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Biomedical subjects

S Treves

Publications and source records attributed to S Treves.

At least 55 records · Page 3Linked to original sources
PubMed1988

Role of Na+/H+ exchange in thrombin- and arachidonic acid-induced Ca2+ influx in platelets.

Platelet activation is accompanied by an increase of cytosolic free Ca2+ concentration, [Ca2+]i, (due to both extracellular Ca2+ influx and Ca2+ movements from the dense tubular system) and an Na+ influx associated with H+ extrusion. The latter event is attributable to the activation of Na+/H+ exchange, which requires Na+ in the extracellular medium and is inhibited by amiloride and its analogs. The present study was carried out to determine whether a link exists between Ca2+ transients (measured by the quin2 method and the 45CaCl2 technique) and Na+/H+ exchange activation (studied with the pH-sensitive intracellular probe, 6-carboxyfluorescein) during platelet stimulation. Washed human platelets, stimulated with thrombin and arachidonic acid, showed: (1) a large and rapid [Ca2+]i rise, mostly due to a Ca2+ influx through the plasma membrane; (2) a marked intracellular alkalinization. Both phenomena were markedly inhibited in the absence of extracellular Na+ or in the presence of an amiloride analog (EIPA). Monensin, a cation exchanger which elicits Na+ influx and alkalinization, and NH4Cl, which induces alkalinization only, were able to evoke an increase in [Ca2+]i, mostly as an influx from the extracellular medium. Our results suggest that Ca2+ influx induced by thrombin and arachidonic acid in human platelets is strictly dependent on Na+/H+-exchange activation.

Ammonium Chloride↗
PubMed1988

Regulation of arachidonic acid-dependent Ca++ influx in human platelets.

Quin2 was used to study the rise in cytoplasmic free calcium ([Ca++]i) and the role of prostaglandin (PG) endoperoxides/thromboxane A2 (TxA2), reduced glutathione (GSH), ADP and the glycoprotein (GP) IIb-IIIa complex in mediating [Ca++]i rise during arachidonic acid (AA)-induced platelet aggregation. Ca++ mobilization, mostly due to an influx across the plasma membrane, is completely inhibited by aspirin and persists after selective blockade of TxA2 synthase by dazoxiben. GSH total depletion causes a complete aggregation block and 90% inhibition of the transient: U-46619, a stable analog of cyclic endoperoxide PGH2, stimulates [Ca++]i transient in aspirin-treated or in GSH-depleted platelets. ADP-scavengers, ATP (which competes for the ADP receptor), and monoclonal antibodies against the GP IIb-IIIa complex reduce AA-induced Ca++ influx. Therefore, PG endoperoxides alone or a PGH2/TxA2 mimetic stimulate Ca++ influx. Synthesis of PGH2 and TxA2 depends on the availability of GSH, which acts as the reducing cofactor for the PG-peroxidase activity. ADP and GP IIb-IIIa are regulating factors of AA-mediated Ca++ influx during platelet activation.

Adenosine Diphosphate↗
PubMed1988

Platelet arachidonic acid metabolism in patients with cardiovascular disorders.

There is increasing evidence that prostaglandins (PG) and thromboxane (Tx) play a major role in the pathogenesis of coronary artery disease. The regulation of arachidonic acid (AA) metabolism through cyclooxygenase (COx) pathway and the AA-dependent Ca2+ influx were investigated in platelets from 10 patients with unstable angina and 10 controls. The activation of the hexose monophosphate shunt (HMS), a sensitive index of the flux through the PGG2 to PGH2 step of the COx pathway, in response to AA was significantly enhanced in platelets from patients. AA-induced malonyldialdehyde (MDA) production as well as AA-evoked Ca2+ flux and glutathione-dependent peroxidase activity resulted significantly increased. Moreover, platelet sensitivity to prostacyclin (PGI2), measured as inhibition of Ca2+ flux, was highly decreased. Thus far, evidence is presented for intrinsic platelet hyperactivity (at the PG-peroxidase reaction of the COx pathway) in patients with unstable angina: the resulting increase in PGH2 and TxA2 synthesis, alone or in combination with decreased PGI2 sensitivity, may account for a facilitated thrombus formation.

Angina Pectoris↗
PubMed1987

Calcium and inositolphosphates in the activation of T cell-mediated cytotoxicity.

