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Biomedical subjects

A Nir

Publications and source records attributed to A Nir.

At least 19 recordsLinked to original sources

Angiotensin converting enzyme inhibition modulates endogenous endothelin in chronic canine thoracic inferior vena caval constriction.

Endothelin (ET) is a potent vasoconstrictor peptide which is elevated in plasma in congestive heart failure. Recent studies suggest an important role for angiotensin II (AII) in the activation of ET in cultured cardiomyocytes. Chronic thoracic inferior vena caval constriction (TIVCC) is a model of reduced cardiac output that mimics the neurohumoral activation observed in congestive heart failure. We hypothesized that activation of the renin-angiotensin system in TIVCC plays a role in the activation of ET and that the elevation of endogenous ET contributes to the systemic and renal vasoconstriction that characterizes this model of venous congestion. We studied conscious dogs after 7 d of TIVCC in the presence or absence of chronic angiotensin converting enzyme inhibition with enalapril. TIVCC resulted in marked activation of plasma AII and ET in plasma, right atrium, lung, and renal medulla which was further localized to cardiomyocytes, pulmonary, and renal epithelial cells. Chronic angiotensin converting enzyme inhibition abolished the increases in plasma AII and ET during TIVCC. Acute endothelin A receptor blockade with FR-139317 resulted in significant decreases in mean arterial pressure and systemic vascular resistance in TIVCC. We conclude that activation of the renin-angiotensin system contributes to the activation of circulating and local ET in TIVCC and that this activation plays an important role in the regulation of arterial pressure and systemic vascular resistance in this model of congestive failure.

Angiotensin-Converting Enzyme Inhibitors

Tuberous sclerosis and cardiac rhabdomyoma.

We conclude that echocardiographically detected cardiac rhabdomyomata are common in patients with tuberous sclerosis complex, and are more prevalent and prominent in the younger patient. Tumors regress in size or number, or both, in most patients aged < 4 years, and less so in older patients. Cardiac rhabdomyomata are associated with a higher incidence of preexcitation and may increase the risk for arrhythmia.

Adolescent

Presence of C-type natriuretic peptide in human kidney and urine.

The current study was undertaken to investigate the presence of CNP immunoreactivity in both human kidney and urine. Immunohistochemical staining with an indirect immunoperoxidase method utilizing an antibody which is 100% cross-reactive to both CNP-53 and CNP-22 was performed on five human kidney specimens (three biopsies of normal cadaveric donor kidneys and two of normal autopsy specimens). CNP immunoreactivity was positive in proximal, distal and medullary collecting duct tubular cells in a cytoplasmic and granular staining pattern. CNP immunoreactivity was also determined in the urine of five healthy volunteers utilizing a sensitive and specific double-antibody radioimmunoassay with a mean concentration of 10.8 +/- 1.0 pg/ml. With the utilization of high pressure liquid chromatography, this immunoreactivity proved to be consistent with both the low molecular weight form, CNP-22, as well as the high molecular weight form, CNP-53. Urinary excretion of CNP was also measured in normal subjects (N = 5) and in patients with congestive heart failure (CHF, N = 6). CHF patients excreted over three times more CNP than normals (27.2 +/- 2.8 vs. 8.7 +/- 0.81 pg/min, P < 0.004) despite no difference between the two groups in plasma CNP concentrations (6.97 +/- 0.28 vs. 8.08 +/- 1.52 pg/ml, P = NS). This study demonstrates for the first time the presence of CNP immunoreactivity in human kidney and suggests that renal tubular cells may be an additional non-vascular site of synthesis for this cardiorenal acting peptide. This study also demonstrates an increase in urinary CNP excretion in congestive heart failure.

Adult

CNP is present in canine renal tubular cells and secreted by cultured opossum kidney cells.

