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T Welte

Publications and source records attributed to T Welte.

123 records · Page 7Linked to original sources
PubMed1997

[Why do adults with mucoviscidosis refuse a medically recommended course of intravenous antibiotic therapy?].

BACKGROUND: Regular courses of intravenous antibiotics are recommended for the treatment of chronic Pseudomonas aeruglnosa (PA) infection in patients with cystic fibrosis. We report the results of interviews performed to evaluate why a subgroup of patients vote against regular intravenous (i.v.) antibiotic treatment. METHODS: Structured interviews covering a) the individual's perception of chronic PA infection, b) the patient's expectations regarding the effectiveness of i.v. treatment, c) the patient's personal reasons for refusal of i.v. treatment. STUDY COHORT: 16 out of 18 adult patients treated in the adult CF outpatient clinic at Hannover Medical School who had voted against the physician's recommendation to receive regular i.v. therapy twice a year. RESULTS: More than one half of the patients did not regard chronic PA infection as important due to the lack of specific symptoms. A subgroup of patients had no idea of what their clinical status should be if i.v. antibiotics would be necessary; these patients reported prior experience of treatment courses which had been ineffective and had been instituted after talking into the patients. The most frequent reasons against IV treatment were not being sick enough and fear of adverse drug effects. ASSESSMENT: The results are being discussed considering the physician-patient relationship. The reasons why patients refuse help should be extensively explored rather than simply addressing this attitude as "non-compliance". Patients, too, come to reasonable decisions, and it is important to know their thoughts and reasoning if one intends to influence them.

Adult↗
PubMed1996

Comparative study on the phosphotyrosine motifs of different cytokine receptors involved in STAT5 activation.

Several cytokines and growth factors activate transcription of their target genes via the JAK/STAT signalling pathway. It has been shown that the interaction between SH2 domains of STAT factors and receptor phosphotyrosine residues plays an essential role in the specific recruitment of STATs. For STAT5, however, the importance of receptor tyrosines is still controversial. Using a chimeric receptor system in COS-7 cells, we studied the activation of STAT5 through the interleukin-6 signal transducer gp130. In contrast to previous reports, we did not detect gp130-mediated STAT5 activation. However, STAT5 activation was achieved when tyrosine motifs of other cytokine receptors were fused to the membrane-proximal part of gp130. The comparison of the relative potency of different tyrosine motifs revealed that hydrophobic amino acids, preferentially leucine, in positions +1 and +3, and an aspartate residue in position -1 or -2 with respect to the tyrosine are likely to be required for efficient STAT5 recruitment. In summary, we show here for the first time that phosphotyrosine motifs can confer the ability to activate STAT5 to a heterologous receptor.

Animals↗
PubMed1996

Circulating complement proteins in patients with sepsis or systemic inflammatory response syndrome.

The systemic inflammatory response of the body to invading microorganisms, termed sepsis, leads to profound activation of the complement system. Pathophysiological concepts suggest that complement activation occurs very early in this syndrome. Thus, we discuss whether the determination of concentrations of the complement components C3a, C5a, and C3 in plasma as well as of the C3a/C3 ratio might be helpful to diagnose sepsis early. For this purpose, 33 patients from an intensive care unit were monitored for 10 days. In comparison with healthy donors, C3a levels and the C3a/C3 ratio of intensive-care-unit patients were significantly elevated (P < 0.0001) on admission. In contrast, C3 levels were significantly reduced (P < 0.0001) but increased during the study. C5a levels in the plasma of healthy donors and patients were identical. Twenty-two of 33 patients fulfilled microbiological and clinical criteria of sepsis. Eleven patients had signs of systemic inflammatory response syndrome but no microbiological evidence of sepsis. The groups could be differentiated from each other by their C3a levels or their C3a/C3 ratios during the first 24 h after the clinical onset of sepsis (P < 0.05). Septic patients in shock had higher C3a levels than normotensive septic patients, although the differences were not significant. Nonsurvivors had significantly higher C3a levels on admission than survivors (P = 0.0185). No differences were found between septic patients who developed adult respiratory distress syndrome and those who did not. Thus, determination of C3a concentrations in plasma may prove useful (i) to diagnose sepsis early, (ii) to differentiate between patients with sepsis and those with systemic inflammatory response syndrome, and (iii) to assess prognosis.

Adolescent↗
PubMed1995

CCAAT/enhancer-binding protein isoforms beta and delta are expressed in mammary epithelial cells and bind to multiple sites in the beta-casein gene promoter.