Reports from a number of laboratories have shown that mAbs against the T3-Ti receptor complex cause an increase in cytosolic-free Ca2+ [( Ca2+]i) and the hydrolysis of phosphatidylinositolbisphosphate (PIP2) in CTLs. In the present report we show that activation of CTLs by their specific targets causes: (a) release of Ca2+ from intracellular stores; (b) transient formation of inositol trisphosphate (InsP3); and (c) an increased permeability to Ca2+ of CTL plasma membrane. Killing of unrelated targets could be induced by cocentrifugation of the unrelated targets with CTLs in the presence of A23187 or PMA. We conclude that: (a) activation of CTLs by specific antigens triggers the generation of the same intracellular mediators generated by stimulation of lymphocytes with anti-T3-Ti receptor antibodies and/or with polyclonal mitogens; and (b) intracellular signals that mediate the delivery of the lethal hit by CTLs are indistinguishable from those that induce cell proliferation.

Animals↗
PubMed1987

Effect of cytochalasins on cytosolic-free calcium concentration and phosphoinositide metabolism in leukocytes.

Cytochalasins are routinely used to stimulate a variety of functions in eukaryotic cells even though their precise mode of action remains to be elucidated. In the present work we used the fluorescent Ca2+ indicator quin2 to study the effect of various cytochalasins, cytochalasins A, B, C, D, E (CA, CB, CC, CD, CE) and dihydrocytochalasin B (dhCB) on the intracellular Ca2+ concentration ([Ca2+]i) in various types of leukocytes, viz, neutrophils and lymphocytes. In human neutrophils, cytochalasins increase [Ca2+]i mainly by releasing Ca2+ from membrane-bound, intracellular stores. Thus, in order to readily appreciate the effect of cytochalasins on [Ca2+ )i, these cells must be loaded with low intracellular quin2 concentrations. On the other hand, in peripheral blood lymphocytes, splenocytes and thymocytes, the increase in [Ca2+]i is predominantly due to an increased Ca2+ influx from the extracellular medium. In addition, we found that in neutrophils these drugs prolong the increase in [Ca2+]i induced by chemotactic peptides, probably by increasing the cell permeability to Ca2+. Finally, in thymocytes, cytochalasins potentiate the production of inositol phosphates induced by the polyclonal mitogen concanavalin A (conA).

Animals↗
PubMed1986

A 133-xenon inhalation system for cerebral blood-flow measurements in ventilated premature babies.

We constructed a Xenon-133 inhalation and trapping system in order to measure cerebral blood flow of ventilated premature babies by means of the noninvasive 133Xe clearance method. The completely lead-shielded inhalation device is a closed system driven by the baby's own respirator and can thus be safely used at the patients bedside in the intensive care unit. Reproducible proximal airway concentrations of 133Xe (with or without leaks around the endotracheal tube) were obtained by in vitro simulation.

Cerebrovascular Circulation↗
PubMed1986

The development of an 191Os----191mIr generator using an osmium chelate parent complex--I. Trans-dioxobismalonatoosmate(VI).

A 191Os----191mIr generator has been developed that has higher 191mIr yield and lower 191Os breakthrough than previous designs. These improvements have been realized through the use of the osmium chelate complex trans-dioxobismalonatoosmate(VI) as the parent species on the generator. The new generator provides an initial 191mIr yield of 40%/mL and 191Os breakthrough of 2-3 X 10(-3)% when eluted with a solution of 0.05 M malonic acid/0.10 M sodium chloride at pH 4. Other advantages of the new design include faster clearance of the 191Os breakthrough products and simpler assembly.

Angiography↗
PubMed1985

Inositol phosphate formation in fMet-Leu-Phe-stimulated human neutrophils does not require an increase in the cytosolic free Ca2+ concentration.

The accumulation of inositol phosphates in myo-[3H]inositol-labelled human neutrophils stimulated with the chemotactic peptide fMet-Leu-Phe was measured. The challenge with the chemotactic peptide caused the generation of inositol monophosphate (InsP), inositol bisphosphate (InsP2) and inositol trisphosphate (InsP3). The formation of the three inositol phosphates followed a differential time course: InsP3 accumulated very rapidly and transiently, whereas InsP increased steadily for more than 2 min. Inositol phosphate formation was only partially decreased by procedures which prevented the fMet-Leu-Phe-dependent increase of cytosolic free Ca2+ concentration.

