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Biomedical subjects

J Wiener

Publications and source records attributed to J Wiener.

At least 73 records · Page 4Linked to original sources
PubMed1985

Cholinergic-adrenergic receptor interactions in cerebral microvessels.

Enriched capillary preparations isolated from rat cerebral cortex were used to evaluate cholinergic-adrenergic receptor interactions in cerebral endothelium. Possible receptor interactions were determined by measuring an intracellular mediator, cyclic AMP and alterations in GTP-sensitive agonist binding. Unstimulated microvessel homogenates generate 66 +/- 16 pmol/mg/10 min of cyclic AMP. Adrenergic agonists norepinephrine and isoproterenol increase cyclic AMP to 147 +/- 31 and 149 +/- 23 pmol/mg/10 min, respectively. Addition of the muscarinic agonist carbachol has no effect on basal cyclic AMP but it completely blocks the stimulation elicited by adrenergic agonists. The displacement of quinuclidinyl benzilate (QNB) by carbachol yields an IC50 of 1.5 +/- 0.45 X 10(-4) M and a Hill coefficient of 0.54 +/- 0.07, indicating a heterogeneous population of binding sites. Guanine nucleotides shift the displacement curve to the right (IC50, 4.7 +/- 0.16 X 10(-4) M) and convert the binding site population to greater homogeneity (0.76 +/- 0.18). Isoproterenol prevents both the affinity shift and binding site conversion evoked by guanine nucleotides. These data suggest that cholinergic-adrenergic interactions occur at both the level of receptor binding and the generation of an intracellular messenger. Since cyclic AMP has been purported to play a role in regulation of blood-brain barrier permeability, the existence of adrenergic-cholinergic, i.e., excitatory-inhibitory modulators of adenylate cyclase in cerebral endothelium, suggests that these receptors may mediate physiological and/or pathological alterations of cerebrovascular permeability.

Adenylyl Cyclases↗
PubMed1985

Pyruvate dehydrogenase activity in cardiac mitochondria from genetically diabetic mice.

Pyruvate dehydrogenase (PDH) was studied in isolated heart mitochondria from genetically diabetic mice (C57BL/KsJ db/db) with progressive cardiomyopathy. Both the basal activity (active enzyme) and the total activity (the sum of active and inactive enzyme) were determined. In mitochondrial extracts from 8-18-wk-old db/db mice, there was a 73% decrease of basal activity accompanied by a 38% decrease of total activity as compared with controls. The lower basal activity at 8 wk of age suggests an increased conversion of the enzyme into the phosphorylated (inactive) form. Evidence is also given that the conversion of inactive (phosphorylated) enzyme into active (dephosphorylated) enzyme is inhibited in cardiac mitochondria prepared from 8-wk and older db/db mice. These changes coincide with the onset of defective oxidative metabolism and can explain the depressed pyruvate oxidation reported previously.

Adenosine Triphosphate↗
PubMed1985

An overview of long-term care.

Long-term care (LTC) refers to health, social, and residential services provided to chronically disabled persons over an extended period of time. Especially during the last 20 years, State and Federal Governments have played an increasing role in the financing of long-term care. The aging of the population underlines the future importance of this topic. This article provides background data on need, supply, and expenditures; discusses government financing programs; and addresses quality of care concerns and options for LTC reform.

Aged↗
PubMed1985

Akinesia and mutism following a methylphenidate challenge test.

A case of akinesia and mutism is described in a menopausal, depressed woman with onset following a mood challenge with 40 mg of methylphenidate taken orally over a 3-hour period. Various diagnoses are considered with preference given on clinical grounds to conversion disorder precipitated by drug-induced dysphoria. It is suggested that increased susceptibility to dysphoria may have been related to prior clomipramine administration and hypoestrogenism.

Adult↗
PubMed1984

The role of alkaline protease in the development of cardiac lesions in myopathic hamsters: effect of verapamil treatment.

