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Biomedical subjects

J B Hook

Publications and source records attributed to J B Hook.

At least 127 records · Page 7Linked to original sources
PubMed1980

A method for identifying Ca ionophores using a unicellular organism.

A method is described for identifying Ca++ ionophores using the protozoa Actinosphaerium. This organism is a free-floating spherical form with filamentous axopods radiating from the surface. The axopods are composed of microtubules that disaggregate upon exposure to intracellular Ca++. In the presence of an appropriate ionophore, extracellular Ca++ will pass the cell membrane, enter the cell, and disrupt microtubules. The resultant shortening of axopods can be easily quantified under a microscope. This system may prove to be a valuable research tool in the identification of compounds that possess the ability to facilitate transmembrane Ca++ movement.

Animals↗
PubMed1980

The effects of aluminum on microtubular integrity using in vitro and in vivo models.

Since neuronal lesions produced by aluminum (Al) are morphologically similar to lesions produced by microtubule inhibitors, the effect of aluminum on microtubule integrity was investigated. Aluminum inhibited microtubule formation at concentrations as low as 0.1 mM. This approaches the aluminum concentrations found in brains of patients with several disorders which result in progressive dementia.

Aluminum↗
PubMed1980

Postnatal morphology and functional capacity of the kidney following prenatal treatment with dinoseb in rats.

Dinoseb has produced alterations that are suggestive of renal damage in mice and rats. Therefore it was of interest to determine the postnatal morphology and functional capacity of the kidney following prenatal treatment with dinoseb in rats. Fetal and neonatal rats treated with dinoseb on gestational d 10-12 had dilated renal pelves and ureters. Kidneys had dilated tubules and excessive mesenchymal tissue when examined perinatally. These pathological changes were reduced in incidence (kidney) or not detected (ureter) at 42 d postpartum and were not correlated with alterations in postnatal renal function. Livers from rats treated prenatally with dinoseb were vacuolated and necrotic even at 42 d postpartum. Rats treated prenatally with dinoseb had reduced body weights at 1 and 7 d postpartum. However, body weights of control and dinoseb-treated rats were not significantly different at 42 d of age. These results emphasize the need to determine the pesistence and functional consequences of anomalies detected in near-term fetuses for safety assessment of a chemical.

Animals↗
PubMed1980

Age-related differences in angiotensin I metabolism by isolated perfused rat lungs.

The pulmonary vasculature has been implicated in the clearance of several vasoactive substances from the circulation including angiotensin I (AI). In view of the previously reported age-related differences in angiotensin-converting enzyme (ACE) activity of lung homogenates, it was of interest to examine the ability of intact perfused lungs to metabolize AI. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 1.0 ng/ml AI in a single-pass, nonrecirculating system. The rate of perfusion was normalized to lung mass. Removal of AI was determined from the transpulmonary difference in radioimmunoassayable AI. Lungs from 7-day-old rats removed a smaller fraction of AI from the circulation than did adult lungs. The age-related increase in AI clearance was accompanied by an increase in pulmonary ACE content; however, enzyme content alone could not account for the observed differences. The increased metabolism of AI by the pulmonary vasculature during development may contribute to the age-related increase in circulating angiotensin II concentrations.

Aging↗
PubMed1980

Postnatal development of the renin-angiotensin system in rats.

The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity.

Aging↗
PubMed1980

Effect of saralasin and indomethacin on renal function in developing piglets.

To investigate the influence of angiotensin II (AII) and renal prostaglandins on neonatal renal hemodynamics and sodium excretion, unanesthetized piglets 1-5, 18-20, and 45-50 days of age were treated with saralasin and indomethacin prior to volume expansion (VE) with isotonic saline. Saralasin did not affect basal renal blood flow (RBF) or the intrarenal distribution of blood flow as calculated as the ratio of outer-to-inner slice counts (O/I) in piglets 1-50 days of age. VE increased fractional sodium excretion equally in all animals. In 1- to 5-day-old piglets, saralasin blunted this natriuresis without affecting renal hemodynamics. Therefore, low neonatal RBF and O/I do not appear to be due to AII. In addition, indomethacin did not change renal hemodynamics in newborn piglets and did not affect the natriuresis after VE in any age group. Indomethacin decreased RBF and increased O/I of conscious 45- to 50-day-old animals. Renal prostaglandins do not appear to be a factor in control of renal hemodynamic in newborn pigs and do not influence the natriuresis in neonates following saline loading.

Aging↗
PubMed1980

Disposition of 5-hydroxytryptamine in lungs of developing rats.

The pulmonary vasculature has been implicated in the clearance of several vasoactive peptides, prostaglandins, and biogenic amines from the circulation. In view of the age-related differences in the metabolism of angiotensin by intact lungs, it was of interest to examine the maturation of 5-hydroxytryptamine (5-HT) disposition by isolated perfused lungs. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 0.1 microM 5-[14C]HT and samples of the effluent medium collected and analyzed for 5-HT and metabolite. Adult lungs removed and a greater fraction of perfused 5-HT than did lungs from 7-day-old rats. No age-related difference in monoamine oxidase (MAO) activity was observed; however, lung slices from adult rats incubated with 5-[14C]HT accumulated radiolabel at a greater rate than did slices from lungs of 7-day-old rats. The age-related difference in 5-HT clearance by intact lungs may be attributable to a relative deficiency in the facilitated transport process for 5-HT in newborns and may reflect a general functional maturation of processes associated with pulmonary endothelial cell membranes.