Calcium↗
PubMed1985

Hypertension in children. Increased efficacy of technetium Tc 99m succimer in screening for renal disease.

Renal scintigraphy with technetium Tc 99m succimer (DMSA) and technetium Tc 99m pentetate (DTPA) was used to study 80 hypertensive pediatric and adolescent patients. Renal abnormalities such as asymmetry of function, size, or shape were identified in 13 patients. Both excretory urography and technetium Tc 99m pentetate studies were successful in detecting 54% of the abnormalities in patients studied; technetium Tc 99m succimer identified 92%. The accuracy of the latter was 96%, with a specificity of 97%. The ability of technetium Tc 99m succimer renal scintigraphy to identify accurately the presence or absence of renal abnormalities warrants its inclusion in the initial examination of pediatric and adolescent patients with hypertension.

Adolescent↗
PubMed1985

Testicular torsion in children: scintigraphic assessment.

Seventy-five patients with suspected testicular torsion who had scintiscans and adequate clinical follow-up were analyzed retrospectively. The scintiscans diagnosed 12/13 cases of surgically proven missed torsion and 3/3 cases of surgically proven acute complete torsion. The scintiscans successfully distinguished all 35 cases of epididymo-orchitis, 14 cases of torsion of the appendix testes and 8 other miscellaneous conditions from testicular torsion. The incidence of testicular torsion in our patients undergoing scrotal scintigraphy was approximately 24%.

Adolescent↗
PubMed1985

Differing effects of antiinsulin serum and antiinsulin receptor serum on 123I-insulin metabolism in rats.

Anesthetized rats were treated with saline, antiinsulin receptor serum, or antiinsulin serum, and the biodistribution of high pressure liquid chromatography-purified 123I-Tyr A14-insulin was studied by scintillation scanning. Time activity curves over organs of interest were calibrated by sacrificing the rats at the end of the experiment and directly determining the radioactivity in the blood, liver, and kidneys. Saline-treated rats exhibited normal insulin biodistribution. The highest concentration of 123I-insulin was found in the liver, and reached 30% of total injected dose between 3 and 5 min after injection. After this peak, activity rapidly decreased with a t1/2 of 6 min. Activity of 123I-insulin in kidney showed a more gradual rise and fall and was approximately 15% of injected dose at its maximum. In rats treated with antiinsulin antiserum, insulin biodistribution was markedly altered. Peak liver activity increased with increasing antibody concentration with up to 90% of injected dose appearing in the liver. In addition, there was no clearance of the liver 123I-insulin over 30 min. Autoradiographic studies demonstrated that in contrast to the normal rats in which radioactivity was associated with hepatocytes, in rats passively immunized with anti-insulin serum, 125I-insulin was associated primarily with the Kuppfer cells. In contrast, antibodies to the insulin receptor markedly inhibited 123I-insulin uptake by the liver. Kidney activity increased, reflecting the amount of free 123I-insulin that reached this organ. This is similar to the pattern observed when insulin receptors are saturated with a high concentration of unlabeled insulin. Thus, both insulin antibodies and anti-receptor antibodies alter the distribution of insulin, but with very different patterns. The use of 123I-insulin and scintillation scanning allows one to study specific alterations in insulin distribution in animal models of insulin-resistant states, and should also be useful in human disease states.

Animals↗
PubMed1985

Bone scintigraphy and radiography in young athletes with low back pain.

Radiographs and bone scans of 40 young athletes with low back pain were reviewed retrospectively to correlate the imaging findings and assess the value of scintigraphy in the diagnosis of these patients. The radiographs were positive for spondylolysis with or without spondylolisthesis in 15 (38%), and scintigraphy showed focal disease in the posterior vertebral elements in 14 (35%). Five patients had positive radiographic studies but normal scans, indicating old injuries; four patients had positive scintigrams but normal radiographs, suggesting early or active injuries. The authors use radiography as the initial examination in the evaluation of patients with low back pain. Scintigraphy is most useful in early stages, when radiographs may be normal; and in cases in which the age and activity of a radiologic abnormality cannot otherwise be accurately determined before therapy.

Adolescent↗
PubMed1984

In vivo imaging and quantitative analysis of insulin-receptor interaction in lean and obese Zucker rats.

