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Biomedical subjects

O Zinder

Publications and source records attributed to O Zinder.

At least 73 records · Page 4Linked to original sources

The value of serum copper levels in non-Hodgkin's lymphoma.

A study of 306 serum copper levels (SCL) determinations in 115 patients with non-Hodgkin's lymphoma indicates a positive correlation between SCL and the state of disease. Patients with advanced disease (Stages II, III and IV) before treatment, those with active disease while under treatment, or in a relapse had a significantly higher SCL than patients in Stage I or those with no evidence of disease (NED). The mean SCL of patients with Stage I was similar to that of patients with NED. The mean values of these two groups did not differ significantly from that of healthy controls. Histological subtypes, according to the Rappaport classification, has no influence on SCL. Grouping into nodular versus diffuse lymphoma, histiocytic versus lymphocytic lymphoma and favorable versus unfavorable histology failed to demonstrate a difference between the groups. Within each subset a wide range of SCL was evident. However, good correlation was observed with the degree of disease activity. SCL may provide a useful parameter for patient monitoring. In this series, however, SCL was not useful for the prediction of an early relapse.

Adult↗

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↗

Ascorbic acid and catecholamine secretion from cultured chromaffin cells.

Ascorbic acid was found to be secreted from cultured bovine adrenal chromaffin cells coincidentally with catecholamines using a variety of secretagogues, including veratridine, nicotine, acetylcholine, and potassium chloride. Secretion of ascorbic acid was measured by preloading the cells for 3 h with (R)-[14C]ascorbic acid and then quantitating release of the label. The newly transported ascorbic acid constituted nearly 90% of total cellular ascorbic acid. Although chromaffin granules are known to contain endogenous ascorbic acid, only 16% of the total labeled ascorbic acid taken up by cultured cells was localized to the chromaffin granule fraction. Under the same isolation conditions, 95% of the endogenous catecholamines was found in the granule fraction. The secretion of both (R)-[14C] ascorbic acid and catecholamines was calcium dependent. However, only catecholamine secretion was effectively inhibited by the presence in the medium of isethionate, an impermeant ion that inhibits catecholamine secretion from isolated chromaffin granules. Analysis of the ratios of cellular and granular (R)-[14C] ascorbate as well as secreted (R)-[14C]ascorbate and catecholamines revealed that the secreted (R)-[14C]ascorbic acid did not come exclusively from the chromaffin granule fraction but also from a nonsedimenting cytoplasmic compartment. Indeed, for all four agonists, the amounts of (R)-[14C]ascorbic acid secreted were more than 1.5 times greater than could be accounted for by chromaffin granule ascorbate alone. We took these data to indicate that, while ascorbic acid and catecholamines were secreted concomitantly, the sources of the secreted substances were not necessarily identical.

Acetylcholine↗

The diagnostic value of serum copper/zinc ratio in gynecological tumors.

Serum copper levels (SCu) and serum zinc levels (SZn) were determined on admission in 73 women hospitalized for suspected gynecological tumor. Twenty-five of the women were subsequently found to have malignant tumor, while 48 had benign growths. The serum Cu/Zn ratio of the malignant group (2.13 +/- 0.53) was significantly (p less than 0.001) higher than that of the benign group (1.45 +/- 0.25). A good correlation was established between the Cu/Zn ratio and the stage of the malignant tumor. Serum copper level showed a linear correlation (R = 0.878) with serum ceruloplasmin values. These results indicate that the serum Cu/Zn ratio may be used as a valuable predictor of the presence of malignant gynecological tumor and its stage.

Ceruloplasmin↗

Alpha- and beta-receptor control of catecholamine secretion from isolated adrenal medulla cells.

The regulation of secretion of catecholamines from bovine adrenal medulla cells was investigated by use of an improved and highly efficient method for isolating viable and responsive cells from this tissue. The method involves an in situ collagenase perfusion affecting only the connective tissue matrix of the medulla while leaving the cortex intact. The cells released both epinephrine and norepinephrine in response to stimulation by 100 microM acetylcholine. The ratio of epinephrine to norepinephrine in the medium following non-stimulated (basal) release, was similar to that found in the intact cells. On the other hand, a lower ratio of epinephrine to norepinephrine was found in the medium following stimulation by acetylcholine due mainly to preferential secretion of norepinephrine. This release ceased after 15 min of incubation and consisted of 15--20% of the catecholamines initially present in the cells. Exogenous epinephrine was found to inhibit total catecholamine secretion; however, it stimulated norepinephrine release. Addition of isoproterenol caused a stimulation of release while propranolol was inhibitory. Norepinephrine inhibited total release not favoring any specific catechol. Other alpha-agonists, such as clonidine, also had an inhibitory effect. These results suggest a receptor-mediated mechanism for the fine regulation of secretion from the adrenal medulla.

