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Biomedical subjects

W Rohde

Publications and source records attributed to W Rohde.

At least 199 records · Page 11Linked to original sources

Inhibition of amino acyl tRNA synthetase activity by copper complexes of two metal binding ligands. N-Methyl isatin beta-thiosemicarbazone and 8-hydroxyquinoline.

Copper complexes of N-methyl isatin beta-thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone and thiosemicarbazide inhibit amino acyl tRNA synthetase activity. Copper complexes of 8-hydroxyquinoline and 8-mercaptoquinoline also inhibit. The 1 : 1 ligand-metal complex is significantly more active than the 2 : 1 complex. The free ligand alone and copper sulfate alone have little, if any, effect. These complexes have no effect on the ATP-PPi exchange reaction and do not cause deacylation of amino acyl tRNAs. This indicates that the process inhibited by these complexes is the amino acylation reaction. This is the first report that these copper binding ligands can inhibit enzymatic processes which involve nucleic acids but which are not viral, bacterial or mammalian cell polymerases.

Amino Acyl-tRNA Synthetases↗

Inactivation and inhibition of Rous sarcoma virus by copper-binding ligands: thiosemicarbazones, 8-hydroxyquinolines, and isonicotinic acid hydrazide.

We have shown that three types of copper-binding ligands, thiosemicarbazones, 8-hydroxyquinolines, and isonicotinic acid hydrazide and their copper complexes, inactivate the transforming ability of RSV and inhibit its RNA-dependent DNA polymerases. Three other compounds, 2-pyridine thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone, and diphenyl thiocarbazone inhibit transformation by RSV intracellularly. Most but not all of these compounds bind to nucleic acids in the presence of copper, which may be important in their mode of action.

Avian Sarcoma Viruses↗

Genetic relationship between an influenza A and a B virus.

The base sequence homology between all eight 32P-labelled RNA segment of fowl plague virus (FPV) and the complementary RNA (cRNA) of an influenza B virus (B-mass), and between segment 8 of virus N and the cRNA of the same influenza B strain has been determined. All segments of FPV and segment 8 of virus N show a significant base sequence homology, ranging from 18 to 50% suggesting that influenza A and B viruses have a common ancestor. The conserved regions in segments 4,6 and 8 of the influenza A strains are identical to corresponding regions of the influenza B virus tested.

Base Sequence↗

Plasma basal levels of FSH, LH and testosterone in homosexual men.

Plasma basal levels of FSH, LH and total as well as apparent free testosterone were determined in homosexual and heterosexual males. Significantly higher FSH concentrations (mean +/- SD = 6,89+/-5.00 mlU/ml; P less than 0.01) and LH concentrations (28.2+/-30.7 mlU/ml; P less than 0.002) were found in plasma of 50 homosexual males compared with those of 24 or 40 heterosexual males 4.17 +/- 2.34 mlU/ml and 12.6 +/- 7.6 mlU/ml, respectively). Significantly lower free plasma testosterone was observed in 35 homosexual males (10.7 +/- 3.3 ng/100 ml; P less than 0.01) than in 38 heterosexual males (13.3 +/- 4.5 ng/100 ml), whereas total testosterone in plasma of homosexual males (590 +/- 148 ng/100 ml) showed no significant difference in comparison with the heterosexual control group (562 +/- 126 ng/100 ml). The tendency to higher FSH and LH values as well as to lower free testosterone concentrations in plasma compared with the heterosexual control group was more evident for effeminized than for non-effeminized homosexual males. FSH and LH concentrations in plasma of 5 transsexual males were also significantly higher (11.74 +/- 5.06 and 18.3 +/- 3.4 mlU/ml, respectively; P less than 0.02) than those of the heterosexual control group. Our findings may be explained by the possible existence of a prenatal testicular androgen deficiency in homosexual males that is widely compensated by increased gonadotrophin secretion in adult life.

Follicle Stimulating Hormone↗

Maturation of the oestrogen-dependent LH-stimulating activity of the mediocortical amygdala in female rats.

