Ethanol and (Na+,K+)-ATPase: Alteration of Na+-K+ Selectivity

Relative internal concentrations of Na+ and K+ are important in regulating (Na+,K+)-ATPase in situ. Ethanol is known to inhibit (Na+,K+)-ATPase and to reduce K+ affinity, but the concentrations required for these effects in vitro are large compared with those probably attainable in vivo. Yet, there is evidence suggesting that ethanol has physiologically relevant effects on (Na+,K+)-ATPase. We have investigated the effects of ethanol on selectivity for Na+ versus K+. At 150 mM, ethanol had little effect on (Na+,K+)-ATPase activity under the usual assay conditions, slightly (but nonsignificantly) reduced K+ affinity, and had no effect on extrapolated Na+ affinity in the absence of K+. However, ethanol had marked effects on cation selectivity, doubling the Ki for K+ on Na+ affinity and halving the Ki for Na+ on K+ affinity. These data show that ethanol, at concentrations too small for effects on (Na+,K+)-ATPase activity under optimal assay conditions, can alter its responses to changes in Na+ or K+.     

Anti-Dia and the Dia Blood Group

Abstract. In an Austrian family the Di^a antigen was discovered by causing hemolytic disease of the newborn. No mongoloid admixture has so far been detected. No linkage to other blood groups, serum groups or red cell enzymes could be found.     

The Sda Blood Group Antigen

Abstract. Material with high Sd^a blood group activity can be prepared from urine by precipitation with ethanol. Partial separation of substances with Sd^a and A activity can be effected by gel-filtration, ultracentrifugation or precipitation with anti-A serum. Substances with Sd^a activity are inactivated by acid, alkali and periodate and are partly soluble in phenol.     

pH-Regulated Na+ Influx into the Mammalian Ventricular Myocyte: The Relative Role of Na+-H+ Exchange and Na+-HCO3− Co-Transport

In the heart, intracellular Na⁺ concentration (Na⁺_i) is a controller of intracellular Ca²⁺ signaling, and hence of key aspects of cell contractility and rhythm. Na⁺_i will be influenced by variation in Na⁺ influx. In the present work, we consider one source of Na⁺ influx, sarcolemmal acid extrusion. Acid extrusion is accomplished by sarcolemmal H⁺ and HCO₃⁻ transporters that import Na⁺ ions while exporting H⁺ or importing HCO₃⁻. The capacity of this system to import Na⁺ is enormous, up to four times the maximum capacity of the Na⁺-K⁺ ATPase to extrude Na⁺ ions from the cell. In this review we consider the role of Na⁺-H⁺ exchange (NHE) and Na⁺-HCO₃⁻co-transport (NBC) in mediating Na⁺ influx into cardiac myocytes. We consider, in particular, the role of NBC, as so little is known about Na⁺ influx through this transporter. We show that both proteins mediate significant Na⁺ influx and that although, in the ventricular myocyte, NBC-mediated Na⁺ influx is less than through NHE, the proportions may be altered under a variety of conditions, including exposure to catecholamines, membrane depolarization, and interference with activity of the enzyme, carbonic anhydrase.     

Confirmation of K11 and K17 as Alleles in the Kell Blood Group System

Tests of three new unrelated K:-11 people and their relatives confirm that K11 is allelic to K17 (Wka) and belongs to the Kell system.     

Role of Na+:Ca2+ Exchange Current in Cs+-Induced Early Afterdepolarizations in Purkinje Fibers

