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Biomedical subjects

C A Clarke

Publications and source records attributed to C A Clarke.

At least 55 records · Page 3Linked to original sources
PubMed1983

Effects of glucose on rat embryos in culture.

To elucidate the role of hyperglycaemia in causing fetal malformation, rat embryos have been grown in vitro from the head-fold stage for 48 h in the presence of excess glucose during different parts of the culture period. Culture of rat embryos for 10 or 21 h in 55 mmol/l exogenous glucose produced abnormalities observable after 48 h in culture. When embryos cultured for 10 or 21 h in excess glucose were observed by scanning electron microscopy at the end of the glucose treatment, abnormalities could be observed which may indicate how later malformations are formed. Thus it is possible that a relatively brief hyperglycaemic episode at a critical stage of embryogenesis may endanger the fetus of a diabetic mother.

Abnormalities, Drug-Induced↗
PubMed1983

Activation of Na+/H+ exchange in lymphocytes by osmotically induced volume changes and by cytoplasmic acidification.

After swelling in hypotonic solutions, peripheral blood mononuclear cells (PBM) shrink toward their original volumes. Upon restoration of isotonicity, the cells initially shrink but then regain near-normal size again. This regulatory volume increase (RVI) is abolished by removal of Na+o or Cl-o or by addition of amiloride. RVI is unaffected by removal of K+o or by ouabain and is only partially inhibited by 1 mM furosemide. As a result of increased influx, the cells gain both Na+ and K+ during reswelling. In contrast, only Na+ content increases in the presence of ouabain. Amiloride largely eliminates the changes in the content of both cations. Using diS-C3-(5), no significant membrane potential changes were detected during RVI, which suggests that the fluxes are electroneutral. The cytoplasmic pH of volume-static cells was measured with 5,6-dicarboxyfluorescein. After acid loading, the addition of extracellular Na+ induced an amiloride-inhibitable alkalinization, which is consistent with Na+/H+ exchange. Cytoplasmic pH was not affected by cell shrinkage itself, but an internal alkalinization, which was also amiloride sensitive and Na+ dependent, developed during reswelling. In isotonic lightly buffered solutions without HCO-3, an amiloride-sensitive acidification of the medium was measurable when Na+ was added to shrunken PBM. K+ was unable to mimic this effect. The observations are compatible with the model proposed by Cala (J. Gen. Physiol. 1980. 76:683-708), whereby an electroneutral Na+o/H+i exchange is activated by osmotic shrinking. Cellular volume gain occurs as Cl-o simultaneously exchanges for either HCO-3i or OH-i. Na+i is secondarily replaced by K+ through the pump, but this step is not essential for RVI.

Acid-Base Equilibrium↗
PubMed1983

Volume-induced anion conductance in human B lymphocytes is cation independent.

Peripheral blood T lymphocytes swollen in hypotonic media regain normal size by releasing internal KCl through activation of conductive K+ and Cl- pathways. In contrast, no regulatory volume decrease (RVD) is observed in tonsillar B lymphocytes. The volume-induced K+ permeability is minimal in these cells, but little was known about the effect of swelling on anion transport and its coupling to cation translocation. The induction of an anion-conductive pathway on swelling of B cells was demonstrated in the following way: 1) when an exogenous cation ionophore was added, hypotonic swelling was followed by secondary volume changes, the direction of which was dictated by the electrochemical gradients of the diffusible ions; 2) the rate of 36Cl efflux was markedly increased by swelling; and 3) upon swelling, the membrane potential approached the Cl- equilibrium potential. Quinine, which blocks K+ transport and RVD in swollen T cells, has no effect on volume-induced anion fluxes. Consequently, secondary volume changes could be elicited by gramicidin in cells pretreated with quinine. It can be concluded that in B cells, swelling leads to activation of a conductive Cl- permeability but not of K+ permeability. These and other findings support the view that the Cl- pathway functions independently of the K+ pathway.

Anions↗
PubMed1982

Increased anion permeability during volume regulation in human lymphocytes.

