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Biomedical subjects

C Schuster

Publications and source records attributed to C Schuster.

At least 55 records · Page 3Linked to original sources

Decidua and placenta in mice after treatment with a synthetic glucocorticoid.

To investigate a possible long-term effect of glucocorticoids on decidua and placenta of mice, a single dose of 24 mg kg-1 body weight triamcinolone acetonide in crystalline suspension was given subcutaneously to NMRI mice on gestational day (GD) 2. Deciduae and placentae, as well as corticosterone and triamcinolone concentrations in maternal plasma of GDs 10 and 17 were examined. NADPH-cytochrome P450 reductase involved in drug biotransformation was detected immunocytochemically and showed co-localization with NADPH diaphorase histochemistry in the decidua and placenta. Both reactions were higher in endothelial cells of decidual sinusoids on GD 10, but were lower on GD 17 in the trophoblast, spongiotrophoblast and extraplacental visceral yolk-sac epithelial cells of treated mice than in untreated animals. Histochemistry of 11 beta-hydroxysteroid dehydrogenase, an enzyme that metabolizes biologically active adrenocortical steroids and their synthetic congeners in the placenta, showed higher activity on GD 17 in enlarged labyrinthic trophoblast I cells of treated mice than in untreated animals. As corticosterone concentrations were still decreased on GD 17, when triamcinolone concentrations were no longer detectable, a long-term suppression of adrenal gland function seems obvious.

11-beta-Hydroxysteroid Dehydrogenases↗

Point mutations 5' to the tRNA selenocysteine TATA box alter RNA polymerase III transcription by affecting the binding of TBP.

The selenocysteine tRNA(Sec) gene possesses two external promoter elements, one of which is constituted by a strong TATA box. Point mutant analysis performed in this study led to the conclusion that the functional TATA promoter actually encompasses the sequence -34 GGGTATAAAAGG-23. Individual changes at T-31 do not affect transcription much. Position T-29 is less permissive to mutation since transversion to a G, for example, is less well tolerated than at T-31. Interestingly, a double point mutation, converting GG(-33/-32) to TT, causes abrogation of transcription in vivo and severe reduction of transcription in vitro with human TBP. Therefore, data obtained underscore the fact that, in the Xenopus tRNA(Sec), these two Gs are an integral part of the TATA promoter. Gel retardation experiments indicate that the GG to TT substitution, which led human TBP to lose its ability to support efficient transcription in vitro, correlates with the appearance of an altered pattern of retarded complexes. Altogether, the data presented in this report support a model in which TBP interacts directly with the TATA element of the tRNA(Sec) gene, in contrast to the type of interaction proposed for classical TATA-less tRNA genes.

Animals↗

Promoter strength and structure dictate module composition in RNA polymerase III transcriptional activator elements.

RNA polymerase III transcription of genes with external promoters only (e.g. U6 snRNA) or containing in addition an internal B box (selenocysteine tRNA(Sec)) is stimulated by upstream elements; a distal sequence element (DSE) for U6 or an activator element in the tRNA(Sec) gene. In contrast to the composite structure of the DSE which requires an octamer motif, the Xenopus tRNA(Sec) activator element contains an SPH motif only. In vivo transcription is optimally stimulated by SPH in an absolute octamer-independent manner since adding octamer does not induce superstimulation. Experiments performed in the work presented here led to the following observations. Co-operation between SPH and octamer motifs can be detected in two distinct cases: first when these motifs are placed in front of B box-less tRNA(Sec) or U6 external promoters and second, if either element of the external promoter (proximal sequence element or TATA element), or the SPH motif itself, are altered. Altogether, our data provide evidence that an SPH motif can function alone in an optimized promoter only. In contrast, an octamer becomes indispensable when the basal promoter is weak or disabled. It follows that module composition of Pol III transcriptional activator elements is dependent on the structure and strength of the promoter. This reveals the existence of cross-talk between activator and promoter elements, mediated by the bound transcription factors, which are thus able to compensate for each other in order to allow successful assembly of the transcription complex.

Animals↗

Antiproliferative action of the steroid RU486 in cultured human lymphoma cells.

