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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 181 records · Page 10Linked to original sources

Biosynthesis of ependymins from goldfish brain.

Ependymins beta and gamma constitute a novel family of secretory proteins in the extracellular fluid of goldfish brain. Here we demonstrate that at least two different transcripts exist in goldfish brain differing mainly in the length of their 3' noncoding regions but encoding very similar precursors for ependymins. Both precursors consist of 216 amino acid residues including two potential N-glycosylation sites. Prepro-ependymin-I is the main but not the only precursor of ependymin beta, whereas prepro-ependymin-II is preferentially processed to ependymin gamma. This is in line with our results showing that both ependymins beta and gamma represent different glycoforms with very similar protein backbones. Additionally, we show that both ependymins share the same C-terminal ends indicating that ependymin gamma is not a proteolysis product of ependymin beta. We also demonstrate that processing at three internal pairs of basic residues does not occur in either ependymin.

Algorithms↗

Molecular characterization of an ependymin precursor from goldfish brain.

Ependymins are thought to be implicated in fundamental processes involved in plasticity of the goldfish CNS. Gas-phase sequencing of purified ependymins beta and gamma revealed that they share the same N-terminal sequence. Each sequence displays microheterogeneities at several positions. Based on the protein sequences obtained, we constructed synthetic oligonucleotides and used them as hybridization probes for screening cDNA libraries of goldfish brain. In this article we describe the full-length sequence of a mRNA encoding a precursor of ependymins. A cleavable signal sequence characteristic of secretory proteins is located at the N-terminal end, followed directly by the ependymin sequence. Also, two potential N-glycosylation sites were detected. A computer search revealed that ependymins form a novel family of unique proteins.

Amino Acid Sequence↗

Effects of carbamazepine, valproate calcium, clonazepam and piracetam on behavioral test methods for evaluation of memory-enhancing drugs.

The effect of three anticonvulsants on several test methods for evaluation of memory-enhancing drugs have been studied in rats and mice. The results were compared to the results obtained from the nootropic piracetam and from imipramine. In an active avoidance test (pole jumping), repeated administration of carbamazepine (5 mg/kg i.p.) and piracetam (300 mg/kg p.o.) protected against impairment of learning rate caused by repeated application of an electroconvulsive shock. Valproate calcium (repeated administration of 30 mg/kg i.p.) was only weakly active, while clonazepam (repeated administration of 0.3 mg/kg i.p.) decreased the learning rate even more. Drugs were given in dosages which have no anticonvulsive activity in this test. The impairment of learning rate caused by repeated application of ethanol was prevented by carbamazepine (5 mg/kg i.p.), valproate calcium (30 and 100 mg/kg i.p.) and piracetam (100 mg/kg i.p.). Clonazepam (0.3 and 1 mg/kg i.p.) had a worsening effect on learning rate. In Porsolt's behavioral despair test, carbamazepine (5, 10 and 30 mg/kg i.p.) and valproate calcium (30 and 100 mg/kg i.p.) shortened the duration of immobility, which indicates an increased psychomotor activity. Clonazepam was ineffective. Results obtained with carbamazepine are similar to those obtained with piracetam. The data are discussed in view of the so-called psychotropic effects of carbamazepine in clinical trials.

Animals↗

[Results of work schedule studies of hospital physicians of the Cottbus district hospital].

The accomplishment of a scientific organisation of work is not an end in itself, but it is an objective necessity in Public Health, too. That is why studies of the working hours are an important instrument of management. At the district hospital Cottbus these studies were carried out not only in nurses, but also in doctors on wards of the clinic for internal diseases, of the clinic for surgical diseases, of the clinic for pediatric diseases and of the clinic for gynecological diseases. The effective action on the patient of ward physicians and interns in these departments amounts to the very balanced daily portion of about 70 to 85% on weekdays. The portion of only 2 to 5% of management of senior physicians in 2 of the 4 inspected departments seems to be too small. The portion of social and scientific work of doctors from several departments can also not be evaluated as sufficiently. The analysis of this pilot study shows a range of important results and conclusions concerning the effective utilization of the working hours fund and the opening of working hours reserves.

Germany, East↗

Superior prevention of reinfarction by 30 mg per day aspirin compared with 1000 mg: results of a two years follow-up study in Cottbus.

The clearly significant overall results of the study indicating the superiority of the very low aspirin dose of 30 mg/d was differentiated by subgroup evaluations: The absolute benefit produced by the low aspirin dose was greatest among patients aged over 60, male patients, patients with a history of angina pectoris, patients with ST-depression of 0.5 mm or more in the 2th week after the cardiac event, among hypercholesterolaemic patients and those with all MI-locations except of the posterior site. The side effects were negligible (5% compared with 20-25% with 1000 mg/per day aspirin) and the drug costs are small. There was no evidence of any benefit of the high dose aspirin with respect to the odds of mortality and reinfarction.

Aged↗

Amino acid sequence microheterogeneities of a type I cytokeratin of Mr 51,000 from Xenopus laevis epidermis.

The complete cDNA-derived sequence of a type I cytokeratin (designated no. 3) from Xenopus laevis skin is described. The deduced protein has an Mr of 51,888 and consists of a glycine-rich head domain, a well-conserved alpha-helical region and a tail rich in hydroxyamino acid residues. Various cDNA clones encoding two different mRNAs were isolated that differed by short deletions/insertions and point mutations. These microheterogeneities are mainly located in a 'hypervariable region' at the C-terminal non-alpha-helical region.