Aging↗
PubMed1980

Inhibition of N-2-fluorenylacetamide-induced mammary tumorigenesis in rats by dietary polybrominated biphenyls.

Female SD rats were maintained for approximately 1 year on diets containing 300 ppm N-2-fluorenylacetamide (2-FAA), 50 ppm polybrominated biphenyls (PBB), or a combination of these chemicals (PBB + 2-FAA). Ingestion of 2-FAA significantly reduced the average survival time of the rats; this effect was virtually blocked by the simultaneous ingestion of PBB. Simultaneous ingestion of PBB also significantly reduced the overall incidence of 2-FAA-induced tumors during the examination period. The lower incidence of tumorigenesis was accompanied by an increase in the latency time for tumor induction; tumors were found in 100% of the animals given 2-FAA after 29 weeks of carcinogen ingestion, whereas only 50% of the PBB + 2-FAA-fed animals had tumors at the end of the experiment (53 wk of carcinogen ingestion). PBB significantly reduced the incidence of 2-FAA-induced tumors at nonhepatic locations (mammary gland and ear duct) but did not affect the incidence of hepatic tumors to a statistically significant extent. PBB ingestion did not significantly increase the incidence of tumors when compared with controls; 1 tumor was found in 1 of 12 rats fed 50 ppm PBB for 57 weeks, and no tumors were detected in 8 controls.

2-Acetylaminofluorene↗
PubMed1980

Regulation of plasma renin in developing piglets.

Plasma renin activity (PRA) was determined in conscious piglets between 1 and 50 days of age before and after treatment with saralasin and indomethacin. Following drug treatment, animals were volume expanded with isotonic saline. Saralasin increased PRA in piglets 1-5 and 18-22 days of age but not 45-50 days. Neither indomethacin nor VE changed PRA at any age. Volume expansion of saralasin- and indomethacin-treated pigs decreased PRA. Neonatal hyperreninemia does not appear to result from renin release stimulated by prostaglandins or by the absence of angiotensin II negative feedback. In addition, the plasma half-life of renin was not different between young and more mature animals suggesting that immature hapatic metabolism of renin cannot be entirely responsible for the high PRA in newborns.

Age Factors↗
PubMed1980

Effect of furosemide on renal function of the newborn piglet.

The effects of development of renal function on the response of newborns to furosemide was evaluated in an animal model, the newborn piglet. Three ages of piglets were used: 5-day-old, 20-day-old, and 50-day-old. Intravenous administration of furosemide (2 mg/kg) produced a prompt natriuresis in all animals. The natriuresis after furosemide was greatest in the older piglets (110 microEq/min for 50-day-old piglets were 210 microEq/min for 5-day-old piglets). However, the fractional sodium excretion at the peak of the response was near 20% in animals in each age group. Neither the time of peak response nor duration of natriuresis was affected by age. Potassium excretion increased after furosemide and remained elevated after both urine flow and sodium excretion had returned to control. The pattern of potassium excretion was identical for each of the three age groups. Thus, while renal maturation does not markedly affect the response to furosemide, both newborns and older piglets continue to excrete relatively large amounts of potassium after sodium excretion returns to control.

Aging↗
PubMed1980

Metabolic activation of nephrotoxic haloalkanes.

Worldwide industrialization and environmental pollution have increased the incidence of human exposure to halogenated aliphatic hydrocarbons, many of which are injurious to the mammalian kidney. Evaluation of human risk from haloalkane exposure requires knowledge about the mechanisms of the nephrotoxic effects of these agents so that appropriate animal models of human response can be developed. Recent studies indicate that nephropathy following methoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) anesthesia is caused by hepatic enzymatic release of inorganic fluoride ion, a nephrotoxic component of the parent molecule. Thus, the toxic effect is dependent upon hepatic metabolism of methoxyflurance. Acute chloroform injury to the kidney also may be caused by a toxic metabolite. In this case, however, the metabolite is most likely produced within the kidney. Chloride ion is relatively innocuous, suggesting that a carbon fragment of chloroform is the nephrotoxic agent. These results indicate that haloalkane metabolism, both renal and hepatic, can be important determinants of haloalkane nephropathy.

Animals↗
PubMed1979

Action of exogenously administered steroid hormones following perinatal exposure to polybrominated biphenyls.

Polybrominated biphenyls (PBBs) have produced a variety of effects including alterations in the endocrine system and in the activity of microsomal mixed-function oxidases (MFOs). Because steroid hormones are substrates for MFOs, effects of PBBs on the endocrine system may be a consequence of enhanced steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone catabolism. Therefore, as a first step in evaluating the effect of PBBs on steroid hormone metabolism, it was of interest to determine effects of perinatal exposure to PBBs on the response to exogenously adminstered steroid hormones. Rats were exposed to 0, 10, or 100 ppm PBBs from d 8 of gestation until d 28 postpartum, when experiments were conducted. Responses to labeled steroid hormones were generally modified in a manner directly related to PBB dose and were correlated with changes in serum and target tissue retroactivity. Stimulated metabolism of steroid hormones may account, at least in part, for endocrine-related alterations produced by PBBs. Although the potential for decreased reproductive capacity following PBBs cannot yet be accurately predicted, these experiments suggest that fertility may be reduced following PBBs as a consequence of accelerated steroid hormone metabolism and/or excretion.

Animals↗