The antiproliferative properties of the synthetic steroid RU486 on the human lymphoma cell line Daudi are described. In suspension cultures, RU486 (10 microM) caused a time dose and cell density dependent reduction of cell proliferation. This effect was reversed within 48 h of withdrawal of RU486 from the growth medium. High concentrations of foetal calf serum can mask the inhibitory effect. In semi-solid cultures RU486 also impaired cell proliferation. Thus RU486 was able to suppress in this tumor cell line the expression of some properties frequently associated with the transformed status of the cells.

Cell Count↗

The Colorado Tobacco-Free Schools and Communities Project.

This article defends the appropriateness of tobacco-free school policies as an effective tool toward ensuring young people develop into healthy and intellectually strong adults, and demonstrates how such a policy can be introduced into a school district. Health education efforts to eliminate tobacco use are widely considered more effective when carried out in concert with school policies and adult role models offering the consistent message that tobacco use is unhealthy and unacceptable. Studies indicate students who attend schools with strict smoking policies are less likely to begin smoking than students who attend schools without such policies. Through research, support, and guidance, the Colorado Tobacco-Free Schools and Communities Project successfully has assisted almost half the 176 school districts in Colorado to adopt such policies.

Adolescent↗

[Prenatal diagnosis of thanatophoric dwarfism].

Thanatophoric dwarfism is a rare malformation, occurring in less than 1:10,000 pregnancies. It can be discovered by standard ultrasound examination, but other skeletal dysplasias such as achondroplasia, achondrogenesis and polydactyly syndromes must be taken into consideration. Sonographic findings are polyhydramnia, narrow chest, symmetric tetramicromelia and macrocephaly. Macrocephaly might cause a problem for vaginal delivery. The narrow chest with secondary lung hypoplasia determines the infaust prognosis.

Adult↗

Altered murein composition in a DD-carboxypeptidase mutant of Streptococcus pneumoniae.

The muropeptide composition of a Streptococcus pneumoniae mutant in which the DD-carboxypeptidase (penicillin-binding protein 3) gene was interrupted by plasmid insertion close to the 3' end of the gene was examined. Extensive compositional changes were observed: the linear pentapeptide, a minor component of the parental cells, became the most abundant monomeric peptide in the mutant wall, while the proportion of tripeptides that represent the main monomers in the parental cells was greatly reduced. The amount of the major dimer of parental cells, the directly cross-linked tri-tetrapeptide, was also reduced by a factor of 4. It was partially replaced by a novel dimer: the cross-linked product of a linear pentapeptide and a pentapeptide carrying a serylalanine dipeptide substituent on the epsilon-NH2 group of its lysine residue. This dimer together with two other dimeric peptides, each containing the serylalanine cross bridge, became the quantitatively major components of the mutant peptidoglycan.

Amino Acid Sequence↗

[Nitrogen and chemical oxygen demand burden of waste water caused by trout raising influenced by the protein content of the feed].

A possibility was shown, how to quantify the water content of nitrogen and COD (Chemical Oxygen Demand) from intensive fish production, independent of flow rate and feeding time. The nitrogen excretion could be reduced 50% by feeding a protein reduced fish feed (A: 38.4% XP) compared with an fish feed B contending 47.9% protein (XP). The excretion-compartments were evaluated with the waste water parameter COD. Doing this, it could be shown that the COD input by feed A is reduced 20% in opposite to feed B. Further more the separation of fish faeces would achieve an COD reduction from about 50% to 70%.

Animal Feed↗

Relatedness between Streptococcus pneumoniae and viridans streptococci: transfer of penicillin resistance determinants and immunological similarities of penicillin-binding proteins.