C-type natriuretic peptide (CNP) is a vasoactive and antimitogenic peptide that is structurally similar but genetically distinct from atrial natriuretic peptide. While first discovered in the brain, CNP has been shown to be produced by endothelial cells and may function in a paracrine and autocrine fashion in the control of vascular tone. Recently, CNP immunoreactivity and B-type natriuretic peptide receptors (NPR-B), for which CNP is a specific ligand, have been identified in the kidney. The present study was designed to determine whether renal epithelial cells produce and secrete CNP and whether CNP immunoreactivity is present in canine kidney. Opossum kidney (OK) cells that express proximal tubular cell characteristics were incubated for 6 h in fetal calf serum-free Dulbecco's modified Eagle's medium (DMEM). CNP immunoreactivity was measured in the preincubation and 6-h conditioned media by radioimmunoassay (RIA) using a specific antibody to CNP-22. Furthermore the molecular form of this CNP-like protein was determined by reverse-phase high-performance liquid chromatography (HPLC), and intracellular localization of the CNP immunoreactivity was determined by immunohistochemical staining. CNP immunoreactivity was also determined in renal tissue from dogs subjected to saline or endothelin infusion. Six-hour incubation in DMEM resulted in accumulation of CNP immunoreactivity (baseline below detection level vs. 6 h = 117.3 +/- 8.3 pg/ml, P < 0.001). Intracellular CNP concentration determined after sonication was 1.9 +/- 0.2 micrograms/g protein, and immunohistochemical staining for CNP was markedly positive in the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Acute hypoxia and endogenous renal endothelin.

Endothelin (ET) is a potent vasoconstrictor peptide of endothelial cell origin. Recent studies have suggested a nonvascular paracrine and/or autocrine role for endothelin in the kidney. This study was designed to elucidate the renal ET response to acute moderate hypoxia, as reflected by urinary ET excretory rate and renal tissue ET immunoreactivity, and to correlate these responses to the hemodynamic and excretory changes during hypoxia. Experiments were conducted in two groups of anesthetized dogs: hypoxic group (10% O2 ventilation: PO2, 44 mm Hg; N = 7) and time control group (room air ventilation: PO2, 111 mm Hg; N = 6). After 60 min of hypoxia or room air ventilation, kidneys were harvested and stained immunohistochemically for ET. Acute moderate hypoxia was associated with significant increases in urinary ET excretion, urine flow, urinary sodium excretion, and fractional excretion of sodium (P < 0.05). There was no significant change in GFR, RBF, renal vascular resistance, or mean arterial pressure. Renal immunohistochemistry for ET revealed increased staining in the proximal and distal tubules in the hypoxic group as compared with controls. This study demonstrates that acute moderate hypoxia results in increased urinary ET excretion and renal tubular ET immunoreactivity, in association with diuresis and natriuresis, and suggests a nonvascular role of endogenously produced renal ET in the regulation of sodium homeostasis during hypoxia.

Animals

Cardiorespiratory response to exercise after the Fontan operation: a serial study.

OBJECTIVES: The purpose of this study was to assess whether there is deterioration of aerobic capacity over time after the Fontan operation in individual patients. BACKGROUND: We previously observed that maximal aerobic capacity after the Fontan operation was lower in older patients than in younger patients. It was unclear whether this represented a decrease in aerobic capacity with time after operation or was a function of studying patients of different ages at different times postoperatively. METHODS: All patients who had more than one postoperative exercise study were included. There were 25 patients (19 male, 6 female), aged 3.8 to 39 years at the time of the operation. The first exercise test was performed, on average, 2.2 years after the Fontan operation, and the last exercise test was performed, on average, 5.9 years (range 1.8 to 13) after the operation. In 11 patients, coronary sinus drainage was left on the pulmonary venous side. Five patients had had a previous Glenn operation. Exercise was performed to exhaustion with use of a 3-min incremental cycle protocol. RESULTS: Exercise duration, oxygen uptake, blood pressure, respiratory rate, minute ventilation, pulmonary blood flow index, exercise factor, ST-T wave changes and the prevalence of arrhythmias were similar during the first and last tests. Exercise systemic arterial blood oxygen saturation decreased from the first to the last postoperative test (p < 0.006) regardless of age. The percent of predicted heart rate, at rest and during maximal exercise, decreased more in older patients from the first to the last test (p < 0.05 for rest and exercise). CONCLUSIONS: In this select group of patients, exercise tolerance remained relatively unchanged over the range of 13 years after the Fontan operation. Heart rate at rest and during maximal exercise decreased more than predicted for age in older patients. A small but significant progressive decrease in systemic arterial blood oxygen saturation was found. The former might represent abnormal sinus node function in patients with functional single ventricle, and the latter might represent a tendency toward development of abnormal ventilation/perfusion patterns resulting from the development of small pulmonary arteriovenous fistulas or an effect of position of the coronary sinus postoperatively.

