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Biomedical subjects

E Levi

Publications and source records attributed to E Levi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Calmodulin content in pancreatic islets and the response of islet membrane Ca2+ ATPase to calmodulin in phosphate depletion.

Chronic phosphate depletion is associated with a reduced Vmax of Ca2+ ATPase in many cells. The mechanisms underlying this phenomenon are not fully understood. One of the regulators of the Ca2+ ATPase enzyme is calmodulin, and the reduced availability of calmodulin or impaired interaction between it and Ca2+ ATPase could be responsible for the impaired activity of this enzyme in phosphate depletion. The present study examined the calmodulin content of pancreatic islets and the effect of calmodulin on the Vmax of Ca2+ ATPase in islets harvested from phosphate-depleted (PD) and pair-weighed (PW) rats. The calmodulin contents in islets from the 2 groups of animals were not different. Basal levels of Vmax of Ca2+ ATPase of islets from PD rats were significantly (p < 0.01) lower than in PW rats. Calmodulin produced a significant (p < 0.01) increase in Vmax of Ca2+ ATPase in islets of PW rats but failed to do so in islets of PD rats. The results indicate that the impaired activity of Ca2+ ATPase in islets of PD rats is not due to the reduced availability of calmodulin but an impaired response of the enzyme to calmodulin is at least partly responsible for the reduction in the Vmax of the enzyme.

Adenosine Triphosphate↗
PubMed1995

13,14-Dihydroxy-retinol, a new bioactive retinol metabolite.

Deprivation of vitamin A (retinol) leads to reduced potential of B cell proliferation and nearly complete block of T cell activation in vitro. Retinol, which is thought to function as a pro-hormone, is enzymatically converted into intracellular messenger molecules. Thus, 14-hydroxy-retro-retinol (14-HRR) is an intracellular messenger molecule linked to activation and growth regulation of lymphocytes; whereas, anhydroretinol, another natural retro-retinoid, is an antagonist of 14-HRR effects. In this article, we describe the isolation, structure determination, synthesis, and biological properties of a new intracellular retinol derivative, 13,14-dihydroxy-retinol (DHR), which also supports the viability of retinol-deprived lymphocytes. DHR is found in numerous cell lines representing a large cross-section of tissues and animals from insects to mammals. In T lymphocytes the production of DHR and 14-HRR is up-regulated by phorbol ester. DHR is converted to 14-HRR by mild acid treatment, but not by cells; therefore DHR is not a biosynthetic intermediate in the conversion of retinol to 14-HRR. DHR is a distinct end point of retinol metabolism. Although it is linked to cell proliferation, its biological role remains to be determined.

Cell Line↗
PubMed1994

Sequence of appearance of the metabolic derangements in rat brain synaptosomes during phosphate depletion.

Chronic phosphate depletion (PD) causes a rise in basal level of cytosolic calcium ([Ca2+]i) in rat brain synaptosomes, a decrease in their ATP content and a reduction in Vmax of their Ca2+ ATPase and Na(+)-K+ ATPase. The chronology of the events that lead to these derangements is not elucidated. The present study examined this issue by evaluating the changes in rat in these parameters in brain synaptosomes during the evolution of PD over a period of 6 weeks. The results show that the initial derangement is a rise in the Vmax of Ca2+ ATPase during the first 2 weeks of PD. This is followed by a rise in [Ca2+]i, a fall in ATP content and decrease in the Vmax of Ca2+ ATPase and Na(+)-K+ ATPase by the end of the 3 week and most of these derangement worsened during the 4th to 6th weeks of PD. Taken together our data are consistent with the notion that PD is associated with an initial increase in calcium influx into the synaptosomes. This is followed by a modest but significant rise in [Ca2+]i which in turn would inhibit mitochondrial oxidation and ATP generation leading to a decrease in ATP content. The latter compromises the activity of Ca2+ ATPase and Na(+)-K+ ATPase which are involved, directly or indirectly, in calcium extrusion out of the synaptosomes. The increased entry of calcium combined with decreased calcium extrusion are followed by a further rise in basal levels of [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state.

