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Biomedical subjects

K L Klein

Publications and source records attributed to K L Klein.

32 records · Page 2Linked to original sources
PubMed1981

Indomethacin--placental transfer, cytotoxicity, and teratology in the rat.

Aspirin is a well-known teratogen in laboratory animals and is an inhibitor of prostaglandin synthesis. To further investigate the inhibition of prostaglandin synthesis as a mechanism of teratogenesis, we examined the teratologic potential, cytotoxic potential, and placental transfer of indomethacin in the rat. Indomethacin was not teratologic, not cytotoxic to cells in the embryonic hindlimb bud, and did not cross the placenta in physiologically significant amounts on days 11 to 12 of gestation. Near parturition, however, indomethacin crossed the placenta in pharmacologically significant amounts. The pharmacokinetics of placental drug transfer are discussed.

Abnormalities, Drug-Induced↗
PubMed1981

Aspirin-induced teratogenesis: a unique pattern of cell death and subsequent polydactyly in the rat.

Offspring of pregnant rats treated with a high dose of aspirin on day 11 of gestation frequently had predominantly right-sided polydactyly of the hindlimbs at term. Aspirin-treated embryos removed on day 12 exhibited a unique pattern of preaxial mesodermal cell death in the hindlimb buds. In addition, these embryos had a delay of the normal episode of cells death in the preaxial apical ectodermal ridge and an absence of cell death in a zone of physiological necrosis in the preaxial mesoderm thought to be instrumental in controlling preaxial digit formation. The role of cell death in the pathogenesis of polydactyly is discussed.

Abnormalities, Drug-Induced↗
PubMed1981

Instantaneous and continuous measurement of 14C-labeled substrate oxidation to 14CO2 by minute tissue specimens: an ionization chamber method.

The vibrating reed electrometer and ionization chamber have been adapted for the instantaneous and continuous measurement of 14C-labeled substrate oxidation to 14CO2 by minute quantities of isolated tissues. This modified technique, utilizing a "closed" circulation incubation system, is 10-50 times as sensitive as the previously described "open" circulation techniques. Substrate oxidation curves are described for human erythrocytes and polymorphonuclear leucocytes, canine parietal cells and isolated segments of the rat nephron. This apparatus should prove to be a useful tool for metabolic studies of small quantities of isolated tissue.

Animals↗
PubMed1981

Measurement of prostaglandins in embryonic tissue using radioimmunoassay.

Although prostaglandins appear to play an important role in numerous physiological processes in the adult, neonate, and fetus, very little is known about the role of these compounds in the embryo. This study demonstrates that rat embryo homogenates synthesized 6-oxo-PGF1 alpha, PGE and PGF in markedly different amounts from endogenous substrate. Synthesis was inhibited by indomethacin (10 microM) in varying degrees (70-89%) depending on the prostaglandin. The metabolite of PGF2 alpha, 13, 14-dihydro-15-keto PGF2 alpha (PGF2 alpha-M), was produced in limited amounts in the absence of exogenous NAD. In the presence of exogenous NAD and PGF however, embryonic homogenates produced PGF2 alpha-M. The potential role of prostaglandins during embryogenesis is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Substrate oxidation by isolated single nephron segments of the rat.

Substrate oxidation was assessed by measuring 14CO2 production from 14C-labeled substrates in proximal convoluted tubules (PCT), medullary (MTAL), and cortical (CTAL) thick ascending limb of Henle, nephron segments rich in mitochondria and characterized by active solute transport. PCT, MTAL, and CTAL were dissected from the outer cortex, outer medulla, and the medullary rays of the cortex, respectively, of collagenase-treated rat kidney slices. Tubules were incubated at 37 degrees C in 150 microliters of Krebs-Ringer-bicarbonate buffer (pH, 7.4) with 14C-labeled substrate. 14CO2 production was linear up to 4 and 2 hours in PCT and MTAL, respectively. Freeze-thawing of the tubules markedly decreased 14CO2 production, and the addition of cyanide completely abolished it. The PCT demonstrated marked 14CO2 production from labeled succinate, 2-oxoglutarate, glutamate, glutamine, and malate (approximately 10 to 45 pmoles/mm/hr) and moderate 14CO/ production from citrate (approximately 3 pmoles/ml/hr). Little 14CO2 was released from labeled glucose and lactate in PCT. These results are consistent with the existence of gluconeogenesis in this nephron segment. By contrast, MTAL and CTAL oxidized glucose, 2-oxoglutarate, lactate, glutamate, and glutamine, but not malate, succinate, and citrate. The pentose shunt pathway accounted for approximately half of the 14CO2 produced from 1-14C glucose in MTAL and CTAL. Palmitate oxidation occurred in MTAL and CTAL but minimally in PCT. The results demonstrate a distinct pattern of substrate oxidation in PCT, MTAL, and CTAL where oxidative metabolism is critical to support active solute transport.