Adolescent

A fluid-mechanical model of deformation during embryo exogastrulation.

Embryo deformation during gastrulation is simulated using a fluid-mechanical approach. The possibility that the deformation is governed by the forces originated at the embryo surface rather than by pulling by filopodia is considered. The slow viscous flow and the deformation during in vitro exogastrulation is solved using a boundary integral equation formulation. The results show a distinct anisotropic distribution of meridional and circumferential tensions, which are capable of producing the dynamics and shape of the archenteron development. This anisotropy suggests the existence of a specific biochemical activity at particular surface regions prior to and during the gastrulation process. The mechanical model can serve as a tool to help discriminate between the possible suggested mechanisms.

Biomechanical Phenomena

Is eye cosmetic a source of lead poisoning?

Kohl is a lead-containing eye cosmetic applied to many infants in Israel and in other countries in the Middle East. Seven samples of kohl used in our region contained 17.3%-79.5% lead. We assessed 24 kohl users and 30 non-kohl users, aged 6-16 months, for blood lead, zinc protoporphyrin, hemoglobin, mean corpuscular volume (MCV), serum iron and calcium. Blood lead levels were significantly higher in the infants to whom kohl was applied (11.2 vs. 4.3 micrograms/dl, P less than 0.001) and were greater than 20 micrograms/dl in three of them. In the non-kohl users, blood lead levels were significantly higher in infants whose mothers used kohl (5.2 vs. 2.8 micrograms/dl, P less than 0.02). No significant differences were found in the other parameters. The kohl-using infants were significantly shorter at 3-5 weeks of age (P less than 0.005) but not at the time of the study. No significant differences were found in weight and head circumference at birth or at the time of the study between kohl-using infants and controls. Regression analysis showed that among the analyzed variables the infant's blood lead level was related only to the use of kohl. We conclude that application of kohl to the infant's or mother's eyes is associated with a significant increase in the infant's blood lead levels and in the minority of cases with asymptomatic lead poisoning.

Birth Weight

Anatomic evidence of spontaneous intrauterine closure of a ventricular septal defect.

An infant, born to a mother on carbamazepine monotherapy, had a complex cardiac anomaly, consisting of double-outlet right ventricle (DORV), right-sided aorta, pulmonary artery hypoplasia, left ventricular endocardial fibroelastosis, and anatomic evidence of a spontaneously closed muscular ventricular septal defect (VSD). The last finding is one which, to the best of our knowledge, has never been illustrated before.

Asphyxia Neonatorum

Surface viscoelastic effects in cell cleavage.

The effect of passive surface traction on the cleavage of cells is incorporated in the cytokinesis hydrodynamic model of Zinemanas and Nir [Biomechanics of cell Division, pp. 281-305, Plenum Press, New York (1987)]. Different rheological behaviours were examined to model the surface tensions which arise due to the passive deformation of the cortex: a Mooney-Rivlin material, an STZC material and a viscoelastic material. The calculations show that passive surface tensions may play a significant role in determining the local surface deformations as well as in the modulation of the surface forces. Varying the rheological model has limited effect on the overall deformations. The latter appear to be affected mostly by contractile filament interactions.