OBJECTIVES: The present study evaluated our experience with coronary artery bypass grafting in patients with severe left ventricular dysfunction. BACKGROUND: Despite the ominous prognosis of advanced ischemic cardiomyopathy, coronary artery bypass grafting in this setting remains controversial because of concerns over operative risk and lack of functional or survival benefit. METHODS: We analyzed the data of 83 consecutive patients (69 men, 14 women, aged 42 to 83 years [mean 66.8]) with a left ventricular ejection fraction < or = 30% who underwent isolated coronary artery bypass grafting (without aneurysmectomy, valve replacement or other open heart procedures) performed by one surgeon during a 6-year period. The ejection fraction ranged from 10% to 30% (mean 24.6%). Preoperatively, 49% of patients had angina, 52% had congestive heart failure (17% with pulmonary edema) and 30% manifested significant ventricular arrhythmia. The mean number of grafts was 2.7/patient. The internal mammary artery was used in 82% of grafts to the left anterior descending coronary artery. The intraaortic balloon pump was required therapeutically (for angina or pump failure) in 19% of patients and was prophylactically placed preoperatively in another 43% of patients. RESULTS: The hospital mortality rate was 8.4% (7 of 83). The mortality rate was 3.3% (2 of 61) in those patients who did not require admission to an intensive care unit immediately before operation. Canadian Cardiovascular Society angina class improved postoperatively by 1.9 categories and New York Heart Association congestive heart failure class by 1 category. Left ventricular ejection fraction (assessed postoperatively in 68 of 76 hospital survivors) improved from 24.6% preoperatively to 33.2% postoperatively (36% increase) (p < 0.001). At 1 and 3 years, respectively, all-cause survival was 87% and 80% and freedom from cardiac death was 89.8% and 84.5%. CONCLUSIONS: In patients with coronary artery disease and advanced ventricular dysfunction: 1) coronary artery bypass grafting can be performed relatively safely, 2) good medium-term survival is attained, 3) improvement in left ventricular function can be documented objectively after bypass grafting, 4) quality of life is improved (as reflected by improvement in anginal and congestive heart failure status), and 5) the internal mammary artery can safely be used as a conduit. The use of coronary artery bypass grafting is encouraged for this group of patients and may provide a viable alternative to transplantation in selected patients.

Actuarial Analysis↗
PubMed1993

Heat acclimation improves cardiac mechanics and metabolic performance during ischemia and reperfusion.

Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of heat-acclimated (AC) rats (at 34 degrees C for 1 mo) and their age-matched controls (C). Diastolic and systolic pressures, coronary flow, and the appearance of ischemic contracture (IC) were measured during progressive graded ischemia, total ischemia (TI), and reperfusion. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with the use of 31P-nuclear magnetic resonance spectroscopy. Systolic pressure was greater in AC hearts than in C hearts (P < 0.0001). During 50% of perfusion pressure 15 and 46% of AC and C hearts, respectively, showed IC (P < 0.001). During 25% of perfusion pressure 85% of the hearts in both groups developed IC. The onset of IC in AC hearts was delayed compared with in C hearts. On reperfusion 93 and 66% of AC and C hearts, respectively, resumed contraction. Recovery of diastolic pressure was 78 and 36% for the AC and C hearts, respectively (P < 0.05). During TI ATP declined by 0.94 and 1.20 mumol/min in AC and C hearts, respectively, resulting in 21 +/- 2.8% preservation of the ATP pool in AC hearts after 30 min of TI (P < 0.001). The AC group also showed a delayed decline in intracellular pH (P < 0.001). The data suggest beneficial effects of heat acclimation on the heart, which were exhibited by greater pressure generation and by the emergence of protecting features during ischemia and reperfusion, possibly via energy-sparing mechanisms.

Acclimatization↗
PubMed1993

Coping and satisfaction with growth hormone treatment among short-stature children.

The ability of children to cope with a chronic medical problem requiring prolonged treatment has an effect on the quality of life of these children and of their parents and serves as an index of the quality of treatment. This study deals with coping ability and satisfaction with treatment of children whose stature was two or more SD below the average for age and gender. The study population included 96 patients, 53 of whom were male, who were on growth hormone (GH) treatment for at least 1 year. 65 patients were without any underlying disease, 15 had classical GH deficiency and 16 had Turner syndrome or renal disease. All patients were treated with daily injections at home from 12 to 66 months. Using a self-administered questionnaire, the ability to cope and the degree of satisfaction and compliance with treatment were assessed. No significant differences were found with respect to gender, the presence of an underlying disease, age at which treatment commenced or duration of treatment. Despite the fact that the outcome of GH treatment on final height has yet to be established, satisfaction and compliance were high.

Adaptation, Psychological↗
PubMed1992

Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells.

Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.

3T3 Cells↗
PubMed1992

Effect of erythrocyte deformability on renal hemodynamics and plasma renin activity.

