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Biomedical subjects

G B Weiss

Publications and source records attributed to G B Weiss.

At least 73 records · Page 4Linked to original sources

Calcium and excitation--contraction coupling in vascular smooth muscles.

The roles of Ca2+ in excitation--contraction coupling in vascular smooth muscle have been difficult to delineate, primarily because unambiguous association of specific Ca2+ components with morphologically defined cellular structures could not be attained. More recent use of washouts in La3+-substituted solutions at low temperature (to remove superficial Ca2+ and retain cellular Ca2+), Scatchard-coordinate plots (to identify incubation conditions appropriate for examining predominantly high or low affinity Ca2+ components), and high concentrations of Sr2+ (to remove high but not low affinity Ca2+) have facilitated qualitative and quantitative separation of different Ca2+ fractions. The release of high affinity Ca2+ elicited with norepinephrine and the increase in uptake of low affinity Ca2+ obtained with high K+ have been clearly demonstrated, and may directly measure or indirectly reflect changes in the level of intracellular free Ca2+. In other types of vascular smooth muscle (e.g., renal vessels, coronary arteries), similar Ca2+ components also appear to be present, but their relative size and functional importance for regulation of contractile responsiveness can differ.

Animals↗

Specific alterations in binding and uptake of high and low affinity Ca++ in canine aortic microsomes.

The effects of Sr++, aminoglycoside antibiotics and other agents on Ca++ incorporation by canine aortic microsomes have been examined in 0.03 mM Ca++ (high affinity Ca++ components predominate) and in 3.0 mM Ca++ (low affinity Ca++ components predominate) in the presence of 45Ca uptake) and absence (45Ca binding) of ATP. Sr++ inhibited high affinity Ca++ uptake more than binding of Ca++ and reduced low affinity Ca++ uptake and binding only at higher concentrations (3.0-5.0 mM). Similar results were obtained with Sr++ in canine aortic media intimal strips. Neomycin (0.4-1.4 mM) or gentamicin (0.6-2.0 mM) had no significant effect on high affinity Ca++ uptake, but reduced high affinity Ca++ binding and inhibited low affinity Ca++ uptake and binding. Nitroprusside inhibited only high affinity Ca++ uptake and D-600 was without effect. Thus, measurement of Ca++ uptake and binding in smooth muscle microsomal membrane preparations demonstrates that agents affecting smooth muscle contractility can alter binding or uptake of Ca++ in differing ways or, in some cases (e.g. D-600), exert their action by blocking other Ca++-related effects.

Animals↗

Growth of human malignant micromegakaryocytes in vitro.

Mononuclear cells from the peripheral blood of a patient with megakaryoblastic transformation of Philadelphia chromosome-positive chronic myelogenous leukemia were cultured. Morphological and cytochemical studies and cell ploidy determinations were done daily for 4 days. PAS staining of the cells increased progressively during culture. Ultrastructural study of circulating and cultured cells revealed demarcation membranes and alpha granules indicating the cells were micromegakaryocytes. Deoxyribonucleic acid synthesis, determined by 3H-thymidine uptake, peaked at 72 hours. The DNA content of cultured cells was diploid at all times. All 15 metaphases analyzed at 72 hours were Ph1-positive. Malignant (Ph1-positive) megakaryoblasts and micromegakaryocytes grown successfully were capable of partial cytoplasmic maturation as demonstrated by glycogen deposition and increase in subcellular organelles, while endoreduplication was impaired. Malignant megakaryoblasts and micromegakaryocytes can be grown successfully in short term liquid culture and have more complete maturation in vitro than observed in vivo.

Cell Division↗

A comparison of Ca++ incorporation in microsomal fractions from bovine, canine and rabbit aortic smooth muscle.

A comparative study was made of high and low affinity Ca++ uptake (ATP present) and binding (ATP absent) in microsomal fractions prepared by the same method from bovine, canine and rabbit aortic smooth muscle. Rabbit aortic microsomes incorporated slightly more Ca++ under control conditions than did the bovine or canine preparations. The effects of Sr++ (3.0 mM), neomycin sulfate (1.4 mM) and sodium nitroprusside (1.0 mM) on Ca++ incorporation in aortic microsomes from the three species were qualitatively and quantitatively similar. Sr++ inhibits primarily high affinity Ca++ uptake and binding; neomycin inhibits high and low affinity Ca++ binding and nitroprusside inhibits high affinity Ca++ uptake. Addition of oxalate potentiated high affinity Ca++ uptake in aortic microsomes from all three species. Thus, correlations between studies of effects of agents on Ca++ and tension in aortic strips of one of these species and on Ca++ uptake and binding by an aortic microsomal fraction of one of the other two species examined in this study would appear to be based upon qualitatively appropriate similarities.

Adenosine Triphosphate↗

Comparison of direct harvest and cultures for karyotyping EDTA anticoagulated marrow.

Studies were undertaken to determine whether EDTA was a satisfactory anticoagulant for tissue specimens for cytogenetic analysis and to investigate a modification of a currently used culture technique for obtaining metaphases. The latter involved to prolonged exposure to very low-dose colcemid and was successful in qualitative or quantitative enhancement, or both, of the temperature yield over that obtained from direct harvest in 53% of the patients studied. EDTA is a suitable anticoagulant for cytogenetic studies of specimens from either direct harvest or short-term culture if the specimen is either processed within 24 hr after collection or diluted 1:1 with Eagles minimal essential media, supplemented with fetal bovine serum and refrigerated until processed. Success has been obtained with specimens stored up to 144 hr.

