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Biomedical subjects

R Beier

Publications and source records attributed to R Beier.

At least 19 recordsLinked to original sources

Regulation of fusion activity by the cytoplasmic domain of a paramyxovirus F protein.

SER virus is a member of the family Paramyxoviridae, genus Rubulavirus, which has been isolated from pigs. It is very closely related to SV5 virus serologically, in protein profile, and in nucleotide sequence. However, unlike SV5, SER induces minimal syncytium formation in infected CV-1 or BHK cells. Fluorescence transfer experiments between labeled erythrocytes and infected MDBK cells revealed that SER also induces hemifusion and pore formation with reduced efficiency. The virion polypeptide profiles of SER and SV5 are very similar, except that the SER F1 subunit shows an apparent molecular weight that is about 2 kDa higher than that of SV5. Comparison of the deduced amino acid sequences revealed the SER F (551 aa) to be longer than SV5 F (529 aa) by 22 residues in the cytoplasmic tail (CT) domain. The HN and M gene sequences of the viruses were found to be very similar. The SER F showed minimal fusion activity when coexpressed with either SV5 or SER HN. In contrast, SV5 F was highly fusogenic when coexpressed with either HN protein, indicating that the restricted fusion capacity of SER virus is a property of its F protein. Truncation in the CT of SER F by 22 residues completely rescued its ability to cause syncytium formation, whereas other truncations rescued syncytium formation partially. These results demonstrate that an elongated CT of a paramyxovirus F protein suppresses its membrane fusion activity.

Animals↗

Pharmacokinetics of native Escherichia coli asparaginase (Asparaginase medac) and hypersensitivity reactions in ALL-BFM 95 reinduction treatment.

Repeated asparaginase treatment has been associated with hypersensitivity reactions against the bacterial macromolecule in a considerable number of patients. Immunological reactions may range from anaphylaxis without impairment of serum asparaginase activity to a very fast decline in enzyme activity without any clinical symptoms. Previous investigations on a limited number of patients have shown high interindividual variability of asparaginase activity time courses and hypersensitivity reactions in about 30% of patients during reinduction treatment. Therefore, monitoring of reinduction treatment was performed prospectively in 76 children with newly diagnosed acute lymphoblastic leukaemia (ALL). According to the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol, 10 000 U/m2 body surface area of native Escherichia coli asparaginase (Asparaginase medac) was given on d 8, 11, 15 and 18. In 45/76 children, trough and peak activities were determined with every dose, and also on d 4 and d 11 after the last administration. Data on asparaginase activity were not available from the remaining 31 patients, but information with regard to hypersensitivity reactions only was given. Eighteen out of 76 patients (24%) suffered a clinical hypersensitivity reaction; however, no silent inactivation was observed. Activity in the therapeutic range of greater than 100 U/l for at least 14 d was determined in 43 of the 45 patients who were analysed for enzyme activity.

Adolescent↗

Induction of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth by Myc are genetically separable events.

The c-myc gene has been implicated in three distinct genetic programs regulating cell proliferation: control of cyclin E-cdk2 kinase activity, E2F-dependent transcription and cell growth. We have now used p27(-/-) fibroblasts to dissect these downstream signalling pathways. In these cells, activation of Myc stimulates transcription of E2F target genes, S-phase entry and cell growth without affecting cyclin E-cdk2 kinase activity. Both cyclin D2 and E2F2, potential direct target genes of Myc, are induced in p27(-/-) MycER cells. Ectopic expression of E2F2, but not of cyclin D2, induces S-phase entry, but, in contrast to Myc, does not stimulate cell growth. Our results show that stimulation of cyclin E-cdk2 kinase, of E2F-dependent transcription and of cell growth by Myc can be genetically separated from each other.

3T3 Cells↗

Kinetics of particle uptake in the domes of Peyer's patches.