Acetylcholine↗

Congenital esophageal atresia: lipase activity is present in the esophageal pouch and stomach.

Lipolytic activity was studied in aspirates from the esophageal pouch and from the stomach of eight infants with congenital esophageal atresia. Lipolytic activity, tested with doubly labeled ([3H]glyceryl, [14C]fatty acid) long-chain triglyceride was present in esophageal and gastric aspirates. The activity in esophageal aspirates was in the range of 2.7-130 nmol/min/ml aspirate and that in gastric aspirates was in the range of 2.9-40.4 nmol/min/ml aspirate. The reaction products of lipolytic activity in esophageal and gastric aspirates were a mixture of mono- and diglycerides, glycerol, and free fatty acids. The lipolytic activity at the two sites--esophagus and stomach--varied with respect to pH optimum (5.0-7.6 and 6.0-6.5, respectively) and reaction products (glycerol 41.6 +/- 20% and 7.3 +/- 4.6%, respectively). These findings confirm the earlier observations that digestion of dietary fat is initiated in the stomach and suggest that the lipolytic activity present in gastric contents originates concomitantly from the oral-esophageal area as well as from the stomach. These studies do not exclude the possibility that the lipolytic activity in the stomach of infants with esophageal atresia could originate in regurgitated intestinal contents.

Esophageal Atresia↗

Tensile strength of the chromaffin granule membrane.

Catecholamine release from chromaffin granules, suspended in sucrose solutions of various osmotic strengths, was determined at different temperatures between 2 degrees and 44 degrees C. Dynamic measurements showed that steady state is achieved within 15 min of incubation at all temperatures. The effect of temperature on the release was established in terms of the median granular fragility (MGF) defined as the concentration of sucrose solution causing 50% lysis. The MGF was determined as the inflection point of the Gaussian distribution of granular fragility. The MGF was found to decrease with fall in temperature implying a corresponding increase of the tensile strength of the vesicle membrane. Critical resultant forces at lysis were calculated and found to vary from 8.2 dyn/cm at 2 degrees C to 4.2 dyn/cm at 44 degrees C. These compare well with tensions at lysis found earlier for erythrocytes.

Adrenal Medulla↗

Pellagra as the presenting manifestation of Crohn's disease.

An 18-yr-old woman hospitalized with classical signs of pellagra was found to have Crohn's disease of the small and large bowel as well as malabsorption of nicotinic acid and iron. The symptoms of pellagra disappeared after intramuscular treatment with nicotinic acid, while the malabsorption was corrected following steroid therapy for the Crohn's disease. Pellagra should thus be added to the list of complications of Crohn's disease that are secondary to malabsorption. Although this complication seems to be very rare, it may be worthwhile to check for nicotinic acid malabsorption in untreated cases of Crohn's disease in order to determine its real prevalence.

Adolescent↗

The effect of copper on spermatozoal motility and viability evaluated objectively with the aid of the multiple-exposure photography method.

The antispermatozoal effect of the copper intrauterine contraceptive device (IUD) was investigated in an attempt to explain one aspect of its contraceptive mechanism. For this purpose, 42 specimens of normal semen were incubated in vitro with the metallic portion of two types of copper IUDs for 24 hours. Periodic determinations of sperm velocity and percentage of motility and viability were performed objectively with the aid of the multiple-exposure photography (MEP) method. No significant effect concerning these parameters was found when specimens were incubated continuously with either type of these IUDs at 23 degrees C. On the contrary, sperm velocity and percentage of motility dropped markedly, and the number of dead spermatozoa increased reciprocally when specimens were incubated with those IUDs at 37 degrees C for 4 hours. However, motility was almost unaffected in specimens that were incubated at 37 degrees C with amounts of copper that exist usually within uterine cavities bearing this sort of IUD. The conclusion was that a copper IUD does not seem to exert its contraceptive effect by inhibiting spermatozoal activity.

Copper↗

The concentration of high density lipoprotein in patients with type IV hyperlipoproteinemia and the effect of clofibrate.

