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Biomedical subjects

M Lieberman

Publications and source records attributed to M Lieberman.

At least 199 records · Page 11Linked to original sources

Developmental aspects of potassium flux and permeability of the embryonic chick heart.

1. The rate coefficient of 42K efflux, the transmembrane potential, the intracellular concentrations of Na and K and the volume/surface area have been measured in embryonic chick hearts of different ages. 2. With respect to age, the rate coefficient for 42K efflux was minimal for preparations from 6-8 day old embryos, and distinctly higher values were obtained for the hearts of 3-5 and 18-20 days. With respect to the effect of external K concentration (Ko), all age groups showed a five- to sevenfold increase in rate coefficient between 2-5 and 140 mM-Ko. The effect of Ko was found to be indepedent of extracellular Na, except in the 18-20 day hearts bathed in K-free solution. 3. Intracellular concentrations of K and Na were found to decrease, membrane potential to increase with age. The volume/surface area measured by stereologic and morphometric techniques did not change with age. 4. The permeability coefficient for K (PK), calculated from the absolute K flux and the measured membrane potentials, was fairly constant for a given age between 2-5 and 20 mM-Ko. In K-free solution, PK was markedly reduced (factor 4). At a given Ko, PK increased twofold between 6-8 and 18-20 days while PNa remained relatively constant.

Animals↗

Increase of potassium flux by valinomycin in embryonic chick heart.

The effect of different concentrations of the antibiotic valinomycin, was determined on 42K efflux and Na, K content of embryonic chick hearts. Valinomycin produces an increase of K efflux which is progressive in time and markedly dependent on the concentration of external K (0-5 mM) and valinomycin (10(-8) to 10(-5) M). The changes in K efflux is not due to a reversal of the Na-K pump mechanism, secondary to ATP depletion: i) the increase of K efflux by valinomycin persists in the absence of external Na ions. ii) analysis of Na and K content and 42K influx measurements with and without valinomycin indicate that active K influx is not inhibited in a solution containing 0.5 mM K and only slightly decreased in a solution containing 5 mM K. Valinomycin, acting as a K carrier, presumably increases K conductance of the cell membrane resulting in a rise in K efflux.

Animals↗

A synthetic strand of cardiac muscle: its passive electrical properties.

The passive electrical properties of synthetic strands of cardiac muscle, grown in tissue culture, were studied using two intracellular microelectrodes: one to inject a rectangular pulse of current and the other to record the resultant displacement of membrane potential at various distances from the current source. In all preparations, the potential displacement, instead of approaching a steady value as would be expected for a cell with constant electrical properties, increased slowly with time throughout the current step. In such circumstances, the specific electrical constants for the membrane and cytoplasm must not be obtained by applying the usual methods, which are based on the analytical solution of the partial differential equation describing a one-dimensional cell with constant electrical properties. A satisfactory fit of the potential waveforms was, however, obtained with numerical solutions of a modified form of this equation in which the membrane resistance increased linearly with time. Best fits of the waveforms from 12 preparations gave the following values for the membrane resistance times unit length, membrane capacitance per unit length, and for the myoplasmic resistance: 1.22 plus or minus 0.13 x 10-5 omegacm, 0.224 plus or minus 0.023 uF with cm-minus 1, and 1.37 plus or minus 0.13 x 10-7 omegacm-minus 1, respectively. The value of membrane capacitance per unit length was close to that obtained from the time constant of the foot of the action potential and was in keeping with the generally satisfactory fit of the recorded waveforms with solutions of the cable equation in which the membrane impedance is that of a single capacitor and resistor in parallel. The area of membrane per unit length and the cross-sectional area of myoplasm at any given length of the preparation were determined from light and composite electron micrographs, and these were used to calculate the following values for the specific electrical membrane resistance, membrane capacitance, and the resistivity of the cytoplasm: 20.5 plus or minus 3.0 x 10-3 omegacm-2, l.54 plus or minus 0.24 uFWITHcm-minus 2, and 180 plus or minus 34 omegacm, respectively.

Action Potentials↗

Ethylene-forming Systems in Etiolated Pea Seedling and Apple Tissue.

Auxin-induced ethylene formation in etiolated pea (Pisum sativum L. var. Alaska) stem segments was inhibited by inhibitors of RNA and protein synthesis. Kinetics of the inhibitions is described for actinomycin D, cordycepin, alpha-amanitin, and cycloheximide. alpha-Amanitin was the most potent and fast-acting inhibitor, when added before induction or 6 hours after induction of the ethylene-forming system. The ethylene-forming system of postclimacteric apple (Malus sylvestris L.) tissue, which is already massively induced, was not further stimulated by auxin. Ethylene production in apples was inhibited least by alpha-amanitin and most by actinomycin D. The relative responses of the ethylene system in apples to RNA inhibitors were different from the ethylene system of pea stems. However, the protein synthesis inhibitor, cycloheximide, appeared to act equally in both tissue systems. The effect of cycloheximide on ethylene production in postclimacteric apple tissue, already producing large quantities of ethylene, suggests a dynamic regulating system for the synthesis and degradation of the ethylene-forming system.

Journal Article↗

Focal infection and transformation in situ of thymus cell subclasses by a thymotropic murine leukemia virus.

Studies on the maturational lineages of thymic lymphocytes have revealed several subclasses which are distinguishable on the basis of cell size, topographic distribution within the thymus, DNA synthetic and mitotic activity, migratory behavior, and other properties. Strain C57BL/Ka mice were inoculated with radiation leukemia virus at different concentrations, and tissues were removed at defined intervals. Sequential sections were analyzed for virus-specific cytoplasmic antigen expression, for morphological evidence of neoplastic transformation, and for alkaline phosphatase activity. The first detectable sign of MuLV infection was the focal appearance of cytoplasmic viral antigens in cells of the outer thymic cortex, followed by coalescence of such foci and, several weeks later, by the appearance of morphologically transformed and alkaline phosphatase-positive cells, again often focally distributed in the outer thymic cortex. These observations strongly suggest that the large, mitotically active cells of the outer thymic cortex are the principal source of target cells for both productive infection and subsequent lymphoma induction by the virus.