Uptake of particulate antigenic matter, including microorganisms and vaccine-bearing microspheres, by the intestinal mucosa takes place in the domes of the gut-associated lymphoid tissues and is achieved by membranous (M) cells, which continuously transport particles from the lumen to the underlying tissue where some particle components initiate immune reactions. Using yeast as tracer, we investigated the kinetics of particle uptake in the Peyer's patches of pigs. A suspension of baker's yeast (Saccharomyces cerevisiae) was injected into the gut lumen of anesthetized minipigs; the position of yeast cells in the tissue was determined after 1, 2.5, 4, and 24 h using fluorescence light- and thin-section electron microscopy. After 1 h, 18.5% of all M cells had taken up or were in close contact with yeast cells. The intercellular space of the epithelium contained a maximum of 60.8% of all yeast cells found in the tissue after 2.5 h, but only 1.3% had been phagocytosed by macrophages. After 4 h most yeast cells (77.8%) were found beneath the basal lamina, and most of these (89%) were found in macrophages. No yeast cells were detected in the Peyer's patch domes 24 h after application. The data show that transcytosis of yeast particles (3.4 +/- 0.8 micron in diameter) by M cells takes <1 h. Without significant phagocytosis by intraepithelial macrophages, the particles migrate down to and across the basal lamina within 2.5-4 h, where they quickly get phagocytosed and transported out of the Peyer's patch domes.

Animals↗

Psychosocial problems in adults with epilepsy: comparison of findings from four countries.

Psychosocial problems in groups of adults with epilepsy from Canada, Finland, the German Democratic Republic, and the United States were evaluated by the Washington Psychosocial Seizure Inventory. A number of similarities in psychosocial concerns were found across the four countries. At the forefront for each group were emotional problems, followed by concerns pertaining to adjustment to the seizures themselves. Where far-reaching governmental support of a financial and vocational nature was lacking, difficulties in these areas were also noted. In all cases, few problems were found in matters pertaining to family relationships and to medical care. Hypotheses to account for differences between the groups were discussed.

Adolescent↗

[Phenytoin kinetics in toxic serum levels].

After discontinuing Phenytoin, the elimination kinetics was determined in 12 patients with toxic serum levels of more than 30 micrograms/ml. The half-lives of the elimination were between 72 and 122 h (97 h). The Michaelis constant amounted to 16,3 +/- 5,6 micrograms/ml and per day and the maximum rate of metabolism 9,9 +/- 1,1 microgram/ml and per day. The elimination half-lives was dependent on the concentration: the higher the serum concentration the longer the half-live. A method applicable in general practice for determining the course of the serum level with initial values of more than 30 micrograms/ml was described.

Adolescent↗

[Changed phenytoin kinetics in chronic alcoholism].

Signs of changes in the kinetics of phenytoin were observed in 12 alcoholics treated with this substance for generalized seizures. In 10 of the patients serum phenytoin concentrations were decidedly low after administration, probably due to increased metabolic activity resulting from chronic alcohol abuse. The serum phenytoin levels of two patients were very high after the drug had been applied. This is probably an expression of reduced enzymatic activity caused by severe liver damage.

Adult↗

[The treatment of epilepsies with Convulsofin].

The testing of Convulsofin carried out in 220 patients at 14 clinics over a period of six months confirms the international experience gained with valproic acid and sodium valproinate. The main field of application of Convulsofin according to the experience gained will again be the treatment of fits in generalised primary epilepsy for which it permits to carry out a monotherapy to a remarkable extent. The favourable effect of the preparation in photosensitivity could be confirmed. Also in generalised secondary epilepsy and in fits of partial epilepsy. Convulsofin is partly effective, so that it can recommended as a co-medication in the treatment of therapy-resistant forms of these epilepsies which are difficult to treat. Decrease in thrombocytes, transient increase in serum transaminases, gastrointestinal disorders, loss of hair and undesired increases in body-weight were the more frequently occurring side-effects.

Adolescent↗

[Psychic attitude of women to irreversible contraception (author's transl)].

