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Biomedical subjects

S Hahn

Publications and source records attributed to S Hahn.

At least 181 records · Page 10Linked to original sources

Modulation of cytokine expression in PB-3c mastocytes by IBMX and PMA.

Stimulation of mast cells, either via the IgE receptor or with calcium ionophore triggers the production of several cytokines, such as interleukins-3, -4, -5, and -6, and GM-CSF. In PB-3c mastocytes, ionophore-induced IL-3 and GM-CSF expression is primarily the result of mRNA stabilization, and is enhanced by oncogenic ras. Apart from mobilizing calcium, the IgE receptor activation leads to production of DAG and elevation of cAMP levels, thereby activating protein kinases C and A, respectively. The influence of these two secondary messengers on cytokine production was examined using the cAMP elevating agent IBMX, the phorbol ester PMA, and the staurosporine derivative CGP 41251, which preferentially inactivates PKC. IBMX was determined to be a potent coinducer of IL-3 expression, whereas elevation of IL-6 and GM-CSF was more pronounced in PMA-treated cells. Both PMA and IBMX were shown to act posttranscriptionally on IL-3, by extending the half-life of the mRNA. Ionophore-induced cytokine expression appears to require serine/threonine kinase activity, as it could be abolished by treatment with the drug CGP 41251. Our results therefore suggest that the factors regulating cytokine expression and mRNA stability are subject to regulation by serine/threonine phosphorylation.

1-Methyl-3-isobutylxanthine↗

[Elder care in nursing homes during national socialism in Germany].

The situation of the elderly during the Third Reich has hitherto been neglected by research. This paper deals with the living conditions and the fate of the aged in institutional homes in Saxony. Those no longer able to care for themselves were subjected to the aggressive social and military goals pursued by the National Socialists and were victimized in the organisation of medical care. Many conditions contributed to the destruction of their lives: not only the emptying of homes for the elderly to make room for military hospitals, disorienting relocation programmes, and the murderous "T4" programme, but also the death of children during the war, the destruction of property and the loss of a home due to forced dislocation.

Aged↗

Crystal structure of a yeast TBP/TATA-box complex.

The 2.5 A crystal structure of a TATA-box complex with yeast TBP shows that the eight base pairs of the TATA box bind to the concave surface of TBP by bending towards the major groove with unprecedented severity. This produces a wide open, underwound, shallow minor groove which forms a primarily hydrophobic interface with the entire under-surface of the TBP saddle. The severe bend and a positive writhe radically alter the trajectory of the flanking B-form DNA.

Amino Acid Sequence↗

Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism.

OBJECTIVE: The study investigated the neuropsychological status of women with induced hypoestrogenism. DESIGN: An ABA design was employed in which neuropsychological measures were repeated prior to, during, and after induction of hypoestrogenism with leuprolide acetate. SETTING: The study took place in a medical school affiliated in vitro fertilization clinic. INTERVENTIONS: Leuprolide acetate was administered to all subjects as part of in vitro fertilization. METHODS: Eighteen women receiving in vitro fertilization treatment underwent neuropsychological testing before, during, and after treatment with leuprolide acetate and gonadotrophins. The neuropsychological test battery was selected on the basis of previous patients' symptomatic complaints during periods of hypoestrogenism with leuprolide acetate. RESULTS: Depending upon the tests administered, some individuals showed significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two-point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances. However, in terms of group statistics, only two-point discrimination and delayed recall memory test performance proved significant. Not all measures were sensitive for the group, as many tests displayed a balance between individuals who showed practice effects and those who showed detrimental effects. CONCLUSIONS: For a substantial portion of individuals, hypoestrogenism can result in statistically significant or clinically noteworthy problems with memory, dexterity, and two-point discrimination.

Adult↗

An ATP-dependent inhibitor of TBP binding to DNA.

An activity in yeast nuclear extracts (termed ADI) is described that inhibits the binding of the TATA-binding protein (TBP) to DNA in an ATP-dependent manner. The effect is reversible, ATP specific, rapid, and is not promoter specific. ADI is specific for TBP because three other protein-DNA complexes are not affected by ADI. The action of ADI is blocked by association of TFIIA with the TBP-DNA complex. ADI activity at the adenovirus major late promoter requires a segment of DNA upstream from the TATA sequence, suggesting that ADI recognizes aspects of both TBP and DNA. The evolutionarily conserved carboxy-terminal domain of TBP is sufficient for ADI recognition, and amino acids in the basic region of TBP are required for ADI action. ADI can repress transcription in vitro in an ATP-dependent manner. In the presence of ADI, both TFIIA and TBP are required to commit a template to transcription. A model of ADI action is proposed, and possible roles of ADI in the regulation of the transcription complex assembly are discussed.