Amino Acid Sequence↗

A new repetitive protein from Xenopus laevis skin highly homologous to pancreatic spasmolytic polypeptide.

A cDNA sequence has been used to derive the precursor structure of a highly repetitive protein in Xenopus laevis skin. From the sequence of a whole family of secretory proteins can be predicted containing a classical hydrophobic signal sequence at the NH2-terminal end of the precursor. The proteins contain four domains with high homology to porcine pancreatic spasmolytic polypeptide. These four cysteine-rich, presumably physiologically active domains are separated in the molecule by a repetitive element, locating two such domains to the NH2 terminus of the precursor protein and the remaining two to the COOH-terminal end. The separating spacer consists of very unusual, precise, threonine and proline-rich repeats containing 9 residues which could be targets for extensive O-glycosylation. Additionally, processing at two pairs of basic residues is suggested to liberate two polypeptides ("spasmolysins") and "spasmolysin-glycoprotein."

Amino Acid Sequence↗

[Tetralogy of Fallot following coumarin administration in early pregnancy--an embryopathy?].

A case report of a 35-year old woman is presented who continued a coumarin therapy unconscious of an early pregnancy up to day 61. At term she delivered a baby with tetralogy of Fallot, up to now not mentioned in the symptom complex of malformations due to a coumarin therapy. In the case presented the typical symptoms of a warfarin embryopathy including a chondrodysplasia punctata and other morphological changes were lacking. Although some cases of cardiac malformations have been reported in literature following coumarin therapy in early pregnancy, a causal connection could not be confirmed.

4-Hydroxycoumarins↗

[Sequential treatment of progressive metastatic colorectal cancer with 5-fluorouracil/folinic acid, dipyramidole and mitomycin C].

A number of reports have described enhanced therapeutic activity of 5-fluorouracil (5-FU) when combined with high-dose folinic acid (dl-CF). In the present phase-II study 35 patients with colorectal cancer were entered into a first-line chemotherapeutic protocol consisting of dl-CF 200 mg/m2 i.v. push directly followed by 340 mg/m2 5-FU i.v. pushon - days 1-5. Thus far a response rate of 37.5% (12 PR) has been achieved, and minor responses or no change were registered in 43.7% (14 MR or NC), lowering the rate of primary therapeutic failures to 18.8%. Median time to progression was 6.2 months. Toxic side effects consisted mainly of diarrhea, nausea and mucositis. As second-line therapy 5-FU/dl-CF and dipyramidole p.o. were administered to 10 patients with resulting 4 NC. Mitomycin C was given to 9 patients as a third-line regimen with resulting 5 NC for 2-4 months.

Adult↗

Superior prevention of reinfarction by 30 mg/d aspirin compared with 1000 mg/d: results of a two years follow-up study in Cottbus.

In a two years reinfarction study including all patients suffering from myocardial infarction in the district of Cottbus (900000 inhabitants) between the 1.1.1981 and 31.8.1983 (totally 701 patients) we found a statistically significant lower rate of reinfarctions, in patients over 60 years also of the total mortality treated with 30 mg aspirin per day compared with 1000 mg per day. A statistically significant superiority of the 30 mg aspirin dosage compared with the 1000 mg dosage was found in patients aged over 50 years, in male patients, in patients with angina pectoris in their anamnesis, in patients with ST-depression of greater than 0.5 mm 2 weeks after the cardiac event, in patients with all kinds of infarct localization except posterior myocardial infarction and in patients with hypercholesterolaemia (greater than = 7.3 mmol/l).

Aged↗

[The effect of nootropics on impared learning performance in a pole jumping test after repeated ethanol administration].

The influence of ethanol administration (4 ml of 10% ethanol/d p.o.) for 6 and 13 d respectively, on learning behaviour of rats has been studied using an active avoidance reaction. While the formation of an active avoidance reaction was only insignificantly impaired by the application of ethanol for 6 d, the learning performance of rats showed a significant deficit after 13d of ethanol ingestion. Repeated nootropic pretreatment (d11 to 14 following first ethanol dose b.i.d.) resulted in an attenuation of learning deficits. The nootropics piracetam (100 mg/kg i.p.) methyl-glucamine orotate (225 mg/kg i.p.), meclofenoxate hydrochloride (100 mg/kg i.p.), pyritinol (100 mg/kg i.p.) and dihydroergotoxine mesilate (1 mg/kg i.p.) showed to be effective. The possible mechanism of action is discussed.

Animals↗

CAN1-SUC2 gene fusion studies in Saccharomyces cerevisiae.

Various gene fusions between the arginine permease and invertase have been constructed in order to obtain information about whether parts of the CAN1 gene product can induce secretion of biologically active invertase missing its own signal sequence. A construction containing 30 N-terminal amino acid residues of the CAN1 gene product fused to invertase was not secreted. When the CAN1 portion was elongated to 477 or 560 amino acid residues, secretion of the fusion proteins was observed. A fusion lacking 59 amino acids at the amino-terminal end of the arginine permease was also secreted. These results indicate that the amino-terminal end of the arginine permease is neither sufficient nor essential for membrane insertion; instead this enzyme should contain an internal targeting sequence facilitating secretion. Some general implications on the biosynthesis and topology of membrane proteins are also discussed as well as the homology with histidine permease.

ATP-Binding Cassette Transporters↗