Search PubMed⌕ Search

Biomedical subjects

A Sherman

Publications and source records attributed to A Sherman.

At least 55 records · Page 3Linked to original sources
PubMed1995

A role for calcium release-activated current (CRAC) in cholinergic modulation of electrical activity in pancreatic beta-cells.

S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. The ability of this single hypothesis, that CRAC is present in beta-cells, to explain so many phenomena motivates a more complete characterization of this current.

Acetylcholine↗
PubMed1995

Critical care management of the heart failure patient in the home.

Deaths due to cardiovascular disease have decreased as the result of advances in medical therapeutics, advanced technology, and health promotion activities. Increased survival has resulted in a significant rise in the number of patients with chronic, refractory heart failure requiring intensive medical management and follow-up. Home care nurses trained in advanced cardiac assessment can decrease the cost of care by providing advanced technologic care in the home. Home dobutamine infusions are one example of provision of high-technology services in the home. With careful patient selection, adequate preparation, and home monitoring, dobutamine infusions can be provided in the home to improve the functional status and quality of life of patients with severe heart failure.

Aged↗
PubMed1994

Phase independent resetting in relaxation and bursting oscillators.

Relaxation oscillators that depend on one slow variable, such as the Fitzhugh-Nagumo oscillator, reset in a phase-dependent manner. A complete oscillation can be divided into two parts, the "plateau" and "trough", and a prematurely induced plateau or trough is significantly shorter than normal. The class of square-wave bursting oscillators can be viewed as relaxation oscillators with rapid spikes during the plateau, and reset similarly when modeled with one slow variable. However, it has been reported that a physiological bursting oscillator, the membrane potential of the pancreatic beta-cell, resets in a phase-independent manner, such that a prematurely induced plateau/trough has normal length. A possible model for such an oscillator requires two slow variables, one to control the length of the plateau and the other the length of the trough. Here, we explore the geometric solution structure of two such models, which exhibit the desired resetting. One is a generalization of the Fitzhugh-Nagumo equations, and the other is a bursting oscillator using known beta-cell electrical currents with an additional hypothetical slow outward current.

Biological Clocks↗
PubMed1994

Anti-phase, asymmetric and aperiodic oscillations in excitable cells--I. Coupled bursters.

I seek to explain phenomena observed in simulations of populations of gap junction-coupled bursting cells by studying the dynamics of identical pairs. I use a simplified model for pancreatic beta-cells and decompose the system into fast (spike-generating) and slow subsystems to show how bifurcations of the fast subsystem affect bursting behavior. When coupling is weak, the spikes are not in phase but rather are anti-phase, asymmetric or quasi-periodic. These solutions all support bursting with smaller amplitude spikes than the in-phase case, leading to increased burst period. A key geometrical feature underlying this is that the in-phase periodic solution branch terminates in a homoclinic orbit. The same mechanism also provides a model for bursting as an emergent property of populations; cells which are not intrinsic bursters can burst when coupled. This phenomenon is enhanced when symmetry is broken by making the cells differ in a parameter.

Biological Clocks↗
PubMed1994

Alcohol and drug abuse treatment of homeless persons: results from the NIAAA Community Demonstration Program.

In a national evaluation, we assessed the implementation and outcomes of a multisite demonstration program for homeless persons with alcohol and other drug problems. We developed comprehensive case studies from data on client characteristics, utilization of services, implementation of interventions, and community systems of care at nine project sites. Client-level outcome data were analyzed to estimate the effectiveness of the interventions in a subset of projects with experimental or quasi-experimental evaluation designs. After controlling for baseline predictors, treatment clients in the majority of sites were significantly more likely than comparison clients to report improvement on one or more outcome dimensions. On alcohol use, for example, under conservative assumptions the average treatment client was drinking less at follow-up than were 57 percent of comparison clients. Analyses of predictor-by-treatment interactions suggested that clients with fewer problems benefited most from the interventions. The implementation analysis yielded a number of lessons for policymakers and program planners.

Adult↗
PubMed1993

Neuroleptic effects on serine and glycine metabolism.

The concentrations of serine and glycine and the activity of serine hydroxymethyltransferase (SHMT) are abnormal in plasma and brains of schizophrenics. To further elucidate the possible role of neuroleptics on the metabolism of serine and glycine and the activity of SHMT, we studied the plasma of controls and schizophrenics on and off medications, the brains of rats treated with haloperidol, and the activity of purified SHMT in the presence or absence of haloperidol and fluphenazine. Plasmas of neuroleptic-treated schizophrenics had nonsignificantly lower concentrations of serine and glycine. Brains of haloperidol-treated rats had significantly lower concentrations of serine and glycine. At therapeutic levels haloperidol and fluphenazine did not inhibit the activity of purified SHMT. The serine-glycine lowering effects of haloperidol and neuroleptics are discussed in the context of a possible neuroprotective potential of neuroleptics in schizophrenia.