Na⁺:Ca²⁺ Exchanger and EADs. Introduction: The ionic mechanisms for early afterdepolarizations (EADs) have not been fully clarified. It has been suggested that L-type Ca²⁺ current (I_caL) is the primary current generating EADs that occur near the plateau level (E-EADs) of the membrane potential (Vm) when I_caL is enhanced. The purpose of these studies was to determine accurately the range of Vm at which EADs occur in Purkinje fibers with K⁺ currents blocked by Cs⁺ and to investigate the importance of Na⁺:Ca²⁺ exchange current (I_Na:ca) as opposed to l_CaL and other currents in the generation of EADs occurring later during repolarization (L-EADs). Methods and Results: Shortened Purkinje strands from dogs and guinea pigs were superfused with physiologic solution containing Cs⁺ (3.6 mM) and a low [K⁺]_o (3.0 or 2.0 mM) to induce EADs. The Vm of origin of EADs and their evolution were measured with the aid of phase plane plots of the rate of repolarization against Vm. L-EADs occurred over a wide range of Vm (?35 to ?90 mV), generally more negative in guinea pig than in dog. Elevation of [Ca²⁺]_o, from 1.8 to 3.6 mM suppressed L-EADs within a few cycles, and they returned with continued exposure. After repeated exposures to high [Ca^:2+]₀, L-EADs migrated toward less negative Vm when |Ca²⁺]₀, was reestablished to 1.8 mM in the presence of Cs⁺. Reduction of [Na⁺]₀ from 147.5 to 112.5 mM by substitution with Li⁺ or sucrose also rapidly depressed L-EADs. Conclusions: The observation of Cs⁺-induced L-EADs over a wide range of Vm indicates that there is not a single inward gated current as a common ionic mechanism for L-EADs but does not exclude an important role for I_Na:Ca, which can operate over a wide range of Vm. The rapid suppression of L-EADs with elevated [Ca²⁺]_o, and reduced [Na⁺]_o, and the migration of EADs to more positive Vm after exposures to high |Ca²⁺]_o, are compatible with I_Nc:Ca as the major charge carrier for L-EADs.     

S2, A New Phenotype in the MN Blood Group System

A new MN phenotype has been described, the type S₂ being a weak variant of S. It is apparently produced by a new MN allele, designated MS ₂.

Résumé

Un nouveau phénotype MN a été décrit, le type S₂, qui n'est qu'une variante faible de S. Il est vraisemblablement produit par un nouvel allèle MN dénommé MS₂.

Zusammenfassung

Es wird ein neuer MN-Phänotyp beschrieben. Es handelt sich um den Typ S₂, eine schwache Variante von S. Diese beruht offenbar auf einem neuen MN-Allel, welches als MS₂ bezeichnet wurde.     

Molecular Genetic Analysis of the ABO Blood Group System: 1. Weak Subgroups: A3 and B3 Alleles

We have determined the nucleotide sequences of the coding region in the last two coding exom of ABO genes (which occupy 91% of the soluble form of A¹ transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A₃ phenotype and 3 individuals had a B₃ phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A³ allele and 1 case of the B³ allele were found to contain a single-base substitution which resulted in an amino acid substitution. However, no other cases of A³ and B³ alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level.     

Molecular Genetic Analysis of the ABO Blood Group System: 1. Weak Subgroups: A3 and B3 Alleles

We have determined the nucleotide sequences of the coding region in the last two coding exom of ABO genes (which occupy 91% of the soluble form of A¹ transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A₃ phenotype and 3 individuals had a B₃ phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A³ allele and 1 case of the B³ allele were found to contain a single-base substitution which resulted in an amino acid substitution. However, no other cases of A³ and B³ alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level.     

The Blood Group Antigen Mia in Japanese

The blood group antigen Mi^a was found in one of 3,350 randomly selected Japanese. In the family of the propositus, it could be shown that the Mi ^a gene was traveling on an Ms chromosome. The simultaneous occurrence of the two rare genes Mi ^a and Di ^a in this family has established the lack of genetic relationship between them. No example of Vw + blood was found in the population sampled.

Résumé

L'antigène de groupe sanguin Mi^a a été trouvé chez un japonais sur 3350 pris au hasard. Dans la famille du propositus, il a pu ětre démontré que le gène Mi ^a se situait sur le chromosome Ms. La présence simultanée des deux gènes rares Mi ^a et Di ^a dans cette famille a permis d'établir l'absence de rapports génétiques entre eux. Aucun exemple de sang Vw+ n'a été trouvé. parmi la population étudiée.