Lactogenic hormone-dependent expression of the rat beta-casein gene in mammary epithelial cells is controlled via a complex regulatory region in the promoter. The sequence between -176 and -82 is the minimal region to confer the response to glucocorticoid hormone and prolactin on a heterologous promoter. The response is further enhanced by the region between -282 and -176. DNase I footprinting experiments and electromobility shift assays revealed the presence of four binding sites for CCAAT/enhancer-binding protein (C/EBP) isoforms in the hormone response region between -220 and -132. In nuclear extracts from mammary epithelial cells, the prevalent C/EBP isoform binding to these sites is beta (C/EBP-beta). C/EBP-delta is also present in mammary epithelial cells, whereas C/EBP-alpha is not detectable. The C/EBP sites are located in close proximity to the previously characterized binding sites for the prolactin-inducible mammary gland factor/signal transducer and activator of transcription-5, the nuclear factor YY1, and the glucocorticoid receptor. The importance of the two proximal C/EBP binding sites at the 5' border of the minimal region was tested by mutational analysis. Mutations of each site were found to inhibit strongly both the basal and the lactogenic hormone-induced transcription of a beta-casein gene promoter chloramphenicol acetyltransferase construct. The results implicate C/EBPs as important regulators of beta-casein gene expression in the mammary epithelium.

Animals↗
PubMed1994

Involvement of Ets-related proteins in hormone-independent mammary cell-specific gene expression.

Regulatory regions have been located in the 5' flanking sequence of the mouse whey acidic protein gene which contribute to its tissue- and stage-specific expression in the mammary gland. They can be functionally separated into elements which mediate the action of lactogenic hormones prolactin and glucocorticoids and elements which control mammary cell-specific transcription in the absence of hormones. By mutational analysis, we have located a site in the whey acidic protein promoter between -120 and -100 which is important for hormone-independent promoter function. In stably transfected HC11 mammary epithelial cells, the hormone-independent activity of the mutated promoter was reduced 40-fold, whereas the capability to respond to lactogenic hormones was retained. The site was specifically recognised by two nuclear factors contained in extracts of cultivated mammary epithelial cells or mammary glands. Electrophoretic mobility shift assay, DNase I footprinting and methylation interference experiments indicated a relation of both factors to the Ets family of DNA-binding proteins. One of these factors also recognised a functionally important site in the mammary cell-specific enhancer of the mouse mammary tumor virus long terminal repeat. The results suggest that factors related to the Ets family are important determinants in mammary cell-specific gene expression.

Animals↗
PubMed1994

Prolactin-dependent activation of a tyrosine phosphorylated DNA binding factor in mouse mammary epithelial cells.

The mammary gland factor MGF has been described as a developmentally and environmentally regulated nuclear factor required for transcription of the milk protein gene beta-casein. In the current study the individual role of lactogenic hormones in the activation of MGF DNA binding and the functional relation of MGF to known transcription factors was investigated by electrophoretic mobility shift assays. DNA binding of MGF was rapidly induced by PRL in mammary epithelial cells. The activation was not inhibited by the protein synthesis inhibitor cycloheximide. The effect of PRL on MGF did not require costimulation of cells with the other lactogenic hormones, insulin, and glucocorticoids. Thus, MGF is the first example of a nuclear factor directly regulated by PRL. The MGF complexes formed upon initiation of lactation in the mammary gland and upon stimulation of mammary epithelial cells with PRL migrated at the same position in electrophoretic mobility shift assay, whereas the MGF complex found in mammary gland extracts of pregnant mice exhibited a faster mobility. In cell cultures, PRL-induced activation of MGF as well as up-regulation of beta-casein gene transcription was confined to confluent cultures of mammary epithelial cells and inhibited by long term incubation of cells with epidermal growth factor. MGF was found to be related to the nuclear factors that are activated by tyrosine phosphorylation when cells are stimulated with interferons or cytokines. This notion is supported by experimental evidence for phosphorylation of MGF on tyrosine and by the similar DNA recognition motifs of MGF and cytokine-activated factors.

Animals↗
PubMed1993

Glucocorticoid receptor binding sites in the promoter region of milk protein genes.

The action of glucocorticoids on the induction of the two milk protein genes beta-casein and whey acidic protein (WAP) is delayed and appears to be indirect. The response requires a co-stimulation of cells with prolactin, is restricted to mammary epithelial cells and is dependent on cis-acting sequences localized in the promoter region of the two genes. We have searched for glucocorticoid receptor (GR) binding sites in these hormone response regions. In vitro DNaseI footprinting experiments were performed with a purified preparation of the GR from rat liver. The sequences between -231 and -7 and between -250 and -79 of mouse WAP and rat beta-casein gene promoter, respectively, were found to contain multiple sites which were protected from the attack of DNaseI by the GR preparation. The sites comprise sequence motifs related to the delayed secondary glucocorticoid response elements described (Chan et al., J. Biol. Chem. 266, 22,634-22,644, 1991), which represent half sites of classical GR binding sites. In the WAP gene promoter, the motifs are arranged head to tail with irregular spacing. The GR binding sites are in close proximity or even overlap with the bindings sites for candidate factors involved in mammary cell specific gene expression. The results suggest a direct co-operation between GR and mammary cell specific transcription factors in mediating the expression of milk protein genes.

Animals↗