Adult↗
PubMed1993

nir1, a conditional-lethal mutation in barley causing a defect in nitrite reduction.

Eleven green individuals were isolated when 95000 M2 plants of barley (Hordeum vulgare L.), mutagenised with azide in the M1, were screened for nitrite accumulation in their leaves after nitrate treatment in the light. The selected plants were maintained in aerated liquid culture solution containing glutamine as sole nitrogen source. Not all plants survived to flowering and some others that did were not fertile. One of the selected plants, STA3999, from the cultivar Tweed could be crossed to the wild-type cultivar and analysis of the F2 progeny showed that leaf nitrite accumulation was due to a recessive mutation in a single nuclear gene, which has been designated Nir1. The homozygous nir1 mutant could be maintained to flowering in liquid culture with either glutamine or ammonium as sole nitrogen source, but died within 14 days after transfer to compost. The nitrite reductase cross-reacting material seen in nitrate-treated wild-type plants could not be detected in either the leaf or the root of the homozygous nir1 mutant. Nitrite reductase activity, measured with dithionite-reduced methyl viologen as electron donor, of the nitrate-treated homozygous nir1 mutant was much reduced but NADH-nitrate reductase activity was elevated compared to wild-type plants. We conclude that the Nir1 locus determines the formation of nitrite reductase apoprotein in both the leaf and root of barley and speculate that it represents either the nitrite reductase apoprotein gene locus or, less likely, a regulatory locus whose product is required for the synthesis of nitrite reductase, but not nitrate reductase.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoproteins↗
PubMed1993

Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae.

The IME1 gene of Saccharomyces cerevisiae is required for initiation of meiosis. Transcription of IME1 is detected under conditions which are known to induce initiation of meiosis, namely starvation for nitrogen and glucose, and the presence of MATa1 and MAT alpha 2 gene products. In this paper we show that IME1 is also subject to translational regulation. Translation of IME1 mRNA is achieved either upon nitrogen starvation, or upon G1 arrest. In the presence of nutrients, constitutively elevated transcription of IME1 is also sufficient for the translation of IME1 RNA. Four different conditions were found to cause expression of Ime1 protein in vegetative cultures: elevated transcription levels due to the presence of IME1 on a multicopy plasmid; elevated transcription provided by a Gal-IME1 construct; G1 arrest due to alpha-factor treatment; G1 arrest following mild heat-shock treatment of cdc28 diploids. Using these conditions, we obtained evidence that starvation is required not only for transcription and efficient translation of IME1, but also for either the activation of Ime1 protein or for the induction/activation of another factor that, either alone or in combination with Ime1, induces meiosis.

Amino Acid Sequence↗
PubMed1993

Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis.

Previous mathematical modeling of beta cell electrical activity has involved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel density, and other parameters. We use gap-junctional electrical coupling, with conductances determined by an experimental histogram. We find that, for reasonable parameter distributions, only a small proportion of isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluster of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only with low probability. In large clusters, the dynamics of intracellular calcium compare well with experiments. Also, these clusters possess a dose-response curve of increasing average electrical activity with respect to a glucose-sensing parameter that is sharp when the cluster is coupled, but shallow when the cluster is decoupled into individual cells. This is in agreement with comparative experiments on cells in suspension and islets.

Animals↗
PubMed1993

A short chromosomal region with major roles in yeast chromosome III meiotic disjunction, recombination and double strand breaks.

A multicopy plasmid was isolated from a yeast genomic library, whose presence resulted in a twofold increase in meiotic nondisjunction of chromosome III. The plasmid contains a 7.5-kb insert from the middle of the right arm of chromosome III, including the gene THR4. Using chromosomal fragments derived from chromosome III, we determined that the cloned region caused a significant, specific, cis-acting increase in chromosome III nondisjunction in the first meiotic division. The plasmid containing this segment exhibited high spontaneous meiotic integration into chromosome III (in 2.4% of the normal meiotic divisions) and a sixfold increase (15.5%) in integration in nondisjunctant meioses. Genetic analysis of the cloned region revealed that it contains a "hot spot" for meiotic recombination. In DNA of rad50S mutant cells, a strong meiosis-induced double strand break (DSB) signal was detected in this region. We discuss the possible relationships between meiosis-induced DSBs, recombination and chromosome disjunction, and propose that recombinational hot spots may be "pairing sites" for homologous chromosomes in meiosis.