Zusammenfassung

Unter 3350 unausgewählten Japanern fand sich ein Mi^a-positiver Proband. Die Untersuchung seiner Familie zeigte eine Koppelung des Mi ^a-Gens mit dem Ms -Chromosom. Das gleichzeitige Vorkommen der zwei seltenen Gene Mi ^a und Di ^a in dieser Familie ist zufällig, da ein genetischer Zusammenhang zwischen diesen beiden Blutfaktoren fehlte. Eine Vw+ Blutprobe wurde in dieser Untersuchungs-reihe nicht gefunden.     

Hyperinsulinaemia and Na+, K+ -ATPase activity in thyrotoxic periodic paralysis

OBJECTIVE Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na⁺, K⁺ -ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na⁺, K⁺ -ATPase activity In thyrotoxic periodic paralysis (TPP) was examined. DESIGN In all subjects a standard 75-g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours. SUBJECTS Twenty-five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyrold drugs. MEASUREMENTS Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na⁺, K⁺ -ATPase by the release of phosphate from ATP. RESULTS TPP patients showed glucose intolerance (area under the curve (AUC) 16·5 ± 4·4 (mean ± SD) In TPP compared to 12·9 ± 4·5 In controls (P < 0·01) and hyperinsulinaemia (AUC 189·6 ±100·6 vs 98·5 ±53·4, P < 0·001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na⁺, K⁺ -ATPase were significantly higher in thyrotoxic patients compared to controls and In TPP patients were even higher. Ingestion of glucose increased platelet Na⁺, K⁺ -ATPase in all groups. AUC for platelet Na⁺, K⁺ -ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 ±99·3 vs 482 ± 109·4, P < 0·01) or healthy controls (320 ± 107·3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls. CONCLUSION Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na⁺, K⁺-ATPase activity.     

Anti-A1 Leb in Serum of a Person of a Blood Group A1h

Abstract. An antibody, anti-A₁ Le^b, has been found in the serum of a person belonging to group A₁h, with complete depression of H on the red cells as well as in the saliva. It differs from earlier examples of the antibody in that it can be neutralized by A₁ nL, secretor saliva as well as O Le^b secretor saliva in addition to A₁ Le^b secretor saliva. Although the proposita secretes A substance, she only secretes Le^a substance and not Le^b substance. No such abnormalities were found in the family investigated. An interpretation of the case is given according to the classical hypothesis of ABO and Lewis system development.     

CD3+ CD8+ CD56− clonal large granular lymphocyte leukaemia and HIV infection

High-grade malignant lymphomas associated with HIV infection are usually derived from B lymphocytes. Although a broad spectrum of T-cell-derived malignancies has been described, no case of monoclonal T large granular lymphocyte leukaemia has been reported to date. We report a case of clonal T-LGL (CD3⁺, CD4⁻, CD8⁺, CD56⁻, CD57⁺) in an HIV-infected, HTLV1/2-negative individual. Large granular lymphocytes are thought to represent activated cytotoxic T lymphocytes. HIV infection, as previously reported for HTLV1/2, may represent a pathway of antigen activation and lead to clonal expansion of T large granular lymphocytes.     

Modulation of Cardiac Na+ and Ca2+ Currents by CaM and CaMKII

Sarcolemmal sodium (Na) and calcium (Ca) currents are fundamentally involved in shaping the cardiac action potential. Alterations in Na or Ca currents can change action potential characteristics and therefore might result in cardiac arrhythmias. Also, these ions contribute to excitation-contraction coupling and therefore are important in myocyte shortening and contractility of the heart. This review article summarizes how sarcolemmal Na and Ca channels are regulated with an emphasis on the novel role of Ca-dependent proteins Calmodulin (CaM) and especially Ca/CaM-dependent protein kinase II (CaMKII) to modulate sarcolemmal Na and Ca channels in the heart.