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M Hentze

Publications and source records attributed to M Hentze.

5 recordsLinked to original sources

Systematic genomic screening and analysis of mRNA in untranslated regions and mRNA precursors: combining experimental and computational approaches.

MOTIVATION: The untranslated regions (UTRs) of mRNA upstream (5'UTR) and downstream (3'UTR) of the open reading frame, as well as the mRNA precursor, carry important regulatory sequences. To reveal unidentified regulatory signals, we combine information from experiments with computational approaches. Depending on available knowledge, three different strategies are employed. RESULTS: Searching with a consensus template, new RNAs with regulatory RNA elements can be identified in genomic screens. By this approach, we identify new candidate regulatory motifs resembling iron-responsive elements in the 5'UTRs of HemA, FepB and FrdB mRNA from Escherichia coli. If an RNA element is not yet defined, it may be analyzed by combining results from SELEX (selective enrichment of ligands by exponential amplification) and a search of databases from RNA or genomic sequences. A cleavage stimulating factor (CstF) binding element 3 of the polyadenylation site in the mRNA precursor serves as a test example. Alternatively, the regulatory RNA element may be found by studying different RNA foldings and their correlation with simple experimental tests. We delineate a novel instability element in the 3'UTR of the estrogen receptor mRNA in this way. AVAILABILITY: Strategy, methods and programs are available on request from T.Dandekar. CONTACT: dandekar@embl-heidelberg.de

3' Untranslated Regions

[Prognostic factors for long-term survival in anorexia nervosa].

This work describes the results of a long-term follow-up (mean duration = 13.5 years) of 105 female anorexia nervosa patients, for 93.3% of whom (n = 98) we were able to obtain information. Our objective was to identify factors affecting the long-term prognosis in these cases. Weight gain and a stable partnership after treatment as well as high body weight on termination of treatment were shown to be especially important for long-term recovery. This suggests the following for treatment of anorexia nervosa: besides restoration of normal body functions, the patient should attempt to leave her parents' home and enter a partner relationship. Further weight gain should not be neglected during this process.

Anorexia Nervosa

Long-term stability of anorexia nervosa treatments: follow-up study of 218 patients.

We are reporting about the stability of n = 218 female in-patient treatments of Anorexia nervosa carried out at the University Clinic at Hamburg-Eppendorf from 1965 to 1979 mainly by a special program: introductory interview (with the family present), in-patient medical treatment (bed-rest, phenothiazines, tube-feeding), strict regimen and addressing the patients' conflict situation. The average interval between the end of therapy and the follow-up examination was 9.8 years. We were able to collect data about 93 per cent (n = 202) of the former patients concerning their somatic, psychological and psychosocial status. Based on these data we could assess 30 patients (14 per cent of our basic sample) as free of symptoms while 84 patients (39 per cent) presented slight symptoms so that 53 per cent of the former patients could exercise their profession without being considerably handicapped and able to keep up a relationship with a partner. On the other hand, 39 patients (18 per cent) still showed marked symptoms at follow-up and with 19 patients (9 per cent) there were manifestations of severe or extreme symptoms. Thirty former patients (14 per cent) had died with the mortality rate distinctly increasing over the years. Possible interpretations of our results and consequences for therapy are presented.

Anorexia Nervosa

Enhanced degradation of cathepsin D synthesized in the presence of the threonine analog beta-hydroxynorvaline.

The threonine analog beta-hydroxynorvaline is an inhibitor of asparagine-linked glycosylation. In the presence of the analog human fibroblasts synthesized cathepsin D molecules containing two, one, or no oligosaccharides. The nonglycosylated cathepsin D precursor was but a minor species and was degraded within 45 min of its synthesis, presumably in the lumen of the endoplasmic reticulum. The polypeptides with one or two oligosaccharides were normally segregated into lysosomes and their proteolytic maturation was not affected. The stability of mature glycosylated and nonglycosylated cathepsin D polypeptides within the lysosomes, however, was markedly decreased. The recovery of cathepsin D polypeptides was increased in the presence of inhibitors of cysteine and aspartyl-proteinases. These data suggest that the absence of carbohydrate side chains in cathepsin D results in an enhancement of the degradation rate of the precursor in the endoplasmic reticulum, and the replacement of threonine by beta-hydroxynorvaline in an enhanced degradation of the mature cathepsin D in lysosomes.

Biological Transport