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Biomedical subjects

U Müller

Publications and source records attributed to U Müller.

At least 397 records · Page 22Linked to original sources
PubMed1989

Isolation and DNA-binding characteristics of a protein involved in transcription activation of two divergently transcribed, essential yeast genes.

We have identified a protein, BAF1, which has two oppositely oriented, partially overlapping binding sites within a symmetrical sequence located midway between and upstream of the divergently transcribed YPT1 and TUB2 genes of the yeast Saccharomyces cerevisiae. The 120 kd BAF1 protein was purified to near homogeneity and used to delineate the two binding sites and to identify apparent protein contact sites by the missing contact technique, methylation interference and by site-directed mutagenesis. The BAF1-recognition sequence contains a conserved TCN7ACG element recently identified at autonomously replicating sequences (ARS) and in the 5' and 3' flanking region of other yeast genes. The symmetrical sequence of the YPT1/TUB2 intergene region seems not to be involved in DNA replication but activates transcription in an orientation-independent fashion.

Base Sequence↗
PubMed1989

Phase II clinical trial of high-dose recombinant human tumor necrosis factor.

Based on a phase I study in 1986, 22 patients have been entered in a phase II study of high-dose human tumor necrosis factor (rH-TNF) since May 1987. Of these patients, 18 are evaluable at present, 2 are still under investigation, and 2 have dropped out. All had advanced stages of cancer (9 soft-tissue sarcomas, 3 melanomas, 5 hypernephromas) and inclusion in the study was ethically acceptable (informed consent). The daily dose of rH-TNF was 15 x 10(5) units/m2, escalated to 21 x 10(5) units/m2 (683-956 micrograms/m2 every week; range 1-6 cycles). Additional prophylactic ketoprofen administration was carried out. Of the 18 evaluable patients, 4 responded with no change (2/4, clinical improvement) and 14 showed progressive disease. The main toxicities observed were hypotension (decrease in systolic blood pressure, 21-60 Torr), leukocytosis, increases in ALAT/ASAT (WHO grade 0-4), fever (WHO grade 1-2), chills (mild to moderate), neurotoxicity (WHO grade 0-2), and nausea/vomiting (WHO grade 0-3).

Adult↗
PubMed1989

[The determination of the herbicide glyphosate and its chief metabolite aminomethylphosphonic acid (AMPA) in drinking water with the aid of HPLC].

A method for the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) is described. With a detection limit of 0.02 microgram/l, the method suitably fulfills the requirements of the Swiss legislation (tolerance value of 0.1 micrograms/l water). The compounds are derivatized directly in the original water sample with 9-fluorenylmethyl chloroformate (FMOCC1) in order to obtain extractable and fluorescent derivatives. These are extracted with organic solvents and determined by HPLC using a fluorescence detector. Neither of the compounds could be detected in 151 tap water samples from the Canton of Berne.

Chromatography, High Pressure Liquid↗
PubMed1989

Growth acceleration of Ehrlich ascites tumor cells treated by proteinase in vitro.

Since the cytotoxic effect of ionizing radiation increases in faster proliferating cell populations, the effects of a mild trypsin and bromelain treatment on the growth rate of Ehrlich ascites tumor (EAT) cells cultured in vitro were studied. A continuous exposure to proteinase started at the time of cell plating caused a temporary block of DNA synthesis that was followed by an accelerated growth rate 48 h later (approximately 1.5-fold). EAT cells exposed to bromelain and trypsin after completed adaptation to the substratum demonstrated a similar increase of growth 2 days after the beginning of the enzyme treatment. The acceleration of growth was also observed when exposure to proteinase was interrupted after 24 h but the stimulation effect was reversible and continued only 2 days. It is concluded that bromelain and trypsin are able to modify reversibly the growth rate of EAT cell population cultured in vitro.

Animals↗
PubMed1989

Breakage of the human Y-chromosome short arm between two blocks of tandemly repeated DNA sequences.

