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Biomedical subjects

R Wilhelm

Publications and source records attributed to R Wilhelm.

At least 19 recordsLinked to original sources
PubMed1992

Identification of amino acid residues critical for endonuclease and integration activities of HIV-1 IN protein in vitro.

HIV-IN protein, tagged with a hexahistidine tail was expressed in Escherichia coli and purified by a one-step nickel chelate affinity chromatography procedure. The purified IN protein was characterized in terms of its endonuclease and integrase properties in vitro. Specific cleavage and integration of HIV U5 LTR ends were observed in the presence of 2-5 mM Mg2+ or Ca2+. In the presence of 2 mM Mn2+, cleavage and integration occurred at additional sites indicating a decreased specificity. The properties of mutant IN proteins were examined in vitro. Deletion of 39 amino acids from the N-terminus and a minimum of 25 residues from the C-terminus impaired IN-mediated cleavage and integration activities. The results of site-directed mutagenesis experiments showed that residues critical for IN function are highly conserved. Mutations of conserved residues Asp64, Pro109, Asp116, and Glu152 adversely affected IN function in vitro. Mutations of nonconserved residues Gly189 and Thr112 had no effect. Mutation of a conserved Thr115 to Ala caused a near complete loss of Mg(2+)-dependent integration activity, but only partially effected endonucleolytic cleavage activity of IN. These results suggest that not all conserved residues are involved in both endonucleolytic cleavage and integration activities of HIV-IN.

Amino Acid Sequence↗
PubMed1992

RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. II. Stability to beta-lactamases and affinity for penicillin-binding proteins.

The aminothiazolyl-cephalosporin RU 29 246, the active metabolite of the prodrug-ester HR 916, is active against strains producing the widespread plasmid-encoded TEM-1, TEM-2 and SHV-1 beta-lactamases. Except for TEM-7 the activity of RU 29 246 against strains producing extended broad spectrum beta-lactamases (TEM-3, TEM-5, TEM-6, SHV-2, SHV-4, SHV-5, CMY-1, CTX-M), however, is low. Relative hydrolysis rates of RU 29 246 are comparable with those of cefpodoxime, the active metabolite of CS-807, and are extremely low for the TEM-1 and SHV-1 beta-lactamases. The compound demonstrates remarkable inhibitory activity against the chromosomal beta-lactamase of Enterobacter cloacae P99. In the presence of 1.7 microM this enzyme loses 50% of its activity. At concentrations of 0.43, 0.003 and 0.01 micrograms/ml the compound binds preferentially to the penicillin-binding protein (PBP) 3 of Escherichia coli K12, to the PBPs 2x and 3 of Streptococcus pneumoniae R6 and to PBP 1 of Staphylococcus aureus SG 511, respectively.

Anti-Bacterial Agents↗
PubMed1989

[Postoperative wound infections in surgery of stomach cancer. A bacteriologic analysis].

We reviewed 50 gastric cancer operations during the period from September 1984 to August 1985. The material illustrates the dominance of gram-negative rods and non-sporeforming anaerobes of endogenous gastric cancer microflora and also in postoperative wound infections. The organisms most frequently causing infection after operations are endogenous source. The postoperative wound infection rate was 36%. Therefore, the necessity of adequate use of antibacterial chemotherapeutics in wound infections is emphasized.

Bacteria↗
PubMed1984

O6-methylguanine repair in liver cells in vivo: comparison between G1- and S-phase of the cell cycle.

To compare the formation and persistence of alkylated DNA bases in the G1- and S-phase compartments in liver in vivo, regenerating rat liver was exposed to [14C]dimethylnitrosamine (0.57 mg/kg, IP injection) or N-[methyl14C]-N-nitrosourea (3.3 mg/kg, intraportal injection) during the G1 phase of the cell cycle (12 h after partial hepatectomy), or at 24 h after partial hepatectomy with 30% hepatocytes in DNA synthesis, or at 43 h after partial hepatectomy, 4 h after an hydroxyurea block from 14 to 39 h after operation with 80% hepatocytes in DNA synthesis. At 120 min after dimethylnitrosamine and 90 s, 5, 10, or 60 min after the intraportal pulse of N-methyl-N-nitrosourea the molar fractions of 7-methylguanine (7megua), O6-methylguanine (O6megua), and 3-methyladenine (3mead) and of metabolically labeled guanine were determined from DNA hydrolysates by Sephadex-G10 radiochromatography. After dimethylnitrosamine only minor differences were observed for 7megua formation in the three groups; the 3mead/7megua ratio remained constant irrespective of the number of cells in S phase. In contrast, the O6megua/7megua ratio revealed a loss of O6megua, the extent of which appeared proportional to the fraction of DNA-synthesizing cells in the liver. The rapid loss of O6megua in S-phase cells was confirmed after intraportal administration of N-methyl-N-nitrosourea. During the first 10 min after the methylnitrosourea pulse the O6megua/7megua ratio was constant in G1 cells and dropped from 90 s to 10 min by about 15% in liver containing 30% S-phase cells and by about 40% with 80% cells in DNA synthesis. DNA-synthesizing hepatocytes are apparently endowed with a higher O6megua DNA transferase activity than nonproliferating liver cells. The rapid, though exhaustible elimination of O6megua during S-phase might result in partial protection of DNA-synthesizing cells from base-mispairing and/or from hypomethylation at G-C sites.

