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Biomedical subjects

M G Hamilton

Publications and source records attributed to M G Hamilton.

At least 91 records · Page 5Linked to original sources

Correlation of systemic and biochemical effects of PBB with behavioral effects.

Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals.

Animals↗

The use of guanidine-HCl for the isolation of both RNA and protein from RNA tumour viruses.

The RNA components of two C-type RNA viruses, avian myeloblastosis virus and Friend leukaemia virus, have been isolated by treatment of the viruses with 6 M-guanidine-HCl and precipitation with ethanol. The virus proteins were recovered by lyophilization of the guanidine-HCl-ethanol supernatant after thorough dialysis against 0.5 mM-dithiothreitol. This simple method yielded RNA of similar quality to the phenol and sodium dodecyl sulphate (SDS) extraction methods, and the same amount of 60-70S RNA, although a fraction of the smaller (4S) species remained in the protein fraction. The sedimentation patterns of heat-denatured RNA extracted by either method were similar. Electrophoretic analyses of the extracted proteins in polyacrylamide gel gradients containing SDS gave patterns that were very similar to those obtained by direct analysis of SDS disrupted viruses.

Animals↗

Putative role of isoquinoline alkaloids in alcoholism: a link to opiates.

Although the isoquinoline hypothesis has stimulated and even tantalized the scientific inquiry of a small number of investigators, it has been an area of widespread controversy. For the most part, until recently, alcohol researchers would ascribe very little importance to the role played by insoquinolines in alcohol actions or in the disease state known as alcoholism. To most, there was adequate evidence that these condensation amines had potent pharmacologic properties but little was known about their biochemical and behavioral interaction with ethanol or opiates. As pointed out here, there is an increasing amount of evidence that indicates the putative role of isoquinolines as regulators of alcohol dependence. There is even evidence that suggests a possible "link" to opiates. If this turns out to be the case, then it is rational to consider the possibility that when one imbibes alcohol a central opiate-like substance is, in essence, produced. It would appear that the sum total of evidence to date supports the notion that there are common territories between the two highly addictive classes of drugs--alcohol and opiates. Although still not definite, future studies may well confirm the intermediacy of the TIQ compounds.

Alcoholism↗

Antagonism of smooth muscle responses to oxytocin and vasopressin by salsolinol.

The responses of isolated smooth muscle tissues to the polypeptides oxytocin, vasopressin and bradykinin were evaluated in the presence of the tetrahydroisoquinoline salsolinol. Significant antagonism occurred to oxytocin and vasopressin while the effects of bradykinin were unaltered. These results suggest that the in vivo formation of salsolinol after ethanol consumption could have significant physiological consequences.

Alkaloids↗

Effects of salsolinol on smooth muscle responses to various biogenic amines.

Isolated smooth muscle tissues from rats, guinea pigs and rabbits were used to investigate pharmacological effects of salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline). By itself, salsolinol did not produce any profound or sustained sympathomimetic or 5-hydroxytryptamine-like activity in the concentrations used in these experiments (7.7 and 77 muM). Salsolinol was found to antagonize the contraction of the rabbit aorta induced by noradrenaline but did not affect the adrenaline-induced relaxation of the guinea pig tracheal chain. On both the rat fundus and oestrus rat uterus, salsolinol exhibited significant anti-5-hydroxytryptamine activity but responses of these tissues to acetylcholine and histamine remained unaffected, indicating that the action was not non-specific. These results suggest that in vivo formation of salsolinol after ethanol ingestion could produce significant pharmacological effects.

Acetylcholine↗

Electron microscopic observations on the large subunit of the rat liver ribosome.

Active large subunits obtained by urea treatment of rat liver ribosomes, 59S, were compared with large subunits in intact ribosomes and with the 50S subunits obtained by EDTA treatment. For electron microscopy the specimens were negatively stained or shadow cast. The negatively stained 59S subunits had a slightly ovoidal form; their average dimensions, 244 +/- 17 x 207 +/- 18 A, were very close to the dimensions of the large subunits in intact ribosomes, and lay between the theoretical dimensions for anhydrous and fully hydrated particles that were calculated from the physical properties of the subunits in solution. The shadow-cast preparations showed particles of similar shape. The 50S subunits, which had lost their 5S RNA, were shadow cast at the same time. They appeared to be more spread out than the 59S subunits and had threadlike extensions. In the positively stained regions of uranyl oxalate-stained preparations the 50S particles varied greatly in shape and size, with average dimensions of 330 +/- 21 x 276 +/- 33 A, and showed threadlike extensions like those of the shadow-cast particles. For 50S particles in solution the frictional drag of these extensions probably accounts for their low sedimentation coefficient.

Animals↗