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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 397 records · Page 22Linked to original sources
PubMed1978

The action of adrenaline on pace-maker activity in cardiac Purkinje fibres.

1. Adrenaline is known to shift the activation curve for iK2 (s infinite curve) in a positive direction on the voltage axis. This should cause an increase in the slope of diastolic depolarization, but cannot account for the experimentally observed increase in the maximum diastolic potential (MDP). 2. On application of adrenaline, in voltage clamp studies on short sheep cardiac Purkinje fibres there is a consistent 5-15 mV negative shift of the reversal potential for the pace-maker current, iK2. This shift is not reversed on application of the beta-blockers sotalol or propranolol, or on washout for up to one hour. 3. A computer simulation, including this effect of adrenaline, shows that it can shift the maximum diastolic potential in the hyperpolarizing or depolarizing direction depending on the initial value of [K+]o. In both cases it will add to the increase in rate caused by the positive shift of the activation curve for iK2 (the s infinite shift). 4. Studies of the effects of adrenaline on the MDP and rate in long sheep Purkinje fibres show a slower reversibility of the MDP than the rate, consistent with a slower reversal of the shift in the iK2 reversal potential than the shift in s infinite. 5. Possible mechanisms of the shift in reversal potential are discussed with respect to K+ balance in the intercellular clefts of the Purkinje fibre, including a a stimulation of the Na+- K+ pump. The possible sources of voltage clamp artifact are also discussed.

Action Potentials↗
PubMed1978

The interactions of protons, calcium and potassium ions on cardiac Purkinje fibres.

1. In sheep Purkinje fibres, acidosis shifts the steady-state current-voltage relation in an inward direction over a wide range of negative potentials. The reversal potential for iK2 is shifted in a positive direction. These changes are consistent with K+ accumulation in the extracellular spaces of the Purkinje fibre. 2. These effects of acidosis are completely prevented by increasing [K]0 from the normal range (2.7--5.4 mM) to 10.8 mM. 3. Increasing [Ca]0 from 2 to 6 mM also produces an inward shift in the steady-state current-voltage relation and a positive shift of the iK2 reversal potential. 4. In 10.8 mM-[K]0 these effects are absent even when [Ca]0 is increased to 20 mM. 5. One possible explanation is that K+ ions may protect the Na pump from inhibition by protons and Ca2+ ions. Alternative explanations are also discussed.

Animals↗
PubMed1977

Histocompatibility determinants in Israeli Jewish patients with multiple sclerosis.

The distribution of 24 HLA antigens of the A and B loci was investigated in 197 Israeli Jewish patients with multiple sclerosis (MS) from various Jewish ethnic origins including central and eastern Europe, countries bordering the Mediterranean, the Middle East and from native-born Israelis. The results were compared with the HLA antigen frequencies in a control sample of 455 unrelated individuals representing the general Jewish population. The frequency of HLA-Bw40 among all MS patients (15%) was significantly greater (P less than 0.001) than among the controls (7%). In contrast to the findings in MS patients from other populations, there was no increased frequency of A3 and B7 and Dw2 was present in only one out of 28 patients. The study showed a similar distribution of HLA-A and -B locus antigens, especially of Bw40, in Jews of diverse ethnic origins represented in the control group.

Epitopes↗
PubMed1977

Thymic hormone (THF) therapy in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella.

Four children with lymphoproliferative malignant disease, two with acute lymphocytic leukemia in remission and two with Hodgkin's disease, were treated with a Thymic Hormone, THF, for disseminated varicella infecition. It is suggested that THF increased significantly the number of peripheral blood lymphocytes and T-rosette forming lymphocytes in 3 out of 4 children, who developed the varicella at the time of impaired cellular immunity. On the other hand, in the fourth child, with Hodgkin's disease, who had a normal number of T-rosettes, a decreased absolute number of lymphocytes as well as T-rosettes was observed over a course of 14 days THF treatment, although the percent of T-cells has not changed significantly. All of the four children recovered, including the child who was at high risk, with a marked lymphopenia, severe bilateral pneumonitis, hepatitis secondary infected skin lesions and psudomonas sepsis. It is indicated that THF therapy may restore the depressed cellular immunity in immunosuppressed children with malignant disease, and has its value as a supportive immunotherapy in life-threatening disseminated varicella infection.

Chickenpox↗
PubMed1976

Cellular basis for the T wave of the electrocardiogram.

Differences in action potential duration in different regions of the mammalian ventricle are not systematically present when quiescent tissue is first stimulated, but develop rapidly during repetitive activity. The effects of ouabain and temperature suggest the involvement of the Na+-K+ exchange pump.

Action Potentials↗
PubMed1976

The effects of potassium and temperature on the pace-maker current, iK2, in Purkinje fibres.