Bone Marrow↗

Inhibitors of mitochondrial Ca++ uptake dissociate potassium-induced tension responses from increased 45Ca retention in rabbit aortic smooth muscle.

Effects of antimycin A, oligomycin and KCN on tension responses to high K+ or NE and on related Ca++ movements were investigated in rabbit aortic smooth muscle. Selected concentrations of antimycin A (10(-6) g/ml), oligomycin (10(-6) g/ml) and KCN (1 mM) had little effect on the K+-induced contractile response even though all three agents abolished the increase in La+++-resistant low affinity Ca++ uptake elicited with high K+. Though the mitochondrial inhibitors had varied effects on the NE-induced contractile response, they had no effect on the NE-induced decrease in La+++-resistant high affinity Ca++. Oxygen consumption of the muscle tissue was decreased by antimycin A or oligomycin. These results suggest that the increase in low affinity Ca++ retention elicited with high K+ represents Ca++ uptake by mitochondria. Thus, the correlation between K+-induced uptake of Ca++ and an increased retention of La+++-resistant low affinity Ca++ after exposure to K+ are sequential events that can be associated by inhibitors of mitochondrial Ca++ uptake.

Animals↗

Effect of transmembrane pH gradient changes on potassium-induced relaxation in vascular smooth muscle.

In bicarbonate-buffered solution the Ba++-induced contraction of rat aorta was relaxed by an elevated extracellular K+ concentration. When the pH of the bicarbonate-buffered solution was lowered or the buffer system of the solution changed from bicarbonate to Tris or HEPES, the K+-induced relaxation was strongly inhibited. Raising the pH of the Tris-buffered solution restored the effect of K+. Addition of NH4+, which is known to cause a transient increase in intracellular pH, transiently inhibited and subsequently augmented the K+-induced vasodilation in all solutions. It is suggested that the K+-induced vasodilation results from membrane hyperpolarization following enhanced Na+, K+-ATPase activity and that this K+-induced vasodilation is affected by changes in the transmembrane pH gradient.

Animals↗

Comparison of degree of dependence of canine renal arteries and veins on high and low affinity calcium for responses to norepinephrine and potassium.

The relationships between tension responses to norepinephrine (NE) and high potassium (KCl) and high affinity 45Ca binding and mobilization were compared in canine renal arteries and veins. Contractile responses to 80 mM KCl were inhibited 83 (veins) and 88% (arteries) after respective 5-min and 60-min incubation periods in solutions with no added Ca++; responses to 10(-4) M NE were inhibited 87% (veins) and only 44% (arteries) after 60 min in the same solution. In solutions favoring low affinity binding of Ca++ (5.0 mM), uptake of 45Ca was similar in canine renal arteries and veins. However, in solutions favoring high affinity Ca++ binding (0.03 mM Ca++), 45Ca uptake was greater in arteries than in veins. Comparison of 45Ca efflux rates indicates a more rapid efflux and a greater Ca++-45Ca exchangeability in veins. After incubation with 45Ca and subsequent washout in an isosmotic (80.8 mM) La+++-substituted solution at 0.5 degrees C, 45Ca retention (residual Ca++ uptake) was proportionately greater in arteries than in veins at both high and low affinity sites. NE (10(-6) M) significantly increased La+++-resistant 45Ca uptake at both high and low affinity sites in veins but not in arteries. Thus, the NE-induced responses in veins depend upon extracellular Ca++ to a greater degree than in arteries. Even though veins have a lower number of high affinity Ca++ binding sites and this decreases the ability of the veins to retain sufficient Ca++ at these sites to maintain the response to NE, the responsiveness to NE appears to be maintained by an alternate mechanism, uptake of Ca++ at lower NE concentrations.

Animals↗

HLA type and survival in lung cancer.

A significant positive association between antigens HLA Aw19 and/or HLA B5 and a disease-free survival time of one year for patients with lung cancer has been reported but not confirmed. We have HLA-typed 20 white patients with non-oat-cell bronchogenic carcinoma who have survived at least a year from the time of diagnosis. Half these patients possessed these antigens (P less than 0.08). This highly suggests that the presence of these antigens is associated with prolonged survival time. Now may be the time for performing large scale clinical trails using these antigens as stratification factors.

Adenocarcinoma↗

Effects of prostaglandin E1 on contractility and 45Ca release in rabbit aortic smooth muscle.

Concentrations of prostaglandin E1 (PGE1; 10(-7) M) that do not elicit tension responses in aortic strips potentiate contractions induced by submaximal concentrations (10(-8)-10(-7) M) of norepinephrine (NE) or angiotensin III (Ang III) but not those of high K+ depolarization or maximal NE or Ang III concentrations. Higher concentrations of PGE1 (10(-6) M and above) initiate contractions which are additive with submaximal responses to NE and Ang III but not to K+. These same concentrations of PGE1 also decrease 45Ca retention at high affinity La+++-resistant sites in a manner similar to but not additive with NE and Ang III. Uptake of 45Ca at low affinity La+++-resistant sites (which is increased by high K+-depolarization) is not altered by 10(-6) M PGE1. The effects of PGE1 are not altered by decreased extracellular Ca++ (0.1 mM), decreased temperature, phentolamine or meclofenamate. Thus, PGE1 does not appear to increase uptake of extracellular Ca++ in this smooth muscle tissue. Instead, PGE1 increases mobilization of Ca++ from the same high affinity La+++-resistant sites affected by Ang III and NE and, in this manner, may increase responses to these two stimulatory agents.

Angiotensin III↗