.

Chorionic Villi↗

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Adolescent↗

Purification, subunit structure and pharmacological effects on cardiac and smooth muscle cells of a polypeptide toxin isolated from the marine snail Conus tessulatus.

The most active component in smooth muscle contraction, isolated from the whole venom of the marine snail Conus tessulatus, has a molecular mass of about 55 kDa. The toxin protein, tessulatus toxin, appeared to be constituted by two distinct polypeptide bands of 26 kDa and 29 kDa. The pure toxin caused a marked contraction of both guinea-pig ileum and rabbit aorta at nanomolar concentrations. Tessulatus-toxin-induced contraction was indirectly prevented by classical inhibitors of the voltage-dependent Ca2+ channel. Tessulatus toxin caused a large increase in the initial rate of 45Ca2+ uptake by cardiac cells. This uptake was insensitive to Ca2+ channel blockers at concentrations 100-1000 fold higher than those known to block voltage-dependent Ca2+ channels in these cells. Voltage clamp experiments have confirmed that tessulatus toxin was not directly active on the Ca2+ current. Tessulatus-toxin-stimulated 45Ca2+ influx was inhibited by dichlorobenzamil and suppressed when Na+ was substituted by Li+, indicating that the toxin acted via activation of the Na+/Ca2+ exchange system in cardiac cells. Activation by tessulatus toxin of the Na+/Ca2+ exchange system occurred via a toxin-stimulated Na+ entry into cardiac cells and was observed in the same range of toxin concentration which produced 45Ca2+ entry. The Na+ entry system that was activated by tessulatus toxin was insensitive to classic inhibitors of known Na+ entry systems in cardiac cells. Possible mechanisms by which tessulatus toxin induced Na+ entry into cardiac cells and contractions in smooth muscles are discussed. Tessulatus toxin is cytotoxic when used at high concentrations.

Animals↗

Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration.

Subacute sclerosing panencephalitis (SSPE) is a fatal disease affecting the human central nervous system several years after acute measles infection. Measles virus (MV) genomes replicating in SSPE brains do not give rise to budding particles and present various defects in gene expression, mostly concerning the matrix (M) protein. For one SSPE case (K), shown previously to be devoid of M protein expression, we examined here in detail the features involved in this defect. In the brain of patient K the normal, monocistronic MV M mRNA was completely substituted by a bicistronic RNA containing the coding sequence of the preceding phosphoprotein (P) gene in addition to the M coding sequence. Analysis of the P-M intercistronic region by direct cDNA sequencing showed that the consensus sequence at this RNA processing site was unaltered but revealed several distant point mutations. cDNA cloning and sequencing of the entire M coding region established that one of the point mutations leads to a stop codon at triplet 12 of the M reading frame. It is unknown whether this defect, explaining by itself the lack of M protein, is related also to the block of M mRNA formation. In addition we note that as much as 1% of the nucleotides differed between two overlapping clones from the same brain. This high sequence variability could possibly account for the diversity of defects observed in MV gene expression in SSPE brains and may be a general phenomenon associated with RNA virus persistence.

Amino Acid Sequence↗

Antibodies reveal the cytolocalization and subunit structure of the 1,4-dihydropyridine component of the neuronal Ca2+ channel.

Rabbit brain synaptosomes bind the 1,4-dihydropyridine derivative (+)[3H]-PN 200-110 with an equilibrium dissociation constant of 0.04 nM and a maximal binding capacity of 400 fmol/mg of protein. Using polyclonal antibodies raised against the different components of the skeletal muscle 1,4-dihydropyridine receptor, we have demonstrated that the brain and muscle receptors share the same subunit composition comprising a large polypeptide chain of Mr 140,000 associated by disulfide bridges with a smaller peptide of Mr 32,000. These antibodies have been used in immunofluorescence staining of brain sections. They reveal a distribution of the Ca2+ channel protein similar to that of 1,4-dihydropyridine binding sites with (+)[3H]PN 200-110 by the autoradiographic technique.

Animals↗

A polypeptide toxin from the coral Goniopora. Purification and action on Ca2+ channels.

A polypeptide toxin has been isolated from Goniopora coral with an Mr of 19 000. Goniopora toxin has the following properties: it induces contraction of guinea pig ileum and this contraction is prevented by Ca2+-channel blockers; it stimulates 45Ca2+ influx in cardiac cells in culture and this stimulation is abolished by Ca2+-channel blockers; it prevents binding of (+)-[3H]PN 200-110 to the Ca2+-channel protein of skeletal muscle T-tubule membranes. All these results taken together suggest that Goniopora toxin is a Ca2+-channel activator.

Animals↗