The role of alkaline protease in the development of myocardial lesions in myopathic hamsters was studied. There was abnormal elevation of alkaline protease in the myopathic heart at 1 month of age, preceding the development of cardiac lesions. In vivo treatments of verapamil were carried out in 1-month-old myopathic animals for 30 days. Results indicated that the drug treatment was effective in preventing the occurrence of the severe myocardial lesions found in the untreated animals at 2 months of age. Reduced lesion development was associated concomitantly with lowered levels of alkaline protease activity. Withdrawal of drug treatment caused the return of severe lesions and high levels of alkaline protease. The study of the alkaline protease activity in the skeletal muscle of the myopathic hamster also showed a parallel relationship between the enzyme levels and severity of lesions. The results are discussed in light of possible involvement of a serine protease and a Ca2+-activated protease in producing the cardiac lesions.

Aging↗
PubMed1984

Lysosomal and nonlysosomal proteolytic activities in experimental diabetic cardiomyopathy.

The role of cardiac lysosomal and nonlysosomal protease alterations in the development of the cardiomyopathy that occurs in genetically diabetic C57BL/KsJ db/db mice has been examined. The db/db mice and age-matched controls were sacrificed between 7 and 24 weeks of age. Cathepsin D activity, myofibrillar alkaline protease (MAP) activity (including serine protease activity), and Ca2+-activated protease activity were determined by using [3H]acetyl-casein as substrate. There is a significant decrease in cathepsin D, MAP, and serine protease activities in the myocardium of 7- to 20-week old diabetic mice with a rebound of these activities toward normal levels by 24 weeks of age. Cathepsin D and MAP activities are inversely related to heart weight in diabetic mice with the higher levels being recorded in association with the most pronounced decrease in heart weight. In contrast, Ca2+-activated protease activity in the hearts of diabetic mice does not differ significantly from controls throughout the period of observation. The results suggest that both lysosomal cathepsin D and nonlysosomal MAP may mediate the accelerated cardiac muscle degradation that occurs in the late stage of diabetic cardiomyopathy in the db/db mice.

Aging↗
PubMed1984

Characterization of glomerular permeability and proteinuria in acute hypertension in the rat.

The effects of acute angiotensin II (AII) induced hypertension on renal hemodynamics, urinary excretory rates, and clearances of endogenous proteins, together with colloidal iron staining and numerical density of differently charged ferritins in glomerular basement membrane (GBM) have been studied. AII decreases para-aminohippurate clearance (63%) more than glomerular filtration rate (GFR) (42%), resulting in an increased filtration fraction (54%). Simultaneously, large increments in the excretory rates and clearances of albumin and IgG2a occur. The number of native ferritin particles per unit volume of GBM and its different layers increases significantly in both superficial and juxtamedullary glomeruli as a result of acute hypertension. In contrast, the number of cationized ferritin particles per unit volume of GBM as well as colloidal iron staining of GBM and adjacent cell membranes remain unchanged, irrespective of AII treatment. The results demonstrate that acute AII-induced hypertension enhances glomerular permeability to proteins of different size and shape in the absence of detectable alterations in the fixed negative charges of the GBM. Since both RBF and GFR are decreased, the increased transglomerular passage of proteins in acute hypertension appears to be due to an increase in the pore size of the glomerular filter, induced possibly by either high intracapillary pressure and/or a direct action of AII on GBM constituents.

Acute Disease↗
PubMed1984

Glomerular permeability in acute hypertension.

Acute hypertension induced by intravenous infusion of angiotensin II (AII) leads to enhanced transglomerular passage of albumin and IgG, as demonstrated by electronmicroscopic immunoperoxidase techniques. Although no morphological damage of the capillary wall was detected, significant amounts of macromolecules were present in the mesangial region. On a functional basis, a 42% decrease in glomerular filtration rate and a 63% decline in p-aminohippurate clearance were seen, resulting in a 54% increase in the filtration fraction. Quantitative measurements of albumin and IgG2a clearances showed a 90- and 15-fold increase, respectively. Similarly, the concentration of native ferritin particles in the glomerular basement membrane (GBM) increased 11-fold. On the other hand, the number of cationized ferritin particles and the staining properties of GBM to colloidal iron were not altered. These observations indicate that acute AII-induced hypertension affects glomerular permeability to proteins of different size and shape, possibly by increasing the pore size of the glomerular filter by either high intracapillary pressure and/or a direct action of AII on GBM constituents.

Albumins↗
PubMed1983

Proteolytic activities in hypertensive cardiomyopathy of rats.