Cell Division

Autonomic seizures in an infant: unusual cutaneous and cardiac manifestations.

An eight-month-old infant developed autonomic seizures, manifested by skin reaction (harlequin-like syndrome) and paroxysmal bradycardia. Interictal EEG showed multifocal spikes, 24-hour EEG/ECG monitoring disclosed episodes of cerebral decremental response associated with cardiac nodal rhythm. Head CT and other laboratory tests were normal. Despite excellent seizure control with carbamazepine, the child has moderate psychomotor retardation.

Anticonvulsants

Pregnancy and primary biliary cirrhosis.

Pregnancy is rarely encountered in patients with primary biliary cirrhosis. Ten pregnancies in nine patients have been reported in the literature. All five pregnancies that continued beyond the 31st week had increasing jaundice during late pregnancy. We describe a case of primary biliary cirrhosis with symptomatic onset at age 19, pregnancy a year later, with subsequent resolution of jaundice and pruritus. This course is different than most described by others.

Adult

A theoretical model to study the effect of convection and leaky junctions on macromolecule transport in artery walls.

A mathematical model is presented herein to determine the effect of convection on macromolecular transport across an artery wall due to transmural or osmotic pressure differences. The model is based on an extension of the leaky junction-cell turnover model of Weinbaum et al. (1985) to take into account a combined transport mechanism of convection and diffusion and also to provide the leaky junctions in the model with a finite resistance, thus allowing the results to be extended to intercellular clefts with a retarding extracellular matrix or to macromolecules whose dimensions are nearly the same as the junctional width. The results from this improved model show that the effect of pressure on transarterial macromolecular transport is important especially for cell turnover rates greater than 1% and that significant changes in the equilibrium balance of the cholesterol carrying LDL molecules in the arterial wall can occur due to a very small fraction of leaky junctions. At very high turnover rates (large fraction of leaky junctions) the effect of convection on macromolecular transport becomes dramatic and explains the very large increases in uptake observed experimentally after artificially inducing extensive endothelial damage.

Animals

On mechanical aspects of vesicular transport.

From the chain of events leading to secretion we have identified and isolated stages in which mechanical and physical mechanics may play important roles. These include the vesicle motion towards the cell wall, drainage of the cytoplasmic fluid from the gap between the membranes, reorganization of the membrane constituents, failure of the membrane structure and coalescence into a new configuration. We suggest a unified mechanism, relevant to the neural, secretory and vascular systems, based on physical factors as flow, pressure and stress distributions, and membranes properties. The simulation of several stages of secretion is coupled with experimental observations. By use of the proposed hypothesis it is possible to explain some observed phenomena, such as spontaneous and induced secretion, membrane failure, protein lateral dislocation and the omega-shapes in electron microscopic exposures of fusion sites.

Adrenal Medulla

Temperature effects in the stimulus-secretion process from isolated chromaffin cells.

Temperature effects on the stimulus-secretion coupling process was studied by inducing release of catecholamines (CA) from isolated chromaffin cells of the bovine adrenal medulla. Use was made of three different secretagogues: acetylcholine (ACH), high potassium concentration, and the calcium ionophore A23187, at various incubation temperatures. The latter two agents induced a monotonic increase in secretion with rise in temperature, suggesting different regions of the dependence of total release on temperature. The ACH-induced secretion was, however, markedly different and exhibited a maximal release at 30 degrees C. Kinetic experiments using ACH stimulus revealed that this maximum is produced by different temperature dependence in the stages of activation and desensitization. A proposed model for the total release process yields temperature-dependent parameters that can be divided into three regions of initial rates of secretory activity corresponding to the above independent findings using high K+ concentration and the calcium ionophore. The transitions between the various regions indicate possible transitions in the physical properties of the plasma and secretory granule membranes. Elucidation of the interaction between the membranes is of primary importance in the determining mechanism of CA secretion from the isolated adrenal medulla cell.

Acetylcholine