Adenosine Triphosphate↗

[100 years ago: the first school doctors in Leipzig--a contribution to the history of school health in Germany].

One hundred years ago, in May 1892, the first school doctors began their work. The medical and organizational conditions for activities in school hygiene in Germany, their problematic linkage to "racial hygiene" and the military, and the favourable conditions for school medicine at the national and local levels and among members of the profession in Leipzig and Saxonia are presented. A description of the doctors' hygiene-oriented tasks in the schools completes the picture of the development of school hygiene in imperial Germany and in one of its richest cities.

Child↗

The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor, TFIIIB.

The Saccharomyces cerevisiae RNA polymerase III transcription factor (TF)IIIB has been assembled from three components. An assembly pathway of these polypeptides, which specifies their interactions, has been determined. The TATA-binding protein, TBP, and the TFIIB-related BRF1 gene product BRF, together reconstitute the transcription factor activity and TFIIC-dependent DNA-binding activity of the B' component of TFIIIB. BRF alone weakly binds to a TFIIIC-tRNA gene complex; TBP greatly stabilizes this interaction. B" transcription factor activity is recovered with its previously identified 90 kd polypeptide from SDS-polyacrylamide gels. Incorporation of the 90 kd B" protein into the transcription complex requires TBP. The heparin-resistant TFIIIB-DNA complex retains all three of its constituent proteins, TBP, BRF, and B".

Base Sequence↗

Comparison of wet digestion procedures for the determination of cadmium and lead in marine biological tissues by Zeeman graphite furnace atomic absorption spectrophotometry.

Three wet digestion procedures, namely, nitric acid/sulphuric acid, nitric acid/hydrogen peroxide and nitric acid/perchloric acid were compared for their relative efficiency in determining cadmium and lead in marine biological tissues. The nitric acid/perchloric acid procedure was the most efficient, whereas the nitric acid/hydrogen peroxide procedure was the least efficient. The nitric acid/sulphuric acid procedure was also found to be effective but there was a problem with the method as the presence of sulphuric acid in the matrix markedly suppressed the absorbance signals especially for lead analysis and thus reduced sensitivity. The addition of ascorbic acid as matrix modifier improved sensitivity. However, this analysis still required the standard addition method. No apparent interferences were encountered for cadmium analysis.

Animals↗

Variants of the TATA-binding protein can distinguish subsets of RNA polymerase I, II, and III promoters.

Transcription extracts prepared from yeast that are deficient in the TATA-binding protein (TBP or TFIID) are also impaired in specific promoter recognition by all three nuclear RNA polymerases (pol I, II, and III). Specific initiation can be rescued by the addition of purified recombinant TBP, demonstrating that pol I, II, and III all require this factor. A mutation of TBP has been identified that will function with pol I but not with pol II or III. Conversely, another mutation, which inactivates TATA element binding in vitro, will function with pol I and III promoters but is inactive for a pol II promoter. Thus, it is possible to identify TBP variants that will only function on different subsets of all nuclear promoters.

DNA-Binding Proteins↗

Isolation of two genes that encode subunits of the yeast transcription factor IIA.

The yeast transcription factor IIA (TFIIA), a component of the basal transcription machinery of RNA polymerase II and implicated in vitro in regulation of basal transcription, is composed of two subunits of 32 and 13.5 kilodaltons. The genes that encode these subunits, termed TOA1 and TOA2, respectively, were cloned. Neither gene shares obvious sequence similarity with the other or with any other previously identified genes. The recombinant factor bound to a TATA binding protein-DNA complex and complemented yeast and mammalian in vitro transcription systems depleted of TFIIA. Both the TOA1 and TOA2 genes are essential for growth of yeast.

Amino Acid Sequence↗

CD4+ T cell-mediated killing of major histocompatibility complex class II-positive antigen-presenting cells (APC). III. CD4+ cytotoxic T cells induce apoptosis of APC.

