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Biomedical subjects

Daniela Hahn

Publications and source records attributed to Daniela Hahn.

5 recordsLinked to original sources

Proteolytic activation of executioner caspase-3 and -7 regulates different physiological processes in mice.

Caspase-3 (CASP3) and caspase-7 (CASP7) are the two major executioner caspases that are proteolytically activated by upstream initiator caspases. They possess almost indistinguishable activity, which has led to the overall view that these caspases have functionally redundant roles. Here, we generate knock-in mice expressing cleavage-resistant CASP3(D175A) or CASP7(D198A). Our results show that proteolytic activation of CASP3 and CASP7 is decisive for their activity in vivo and controls redundant processes during embryonic development as combined expression of both CASP3(D175A) and CASP7(D198A) causes embryonic lethality. In adult mice, however, activation of CASP3 and CASP7 controls different processes in different tissues, without the involvement of apoptosis. While CASP7 activation is required for male fertility by controlling spermatogenesis, CASP3 activation appears crucial for lymphoid tissue development by regulating interferon signalling. Our findings shed light on emerging roles of caspases in non-apoptotic processes and provide impetus for reconsidering their involvement in physiological and pathological conditions.

Animals↗

Psychological comorbidity in medical rehabilitation--the need for education.

PURPOSE: Prevalence of comorbid mental disorders in rehabilitation patients is high. In spite of the bio-psycho-social approach in rehabilitation, recognition and treatment rates of comorbid mental disorders during rehabilitation are low. The purpose of the study was to raise specific information about current clinical practice concerning comorbid mental disorders and training needs of rehabilitation personnel. METHOD: 435 questionnaires were sent out to medical personnel in 54 rehabilitation hospitals in south-west Germany. RESULTS: Psychologists in rehabilitation spend most of their time on counselling (45%) and group interventions (29%). Physicians and psychologists both feel highly responsible for recognizing mental disorders and motivating patients to seek aftercare. Screeners are rarely used by psychologists and physicians. Seventy-six percent of the participants would take part in specific training sessions. High training needs were stated for affective, anxiety and somatoform disorders. A specific training session for mental health in rehabilitation should last at least half a day and cover affective, anxiety and somatoform disorders. CONCLUSIONS: Taking these results into account, it is possible to put together a training program in diagnostics of comorbid mental disorders, which fits the needs of the professionals.

Comorbidity↗

Two adjacent nuclear genes are required for functional complementation of a chloroplast trans-splicing mutant from Chlamydomonas reinhardtii.

The chloroplast tscA gene from Chlamydomonas reinhardtii encodes a co-factor RNA that is involved in trans-splicing of exons 1 and 2 of the psaA mRNA encoding a core polypeptide of photosystem I. Here we provide molecular and genetic characterization of the trans-splicing mutant TR72, which is defective in the 3'-end processing of the tscA RNA and consequently defective in splicing exons 1 and 2 of the psaA mRNA. Using genomic complementation, two adjacent nuclear genes were identified, Rat1 and Rat2, that are able to restore the photosynthetic growth of mutant TR72. Restoration of the photosynthesis phenotype, however, was successful only with a DNA fragment containing both genes, while separate use of the two genes did not rescue the wild-type phenotype. This was further confirmed by using a set of 10 gene derivatives in complementation tests. The deduced amino acid sequence of Rat1 shows significant sequence homology to the conserved NAD+-binding domain of poly(ADP-ribose) polymerases of eukaryotic organisms. However, mutagenesis of conserved residues in this putative NAD+-binding domain did not reveal any effect on restoration efficiency. Immunodetection analyses with enriched fractions of chloroplast proteins indicated that Rat1 is associated with chloroplast membranes. Using the yeast three-hybrid system, we were able to demonstrate the specific binding of tscA RNA by the Rat1 polypeptide. We propose that the two nuclear factors Rat1 and Rat2 are involved in processing of chloroplast tscA RNA and in subsequent splicing of psaA exons 1 and 2.

Algal Proteins↗

Glucocorticoids decrease the bioavailability of TGF-beta which leads to a reduced TGF-beta signaling in hepatic stellate cells.

Glucocorticoids bound to their receptors transmit information, which regulates numerous physiological and pathophysiological responses, amongst others glucose metabolism, wound healing, inflammation, and stress, either directly as transcription factors by binding DNA elements of target genes or indirectly by protein-protein interactions with other transcription factors. TGF-beta, a key factor in activation of hepatic stellate cells (HSC), induces production of extracellular matrix, this being a prerequisite for the development of liver fibrosis. Glucocorticoids and their receptors may provide a crosstalk with the TGF-beta-Smad signaling pathway by antagonizing TGF-beta effects. We studied the influence of glucocorticoids on the TGF-beta isoform and Smad mRNA expression, TGF-beta secretion, and signaling in activated HSC using gene-specific real-time PCR, ELISA, and transfection techniques. Dexamethasone treatment reduces TGF-beta mRNA transcription in a time-dependent manner. Activated HSC produce TGF-beta and secrete it into the cell culture medium. After dexamethasone treatment, TGF-beta secretion into the medium is reduced dose-dependently but restorable by mifepristone. Further, we found that reduced secretion of endogenous TGF-beta is accompanied by a reduced TGF-beta signal. Additionally, reporter gene analysis after adenoviral infection with a recombinant virus encoding a Smad-binding-element showed that TGF-beta-Smad signaling is significantly down-regulated by dexamethasone in primary HSC and CFSC, a HSC related cell line. Our data suggest that glucocorticoids inhibit TGF-beta expression, prevent TGF-beta from efficient secretion, and finally lead to reduced TGF-beta signaling in primary HSC.

Adrenal Cortex Hormones↗

Prophylaxis of ophthalmia neonatorum--a nationwide survey of the current practice in Austria.

UNLABELLED: The aim of this study was to analyze the current practice of Ophthalmia neonatorum prophylaxis in Austria. Questionnaires were sent to 107 hospitals with obstetric units, as well as to 490 registered community midwives, together looking after a yearly total of approximately 70,000 births. The overall return of the hospitals and midwives was 91.6% and 7.6%, respectively. RESULTS: Ophthalmia neonatorum prophylaxis is being applied by 93.8% of all respondents (hospitals 96.9%, and community midwives 82.3%). The three most frequently applied substances were Erythromycin (41.8%), Gentamicin (21.3%) and Silver nitrate (19.7%). Other substances were Tetracycline, Povidone-Iodine, Neomycin and Chloramphenicol. The reported overall-observation of chemical conjunctivitis after application of a prophylactic agent was 42.3% (55/133), typically after the use of Silver nitrate, Erythromycin or Tetracycline. The agent was determined by pediatricians (29%), in accordance to governmental decree (15%), by hospital policy (12%), effectiveness against Chlamydia and Gonococci (9%), by pharmacists (3%) and ophthalmologists (3%). 18% did not give any reason for the choice of agent. CONCLUSION: The rationale for prophylaxis and the substances used in Austria show heterogeneity. Seven prophylactic agents are used, two antiseptics and five antibiotics. 25% of the routine applicants are using substances (Gentamicin, Neomycin or Chloramphenicol) for which no evidence based efficacy for prophylaxis of Ophthalmia neonatorum has been demonstrated through clinical trials. However, 83.5% of the maternity units do not want changes in their current routine, unless there is a nation-wide agreement for Ophthalmia neonatorum prophylaxis.

Anti-Infective Agents, Local↗