Increased blood viscosity has been previously noted in a subgroup of patients with essential hypertension with concomitant high plasma renin activity (PRA). It has been suggested that the cause of hyperviscosity in hypertensives is the presence of circulating red blood cells (RBCs) that were rendered less deformable by significant alterations in their cationic milieu, namely an increase in intracellular concentration of calcium and sodium. The relation between RBC deformability and PRA however is not clear. Our study was conducted to examine this issue. RBC deformability was reduced experimentally, and its effects on renal blood flow, renal artery resistance, glomerular filtration rate and PRA were investigated in experimental (n = 8) and control (n = 4) groups of dogs. Blood was collected from the animals before the experiments and incubated with 0.025% glutaraldehyde. These hardened RBCs were administered to the animals through exchange transfusions. Following the exchange transfusion with the hardened RBCs, there were no changes in renal blood flow, renal artery resistance, and the creatinine clearance. The only change observed was an increase in PRA. In the control group, all parameters that were determined remained unchanged. The data are consistent with the notion that the presence of circulating hardened RBCs may by itself increase PRA, and this effect can be important in some types of hypertension and some other disorders in which impaired deformability of RBCs have been reported.

Animals↗
PubMed1992

Verapamil reverses glucose intolerance in preexisting chronic renal failure: studies on mechanisms.

Glucose-induced insulin secretion is impaired in chronic renal failure (CRF), and this abnormality is due to the elevation of cytosolic calcium [Ca2+]i and other derangements in pancreatic islet metabolism. Verapamil given to rats from day 1 of CRF prevented the rise in [Ca2+]i of islets and the impairment in insulin secretion. However, it is not known whether verapamil can reverse the abnormalities of islet function and metabolism in animals with preexisting renal failure. Such a documentation has important clinical implications for the treatment of carbohydrate intolerance in patients with CRF. The present study examined this question. After 6 weeks of CRF, rats were randomized into two subgroups and maintained for additional 6 weeks. One subgroup received intraperitoneal injections of verapamil (0.1 micrograms/kg body weight twice daily) and the other received vehicle only. At the time of randomization, there were no significant differences between the two subgroups in their body weight, plasma levels of calcium, phosphorus and creatinine, serum parathyroid hormone and creatinine clearance. Similarly, at the time of sacrifice (12 weeks), there were no significant differences in these parameters except for a modestly lower plasma level of creatinine and modestly higher creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1992

Evolution of metabolic and functional derangements of pancreatic islets in phosphate depletion.

Phosphate depletion (PD) causes a rise in basal level of cytosolic calcium ([Ca2+]i) of pancreatic islets, a decrease in their basal and stimulated ATP content, a reduction in the maximum velocity (Vmax) of Ca2+ adenosine triphosphatase (ATPase) and Na(+)-K+ ATPase, impaired glucose-induced calcium signal and decreased glucose-induced insulin secretion. The sequence of events that lead to these derangements during the evolution of PD are not defined. The present study examined this issue by measuring the metabolic and functional profile of pancreatic islets weekly during the evolution of PD over a period of 6 weeks, and whether phosphate repletion reverses these abnormalities. The results show that initial abnormalities are a rise in Vmax of Ca2+ ATPase and modest rise in basal [Ca2+]i. This was followed by a fall in basal and stimulated ATP content. With the fall in ATP content, the Vmax of Ca2+ ATPase and Na(+)-K+ ATPase decreases and the rise in [Ca2+]i becomes more pronounced. A decrease in glucose-induced insulin secretion becomes evident with the fall in ATP, the decrease in glucose-induced calcium signal, and/or delta[Ca2+]i/basal[Ca2+]i. All functional and metabolic derangements of the pancreatic islets returned to normal after phosphate repletion. Taken together, our data are consistent with the notion that PD is associated with an initial increase in calcium influx into the islets. This is followed by modest but significant rise in [Ca2+]i which, in turn, would inhibit mitochondrial oxidation and ATP generation leading to a decrease in ATP content. The latter compromises the activity of Ca2+ ATPase and Na(+)-K+ ATPase which are involved, directly or indirectly, in calcium extrusion out of the islets. The increased influx of calcium combined with decreased calcium extrusion is followed by a further rise in basal levels of [Ca2+]i. This sequence of events continues until a steady state is reached and is characterized by reduced basal and stimulated ATP content, reduced Vmax of Ca2+ ATPase and Na(+)-K+ ATPase and elevated basal level of [Ca2+]i. Phosphate repletion reverses all these abnormalities.

Adenosine Triphosphate↗
PubMed1992

Chronology of cellular events leading to derangements in function of pancreatic islets in chronic renal failure.

