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M J Hamilton

Publications and source records attributed to M J Hamilton.

77 records · Page 5Linked to original sources
PubMedDate not supplied

Genomic distribution of heterochromatic sequences in equids: implications to rapid chromosomal evolution.

We describe a molecular model for rapid chromosomal evolution that proposes tandemly repeated DNA sequences as a driving force. A prediction of this model is that when extensive rearrangements of euchromatin have been facilitated by heterochromatin, genomes will be characterized by tandemly repeated sequences that have actively changed chromosomal fields by intragenomic movement. Alternatively, it is proposed that in conservative chromosomal lineage each class of tandemly repeated sequences will be restricted to a specific chromosomal field. To provide baseline data to test this model we examined four classes of tandemly repeated elements in six species of equids (Equus). Distribution of these sequences among species, as determined from slot blot analysis, and restriction site variation, shown by Southern blot hybridization, document that these sequences are in an evolutionarily dynamic state, and in situ hybridization documents extensive intragenomic movement among nonhomologous chromosomes and chromosomal fields. These data are interpreted as being compatible with the predictions of this model. Although this is clearly not the sole molecular factor driving chromosomal evolution, the model appears to be viable as an explanation of certain patterns of chromosomal evolution such as karyotypic megaevolution and some types of karyotypic orthoselection.

Animals↗
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Carbamazepine and lamotrigine in healthy volunteers: relevance to early tolerance and clinical trial dosage.

This study was conducted to examine the effects of acute doses of lamotrigine (LTG) and carbamazepine (CBZ) in healthy subjects and determine whether the low tendency to impairment with LTG observed in animals applied to humans. Twelve healthy men participated in a placebo-controlled, balanced, double-blind comparison of the drugs on a series of psychomotor, autonomic, sensory, and subjective variables. Variables were analyzed by analysis of variance, and p < 0.05 was considered significant. Adaptive tracking and body sway were impaired by CBZ 600 mg. CBZ 400 and 600 mg impaired smooth pursuit eye movements and also reduced mean peak saccadic velocity. No differences from placebo occurred after LTG. CBZ 600 mg increased heart rate (HR), but no drug-related changes were noted in pupil size, salivary secretion, visual near point, or subjective effects. During the controlled study, mean plasma CBZ concentrations at 2 and 6.5 h after the 600-mg dose were 5.28 and 5.36 micrograms/ml; after LTG 300 mg, they were 3.16 and 3.00 micrograms/ml. Increased CBZ saliva concentrations were significantly associated (p < 0.01) with impaired adaptive tracking, smooth and saccadic eye movements and increased HR, and plasma concentrations were associated with impaired eye movements and body sway.

Adult↗
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Observations on the nature, biosynthesis, secretion and significance of endogenous ouabain.

The human circulation contains four readily distinguishable biologically active inhibitors of the sodium pump that appear to be endogenous to mammals. Of these, one has been purified to homogeneity and by numerous chromatographic, mass spectral, biochemical, and physiological analyses has been shown to be a novel steroidal isomer of ouabain in which the location and orientation of two or more steroidal hydroxyl groups differ. The human endogenous "ouabain" (EO) is a high affinity reversible inhibitor of the pump with inotropic and vasopressor activity. Circulating levels of EO depend upon the adrenal cortex and metabolic events preceding and following pregnenolone formation are involved in EO biosynthesis. Within the adrenal gland, the stimulus-secretion mechanisms for EO secretion are distinct from those for aldosterone highlighting different regulation. Among Caucasians with essential hypertension, 30-45% have elevated circulating levels of EO. Sustained elevation of plasma ouabain in rats induces chronic hypertension with characteristics similar to those in patients and whose severity is determined by inherited factors and renal function. In conclusion, at least one of the mammalian counterparts to the cardiac glycosides is a novel steroidal isomer of ouabain. The isomer is secreted by the adrenal cortex, and augments cardiovascular function. The observation of this entity in the human circulation, the demonstration of its biosynthesis, and the existence of specific receptors suggest to us that EO is a novel adrenocortical hormone and may be part of a broader family of novel mammalian steroids that regulate the sodium pump and other processes.

Adrenal Cortex↗