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M Lieberman

Publications and source records attributed to M Lieberman.

At least 73 records · Page 4Linked to original sources
PubMed1991

Apparent affinity of the Na/K pump for ouabain in cultured chick cardiac myocytes. Effects of Nai and Ko.

The measured apparent affinity (K0.5) of the Na/K pump for ouabain has been reported to vary over a wide range. In a previous report we found that changing Nai could alter apparent affinity by at least an order of magnitude and that the model presented predicted this variability. To increase our understanding of this variability, isolated cells or two- to three-cell clusters of cardiac myocytes from 11-d embryonic chick were used to measure the effects of Nai and Ko on the K0.5 of the Na/K pump for ouabain. Myocytes were whole-cell patch clamped and Na/K pump current (Ip) was measured in preparations exposed to a Ca-free modified Hank's solution (HBSS) that contained 1 mM Ba, 10 mM Cs, and 0.1 mM Cd. Under these conditions there are no Ko-sensitive currents other than Ip because removal of Ko in the presence of ouabain had no effect on the current-voltage (I-V) relation. The I-V relation for Ip showed that in the presence of 5.4 mM Ko and 51 mM Nai, Ip has a slight voltage dependence, decreasing approximately 30% from 0 to -130 mV. Increasing Nai in the patch pipette from 6 to 51 mM (Ko = 5.4 mM) caused Ip to increase from 0.46 +/- 0.07 (n = 5) to 1.34 +/- 0.08 microA/cm2 (n = 13) with a K0.5 for Nai of 17.4 mM and decreased the K0.5 for ouabain from 18.5 +/- 1.8 (n = 4) to 3.1 +/- 0.4 microM (n = 3). Similarly, varying Ko between 0.3 and 10.8 mM (Nai = 24 mM) increased Ip from 0.13 +/- 0.01 (n = 5) to 0.90 +/- 0.05 microA/cm2 (n = 5) with a K0.5 for Ko of 1.94 mM and increased K0.5 for ouabain from 0.56 +/- 0.14 (n = 3-6) to 10.0 +/- 1.1 microM (n = 6). All of these changes are predicted by the model presented. A qualitative explanation of these results is that Nai and Ko interact with the Na/K pump to shift the steady-state distribution of the Na/K pump molecules among the kinetic states. This shift in state distribution alters the probability that the Na/K pump will be in the conformation that binds ouabain with high affinity, thus altering the apparent affinity. In intact cells, the measured apparent affinity represents a combination of all the rate constants in the model and does not equate to simple first-order binding kinetics.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

The SCID-hu mouse: a small animal model for HIV infection and pathogenesis.

The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo. Multiple organs of the human hematolymphoid system have been successfully engrafted into the immunodeficient C.B-17 scid scid mouse, including fetal liver, thymus, lymph node, and skin. Co-implantation of human fetal liver and human fetal thymus results in long-term, multilineage human hematopoiesis in vivo. Mature human lymphocytes within the SCID-hu mouse are phenotypically and functionally normal. HIV infection of the SCID-hu mouse reflects a tropism similar to that found in humans: only human organs with CD4+ cells are infected. Viral replication can thereafter be monitored with assays that are safe, reproducible, and quantitative. Given this small animal model, it is now possible to study systematically the infective process of HIV and to address questions about the efficacy of novel antiviral compounds or vaccines in vivo.

Animals↗
PubMed1990

An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets.

mAb 1C11 was raised against the cells of retrovirus-negative, radiation-induced thymomas of C57BL/Ka mice. MAb 1C11 binds to radiation- and RadLV-induced C57BL/Ka lymphomas, to lymphomas of other mouse strains and to B-lineage tumors. The 1C11 Ag is expressed on a subpopulation of normal thymocytes that is enriched in immature cells. After fractionated x-irradiation, this percentage increases gradually during the preleukemic period, hence mAb 1C11 appears to identify a transformation-related cell surface molecule. This conclusion is supported by experiments demonstrating that flow microfluorimetry-sorted, 1C11-expressing preleukemic thymocytes progress rapidly to full neoplasia following intrathymic injection, whereas nonexpressing cells do not. Most of day-14 fetal thymocytes are as strongly positive as thymic lymphomas for the 1C11 Ag whereas Ag-activated T cell lines express moderate levels. Multiparameter flow microfluorimetry analysis shows that 1C11 is expressed predominantly on CD3-/lo thymic blast cells of three phenotypically defined subsets: CD4-8-, CD4-8+, and CD4+8+, all of which contain thymic progenitors. By immunohistochemical staining, the Ag is also found in association with epithelial cells on a variety of normal, nonlymphoid tissue, but is not detectable on heart tissue. The 1C11 antibody immunoprecipitates a disulfide-linked heterodimeric protein of 85/37 kDa and the antigenic determinant is located on the H chain of the molecule. When analyzed by SDS-PAGE under nonreducing conditions, the molecule exists as a 130-kDa protein. Enzymatic digestion of the heterodimer indicates that the H chain, but not the L chain, has at least three N-linked glycosylation sites. We propose that this novel cell surface glycoprotein may be associated with processes of differentiation and lymphomagenesis.