1. The reversal potential for the pace-maker K current, iK2, was measured in sheep cardiac Purkinje fibres at extracellular K concentrations, [K]O, between 2-7 and 8 mM. The reversal potentials were found to be significantly more negative than the values predicted using the Nernst equation for any reasonable value of intracellular K+ concentration or activity. 2. It is suggested that this discrepancy may be explained by postulating that the extracellular K+ concentration [K]e in the cleft spaces between cells is smaller than [K]o as a result of ion pumping and restricted diffusion from the bulk extracellular medium. 3. In conformity with this hypothesis, it was shown that the value of [K]e may be further reduced by hyperpolarizing pulses, presumably as a consequence of K+ depletion during the passage of inward current. 4. The influence of temperature on the kinetics of the gating mechanism, s, controlling iK2 was investigated. The Q10 for the time constant, pis, of current change following voltage clamp steps was found to be about 17. This corresponds to an apparent activation enthalpy of 50 kcal/mole. 5. The Q10 of the maximum amplitude iotaK2, was found to 1-3. 6. The activation curve, s infinity (Em), spread slightly to more negative potentials by cooling from 37 to 30 degrees C and the curve became less steep. 7. There is a large decrease in the inward background current on cooling, as estimated by measuring the net membrane current when iK is presumed to be zero, i.e. at the reversal potential for iK2.

Action Potentials↗
PubMed1976

An analysis of the actions of low concentrations of ouabain on membrane currents in Purkinje fibres.

1. The influence of low concentrations (5 X 10(-8) to 5 X 10(-7) M) of ouabain on the K gradient in sheep cardiac Purkinje fibres was observed by measuring changes in the reversal potential for a K specific current iK2, and by measuring total steady-state current-voltage relations. 2. Provided that the bathing solution K concentration, [K]o was not too low, these doses of ouabain were often observed to increase the K gradient, i.e. the reversal potential was shifted in a negative direction. 3. The change in the reversal potential and in the current-voltage relation could be mimicked by reducing the value of [K]o in the absence of ouabain. It is therefore suggested that ouabain may stimulate the Na+-K+ exchange pump and so reduce the K concentration, [K]e, in the clefts of the preparation. 4. At sufficiently low values of [K]o, a dose of ouabain that was stimulatory may become inhibitory. The reversal potential for iK2 then shifts in a positive direction. 5. During either stimulation or inhibition, the speed of change of reversal potential is consistent with a change in [K]e, which may change fairly rapidly. It is not possible to account for the results solely by changes in intracellular concentration, [K]i. 6. Low concentrations of ouabain were found to have no effect on the activation curve, s infinity (Em), controlling iK2. It is concluded that the changes in iK2 are solely attributable to changes in reversal potential. 7. Since net stimulation of the Na+-K+ exchange pump was observed to occur at doses of ouabain that exert a strong positive inotropic action on Purkinje fibres (Blood, 1975), it is not likely that the inotropic action is causally related to net pump inhibition.

Animals↗
PubMed1976

The effects of pH changes on the frequency of miniature end-plate potentials at the frog neuromuscular junction.

As reported by Landau & Nachshen (1975), a decrease in extracellular pH at the frog neuromuscular junction leads to an increase in min.e.p.p. frequency. 2. Decreasing the extracellular pH still increases the min.e.p.p. frequency when the bathing Ringer contains 10 mM-Ca2+, in place of the usual 2-5 mM. At the mammalian neuromuscular junction, the elevated Ca2+ blocks the effect of the pH change on the min.e.p.p. frequency (Hubbard, Jones & Landau, 1968). 3. In Cl--free solution (isethionate or methylsulphate substitution) min.e.p.p. frequency is no longer a monotonic function of decreasing pH. Instead there is an optimum pH for spontaneous release between pH 6-6 and 8-6. 4. This suggests that in Cl- containing Ringer min.e.p.p. frequency increases with increasing extracellular acidity because there is a change in the PCl of the nerve terminal leading to a depolarization. In agreement with this idea,in low Ca2+ Ringer, acid pH has little effect on the min.e.p.p. frequency. 5. Decreasing the intracellular pH by raising PCO2 produces substantial increases in the min.e.p.p. frequency. The effects are much greater than the effects of equal changes of H+ in the extracellular solution. 6. Possible explanations for the effects of increased PCO2 are discussed. Although release of Ca2+ from mitochondria or other unknown effects of intracellular pH change or molecular CO2 are possible, the results do give some support to the hypothesis that an important step in transmitter release involves an electrostatic repulsion between fixed membrane surface charges on the transmitter containing vesicles and the inner face of the nerve terminal. The surface charge density would be decreased by a lower pH in the axoplasm, and this would increase the rate of spontaneous transmitter release, in agreement with the observations.

Animals↗