Alkaline Phosphatase↗

Ethane evolution: a new index of lipid peroxidation.

Homogenates of mouse liver and brain at 37 degrees C spontaneously formed lipid peroxides and simultaneously evolved ethane. alpha-Tocopherol, a lipid antioxidant, blocked ethane formation. When mice were injected with carbon tetrachloride (a liquid prooxidant for liver), the animals produced ethane. Ethane evolution in vivo was stimulated by prior administration of phenobarbital and it was diminished by prior injection of alpha-tocopherol. These data suggest that ethane production may be a useful index of lipid peroxidation in tissue homogenates and in intact animals.

Aldehydes↗

Selective thymic localization of murine leukemia virus-related antigens in C57BL-Ka mice after inoculation with radiation virus.

The tissue distribution and extent of virus-specific antigen expression were studied by immunofluorescence as a function of time and of lymphoma development in adult C57BL/Ka (Fv-1(b)) mice after intravenous injection of radiation leukemia virus, a B-tropic murine leukemia virus. Viral antigens were detected earlier in the thymus (1 week) than in the bone marrow, spleen, or lymph nodes (2-3 weeks). Despite an initial virus-induced thymic involution, the percentage of immunofluorescence-positive cells in the thymus rapidly increased thereafter to 65-80%, at which level it remained until 9 weeks, at which time increases in size and weight, histological changes, and an increased number of blastoid cells indicated the onset of lymphoma development in the thymus. In contrast, the percentage of immunofluorescence-positive cells in the bone marrow, spleen, and nodes remained low, and gradually decreased to zero within 8 weeks after thymectomy. The selective thymic localization of antigens induced by radiation leukemia virus in C57BL/Ka mice is in striking contrast to the previously reported ubiquitous tissue distribution of the Gross-AKR virus, an N-tropic virus, in its natural host, the Fv-1(n), AKR strain with a high incidence of leukemia.

Animals↗

Effects of ethylene and gibberellic Acid on cellular growth and development in apical and subapical regions of etiolated pea seedling.

Subhook swelling of 4-day-old etiolated pea seedlings (var. Alaska), caused by 0.5 microliter per liter ethylene, was prevented by preincubation and continued growth in 0.1 mm gibberellic acid (GA). The subhook region exhibited normal elongation and cell size and volume. However, inhibition of elongation and cessation of cell division caused by 0.5 microliter per liter ethylene in the apical hook region of the etiolated pea stem were not overcome by GA. Most of the arrested cells were in G(2). These data suggest a possible interaction of GA and ethylene in cell enlargement in the subhook region of the etiolated pea seedlings. They also suggest a different mode of action by ethylene in the apical hook region where the ethylene effect was not counteracted by GA.

Journal Article↗

Low conduction in cardiac muscle. Biophysical model.

Mechanisms of slow conduction in cardiac muscle are categorized and the most likely identified. Propagating action potentials were obtained experimentally from a synthetically grown strand of cardiac muscle (around 50 mum by 30 mm) and theoretically from a one-dimensional cable model that incorporated varying axial resistance and membrane properties along its length. Action potentials propagated at about 0.3 m/s, but in some synthetic strands there were regions (approximately 100 mum in length) where the velocity decreased to 0.002 m/s. The electrophysiological behavior associated with this slow conduction was similar to that associated with slow conduction in naturally occurring cardiac muscle (notches, Wenckebach phenomena, and block). Theoretically, reasonable changes in specific membrane capacitance, membrane activity, and various changes in geometry were insufficient to account for the observed slow conduction velocities. Conduction velocities as low as 0.009 m/s, however, could be obtained by increasing the resistance (r(i)) of connections between the cells in the cable; velocities as low as 0.0005 m/s could be obtained by a further increase in r(i) made possible by a reduction in membrane activity by one-fourth, which in itself decreased conduction velocity by only a factor of 1/1.4. As a result of these findings, several of the mechanisms that have been postulated, previously, are shown to be incapable of accounting for delays such as those which occur in the synthetic strand as well as in the atrioventricular (VA) node.

Action Potentials↗

Continuous propagation of radiation leukemia virus on a C57BL mouse-embryo fibroblast line, with attenuation of leukemogenic activity.

The radiation leukemia virus (RadLV), a murine leukemia virus derived from thymic lymphomas induced by x-irradiation in strain C57BL/Ka mice, has been successfully propagated in sustained high titer in vitro in a newly established line, BL-5, of C57BL/Ka mouse-embryo fibroblasts. In addition, the production of endogenous virus, presumed to be RadLV, has been induced and sustained through multiple serial passages after treatment of BL-5 cell cultures with 5-bromodeoxyuridine. The chronically RadLV-infected subline, designated BL-5 (RadLV), sheds virus into the supernatant culture fluids that is biologically active in vitro in the XC cell plaque assay, in interference assays for focus-formation by murine sarcoma virus, and in the intracellular induction of group-specific antigens detectable by immunofluorescence, but is apparently devoid of leukemogenic activity after intrathymic inoculation into neonatal or immunosuppressed C57BL/Ka mice. Although BL-5 cells exhibited morphological alterations suggestive of transformation in vitro and gave rise to fibrosarcomatous ascites tumors after intraperitoneal inoculation with C57BL/Ka mice, the chronically infected BL-5(RadLV) cells remained normal in morphology and failed to yield fibrosarcomas in vivo.

Animals↗