Animals↗
PubMed1990

Israeli cephalometric standards compared to Downs and Steiner analyses.

A sample consisting of 40 young Israeli adolescents, 18 males and 22 females, was examined cephalometrically. The subjects were classified as Angle Class I, with less than three millimeters of crowding and an orthognathic profile. Steiner and Downs analyses were performed for all subjects. Each analysis was done both manually and by using a computer. The computerized results were processed and subjected to statistical tests. The Israeli sample is characterized by a convex profile, a retrusive mandible, a steep mandibular plane and protrusive incisors.

Adolescent↗
PubMed1990

Na/K pump current in aggregates of cultured chick cardiac myocytes.

Spontaneously beating aggregates of cultured embryonic chick cardiac myocytes, maintained at 37 degrees C, were voltage clamped using a single microelectrode switching clamp to measure the current generated by the Na/K pump (Ip). In resting, steady-state preparations an ouabain-sensitive current of 0.46 +/- 0.03 microA/cm2 (n = 22) was identified. This current was not affected by 1 mM Ba, which was used to reduce inward rectifier current (IK1) and linearize the current-voltage relationship. When K-free solution was used to block Ip, subsequent addition of Ko reactivated the Na/K pump, generating an outward reactivation current that was also ouabain sensitive. The reactivation current magnitude was a saturating function of Ko with a Hill coefficient of 1.7 and K0.5 of 1.9 mM in the presence of 144 mM Nao. The reactivation current was increased in magnitude when Nai was increased by lengthening the period of time that the preparation was exposed to K-free solution prior to reactivation. When Nai was raised by 3 microM monensin, steady-state Ip was increased more than threefold above the resting value to 1.74 +/- 0.09 microA/cm2 (n = 11). From these measurements and other published data we calculate that in a resting myocyte: (a) the steady-state Ip should hyperpolarize the membrane by 6.5 mV, (b) the turnover rate of the Na/K pump is 29 s-1, and (c) the Na influx is 14.3 pmol/cm2.s. We conclude that in cultured embryonic chick cardiac myocytes, the Na/K pump generates a measurable current which, under certain conditions, can be isolated from other membrane currents and has properties similar to those reported for adult cardiac cells.

Animals↗
PubMed1990

Intracellular sodium affects ouabain interaction with the Na/K pump in cultured chick cardiac myocytes.

Whether a given dose of ouabain will produce inotropic or toxic effects depends on factors that affect the apparent affinity (K0.5) of the Na/K pump for ouabain. To accurately resolve these factors, especially the effect of intracellular Na concentration (Nai), we have applied three complementary techniques for measuring the K0.5 for ouabain in cultured embryonic chick cardiac myocytes. Under control conditions with 5.4 mM Ko, the value of the K0.5 for ouabain was 20.6 +/- 1.2, 12.3 +/- 1.7, and 6.6 +/- 0.4 microM, measured by voltage-clamp, Na-selective microelectrode, and equilibrium [3H]ouabain-binding techniques, respectively. A significant difference in the three techniques was the time of exposure to ouabain (30 s-30 min). Since increased duration of exposure to ouabain would increase Nai, monensin was used to raise Nai to investigate what effect Nai might have on the apparent affinity of block by ouabain. Monensin enhanced the rise in Na content induced by 1 microM ouabain. In the presence of 1 microM [3H]ouabain, total binding was found to be a saturating function of Na content. Using the voltage-clamp method, we found that the value of the K0.5 for ouabain was lowered by nearly an order of magnitude in the presence of 3 microM monensin to 2.4 +/- 0.2 microM and the magnitude of the Na/K pump current was increased about threefold. Modeling the Na/K pump as a cyclic sequence of states with a single state having high affinity for ouabain shows that changes in Nai alone are sufficient to cause a 10-fold change in K0.5. These results suggest that Nai reduces the value of the apparent affinity of the Na/K pump for ouabain in 5.4 mM Ko by increasing its turnover rate, thus increasing the availability of the conformation of the Na/K pump that binds ouabain with high affinity.