Imaging and quantitative analysis of insulin-receptor interaction was studied in vivo in lean and obese Zucker rats, using a recently developed technique in which purified Tyr A14 123I-monoiodoinsulin is intravenously injected and the tracer followed by scintillation scanning. The obese rats were 72% overweight, had near normal blood glucose concentrations and an 11-fold increase in plasma insulin concentration. In both groups of rats, the tracer was rapidly taken up by the liver (by a receptor mediated mechanism) and the kidneys (by a non-receptor mediated process). Past this maximum, radioactivity decreased in both organs as 123I-insulin was degraded and free 123I-iodide was released into the plasma compartment. Heart radioactivity (i.e. blood pool) mirrored that of the liver and kidneys. The rapid initial decrease of blood radioactivity was concomitant with liver and kidney uptake of 123I-insulin. Release of free iodide from these organs induced a slow secondary rise of blood radioactivity followed by a final decline corresponding to clearance of plasma iodide, mainly by urinary excretion. Liver radioactivity profiles of lean and obese rats were parallel. When expressed per g weight, liver radioactivity was significantly decreased in obese rats. However, due to hepatomegaly in obese rats, total liver radioactivity was significantly higher in homozygous fa/fa rats than in lean littermates. Furthermore, if the marked hyperinsulinaemia of the obese rats is taken into account, total bound insulin was enhanced in the liver of fa/fa rats whatever reference is used, either g weight or total liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Right ventricular and left ventricular ejection fraction in pediatric patients with normal hearts: first-pass radionuclide angiocardiography.

First-pass radionuclide angiocardiography was used to estimate right ventricular (RV) ejection fraction (EF) and left ventricular (LV) EF in infants, children, and teenagers with normal hearts. The right ventricle was analyzed in 74 patients and the left ventricle in 72 patients. Mean RVEF for the group was 0.53 +/- 0.06 (range 0.43 to 0.73); mean LVEF for the group was 0.68 +/- 0.09 (range 0.49 to 0.86). Lower values tended to be present in younger patients. However, there was no statistical difference in EFs between age groups and no linear correlation between magnitude of EF and age or EF and heart rate for either ventricle. Data obtained demonstrated that RVEF and LVEF in children with normal hearts are similar to those in adults with normal cardiovascular systems. A RVEF of 0.41 to 0.47 or a LVEF of 0.50 to 0.59 would suggest borderline systolic function; a RVEF less than 0.41 (mean -2 SD) or LVEF less than 0.50 (mean -2 SD) would be considered abnormal when this technique of first-pass radionuclide angiocardiography is used.

Adolescent↗
PubMed1984

An automated algorithm for radionuclide angiocardiographic quantitation of circulatory shunting.

Circulatory shunting may be quantitated by analysis of time-activity curves obtained from radionuclide angiocardiography. A new automated algorithm for performing this analysis is proposed. The algorithm uses mathematical deconvolution techniques to increase the temporal separation of the components of this curve and thereby improves the accuracy of the analysis. The stability of the algorithm to random data errors was assessed by experiments on simulated time-activity curves degraded with pseudorandom noise. Excellent performance was obtained on a set of test problems previously used in the literature. The algorithm was used to quantitate left-to-right shunting in patients undergoing radionuclide angiocardiography during cardiac catheterization. A strong correlation (r = 0.96) was found between pulmonary to systemic flow ratios (Qp:Qs) obtained using the algorithm on radionuclide angiocardiographic data and Qp:Qs values obtained by oximetry at cardiac catheterization.

Adolescent↗
PubMed1984

Radionuclide estimation of cerebrospinal fluid shunt flow. Evidence supporting an alternative theoretical model.

Flow of cerebrospinal fluid through a surgically implanted valve may be estimated by analyzing the disappearance curve resulting from the injection of a radiotracer into the valve. The standard method for estimating flow assumes an exponential disappearance of the tracer from the valve. This method models the valve as a single well-mixed compartment. Experimental evidence, showing that estimates of flow were dependent upon the site of injection, is at variance with this assumption. An alternative method of analyzing the disappearance curves, based on the area to height ratio (A/H) of the curves, was found to be more consistent with the experimental evidence and resulted in greater precision than the exponential method. It was concluded that optimal results are obtained using the A/H method with a fixed injection technique.

Cerebral Ventriculography↗