Thirty-four of 100 women who had undergone officially sanctioned irreversible contraception at the Gynaecological Department of Wismar Regional Hospital were selected at random for follow-up investigation, two-and-a-half to one year after the intervention. The following psychological tests were taken: a standardised interview based on abridged psychopathological method, Freiburg personality inventory, record of complaints according to Kasielke, and the multiple-choice vocabulary test according to Lienert. Psychiatric examination was added on the basis of a structured psychopathological record system according to Grünes and Kühne. The following results were obtained from the study: All probands exhibited positive attitudes to the method of irreversible contraception. They said they would choose the same option, if they had to were asked again. They recommended the same decision to other women. Inner conflicts because of the irreversible nature of the intervention, problems of selfvalue, and impairment of partnership relations were not reported. Nor did any of the women wish refertilisation. The gynaecological intervention did in no single case turn out as source for neurotic developments or other psychiatrically relevant symptoms. However, the possibility of neurosis must be reckoned with, as it must with any other medical intervention. This risk may be effectively encountered by due consideration of the patient's personality, clarified indication, adequate information, and therapeutic support for the patient's effort to get to grips with the psychic problem. Hence, irreversible contraception can be an alternative, also for its psychic consequences, for women above 35 to whom safe reversible contraceptives cannot be applied for whatever reasons, although they have completed their own family planning.

Adult↗

[Results obtained from lumbar catheterisation for epidural analgesia for painless labour (author's transl)].

Experience obtained from 115 childbirths with catheterisation for epidural analgesia is reported in this paper. Reduction of labour pain was optimum with all patients.--The rate of CTG alterations and acidosis of foetal blood was not beyond that recordable from normal deliveries. The rate of vaginal surgery was increased to 14.8 per cent due to one patient in whom expulsion was delayed and the expulsion period thus prolonged.

Anesthesia, Epidural↗

[Differential indication of trimipramine - results of a controlled multiclinical study].

The antidepressants trimipramine and imipramine were compared within the framework of a multiclinical study performed under the conditions of a controlled clinical experiment. There has been found a time-different remission of affective und psychomotoric symptoms. The panthymoleptic action of trimipramine and other antidepressants is discussed with reference to these results. Trimipramine influences psychotic states, especially if in depression anxiety is combined with agitation, also in hypochondriac forms of depression.

Clinical Trials as Topic↗

[Phenytoin intoxication and serum level].

The symptomatology of phenytoin intoxication was observed in 8.4% of 225 adult patients and in 9.5% of 74 children, with symptoms of cerebellar affection being noted in the majority of cases. Phenytoin concentrations were found to lie between 14.4 and 77.7 microgram/ml. Interindividual differences as to the toxic limit were quite considerable: One third of the patients showing values higher than 20 microgram/ml were free of striking clinical symptoms, and one patient tolerated a serum concentration in excess of 30 microgram/ml. On the other hand, the intraindividual toxic limit did not show any major variations: The clinical symptomatology of a patient correlated with his phenytoin serum concentration. After phenytoin withdrawal, the serum concentration dropped exponentially. The half-life periods of elimination were found to be between 72 and 122 hours.

Adolescent↗

[Serum phenytoin determination, its value in the treatment of epilepsy].

The concentration of phenytoin in serum was determined by gas chromatography for a total of 101 patients treated on an outpatient basis. In contrast to data reported in the literature, six patients (6 percent) showed therapeutically effective serum concentrations which were far below 7.0 microng/ml. In the majority of cases, however, the therapeutically effective range was from 7.0 to 20.0 microng/ml. A considerable reduction in the frequency of fits was obtained for 23 out of 32 patients who were treated in this manner. Examinations made on patients treated on an inpatient basis showed a definite correlation of daily dose, body weight, and serum concentration. However, interindividual differences were so high that the serum concentration cannot, in general, be safely concluded from the daily dose and body weight. Four percent of the patients showed toxic serum concentrations when normal doses of phenytoin were used. About 50 percent of the patients treated on an outpatient basis showed values indicating very irregular use of the drugs.

Epilepsy↗

[The significance of fetal electroencephalography for the diagnosis of fetal disorders].

In typical cardiotocographic and bloodgasanalytic changes indicating fetal hypoxia the fetal electroencephalography shows frequency slowing, voltage suppression and spike activity. This EEG tracings simultaneously appeared with first cardiotocographic signs of fetal distress. It was not possible to recognize disturbances of fetal oxygenation in an earlier stage by EEG monitoring. Fetal EEG is of difficult technique and interpretation. In so far cardiotocography is of higher security, sensibility and easier handling for fetal monitoring. With regard to future improvements in electroencephalographic techniques it seems possible to get additional and more accurate informations for fetal monitoring and about perinatal morbidity.

Diazepam↗