Y-chromosomal rearrangements, a common cause of sex reversal in man, frequently occur between two blocks of repeated DNA. Both blocks are composed of 20-kb tandemly repeated Y-chromosome-specific DNA sequences. They are located in the proximal portion of the Y short arm on a NotI restriction fragment of approximately 5.3 Mb and on an MluI fragment of approximately 5.5 Mb. Chromosome breaks positioned between the two blocks were detected in two of three 46,XY females with deletions of Yp and in five of six 46,XX males positive for the repeat sequences. The rearranged NotI fragments in the 46,XX males were 4.4 Mb and the MluI fragments were 2.0 Mb in length. This indicates that breaks occur within a small region of Yp defined by the two blocks of specific repeated DNA sequences. The region between the two blocks thus appears to be a focus of structural lability in the human Y chromosome.

Chromosome Aberrations↗
PubMed1989

Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP.

Treatment of adenovirus-infected mouse S49 cells with cAMP analogs leads to the transcriptional induction of early viral genes. E1A proteins and cAMP work in synergy to activate several of these genes. We now demonstrate that the transcription factor AP-1 is modestly induced by cAMP in S49 cells and induced to significantly higher levels by cAMP in the presence of E1A proteins. Cytoplasmic levels of c-fos and junB mRNAs are rapidly increased by cAMP, and the induction is substantially stronger in the presence of E1A protein. The AP-1 activity binds efficiently to both AP-1 and activating transcription factor (ATF)/cAMP response element binding protein (CREB)-binding sites present in E1A-inducible promoters and presumably plays a role in the transcriptional activation of adenovirus genes by E1A proteins and cAMP.

Adenovirus Early Proteins↗
PubMed1989

Predictive value of venom-specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom.

Sixty-seven patients with a history of severe systemic reactions following honey bee stings were treated by immunotherapy (IT) with honey bee venom. During maintenance therapy all were submitted to a sting challenge under clinical conditions. 15 developed mostly minor symptoms of a systemic reaction while 52 showed only a local swelling at the sting site. Phospholipase A2-specific IgE, IgG and IgG subclass serum antibodies were estimated in samples obtained before IT and immediately before the challenge. Specific IgE decreased in reactors and in non-reactors. There was no difference between the two groups at any time. Specific total IgG, IgG1 and IgG4 increased in both reactors and non-reactors during IT. An early increase of specific IgG1, was observed while specific IgG4 remained elevated throughout the treatment. Specific total IgG was higher in reactors than non-reactors before the challenge, specific IgG1 higher in reactors before treatment and specific IgG4 higher in reactors than non-reactors both before treatment and before challenge. In the individual patient, no single antibody estimation or combination of various antibodies was predictive of the outcome of a sting challenge.

Anaphylaxis↗
PubMed1989

Endocrine responses to growth hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone in depression.

To explore and to compare hypothalamic-pituitary-somatotropic (HPS), hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenocortical (HPA) axis function in depression, 30 subjects (15 patients with a major depressive episode and individually matched controls) received 50 micrograms growth hormone-releasing hormone-44 amide at 9:00, 200 micrograms thyrotropin-releasing hormone (TRH) at 9:00 and 100 micrograms human corticotropin-releasing hormone (CRH) at 18:00 on consecutive days as an i.v. bolus dose. Compared with controls, depressed patients showed blunted growth hormone (GH) responses to GHRH, decreased TRH-induced thyrotropin (TSH) release and reduced corticotropin (ACTH) but normal cortisol secretion following CRH. ACTH secretion following CRH and TRH-induced TSH release were positively correlated across depressed patients and controls but no significant correlations between GH responses to GHRH and TRH-induced TSH release or ACTH and cortisol secretion following CRH administration were demonstrated. Our findings suggest that altered HPT and HPA axis function associated with depression are triggered by factors that are at least partly different from those that cause HPS system dysfunction. We conclude that the pathophysiological process resulting in aberrant neuroendocrine secretory dynamics associated with depression may primarily occur at a suprapituitary site, and that HPS, HPT and HPA axis dysfunction may be precipitated by complex central and peripheral regulatory mechanisms involving largely independent factors.

Adrenocorticotropic Hormone↗
PubMed1989

Analysis of complex Y chromosome aberrations using a single DNA probe (Y-367).