In chronic renal failure (CRF), a multitude of metabolic derangements occur in the pancreatic islets, resulting in impaired glucose-induced insulin secretion. These abnormalities include a rise in the basal level of cytosolic calcium ([Ca2+]i) in the islet, a decrease in their basal and stimulated ATP and ATP/ADP ratio, a reduction in the Vmax of Ca2+ATPase and Na(+)-K+ATPase, and an impaired glucose-induced calcium signal. The sequence of events that lead to these derangements and to the impairment in insulin secretion during the evolution of CRF are not defined. The study presented here examined this issue by measuring the metabolic profile of pancreatic islets weekly during the evolution of CRF over a period of 6 wk. The results show that serum levels of parathyroid hormone (PTH) begin to rise during the first week of CRF. The Vmax of Ca2+ATPase and Na(+)-K+ATPase increased during weeks 1 to 3 of CRF but fell to low levels thereafter. At week 3 of CRF, the basal level of [Ca2+]i began to rise, whereas basal and the stimulated ATP content and ATP/ADP ratio started to fall. Glucose-induced calcium signal, delta[Ca2+]i/basal [Ca2+]i, and insulin secretion became abnormally low between weeks 3 and 6 of CRF. The data allow the following formulation: as serum levels of PTH begins to rise, calcium entry into islets is augmented; this in turn will stimulate the activity of Ca2+ATPase and the Na(+)-Ca2+ exchanger, and hence, calcium extrusion out of the islets is increased. As a result, [Ca2+] remains normal during the first 2 wk of CRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Acute effect of parathyroid hormone on Ca2+ ATPase of pancreatic islets.

The Vmax of Ca2+ ATPase of pancreatic islets is reduced in states of chronic excess of PTH. This has been attributed to the reduced ATP content of pancreatic islet and to impaired response of the enzyme to calmodulin. It is also possible that excess PTH directly inhibits the activity of islet Ca2+ ATPase. The present study examined this issue. Small doses of 1-84 PTH (0.0625 and 0.125 x 10(-7) M) stimulated while larger doses (0.25, 0.5, 1.0, 2.0 and 4.0 x 10(-7) M) inhibited the activity of Ca2+ ATPase of intact islets. PTH has no effect on Ca2+ ATPase when the hormone was added to preparation of membrane homogenate of islets. Verapamil abolished both the stimulatory as well the inhibitory effects of PTH on Ca2+ ATPase of intact islets. The data indicate that PTH does not have a direct effect on the Vmax of islet Ca2+ ATPase of islet. Its effect on the enzyme activity of intact islet is most likely mediated through the hormone-induced calcium influx.

Animals↗
PubMed1991

Intracellular signaling by 14-hydroxy-4,14-retro-retinol.

In mammals, retinol is the precursor for retinoids, which affect various aspects of morphogenesis and development. However, B lymphocytes, although retinol-dependent, do not use retinoic acid as mediator. Retinol is metabolized by B lymphocytes and other cell lines to optically active 14-hydroxy-4,14-retro-retinol; it is this compound that mediates the growth control. Thus another second messenger molecule, in addition to retinoic acid and retinal, is derived from retinol.

Animals↗
PubMed1991

Extracellular matrix-resident basic fibroblast growth factor: implication for the control of angiogenesis.

Despite the ubiquitous presence of basic fibroblast growth factor (bFGF) in normal tissues, endothelial cell proliferation in these tissues is usually very low, suggesting that bFGF is somehow sequestered from its site of action. Immunohistochemical staining revealed the localization of bFGF in basement membranes of diverse tissues, suggesting that the extracellular matrix (ECM) may serve as a reservoir for bFGF. Moreover, functional studies indicated that bFGF is an ECM component required for supporting endothelial cell proliferation and neuronal differentiation. We have found that bFGF is bound to heparan sulfate (HS) in the ECM and is released in an active form when the ECM-HS is degraded by heparanase expressed by normal and malignant cells (i.e. platelets, neutrophils, lymphoma cells). It is proposed that restriction of bFGF bioavailability by binding to ECM and local regulation of its release provide a novel mechanism for neovascularization in normal and pathological situations. The subendothelial ECM contains also tissue type- and urokinase type-plasminogen activators which participate in cell invasion and tissue remodeling. These results and studies on the properties of other ECM-immobilized enzymes (i.e. thrombin, plasmin, lipoprotein lipase) and growth factors (GM-CSF, IL-3, osteogenin), suggest that the ECM provides a storage depot for biologically active molecules which are thereby stabilized and protected. This may allow a more localized and persistent mode of action, as compared to the same molecules in a fluid phase.

Animals↗