Animals↗
PubMed1990

Intracellular pH regulation in cultured embryonic chick heart cells. Na(+)-dependent Cl-/HCO3- exchange.

The contribution of Cl-/HCO3- exchange to intracellular pH (pHi) regulation in cultured chick heart cells was evaluated using ion-selective microelectrodes to monitor pHi, Na+ (aiNa), and Cl- (aiCl) activity. In (HCO3- + CO2)-buffered solution steady-state pHi was 7.12. Removing (HCO3- + CO2) buffer caused a SITS (0.1 mM)-sensitive alkalinization and countergradient increase in aiCl along with a transient DIDS-sensitive countergradient decrease in aiNa. SITS had no effect on the rate of pHi recovery from alkalinization. When (HCO3- + CO2) was reintroduced the cells rapidly acidified, aiNa increased, aiCl decreased, and pHi recovered. The decrease in aiCl and the pHi recovery were SITS sensitive. Cells exposed to 10 mM NH4Cl became transiently alkaline concomitant with an increase in aiCl and a decrease in aiNa. The intracellular acidification induced by NH4Cl removal was accompanied by a decrease in aiCl and an increase in aiNa that led to the recovery of pHi. In the presence of (HCO3- + CO2), addition of either amiloride (1 mM) or DIDS (1 mM) partially reduced pHi recovery, whereas application of amiloride plus DIDS completely inhibited the pHi recovery and the decrease in aiCl. Therefore, after an acid load pHi recovery is HCO3o- and Nao- dependent and DIDS sensitive (but not Ca2+o dependent). Furthermore, SITS inhibition of Na(+)-dependent Cl-/HCO3- exchange caused an increase in aiCl and a decrease in the 36Cl efflux rate constant and pHi. In (HCO3- + CO2)-free solution, amiloride completely blocked the pHi recovery from acidification that was induced by removal of NH4Cl. Thus, both Na+/H+ and Na(+)-dependent Cl-/HCO3- exchange are involved in pHi regulation from acidification. When the cells became alkaline upon removal of (HCO3- + CO2), a SITS-sensitive increase in pHi and aiCl was accompanied by a decrease of aiNa, suggesting that the HCO3- efflux, which can attenuate initial alkalinization, is via a Na(+)-dependent Cl-/HCO3- exchange. However, the mechanism involved in pHi regulation from alkalinization is yet to be established. In conclusion, in cultured chick heart cells the Na(+)-dependent Cl-/HCO3- exchange regulates pHi response to acidification and is involved in the steady-state maintenance of pHi.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

Craniographic examination of the condylar angle and the maxillary incisal palatal angle in Bedouin skulls.

Craniographic registrations were used to examine 25 Bedouin skulls. The skulls were divided into three groups according to the anatomy and position of the maxillary incisor. Correlations between condylar guidance angle, maxillary incisal palatal angle, attrition, and flaring were investigated. No correlation was found between the condylar and maxillary incisal palatal angles. In the presence of severe attrition and/or flaring, the maxillary incisal palatal angle was reduced and mild reduction was also found in the condylar guidance angle. A strong correlation was found between the level of attrition and flaring.

Cephalometry↗
PubMed1989

Interaction of (Na + K + 2 Cl) cotransport and the Na/K pump in cultured chick cardiac myocytes.

We have recently reported the presence of an electroneutral (Na + K + 2 Cl) cotransport mechanism that is bumetanide-sensitive and maintains Cli above its electrochemical equilibrium in cultured chick heart cells. In steady state, (Na + K + 2 Cl) cotransport is inwardly directed and so contributes to the Na influx that must be counterbalanced by the activity of the Na/K pump to maintain Nai homeostasis. We now show that manipulating (Na + K + 2 Cl) cotransport by restoring Clo to a Cl-free solution indirectly influences Na/K pump activity because the bumetanide-sensitive recovery of aiNa to its control level and the accompanying hyperpolarization could be blocked by 10(-4)M ouabain. In another protocol, when the Na/K pump was reactivated by restoring Ko (from 0.5 mM to 5.4 mM) and removing ouabain, the recovery of aNa was attenuated by 10(-4)M bumetanide. The relatively slow rate of ouabain dissociation coupled with the activation of Na influx by (Na + K + 2 Cl) cotransport clearly establishes the interaction of these transport mechanisms in regulating Nai. Although (Na + K + 2 Cl) cotransport is electroneutral, secondary consequences of its activity can indirectly affect the electrophysiological properties of cardiac cells.