Immature female Wistar rats were unilaterally implanted with oestradiol benzoate (OB) into the anterior (AMAN) or posterior part (PMAN) of the medial amygdaloid nucleus, or into the central part of the cortical amygdaloid nucleus (CCAN) at different ages. Autopsy was performed 56h after implantation, and the LH concentration in the plasma was estimated by radioimmunoassay. A significant rise of the LH level resulted from implantation of OB: into the PMAN at 21, 26 and 32 days of age, into the AMAN at 32 and into the CCAN at 26 and 36, but not at 32 days of age. The conclusion was drawn that the medial amygdaloid nucleus may be involved in the maturation of the positive oestrogen feedback mechanism. The prepuberal change in the oestrogen-dependent LH-controlling activity of the cortical amygdaloid nucleus indicates that this nucleus may participate in the control of the onset of puberty.

Amygdala↗

Hydroxyquinolines inhibit ribonucleic acid-dependent deoxyribonucleic acid polymerase and inactivate Rous sarcoma virus and herpes simplex virus.

8-Hydroxyquinoline and several of its derivatives inactivate the transforming ability of Rous sarcoma virus and inhibit its ribonucleic acid-dependent deoxyribonucleic acid polymerase activity. The copper complex of these metal-binding ligands is as active as the free ligand. The activity of the 8-hydroxyquinolines is approximately 50-fold more effective than another group of metal-binding compounds that we have tested, the thiosemicarbazones. In contrast to the potency of the 8-hydroxyquinolines to inactivate Rous sarcoma virus, no intracellular inhibition of transformation could be demonstrated at a concentration that did not affect the growth and appearance of the cells. Cellular deoxyribonucleic acid synthesis was inhibited to a greater extent than was ribonucleic acid or protein synthesis. The phenomenon of "concentration quenching" was observed with high concentrations of drug, causing less inhibition of deoxyribonucleic acid synthesis than was observed with lower concentrations. Herpes simplex virus type 1 was inactivated also by the 8-hydroxyquinolines and their copper complexes. No intracellular inhibition of plaque formation was observed. Treatment with 8-hydroxyquinoline sulfate had no effect on the resolution of herpetic keratitis in rabbits. Some 8-hydroxyquinolines bind to deoxyribonucleic acid in the presence of copper, a phenomenon that may be important in their antiviral activity.

Animals↗

Endocrine effects of oestrogen treatment in patients with prostatic cancer.

In 36 men with prostatic cancer, the following findings were obtained: intravenous administration of 12.0 g diethylstilboestrol diphosphate (DSDP) induced a relatively slight decrease of the LH plasma level from 22.7 +/- 11.8 to 7.7 +/- 3.6 mIU/ml (34%), whereas the total testosterone plasma level decreased from 435.3 +/- 187.8 to 29.9 +/- 16.4 ng/100 ml (6.7%) suggesting a direct inhibitory effect of the oestrogen on testicular testosterone secretion. The apparently free, biologically active testosterone plasma level even decreased from 6.2 +/- 3.7 to 0.21 +/- 0.16 ng/100 ml (3.4%), due to the oestrogen-induced increase of the concentration of testosterone-binding beta-globulin (from 9.6 +/- 4.4 to 20.6 +/- 10.7-10(-8) M). 3--7 days after additional orchidectomy plus subcutaneous implantation of 100 mg dienoestrol diacetate a further decrease of the apparently free testosterone plasma level from 0.21 +/- 0.16 to 0.14 +/- 0.07 ng/100 ml was found. In contrast, 6 weeks after orchidectomy without oestrogen implantation a significant increase of th- apparently free testosterone plasma level -rom 0.21 %/- 0.16 to 0.34 +/- 0.15 ng/100 ml was observed (p less than 0.01). In view of these findings the biologically active free testosterone plasma level appears to be even more suppressed by intravenous administration of high DSDP than by orchidectomy. The most effective suppression of apparently free testosterone was achieved, however, by oestrogen treatment combined with orchidectomy.

Aged↗