Peripheral blood lymphocytes (p.b.ls) readjust their volumes after swelling in hypotonic media. An essential component of the regulatory response is an increase in K+ and Cl- permeability. No evidence was found for a tightly coupled co-transport of K+ and Cl-. The flux of either ion proceeds normally in the virtual absence of the transported counterion. Furthermore, alterations in membrane potential recorded during the phase of volume readjustment can be qualitatively accounted for by an increase in Cl- conductance. In tonsillar lymphocytes, a failure of the K+-permeability is nevertheless increased upon swelling. This further suggests that K+ and Cl- are transported during volume regulation through independent pathways. Cytoplasmic free Ca2+ appears to be involved in regulatory volume decrease. K+ and Cl-. Moreover, swelling and shrinking can be induced in isotonic K+-rich and K+-free media, respectively, by the Ca2+ ionophore. The ion flux and volume changes produced by either swelling or internal Ca2+ can be inhibited by similar concentrations of quinine and phenothiazines. The inhibitory activity of the latter drugs, which are powerful antagonists of calmodulin, suggests the participation of this Ca2+-regulator protein in volume regulation.

Anions↗
PubMed1982

Volume-induced increase of anion permeability in human lymphocytes.

Peripheral blood mononuclear cells (PBM) readjust their volumes after swelling in hypotonic media. This regulatory volume decrease (RVD) is associated with a loss of cellular K+ and is thought to be promoted by an increased permeability to this ion. In contrast, no change in volume was observed when K+ permeability of PBM in isotonic media was increased to comparable or higher levels using valinomycin. Moreover, valinomycin-induced 86Rb+ loss in K+-free medium was considerably slower than in K+-rich medium. These results suggest that anion conductance limits net salt loss in isotonic media. Direct measurements of relative conductance confirmed that in volume-static cells, anion conductance is lower than that of K+. In volume-regulating cells depolarization occurred presumably as a result of increased anion conductance. Accordingly, the efflux of 36Cl from PBM was markedly increased by hypotonic stress. Since both membrane potential and intracellular 36Cl concentration are reduced in hypotonically swollen cells, the increased efflux is probably due to a change in Cl- permeability. Anions and cations seem to move independently through the volume-induced pathways: the initial rate of 86Rb uptake in swollen cells was not affected by replacement of external Cl- by SO=4; conversely, 36Cl fluxes were unaffected by substitution of K+ by Na+. The data indicate that anion conductance is rate-determining in salt and water loss from PBM. An increase in anion conductance is suggested to be the critical step of RVD of human PBM.

Anions↗
PubMed1978

Biochemical and haematological markers of alcohol intake.

The serum gamma-glutamyl-transpeptidase (gamma-G.T.), aspartate transaminase (A.T.), urate, and triglyceride levels and the mean cell volume were estimated in 2034 healthy men. In 14.9% gamma-G.T. was elevated, in 8.0% A.T. was raised, and in 4.2% both enzymes were elevated. Findings were almost identical in a subgroup of 146 whose alcohol intake was known. Both enzymes, serum-urate, and mean cell volume showed a progressive rise with increasing alcohol consumption. The sensitivity of these markers is such that elevated levels are present in those whose alcohol intake would be regarded as normal and who are in no sense alcohol-dependent.

Adult↗
PubMed1975

Mechanism of Rh prophylaxis: an experimental study on specificity of immunosuppression.

The mechanism by which Rh immunization is prevented by IgG anti-D was investigated by studying the specificity of immunosuppression. 62 D-negative Kell(K)-negative male volunteers were given two successive stimuli of 1 ml D-positive K-positive red cells. Thirty-one of the volunteers were also given 13-14 mug of IgG anti-K immediately after each stimulus, the others acting as controls. Anti-D developed in 11 of the 31 controls and in one of the 31 volunteers who had received anti-K. This marked suppression of the anti-D response by IgG anti-K was accompanied by the rapid clearance of the injected red cells to the spleen. This shows that the predominant mechanism that must be operating when IgG anti-D prevents Rh immunization is not antigen specific but is one that must involve the whole red cell, probably through destruction within splenic macrophages.

Antibody Formation↗