Animals↗
PubMed1989

Visual field defects detected in patients with Gilles de la Tourette syndrome: preliminary report.

The presence of visual field anomalies was measured using Goldmann kinetic perimetry in twelve patients, age 7 to 39 with Gilles de la Tourette syndrome. Refraction to the cupola was carefully controlled. The visual acuity of the group was good to excellent. Visual field alterations were prechiasmal, generally non-symmetric, and best described as arcuate defects, steps, baring of the blind spot and enlargement of the blind spot. Central fields were most commonly affected, i.e., I/2e to I/1B isopters. There was no evidence of glaucoma in any of the patients although two patients exhibited keratoconus and another one manifested moderate to high astigmatism. Visual involvement other than ocular and lid tics have not been reported in Tourette syndrome. This research represents clear evidence of additional physical components in this condition. Automated visual field measurements are not recommended in this population because of the presence of non-predictable tic and vocal behavior (both may result in head/eye movements). Suppression of tic behavior can be very fatiguing. (Eight of twelve of the patients reported exhibited signs of marked fatigue during testing.)

Adolescent↗
PubMed1989

Monitoring cytosolic free magnesium in cultured chicken heart cells by use of the fluorescent indicator Furaptra.

Cytosolic free magnesium concentration [Mg2+]i and its regulation were studied in cultured embryonic chicken heart cells by use of the fluorescent indicator 2-[2-(5-carboxy)oxazole]-5-hydroxy-6-aminobenzofuran-N,N,O-triacet ic acid (Furaptra). The intracellular location of Furaptra was confirmed by its complete release from cells upon addition of saponin. The basal [Mg2+]i, which averaged 0.48 +/- 0.03 mM (n = 31), increased 3-fold on perfusion with sodium-free solution. This increase could not simply be attributed to intracellular sodium-extracellular magnesium exchange because a similar increase in [Mg2+]i occurred with magnesium-free, sodium-free perfusion. Furthermore, the increase in [Mg2+]i was largely attenuated when calcium was removed from the sodium-free perfusate. Thus, a substantial part of the increase in [Mg2+]i that occurs upon sodium-free perfusion is dependent on an increase in cytosolic free calcium (intracellular sodium-extracellular calcium exchange). The data suggest that [Mg2+]i is altered by calcium, most likely due to a competition for intracellular binding sites.

Animals↗
PubMed1989

Intraosseous drug administration: successful resuscitation from asystole.

The case of a seven-month-old infant presenting in full cardiac arrest and resuscitated utilizing a right tibial intraosseous access line is presented. The child who presented in asystole appears to be the first reported case of the successful use of the intraosseous route as the sole source of drug administration. Flow time from tibia to clinical cardiac response was noted to be less than three minutes, similar to those in animal arrest models.

Arrhythmias, Cardiac↗
PubMed1989

Cytosolic free magnesium concentration in cultured chick heart cells.

Cytosolic free magnesium (Mgi) was measured in embryonic chick heart cells loaded with one of two newly developed 19F nuclear magnetic reasonance (NMR)-sensitive magnesium chelators, 4-methyl,5-fluoro-2-aminophenol-N,N,O-triacetate (MF-APTRA) and 5-fluoro-2-aminophenol-N,N,O-triacetate (5F-APTRA). The cells, embedded in strands of collagen, were superfused at a rate that allowed for solution changes in 2 min. In this preparation 19F- and 31P-NMR spectra were stable for at least 3.5 h. Because Na-coupled Mg countertransport may be a possible mechanism of Mg transport, in some experiments extracellular Na was reduced to 1 mM (choline substituted). This manipulation caused a 2.5-fold increase in Mgi from the basal level of 0.56 mM. A significant proportion of this increase in Mgi could be secondary to an increase in Cai that occurs with low extracellular Na (Nao) perfusion (Nai-Cao exchange). Perfusing cells with nominally Ca-free, 1 mM Na salt solution substantially attenuated the increase in Mgi that occurred with Ca present (1.25 mM) in the low Na (1 mM) solution. Furthermore, perfusion with 1 mM Na, Mg-free salt solution caused a 1.5-fold increase in Mgi, which cannot be attributable to Nai-Mgo exchange. Therefore attempts to describe the regulation of Mgi in heart cells must differentiate between the effects of Nai-Mgo exchange and competition for binding sites that are secondary to stimulation of ion gradient-coupled mechanisms.

Aminophenols↗