Two-kidney, one clip Goldblatt hypertension of 2, 4 and 8 weeks duration was induced in 100-g male Wistar-Kyoto rats. Nucleic acid content was determined in the isolated cardiac muscle cells from the left ventricle. The profile for several major proteolytic activities in either isolated cardiac muscle cells or left ventricle preparations was also studied, using [3H]acetyl-casein as substrate. From the soluble fraction of the tissue or cell preparation, a pH 6 proteolytic activity, two forms of calcium-activated protease as well as cathepsin D were identifiable by inhibitor assay or DEAE-cellulose chromatography. From the myofibrillar fraction of the same preparation, two kinds of proteolytic activity were detected at alkaline pH: a phenylmethylsulfonyl fluoride (PMSF) inhibitable activity that was serine protease-like and the other a N-ethylmaleimide (NEM) inhibitable activity that resembled Ca2+-activated protease. At 2 weeks of hypertension, there was a significant increase in the pH 6 proteolytic activity as well as the calcium-activated protease I and the NEM-inhibitable alkaline protease activities, while the other identifiable proteolytic activities remained unchanged. Lysosomal cathepsin D showed a rise in activity only after 8 weeks of hypertension. These results may be related to the development of myocyte necrosis and lysis that occur in this model of hypertensive cardiomyopathy.

Animals↗
PubMed1983

Identification of muscarinic receptors in rat cerebral cortical microvessels.

Microvessels isolated from rat cerebral cortex consist mainly of capillaries (greater than 85%). Fresh, intact microvessel preparations have been analyzed by radioligand binding techniques for muscarinic receptors. Scatchard analysis of specific quinuclidinyl benzilate (QNB) binding indicates that microvessels possess a large number of muscarinic sites (914 fmol/mg protein) of high affinity (KD = 0.034 nM). The association and dissociation rate constants (0.37 min-1 nM-1 and 0.0067 min-1, respectively) yield an equilibrium KD of 0.018 nM. Displacement of [3H]QNB by muscarinic ligands and control substances is typical of muscarinic receptors. The results indicate that cerebral microvessels possess a large population of muscarinic receptors.

Animals↗
PubMed1983

Defective oxidative metabolism of heart mitochondria from genetically diabetic mice.

Long chain saturated beta-hydroxy fatty acid content and oxidative metabolism were studied in hearts of diabetic mice (C57BL/KsJ db/db) with a progressive cardiomyopathy at intervals of 7, 10, 16, and 26 wk of age. Total beta-hydroxy fatty acid (BHFA) content increases progressively with age in diabetic hearts with a mean value of 143.5 nmol/g dry wt as compared with a mean of 59.6 nmol/g dry wt in control hearts. There was also a redistribution of BHFA in myocardium of diabetic mice when compared with controls, with a relative decrease in beta-hydroxymyristate and an increase of beta-hydroxypalmitate. Oxidative phosphorylation studies using isolated mitochondria from diabetic mice demonstrated depressed state 3 oxidation rates with both palmityl carnitine and pyruvate as substrates. While mitochondrial NADH-oxidase activity was not statistically different from that of controls, there was a significant decrease in mitochondrial total NAD + NADH content in diabetic hearts. In addition, treatment of myocardial tissue with lanthanum demonstrated an abnormal permeability of sarcolemmal, intercalated disc as well as mitochondrial membranes in myocytes of diabetic mice. The data indicate that deficiencies in total NAD + NADH content can account for the depressed state 3 oxidation of palmitylcarnitine and pyruvate in diabetic mice that in turn may explain the abnormal accumulation of BFHA. The latter could play a role in altering the permeability of cardiac cell membranes.

Animals↗
PubMed1982

Adrenoreceptor blockade in angiotensin-induced hypertension: effect on rat coronary arteries and myocardium.