Animals↗
PubMed1981

Adenylate cyclase and cell cyclic AMP of rat cortical thick ascending limb of Henle.

Effects of parathyroid hormone (PTH), calcitonin (CT), vasopressin (VP), and glucagon (GL) on adenylate cyclase activity and cyclic AMP (cAMP) levels in isolated cortical thick ascending limbs of Henle's loop (CTAL) of the rat kidney were examined. PTH, CT, and VP each stimulated adenylate cyclase of this nephron segment in a dose-dependent manner. Stimulation of the enzyme activity was greatest with a maximal dose of PTH and least with VP. With maximal doses, the effects of PTH and CT were not additive; whether or not the effects of maximal doses of VP and PTH or CT were additive was not clear. All three hormones increase cAMP in intact CTAL ina dose-dependent manner. Maximal doses of PTH, CT, VP, and GL resulted in comparable rises in cell cAMP, and there was no additive effect. These data suggest that PTH and CT may stimulate the same adenylate cyclase moieties, whereas VP may stimulate distinct enzyme moieties, and that these three peptide hormones as well as GL definitely act on the same cell group in rat CTAL. Thus, it is possible that these hormones may induce qualitatively similar effects on CTAL functions if such effects are mediated by cAMP.

Adenylyl Cyclases↗
PubMed1981

Parathyroid hormone has a positive inotropic action in the rat.

Parathyroid hormone (PTH: synthetic bovine, amino terminus 1-34 amino acids) demonstrates a positive inotropic action on the isolated papillary muscle of the rat heart. The effect was evident at PTH concentration of 10(-12)M, and the maximum inotropic effect occurred with PTH concentrations greater than 10(-11)M. Biologically inactive PTH (PTH treated with H2O2) was without effect. The inotropic effect of PTH was partially blocked by propranolol and also suppressed in the papillary muscle of the rat pretreated with reserpine. Methoxyverapamil completely blocked the inotropic action of PTH. PTH was without effects on adenylate cyclase activity of the myocardium. Results show the presence of an inotropic action of PTH in vitro and suggest that this action of PTH is partially mediated by releasing the endogenous myocardial norepinephrine which exerts a positive inotropic effect via beta-adrenergic stimulation and by an increase in Ca++ influx across plasma membranes, but independent of adenylate cyclase activation. The inotropic action of PTH may be of significance in normal cardiac function.

Animals↗
PubMed1979

Binding of 125I-insulin to the isolated glomeruli of rat kidney.

To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was less than 25% of total binding. A small fraction of 125I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 125I-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 125I-insulin resulted in a rapid dissociation of approximately or equal to 70% of bound 125I-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glomerular ultrafiltration and the glomerular ultrafiltration and the development of glomerular lesions in diabetes mellitus, a disease in which insulin deficiency or the tissue resistance to insulin exists.

Angiotensin II↗
PubMed1978

Metabolic and endocrine alterations in end-stage renal failure.

Many alterations in metabolic and endocrine function occur in end-stage renal disease. Glucose intolerance is almost always present with uremia; it improves shortly after institution of regular hemodialysis. Hyperlipidemia (type IV) is prevalent, and atherosclerotic cardiovascular disease causes death in about 50% of patients receiving long-term hemodialysis. Although plasma levels of growth hormone usually are elevated, children with chronic renal failure show growth retardation. The occurrence of thyroid disorders is difficult to determine, since many clinical features of uremia are similar to those of hyperthyroidism and hypothyroidism. The incidence of duodenal ulcer is high, possibly due to high gastrin levels. Sex hormone disturbances are common. Anemia is a constant feature of chronic renal failure; patients usually tolerate it well.

Anemia↗