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Biomedical subjects

J W Harding

Publications and source records attributed to J W Harding.

142 records · Page 8Linked to original sources
PubMed1975

Proportional activities of glycerol kinase and glycerol 3-phosphate dehydrogenase in rat hepatomas.

The activities of glycerol 3-phosphate dehydrogenase (EC 1.1.1.8), glycerol kinase (EC 2.7.1.30), lactate dehydrogenase (EC 1.1.1.27), "malic' enzyme (L-malate-NADP+ oxidoreductase; EC 1.1.1.40) and the beta-oxoacyl-(acyl-carrier protein) reductase component of the fatty acid synthetase complex were measured in nine hepatoma lines (8 in rats, 1 in mouse) and in the livers of host animals. With the single exception of Morris hepatoma 16, which had unusually high glycerol 3-phosphate dehydrogenase activity, the activities of glycerol 3-phosphate dehydrogenase and glycerol kinase were highly correlated in normal livers and hepatomas (r = 0.97; P less than 0.01). The activities of these two enzymes were not strongly correlated with the activities of any of the other three enzymes. The primary function of hepatic glycerol 3-phosphate dehydrogenase appears to be in gluconeogenesis from glycerol.

Animals↗
PubMed1975

Flucloxacillin in the treatment of infectious conditions in children.

A multi-centre study was carried out in 107 children with skin and soft-tissue infections (46) or upper respiratory tract infections (61) to assess the effectivness of flucloxacillin (125 mg. q.d.s. for 5 days). Swabs were taken from the lesion sites before and after treatment for bacteriological assessment and sensitivity of the isolated organisms. The clinical success rate achieved was 93% in skin and soft-tissue infections and 94% in upper respiratory tract infections and these results correlate closely with the bacteriological findings. The main causative organism in the skin and soft-tissue infections was Staph. aureus which was resistant to benzyl penicillin and to ampicillin in all but 2 cases. All strains proved sensitive to flucloxacillin. Minimal side-effects were reported and the syrup presentation was well accepted.

Administration, Oral↗
PubMed1970

Successful treatment of osteomyelitis caused by Pseudomonas aeruginosa.

A case of generalized osteomyelitis due to Ps. aeruginosa is described. The condition had failed to respond to therapy with almost all antibiotics available but responded to long-term therapy with carbenicillin in very large doses, and it is suggested that this is now the treatment of choice for severe infections due to this organism.

Biopsy↗
PubMedDate not supplied

Regulatory role of brain angiotensins in the control of physiological and behavioral responses.

Considerable evidence now indicates that a separate and distinct renin-angiotensin system (RAS) is present within the brain. The necessary precursors and enzymes required for the formation and degradation of the biologically active forms of angiotensins have been identified in brain tissues as have angiotensin binding sites. Although this brain RAS appears to be regulated independently from the peripheral RAS, circulating angiotensins do exert a portion of their actions via stimulation of brain angiotensin receptors located in circumventricular organs. These circumventricular organs are located in the proximity of brain ventricles, are richly vascularized and possess a reduced blood-brain barrier thus permitting accessibility by peptides. In this way the brain RAS interacts with other neurotransmitter and neuromodulator systems and contributes to the regulation of blood pressure, body fluid homeostasis, cyclicity of reproductive hormones and sexual behavior, and perhaps plays a role in other functions such as memory acquisition and recall, sensory acuity including pain perception and exploratory behavior. An overactive brain RAS has been identified as one of the factors contributing to the pathogenesis and maintenance of hypertension in the spontaneously hypertensive rat (SHR) model of human essential hypertension. Oral treatment with angiotensin-converting enzyme inhibitors, which interfere with the formation of angiotensin II, prevents the development of hypertension in young SHR by acting, at least in part, upon the brain RAS. Delivery of converting enzyme inhibitors or specific angiotensin receptor antagonists into the brain significantly reduces blood pressure in adult SHR. Thus, if the SHR is an appropriate model of human essential hypertension (there is controversy concerning its usefulness), the potential contribution of the brain RAS to this dysfunction must be considered during the development of future antihypertensive compounds.

Amino Acid Sequence↗
PubMedDate not supplied

Drinking to intracerebroventricularly infused angiotensin II, III, and IV in the SHR.

Spontaneously hypertensive rats (SHR) revealed exaggerated water consumption to the intracerebroventricular (ICV) infusion of angiotensin II (AII), and angiotensin III (AIII), as compared with Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive rat strains, in agreement with an earlier report (30) that employed ICV bolus injections of AII and AIII. However, the ICV infusion of AII(3-8) (AIV) did not yield reliable drinking. A second hypothesis that the infusion of AII and AIII would yield equivalent drinking within members of each strain, as previously observed with bolus ICV injections in SD rats, was not confirmed. In contrast, ICV infusion of AII yielded greater water intake than AIII in members of each strain tested. These results suggest that the slow infusion of these ligands allowed endogenous aminopeptidases to adequately keep pace with the degradation of these peptides in contrast with bolus injections that could temporarily saturate the available aminopeptidases thus extending the half-life of the ligand.

Angiotensin II↗
PubMedDate not supplied

Brain angiotensin: critical role in the ongoing regulation of body fluid homeostasis and cardiovascular function.

The existence of an endogenous brain-angiotensin system and its association with cardiovascular and body water regulation has been recognized for over a decade. Nevertheless, the importance of the brain-angiotensin system to the instantaneous regulation of these processes has not been firmly established. A 5-minute intracerebroventricular (ICV) infusion of the angiotensin antagonist, [Sar1,Thr8]-AII, effectively lowered the blood pressure in normotensive rats. Additionally, application of the selective aminopeptidase inhibitor, bestatin, given alone, resulted in a dramatic increase in blood pressure and a robust drinking response. Both effects were 100% blockable by [Sar1,Thr8]-AII pretreatment. Predictably, an aminopeptidase inhibitor, bestatin, greatly elongated the half-lives of AII and AIII in the cerebroventricles. Since neither of these treatments included the introduction of exogenous angiotensins, we have concluded that perturbations of the endogenous brain-angiotensin system are effective at rapidly influencing both cardiovascular and body fluid homeostasis, thus highlighting the paramount role played by brain angiotensin in their ongoing regulation.

Aminopeptidases↗
PubMedDate not supplied

AT4 receptor binding characteristics: D-amino acid- and glycine-substituted peptides.

The ability of angiotensin IV (AIV) analogs to compete for [125I]AIV binding in heat-treated bovine adrenal membranes was examined. Angiotensin IV displayed a Ki of 2.63 +/- 0.12 nM. Peptides containing mono-substitutions with glycine or the corresponding D-amino acid in positions one, two, or three possessed K(i)s greater than 100 nM. Conversely, substitutions at positions four, five, and six produced peptides with Kis less than 8 nM. These data suggest that the N-terminal domains of the AIV peptide are critical for receptor binding, while the C-terminal domains play a less decisive role in receptor specificity.

Amino Acid Sequence↗
PubMedDate not supplied

Reversible effects of olfactory nerve section on behavior and biochemistry in mice.

Coincident with the sectioning of the primary olfactory nerves in mice there is a dramatic loss of both olfactory-mediated behavior and the ability of the primary olfactory neurons to synthesize and transport the neuron specific marker, carnosine. These deficiencies are only temporary, and the ability of food deprived mice to locate buried food pellets returns within 21 days after olfactory nerve section. The ability of the primary olfactory neurons to synthesize and transport carnosine appears to increase between 8 days and 45 days after surgery. These data support the notion of behaviorally significant functional regeneration of olfactory neurons.

Alanine↗