A subset of CD4+ T cells, belonging to the T helper type 1 (Th1) cells, kills antigen-presenting cells (APC) in an antigen-specific and major histocompatibility (MHC) class II-restricted way. Evidence is presented that CD4+ cytotoxic T lymphocytes (CTL) induce apoptosis or programmed cell death within susceptible APC as witnessed by quantitative DNA fragmentation. Apoptosis is more reliable to determine cell death than the 51Cr-release assay, because some cells demonstrate resistance to CD4-mediated lysis in the 51Cr-release assay. Apoptosis becomes manifest after 2 to 4 h of incubation preceding the disintegration of the target cells which is detectable between 12 and 24 h as measured by the 51Cr-release assay. Unstimulated B cells, which are not killed, but function as APC, do not undergo apoptosis, whereas lipopolysaccharide or anti-mu-activated B cell blasts show apoptosis and are efficiently lysed. Several CD4+ Th2-type cells tested, which did not demonstrate killing of APC as measured by the 51Cr-release assay, are unable to mediate programmed cell death of appropriate APC. Actinomycin D or cycloheximide, inhibitors of transcription and translation, respectively, fail to prevent apoptosis of APC excluding the involvement of newly synthesized soluble products as mediators of killing. Pretreatment of CD4+ CTL, but not of APC with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a specific inhibitor of the anion transport, efficiently prevents apoptosis of APC, although the secretion of interleukins is not affected. We propose, that upon contact of the CD4+ CTL with APC, molecules of yet undefined nature are activated and released in a polar fashion at the contact site and induce the endogenous pathway of programmed cell death.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Topical application of nitroxide protects radiation-induced alopecia in guinea pigs.

We have recently found that treatment of Chinese hamster V79 cells with the stable nitroxide radical TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) afforded significant protection against superoxide, hydrogen peroxide, and X-ray mediated cytotoxicity. Radiation-induced alopecia is a common radiotherapeutic problem. Topical application of TEMPOL was evaluated for possible protective effects against radiation-induced alopecia using guinea pig skin as a model. For single acute X-ray doses up to 30 Gy, TEMPOL, when topically applied 15 min prior to irradiation provided a marked increase in the rate and extent of new hair recovery when compared to untreated skin. TEMPOL was detected in treated skin specimens with electron paramagnetic resonance (EPR) spectroscopy. Similar measurements of blood samples failed to show any signal resulting from topical application, nor could TEMPOL be detected in brain tissue after application on the scalp. TEMPOL represents a new class of compounds with potential for selective cutaneous radioprotection without systemic absorption.

Administration, Topical↗

A yeast TFIIB-related factor involved in RNA polymerase III transcription.

A suppressor gene was identified, which in high copy number rescues a temperature-sensitive mutation in yeast TATA-binding protein (TBP). Suppression was allele specific because the suppressor did not rescue the temperature-sensitive phenotype of another TBP mutant. This suppressor gene encodes a 596-amino-acid protein of which the amino-terminal half is homologous to the Pol II-specific factor TFIIB. Disruption of this gene, termed BRF1, showed it to be essential for growth of yeast. Deletion of sequences at either the amino or carboxyl terminus of BRF1 gave both temperature- and cold-sensitive phenotypes. These temperature- and cold-sensitive strains were used to prepare extracts deficient in BRF1 activity and were tested for transcriptional activity by RNA polymerases I, II, and III in vitro. BRF1-deficient extracts are defective in Pol III transcription and can be reconstituted for Pol III transcription by the addition of recombinant BRF1. Western analysis shows that BRF1 is present in TFIIIB but not the TFIIIC fraction, suggesting that it is a component of TFIIIB. We propose that BRF1 plays a role in Pol III initiation analogous to the role played by TFIIB for Pol II in its interaction with TBP and polymerase. The identification of a Pol III-specific TFIIB-like factor extends the previously noted similarity of transcriptional initiation by the three nuclear polymerases.

Amino Acid Sequence↗

["Rejuvenation" as the outcome of research on aging: dreams and theories--experiments and results].

A report is given on experiments of rejuvenation which were carried out in the first decenniums of the 20th century. The knowledge of the effect of sexual hormones on the one hand and still missing possibilities of synthesisation on the other gave rise to spectacular transplantations and further operation techniques as well as physical forms of therapy on testicles and ovaries. The fundaments of the scientific theory and the social backgrounds of these side branches of gerontology which established itself only at the end of the thirties are mentioned.

Aging↗

[Leipzig Medical Society (founded in 1829)].

The Leipzig Medical Society was founded in 1829 by Justus Radius. More than 100 years this interdisciplinary association was a scientific and cultural centre which promoted scientific life and professional training of the municipal physicians and the university staff. Therefore the Leipzig Medical Society contributed to reputation of Leipzig as an cultural and scientific centre during the last years of the 19th and the beginning of the 20th century.

Germany↗