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Biomedical subjects

C Schwab

Publications and source records attributed to C Schwab.

At least 73 records · Page 4Linked to original sources

Synthesis and conversion study of a radiolabeled putative ecdysone precursor, 5 beta-cholest-7-ene-3 beta,6 alpha,14 alpha-triol in Locusta migratoria prothoracic glands.

In previous studies, we have characterized the last three steps of the biosynthetic pathway of the insect molting hormone, ecdysone. They consist of a series of hydroxylations at the C-25, C-22, and C-2 positions. To explore an early step, we synthesized 5 beta-cholest-7-ene-3 beta,6 alpha,14 alpha-triol in tritiated form. Incubation of this triol with insect prothoracic glands, a well-known site of ecdysone biosynthesis, showed that this molecule can be hydroxylated at the C-25, C-22, and C-2 positions, but neither the triol nor the resulting compounds could be oxidized at the C-6 position to give ecdysone.

Animals↗

Multiple sclerosis and HLA class II susceptibility and resistance genes.

Probes to the HLA class II genes DR beta, DQ beta, and DQ alpha were used to study DNA from unrelated Caucasian multiple sclerosis (MS) patients by sequential restriction fragment length polymorphism (RFLP) analysis in Taq 1 restriction enzyme digests. Comparison of 104 patients and 108 controls, who were not matched for DR type, has identified for the first time a linked series of allele-specific RFLPs or allogenotypes which form an extended haplotype that is preferentially associated with MS. These allogenotypes include DRw15 or DR2(15); DQ beta lb, which corresponds at the DNA level to the DQwl(DQw6) serotype; a DQA1 allogenotype termed DQ alpha lb; and a 2.2 kb DX (DQA2) allogenotype termed DX alpha U (DQA2U). The role of HLA class II genes in susceptibility to MS was found to be complex. First, 23 of 104 MS patients showed DR-DQ linkages which were not observed in our control population. We suggest these anomalous associations may be important in the pathogenesis of MS. Second, homozygosity of a 2.0 kb DX (DQA2) gene, termed DX alpha L (DQA2L), showed a strong negative association with MS. DX alpha L (DQA2L) is in strong linkage disequilibrium with DR1, 5(w11) 7, and a subset of DR4, all of which also showed a negative association with MS. Since DX alpha L (DQA2L) does not code for any known product, DR1, 5(11), 4, and 7 become candidates for disease resistance genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Linkage↗

Different levels of acetylcholinesterase and choline acetyltransferase activities in C57Bl/6 and DBA/2 mice are not accompanied with different density of cortical acetylcholinesterase reactive fibers.

Mice of the inbred strains C57B1/6 and DBA/2 show strain-dependent behavioural differences which have been correlated with variations in the organization of brain cholinergic systems. The aim of our study was to analyse the extent of cholinergic interstrain differences in circumscript brain regions of C57B1/6 and DBA/2 mice. The biochemical determination of choline acetyltransferase and acetylcholinesterase in cortical areas, basal forebrain and striatum showed significantly lower enzyme activities in most of the regions of C57B1/6 mice. The deficit was most pronounced in the basal forebrain/diagonal band, in the piriform cortex, and striatum. The density of acetylcholinesterase-stained cortical fibres did not reflect the biochemical interstrain differences. This may be due to a different enzyme content in the nerve fibers of the two mice strains. The previous findings are discussed in terms of brain cholinergic disorders in which the extent of damage but also the proportions of regional deficits may influence the pattern of behavioural dysfunctions.

Acetylcholinesterase↗

HLA-DR beta, -DQ alpha, and -DQ beta restriction fragment length polymorphisms in multiple sclerosis.

Restriction fragment length polymorphism (RFLP) studies were performed on DNA from unrelated Caucasian patients with multiple sclerosis (MS) using cDNA probes to the HLA class II genes DR beta, DQ alpha, and DQ beta. In a study of 34 patients and 34 controls who were not matched for DR type, we found that the DQ beta allele-specific RFLP or allogenotype, termed DQ beta lb, which corresponds at the molecular level to the DQwl serotype, is preferentially associated with MS. A significant disease association with DR2 was demonstrated by serology but this was not confirmed using DR2/Dw2-specific RFLPs. We suggest that DQ beta lb is largely responsible for HLA-associated susceptibility to MS and that the apparent MS-DR2 serological association is due to the strong linkage disequilibrium between DR2 and DQ beta lb. Homozygosity of one of the two allelic bands of the DX alpha gene, usually termed the DX alpha lower (DX alpha L) band (which cross-hybridizes with the DQ alpha probe), correlated with reduced susceptibility to MS. Similarly a 5.3 kb band identified by the DQ alpha probe in Mspl digests showed a negative correlation with MS. In an analysis of 27 DR2+ controls and 26 DR2+ patients it was found that these individuals all had DR2/Dw2-specific RFLPs and all had identical DR2/Dw2-associated DQ beta (DQ beta lb) and DQ alpha (DQ alpha lb) allogenotypes. We detected no polymorphisms of DR beta, DQ alpha, or DQ beta genes among the DR2+ MS patients which distinguished them from normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

[Ultrastructural findings in the cornea in xeroderma pigmentosum].

Xeroderma pigmentosum is a very rare disease caused by an inherited defect in the DNA repair system. The cells are less able to repair defects caused by UV radiation, which results in early aging of the skin and the development of malignant skin tumors. Robins assumes that the eye is involved in 60% of the cases. In our patient we found a dense opacity of both corneas in addition to the typical lentiginous alteration of the skin. Therefore, a corneal transplantation was carried out on both eyes. The corneal buttons obtained by keratoplasty were examined by light, and transmission electron microscopy. We found massive alterations in the tissues of all corneal layers.

Adult↗

A combined method of acetylcholinesterase histochemistry and [3H]thymidine autoradiography: application to neurogenesis of the rat basal forebrain cholinergic system.

Rats labelled with [3H]thymidine on embryonic day 15 were treated postnatally with diisopropylfluorophosphate and 2-3 h later perfused with 10% buffered formalin. Cryostat sections of the basal forebrain were autoradiographed and subsequently stained for acetylcholinesterase (AChE). It was shown that this procedure did not significantly influence either the AChE activity or the silver grains over [3H]thymidine-labelled nerve cell nuclei. The labelling index evaluated in cholinergic forebrain regions (medial septum, diagonal band of Broca, substantia innominata, nucleus basalis of Meynert) indicated a caudorostral gradient of the formation of AChE-containing neurons while formation of non-cholinergic neurons showed a more even pattern.

Acetylcholinesterase↗

Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder.

Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment. Such a method has been used to establish the dose-effect relationship of perindopril. After a two-week placebo run-in period, 40 patients with essential hypertension (age 56.6 +/- 1.5 years, 31 males, nine females) were treated with placebo or 2, 4 or 8 mg of perindopril once daily for one month following a randomized double-blind design. They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Values (mean +/- SEM) before and after treatment were assessed using analysis of variance. These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose. Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer, confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials.

Adult↗

Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis.

The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport.

Amino Acids↗