Adrenoreceptor blockade has been used to separate the actions of elevated blood pressure, angiotensin II, and catecholamines on the coronary vasculature and myocardium of rats. Twenty-two male Wistar-Kyoto rats received phentolamine (an alpha-receptor blocker, 10 mg/kg body weight) and/or propranolol (a beta-receptor blocker, 1 mg/kg body weight) followed by an infusion for 2 hours of angiotensin amide (1.7 micrograms/min/kg) or saline. Sections of left ventricle were examined by light and electron microscopy. Blood pressure was elevated only in animals receiving angiotensin II with or without propranolol. Epicardial arteries were devoid of lesions in all animals. Small intramural arteries and arterioles in the hypertensive animals exhibited vasoconstriction, endothelial cell vacuolization with bleb formation, and medial smooth muscle cell fragmentation and necrosis. Foci of irreversible ischemic or anoxic myocardial injury consisting of contraction zones and bands and translocated mitochondria with granular matrix densities were seen in angiotensin-infused animals. Similar but less severe myocardial changes were found in the animals pretreated with propranolol. Vascular lesions were also seen in animals receiving phentolamine, propranolol, and angiotensin II; but myocardial alterations consisted solely of areas with contraction zones. Vascular but not myocardial lesions were observed in animals that received angiotensin II and phentolamine. It is concluded that angiotensin II can produce vascular injury in the absence of elevated systemic blood pressure or catecholamine effects. In contrast, irreversible myocardial injury seems to depend upon the increased pressure and/or coronary artery vasoconstriction associated with angiotensin administration.

Adrenergic alpha-Antagonists↗
PubMed1982

Primary culture of rat cerebral microvascular endothelial cells. Isolation, growth, and characterization.

A procedure for the isolation and long-term in vitro cultivation of endothelial cells from rat cerebral cortical microvasculature is described. Migrating cells emerged from collagenase-treated microvessel fragments as early as 1 to 2 days in culture. Migration continued and marked proliferation began 5 to 7 days after isolation and continued up to 12 to 14 days. Cell colonies developed and consisted of endothelial cells as determined by phase contrast microscopy and cell culture behavior. Proliferation of the endothelial cells was significantly enhanced (3- to 4-fold) with the addition of endothelial cell growth supplement at a concentration of 150 microgram. per ml. Cultures with endothelial cell growth supplement (ECGS) retained their characteristic endothelial morphology for 6 to 8 weeks, after which they exhibited a gradual deterioration and loss of their phenotypic appearance. The endothelial origin of these cells was demonstrated by positive immunofluorescent staining for factor VIII antigen and angiotensin-converting enzyme and lack of binding of rat smooth muscle myosin antibody. Ultrastructural examination of confluent endothelial cell cultures revealed intercellular junctional complexes consisting of gap junctions, punctate fusions, and tight junctions. Since long-term endothelial cell cultures derived from the cerebral microvasculature retain characteristic endothelial cell markers and in vivo markers and in vivo features of brain capillary endothelium, they can serve as a useful model system to characterize microvascular endothelium in a variety of disease states.

Animals↗
PubMed1981

Carotid artery constriction in acute hypertension.

The effects of carotid artery constriction on cerebrovascular ultrastructure and permeability in acute hypertension have been assessed. The right common carotid artery of 26 male Wistar-Kyoto normotensive rats was constricted with a silver wire clip. Forty-eight hours later these animals received an angiotensin amide injection (1 microgram/kg body weight) or infusion for 3--4 hours (0.5 or 1.7 microgram/min/kg body weight) or were subjected to subdiaphragmatic aortic constriction. All animals were injected with horseradish peroxidase (HRP) (20 mg/100 g body weight) and sacrificed after 5--15 minutes. Parietal cortex from both hemispheres was processed for light and electron-microscopic examination. The arterial vessels of the right hemisphere from animals given injections of or infused with angiotensin II exhibited increased permeability to HRP, as manifested by the presence of reaction product in interendothelial cell clefts, in subendothelial space, in endothelial and smooth muscle cell pinocytotic vesicles, and along smooth muscle cell basal laminas. In contrast, no alterations in the permeability of ipsilateral vessels were seen in rats with aortic constriction. Cerebral cortical arterial vessels from the left hemisphere in all groups of animals exhibited segmental dilatation and constriction and abnormal permeability to HRP. The results suggest that angiotensin administration can produce increased permeability of cerebral cortical vessels in the absence of elevated blood pressure.

Acute Disease↗
PubMed1981

Glomerular permeability to endogenous proteins in the rat: effects of acute hypertension.