Alkylation↗
PubMed1983

DNA alkylation and tumor induction in regenerating rat liver after cell cycle-related continuous N-nitrosodimethylamine infusion.

Synchronized regenerating rat liver after partial hepatectomy was used to study cell cycle-related DNA base alkylation and liver carcinogenesis. A continuous iv infusion of [14C]N-nitrosodimethylamine (DMN) at a dose of 0.5 mg/kg/hour was given to inbred male Wistar Af/Han rats over a period of 8 hours either during the G1 phase, hydroxyurea-synchronized DNA synthesis, or the G2+M-phase of regenerating liver or to untreated rats (G0-phase liver--carcinogen dose, 1.5 mg/kg/hour). Two hours after the end of the infusion, the amount of 7-methylguanine was highest in the G0-phase liver, with a decrease in the G1 phase, the S-phase, and the G2+M-phase. After continuous DMN exposure, the O6-methylguanine:7-methylguanine ratio was lower in the S-phase and G2+M-phase livers than in the G0-phase and G1-phase livers, indicating an increased O6-methylguanine repair during DNA synthesis and the G2+M-phase. Liver tumors in rats treated by continuous DMN infusion either during the G0 phase or the S-phase developed only after carcinogen exposure during DNA synthesis.

Adenine↗
PubMed1981

[The value of surgical studies for the current state of diagnosis and treatment of bronchial cancer].

A critical consideration of the modern situation of the diagnostics and therapy of the bronchial carcinoma shows compared with the expense a proportionately small healing quotient of nearly 7% of all diagnosed bronchial cancers. The analysis of the possibilities of the present ways for the therapy shows that an additional improvement of the operative and immediate postoperative results could not lead to a substantial modification of the healing quotient altogether. An improvement is possible only through an increase of the number of operable patients at the moment of the diagnosis. This requires a radical modification of the methods for the early diagnosis. Possible ways for them are shown. A smaller improvement of the healing quotient could be achieved by the intensification and the correction of the after treatment in the later time, inclusively the well-timed and effective treatment of relapse and metastases. The healing quotient after five years may probably be doubled with the right use of the above mentioned measures.

Aftercare↗
PubMed1981

[Prophylactic and therapeutic intermittent positive pressure breathing with combined therapeutic aerosols (IPPB/I)--functional and morphological effects. II. Therapeutic IPPB/I in ventilation disturbances of the lung (author's transl)].

The present paper describes the therapeutic use of IPPB/I in postoperative pulmonary complications with ventilation disturbances of the lung. The beneficial effects of IPPB/I are shown in chest X-rays. The suppositions for performing IPPB/I, concerning equipment, staff and organization, are explained.

Adult↗
PubMed1979

[Medical development cooperation in the Confederation. The international framework and the important place of public health in Swiss development cooperation].

The systematic organization of health services in the developing countries to benefit the majority of the population is seen as an important contribution toward the general economic and social development of these countries. This view is uncontested today, but was given less importance in the early years of Swiss development aid. The Swiss Development Cooperation's support of health services is now integrated into its overall program to satisfy the basic needs of the people of the developing countries.

Developing Countries↗
PubMed1979

[New results on hyperglobulinemic purpura of Waldenström in childhood (author's transl)].

The case of a 13 year old girl with benign purpura hypergammaglobulinemica Waldenström. Besides the characteristic clinical symptoms and the respective laboratory results new findings we demonstrated, which might shed some light into the pathogenesis of this disease. The transformation rate of lymphocytes was decreased particularly after stimulation with ConA. The T-lymphocytes which are reduced in their function are unable to sufficiently control the activity of mesenchymal cells which results in an increased production of glycosaminoglycans. The demonstration of glycosaminoglycan-inclusion-bodies in the mononuclear bone marrow cells of the patient could be explained by the above mentioned mechanism. Upon therapy with D-penicillamine the clinical state improved along with a reduction of the sedimentation rate, the serum protein and the serum gamma-globulin.

Adolescent↗
PubMed1979

[Ethanol in parenteral feeding and its effect on liver metabolism].

Investigations of the leucine aminopeptidase (LAP) and the gamma-glutamyl transpeptidase (gamma-GT) as a dimension for a damage of the liver cells under ethanol infusion did not show any damage of the liver parenchyma with a slow infusion velocity and a limited ethanol quantity (25 g daily). Since especially in the postoperative phase a sufficient caloric nutrition improves the therapeutic results, one could make use of the possibility of ethanol supply. This is mainly recommendable for patients who should demand only a small infusion volume or such a one which should not carry a high quantity of sugar (for instance diabetics). The parenteral ethanol application in the postoperative phase is frequently indicated for the immobilisation of alcoholics.

Adult↗
PubMed1978

[The influence of disodium cromoglycate (DNCG) on the phagocytotic activity of neutrophile granulocytes (author's transl)].

Disodium cromoglycate (Intal) inhibits in vitro the phagocytotic activity of neutrophile granulocytes. In thirteen pairs of blinding analysed experiments it could be shown that the DNCG incubatet blood samples had a phagocytotic index below that of the control. The statistical significance of these findings was assessed by a variance analysis.

Analysis of Variance↗