Lipid and lipoprotein concentrations, including high density lipoproteins (HDL) and its subfractions, were contrasted in subjects with Type IV hyperlipoproteinemia, before and after therapy with clofibrate. Very low density lipoprotein (VLDL) levels were raised, whereas both low density lipoprotein (LDL) and HDL values were reduced in the patient group. Clofibrate reversed this trend and VLDL cholesterol and protein levels fell to approximate control values. LDL and HDL cholesterol increased but remained significantly lower than in normal controls. However, LDL and HDL protein did approach control values. Of the HDL subfractions, HDL-3 was significantly reduced in the group with Type IV hyperlipoproteinemia. Clofibrate resulted in a significant increase in the HDL-2: HDL-3 cholesterol ratio, but had only a modest effect on HDL-3 concentrations. HDL-3 may be the critical HDL subfraction responsible for the inverse correlation between levels of HDL and the development of ischemic heart disease.

Adult↗

Zinc concentration in gravida's serum and amniotic fluid during normal pregnancy.

Zinc concentration was determined in maternal serum and amniotic fluid during normal pregnancy. The nonpregnant zinc concentration in the serum of about 110 micrograms% decreases gradually during pregnancy to about half the normal level. Amniotic fluid zinc concentration shows a slight decrease and remains nearly constant until the 34th to 36th week of gestation, and then increases sharply (statistically significant) reaching the highest level at 40-42 weeks from the last menstrual period. The maternal-fetal metabolism of zinc, the various factors effecting zinc levels in maternal serum and amniotic fluid during pregnancy have been discussed in view of our results. These may serve as data base for further studies on the role of zinc in normal and pathological human pregnancies.

Amniotic Fluid↗

Role of intracellular proteins in the regulation of calcium action and transmitter release during exocytosis.

A central problem in cellular neurobiology is how the process of exocytosis of transmitters and hormones is regulated at the molecular level. Calcium is important in the process and may act by initiating the formation of fusion complexes of secretory granules to each other and to plasma membranes. We have discovered and isolated a new 47,000 MW protein (synexin) from adrenal medulla tissue that fuses chromaffin granule membranes only in the presence of calcium. Synexin activity was detected in a number of secretory tissues including human platelets and bovine brain, and the synexin molecule was found by immunofluorescent cytochemistry to be localized to the cytoplasm of chromaffin cells. Purified synexin molecules were found to self-associate in the presence of Ca++ to form paracrystalline arrays of 50 X 150 A rods, and the association was dependent on [Ca++] in an identical fashion to the Ca++ dependence of granule membrane fusion. On the basis of these data we suggest that synexin may be the intracellular receptor for calcium during exocytosis. However, the actual release event of 'fission' of the secretory vesicle-plasma membrane complex did not appear to be related to synexin action, and we have considered the hypothesis that the chemiosmotic mechanism for ATP, Cl--dependent chromaffin granule lysis might provide the necessary localized force. We have now shown that the granule model successfully predicts the secretory properties of human platelets, bovine parathyroid cells, and bovine chromaffin cells. Like the granule lysis system, secretion from these cells required specific anions in the medium was inhibited by anion transport blocking drugs and proton ionophores, and was suppressed by elevated osmotic strength. We suggest that secretory granules fused to plasma membranes in secreting cells, perhaps by synexin, may experience net solute uptake and subsequently undergo local, outwardly directed osmotic lysis, or exocytosis.

Adrenal Medulla↗

Serum and amniotic fluid heat labile alkaline phosphatase and aminotransferases in association with meconium stained liquor. On their origin, distribution and clinical use.

A method for detecting meconium in the amniotic fluid is described. Samples of maternal serum, cord serum and amniotic fluid were tested for alkaline phosphatase and transaminases activity in 32 healthy, term gravidas during labor in whom meconium stained amniotic fluid was found. The values obtained were compared to those of a control group consisting of 32 normal term pregnancies in whom the amniotic fluid was clear. Mean alkaline phosphatase activity was significantly higher in the study group in all three compartments - maternal, fetal and amniotic fluid. A significant and positive correlation between levels of alkaline phosphatase in the amniotic fluid and in maternal serum was found in the study group. Alkaline phosphatase value of 550 IU/L or more in maternal serum was diagnostic and levels between 350--500 IU/L were highly suggestive for the presence of menconium in the amniotic fluid. Mean levels of transaminases (SGOT and SGPT) were similar in the two groups and all were within normal range. The origin of alkaline phosphatase and the mode of transfer of the three enzymes are also discussed. It is suggested that this method can also be used during the third trimester of pregnancy.

Adult↗