The distribution of endogenous albumin and immunoglobulin G (IgG) has been studied by the immunoperoxidase technique in the superficial glomeruli of both normotensive and hypertensive (acute angiotensin II-induced) Munich-Wistar rats. Endogenous IgG has also been detected in rats immunized with horseradish peroxidase. Labeled antibodies have been applied to sections on a conventional manner as well as by an electrophoretic technique. The immunization of animals with horseradish peroxidase, as well as application of the electrophoretic technique, both result in a greater yield of labeled glomeruli. Albumin is present within the capillary lumina of control animals, penetrates the capillary walls, and extends into the urinary space. Endogenous IgG is mainly confined to lumina of glomerular capillaries, with only small amounts visible in the laminae rarae of the basement membrane. After acute hypertension induced by angiotensin II, there is increased staining of albumin and IgG in the basement membrane and of albumin in the urinary space. There is also penetration of IgG into Bowman's space. Both macromolecules are found in dilated mesangial channels. These modifications of glomerular permselectivity in hypertension are not accompanied by discernible ultrastructural changes in the peripheral capillary wall. It is suggested that the transcapillary passage of albumin and IgG is dependent upon hemodynamic factors and/or subtle changes in the filtering membrane.

Animals↗
PubMed1980

Lysosomal enzymes in experimental diabetic cardiomyopathy.

The present study examines the role of cardiac lysosomal enzymes in the pathogenesis of the cardiomyopathy that develops in genetically diabetic C57BL/KsJ db+/db+ mice. Db+/db+ mice and littermate controls were sacrificed as age-matched pairs between 5-26 weeks of age. C57BL/6J ob/ob mice and littermates served as other controls. The hearts were excised, homogenized, and the following enzymatic activities measured: N-Acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucosaminidase, aryl sulphatase, alpha-mannosidase, alpha-glucosidase, beta-galactosidase, beta glucosidase, total p-nitrophenyl phosphatase, acid phosphatase and 5'-phosphodiesterase type IV. There is a progressive decrease in cardiac lysosomal enzyme activities of db+/db+ mice for the period 5-21 weeks of age. All enzyme activity is depressed significantly during the 9-21 week interval with beta-glucuronidase, aryl sulphatase and beta-glucosidase decreased about 40-50%. The decrease in lysosomal enzyme activity can explain the accumulation of large residual bodies and interstitial material in the myocardium of the db+/db+ animals

Acetylglucosaminidase↗
PubMed1980

Lysosomal enzymes in the heart of the genetically diabetic mouse.

The purpose of the present study was to determine the role of cardiac lysosomal enzymes in the pathogenesis of the cardiomyopathy that develops in the genetically diabetic C57BL/KsJ db+/db+ mice. Db+/db+ mice and littermate controls were sacrificed as age-matched pairs between 5 and 26 weeks of age. C57BL/6J ob/ob mice and littermates served as other controls. Following anesthesia, the hearts were excised, homogenized, and the following enzymatic activities measured: N-acetyl-beta-glucosaminidase, N-acetyl-beta-galactosaminidase, beta-glucosaminidase, aryl sulfatase, alpha-mannosidase, alpha-glucosidase, beta-galactosidase, beta-glucosidase, total rho-nitrophenyl phosphatase, acid phosphatase. and 5'-phosphodiesterase type IV. There is a progressive decrease in cardiac lysosomal enzyme activities of db+/db+ mice for the period 5 to 21 weeks of age. All enzyme activity is depressed significantly during the 9- to 21-week interval: alpha-glucosidase, beta-glucosidase, alpha-mannosidase, beta-galactosidase, acid phosphatase, N-acetyl-beta-galactosaminidase, 5'-phosphodiesterase type IV, and total rho-nitrophenyl phosphatase are reduced approximately 10 to 20 per cent, whereas beta-glucosaminidase, aryl sulfatase, and N-acetyl-beta-glucosaminidase are decreased almost 40 to 50 per cent. In contrast, cardiac lysosomal enzymic activity in the ob/ob mice does not differ significantly from controls aside from aryl sulfatase (20 per cent decrease) and beta-glucosidase (10 per cent decrease). This decrease in lysosomal enzyme activity can explain the accumulation of large residual bodies and interstitial material that occurs in the myocardium of the db+/db+ animals as part of the cardiomyopathy.

Acetylglucosaminidase↗