The occurrence of highly variable penicillin-binding proteins (PBPs) in penicillin-resistant Streptococcus pneumoniae suggested that transfer of homologous genes from related species may be involved in resistance development. Antiserum and monoclonal antibodies raised against PBPs 1a and 2b from the susceptible S. pneumoniae R6 strain were used to identify related PBPs in 41 S. mitis, S. sanguis I and S. sanguis II strains mostly isolated in South Africa with MIC values ranging from less than 0.15 to 16 mg/ml. Furthermore, the possibility of genetic exchange was examined with 30 penicillin-resistant strains of this collection (MIC greater than 0.06 mg/ml) as donors using S. pneumoniae R6 as recipient in transformation experiments. The majority of S. mitis and S. sanguis II strains but none of the S. sanguis I strains could transform penicillin resistance genes into S. pneumoniae R6. All positive donor strains and all susceptible isolates of S. mitis and S. sanguis II strains contained PBPs which cross-reacted with the anti-PBP 1a and/or anti-PBP 2b antibodies. On the other hand, only five of the 14 S. sanguis I strains contained a PBP that reacted with one of the antibodies. This strongly suggested the presence of genes homologous to the pneumococcal PBP 1a and 2b genes in viridans streptococci, and documents that penicillin resistance determinants can be transformed from viridans streptococci into the pneumococcus.

Bacterial Proteins↗

Activation of Epstein-Barr virus promoters by a growth-factor and a glucocorticoid.

Transforming growth factor-beta (TGF-beta) and a glucocorticosteroid, Dexamethasone (DXM), both cause transcriptional induction of Epstein-Barr virus (EBV) early antigens (EA) in Daudi lymphoma cells. The viral induction occurs through the viral promoter DR overlapping an origin of replication which is active during the lytic cycle. Each hormone requires specific regions on the DR promoter. Since these regions also mediate the action of two viral transcription factors, EB1 and R, it may be emphasized that EB1 and/or R are involved in the EA induction process by TGF-beta and by DXM.

Antigens, Viral↗

Penicillin-binding proteins in Streptococcus pneumoniae: alterations during development of intrinsic penicillin resistance.

Four out of the five high molecular weight penicillin-binding proteins (PBPs) of Streptococcus pneumoniae are involved in the development of intrinsic penicillin resistance. In beta-lactam resistant laboratory mutants, point mutations in the PBP 2x-genes were identified that result in low penicillin-affinity mutant proteins. In contrast, PBPs 1a, 2x, and 2b of resistant clinical isolates are highly altered as can be recognized biochemically and immunologically; DNA sequence analysis of the PBP 2x gene from resistant strains confirmed these results. The variability of the three PBPs analyzed implies a very heterogeneous gene pool accessible to the pneumococcus that is used for recruitment of resistant PBP genes in wild type strains.

Anti-Bacterial Agents↗

Evidence for a functional glucocorticoid responsive element in the Epstein-Barr virus genome.

Glucocorticoids induce the expression of Epstein-Barr virus early antigens in latently infected Daudi cells. By sequence analysis, we found that fragment C of the BamHI digested Epstein-Barr virus B95-8 genome contains a region with a large degree of homology to the glucocorticoid responsive element of known glucocorticoid-regulated genes. By transfection experiments in Daudi and HeLa cells, different lengths of this region, cloned in front of the bacterial chloramphenicol acetyl transferase linked to the Herpes Simplex virus thymidine kinase promoter (pBLCAT.2), were assayed for their responsiveness to dexamethasone; our results led us to the conclusion that the hormonal effect observed was mediated by a minimal sequence of 15 base pairs presenting 85% homology with the consensus glucocorticoid responsive element sequence.

Base Sequence↗

Unusual septum formation in Streptococcus pneumoniae mutants with an alteration in the D,D-carboxypeptidase penicillin-binding protein 3.

An internal 630-bp DNA fragment of the gene encoding penicillin-binding protein 3 (PBP 3) (dacA) of Streptococcus pneumoniae was identified in a lambda gt11 gene bank screened with anti-PBP 3 antiserum. The deduced 210-amino-acid sequence showed a high degree of homology to the low-molecular-weight PBPs 5 and 6 of Escherichia coli and Bacillus subtilis PBP 5. Viable mutants lacking a C-terminal part of PBP 3 were obtained after a plasmid containing the dacA fragment was integrated into the PBP 3 gene by homologous recombination. The truncated PBP 3* was still active in terms of beta-lactam binding. Most PBP 3 was found in the growth medium, indicating that membrane anchoring of PBP 3 is provided by the C terminus, as has been shown for other D,D-carboxypeptidases. The mutant cells grew with a slower generation time than the wild type in the shape of irregular enlarged spheres. In addition, as revealed by electron microscopy, cell separation was severely affected, septa were found unevenly distributed at multiple sites within the cells, and the murein layer appeared variable in thickness.