A specific cloned DNA sequence (Y-367) detects at least four loci in the euchromatic long arm and in the short arm of the human Y chromosome. Deletion mapping assigns one locus to the distal euchromatic long arm, another to a region close to the centromere on either Yq or Yp, and two additional loci to the Y short arm. Y-367 may thus be used for the rapid screening of even complex Y chromosome aberrations. This is exemplified in a 45,X male with Y chromosome material on the long arm of chromosome 10 by the detection of an inversion of a portion of Yp and by the confirmation of duplications and deletions in two individuals with duplications of part of the Y chromosome.

Chromosome Aberrations↗
PubMed1989

Blunted adrenocorticotropin but normal beta-endorphin release after human corticotropin-releasing hormone administration in depression.

Since the discovery of CRH in 1981, several investigators have reported abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in response to direct stimulation of the corticotroph cells in patients with psychiatric disorders. To further explore HPA system integrity in major depressive disorders, 13 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 100 micrograms synthetic human CRH as an iv bolus dose. Compared to that in the normal subjects, in the depressed patients a significant attenuation of the net ACTH release after CRH administration (772 +/- 597 vs. 263 +/- 286 pmol/min.L; P less than 0.02) was observed, while beta-endorphin and cortisol responses did not differ significantly between the groups. The magnitudes of ACTH and cortisol release were negatively correlated in the patient group only (r = -0.67; P less than 0.01). Thus, the blunted ACTH response to CRH in depression might be related to hypercortisolemia, while the implications of the apparent dissociation of ACTH and beta-endorphin after CRH administration still remain unclear. Our data support the hypothesis that the hyperactivity of the HPA system in depression most likely is a consequence of CRH hypersecretion, the origin of which may be explained by abnormal central glucocorticoid receptor or neurotransmitter regulation.

Adrenocorticotropic Hormone↗
PubMed1989

Ca2(+)-dependent proteolytic modification of the cAMP-dependent protein kinase in Drosophila wild-type and dunce memory mutants.

Two cAMP-dependent protein kinases with different activation constants were separated from Drosophila melanogaster head extracts. Both are only found in nervous tissue. The first cAMP-dependent kinase, with Mr = 190,000, has been already characterized as tetrameric Drosophila type II cAMP-dependent protein kinase R2C2. The second purified cAMP-dependent protein kinase, with Mr = 80,000, is dimeric in structure RPC, and the cAMP-concentration required for half maximal activation is 4 fold lower than for the type II kinase. The generation of RP can be stimulated in vitro by addition of exogenous calcium and is due to an endogenous Ca2(+)-dependent protease that selectively degrades the regulatory subunit. Extraction in the presence of various protease inhibitors does not affect the amounts of RP, suggesting that the observed quantitative change in RP occurs in vivo. The amounts of RP in the nervous tissue of the memory mutants dunce1 and dunce2, which have increased cAMP levels, are different from the amount of RP in wild-type flies. Also treatments of wild-type flies with drugs affecting cAMP-metabolism and acetylcholine levels led to amounts of RP different from untreated flies.

Animals↗
PubMed1989

[A representative study of the scope and structure of faulty admissions of acute hospital patients over 60 years of age].

The extent and the structure of inappropriate, i.e. medically unnecessary hospital utilisation by patients of 60 years of age and over, in German acute hospitals were assessed by reviewing a randomised sample of medical records judged by physicians. This rating method was tested, standardised and evaluated. The most important result of the study was that the mean length of story was 17.4 days of which 2.9 days (17%) were estimated to be inappropriately used. If this result is projected to all West German hospitals, 35,000 hospital beds are inappropriately occupied by patients over 60 years of age for a total of 10.5 million patient days per year.

Aged↗
PubMed1989

Parental origin of the extra chromosome in trisomy 18.

The parental origin of the supernumerary chromosome 18 was investigated by RFLP analysis in 23 individuals with Edwards syndrome. All families were studied with the DNA probe pERT-25, which recognizes a locus of highly polymorphic tandemly repeated DNA sequences on chromosome 18. The extra chromosome was found to be of maternal origin in 19 patients (95%), of paternal origin in one patient (5%), and indeterminate in three patients. In one of the three indeterminate cases, a mosaic, an apparent recombination event had taken place within the pERT-25 locus. The overall high degree of informativeness of pERT-25 illustrates the power of a chromosome-specific variable-number tandem repeat probe (VNTR) in parental origin studies of aneuploidy.

Adolescent↗