Amino Acid Sequence↗

[Electronic data processing-assisted text processing at the clinic and in general practice].

Word processing is currently the most frequent application for personal computers, and a wide variety of standard software is available. The capabilities of modern word-processing software includes the convenient typing and correction of all routine correspondence, as well as the professional layout of scientific manuscripts. The decision to purchase a certain word-processing programm should be made according to local needs and prerequisities. Three to six months may be necessary to fully adapt the organization of a clinic or private practice to the new technology.

Computer Systems↗

Binding studies of the antiglucocorticoid RU38486 in Daudi and Raji lymphoma cells.

The activity of RU38486 has been studied in Burkitt's lymphoma cells which are Epstein-Barr virus (EBV) positive. The early antigens (EA) of the virus are induced by dexamethasone (DXM) in Daudi but not in Raji cells, whereas a growth factor (transforming growth factor-beta, TGF-beta) induces the EA in both cell lines. RU38486 blocks the EA induction obtained by DXM or by TGF-beta in either cell line. In order to understand the interaction of RU38486, we considered its binding to specific receptors. We first investigated the binding of the antagonist in whole cells at 22 degrees C. A number of specific binding sites higher for RU38486 than for DXM was found, suggesting that RU38486 may bind to the glucocorticoid receptor and also to other cellular structures which we called the antiglucocorticoid binding sites ("AGBS"). To support this hypothesis, competition experiments have been conducted between RU38486 and other steroid hormones (progesterone and testosterone) since it is known that RU38486 is also able to interact with their cognate receptors. Binding studies of RU38486 in vitro at 4 degrees C in the presence of cytosolic extracts from Daudi and Raji cells led to conclusions similar to those drawn from the whole cell experiments: more complexes were formed with RU38486 than with DXM. Finally, the steroid-receptor complexes were incubated with DNA-cellulose. Since the binding measured for RU38486 was higher than for DXM, we suspect that sites different from the classical glucocorticoid receptor sites are also able to interact with DNA. The blockage exerted by RU38486 on the EA induced by glucocorticoids or by non-steroidal molecules and the lack of responsiveness to glucocorticoids in Raji cells are discussed in the light of the present findings.

Binding, Competitive↗

[Prevalence and incidence of arterial hypertension in patients with kidney calculi treated by extracorporeal shock wave lithotripsy].

Follow-up studies were conducted on 806 patients to investigate the question of whether or not arterial hypertension can develop subsequent to ESWL. First of all, it was determined that 509 of 518 patients who were subjected to ESWL treatment from December 1985 to December 1986 still had normotension (n = 410) or hypertension (RR greater than or equal to, 160/95, n = 99) prior to and on an average of 9.3 months after ESWL. Six hypertensive patients became normotensive subsequent to ESWL. Only 1 patient developed hypertension following ESWL. Secondly, the 288 patients who were subjected to ESWL treatment from May 1982 to May 1984 revealed a 3.1% incidence of arterial hypertension within a period of 3.6 years following ESWL. This incidence, however, only illustrates that there was a pronounced age-related increase in the prevalence of hypertension (0.8% per year) in these study groups.

Adult↗

[Long-term experiences following extracorporeal shockwave lithotripsy in patients with urinary calculi].

A report is given on the experience we have had over a period of up to 7 years following ESWL treatment in urinary stone patients. 131I-hippuran clearance studies were conducted on 19 patients prior to and 6.6 years subsequent to ESWL. There was no evidence of any degree of deterioration in total renal function or of any form of dysfunction in the kidney treated. Follow-up examinations on 247 patients showed a 7% recurrent stone rate within a period of 3.6 years following ESWL. In 16% of the cases, residual concretions were found 6 months after ESWL, only 4% of which were larger than 5 mm in diameter. In 22%, concretions were discovered 3.6 years after ESWL 36% of which were larger than 5 mm. This size increase in the fragments accounts for the stone growth.

Adult↗