Chromosomes, Fungal↗
PubMed1992

Rhythmogenic effects of weak electrotonic coupling in neuronal models.

Strong gap-junctional coupling can synchronize the electrical oscillations of cells, but we show, in a theoretical model, that weak coupling can phase lock two cells 180 degrees out-of-phase. Antiphase oscillations can exist in parameter regimens where in-phase oscillations break down. Some consequences are (i) coupling two excitable cells leads to pacemaking, (ii) coupling two pacemaker cells leads to bursting, and (iii) coupling two bursters increases burst period. The latter shows that details of the fast spikes can affect macroscopic properties of the slow bursts. These effects hold in other models for bursting and may play a role in the collective behavior of cellular ensembles.

Animals↗
PubMed1992

Multiple sites for double-strand breaks in whole meiotic chromosomes of Saccharomyces cerevisiae.

We present a scheme for locating double-strand breaks (DSBs) in meiotic chromosomes of Saccharomyces cerevisiae, based on the separation of large DNA molecules by pulsed field gel electrophoresis. Using a rad50S mutant, in which DSBs are not processed, we show that DSBs are widely induced in S. cerevisiae chromosomes during meiosis. Some of the DSBs accumulate at certain preferred sites. We present general profiles of DSBs in chromosomes III, V, VI and VII. A map of the 12 preferred sites on chromosome III is presented. At least some of these sites correlate with known 'hot spots' for meiotic recombination. The data are discussed in view of current models of meiotic recombination and chromosome segregation.

Chromosome Aberrations↗
PubMed1991

Model for synchronization of pancreatic beta-cells by gap junction coupling.

Pancreatic beta-cells coupled by gap junctions in sufficiently large clusters exhibit regular electrical bursting activity, which is described by the Chay-Keizer model and its variants. According to most reports, however, isolated cells exhibit disorganized spiking. We have previously (Sherman, A. J. Rinzel, and J. Keizer, 1988. Biophys. J. 54:411-425) modeled these behaviors by hypothesizing that stochastic channel fluctuations disrupt the bursts. We showed that when cells are coupled by infinite conductance gap junctions, so that the cluster is isopotential and may be viewed as a single "supercell," the fluctuations are shared over a larger membrane area and hence dampened. Bursting emerges when there are more than approximately 50 cells in the cluster. In the model the temporal organization of spikes into bursts increases the amplitude of intracellular calcium oscillations, which may be relevant for insulin secretion. We now extend the previous work by considering the case of a true "multicell" model with finite gap junctional conductance. Whereas the previous study assumed that the cells were synchronized, we can now study the process of synchronization itself. We show that, for sufficiently large clusters, the cells both synchronize and begin to burst with moderate, physiologically reasonable gap junctional conductance. An unexpected finding is that the burst period is longer, and calcium amplitude greater, than when coupling is infinitely strong, with an optimum in the range of 150-250 pS. Our model is in good agreement with recent experimental data of Perez-Armendariz, M., D. C. Spray, and M. V. L. Bennett. (1991. Biophys. J. 59:76-92) showing extensive gap junctions in beta-cell pairs with mean interfacial conductance of 213 +/- 113 pS. The optimality property of our model is noteworthy because simple slow-wave models without spikes do not show the same behavior.

Animals↗
PubMed1990

Modulation of the frequency of glucose-dependent bursts of electrical activity by HCO3/CO2 in rodent pancreatic B-cells: experimental and theoretical results.

The burst pattern of electrical activity recorded from pancreatic B-cells in response to 11 mM glucose shows a large islet to islet variability. The relationship between burst frequency and glucose sensing (the threshold for electrical activity and the graded increase in electrical response to glucose, i.e. active phase %) has not been investigated within the same islet. In this work, we show that low HCO3 (5 mM) Hepes buffered solutions reversibly reduce the frequency of bursts compared to control (25 mM) HCO3 buffered solutions in the same islet. There was no change in the threshold or active phase (%). Using the mathematical model of Sherman et al. 1988, we explored mechanisms for a change in frequency independent of a change in active phase (%). Increased exchangeable calcium pool size and increased cell to cell coupling were the two theoretical treatments which could reproduce the experimental data. We conclude that burst frequency can be modulated independent of the active phase and that alteration of a calcium pool size best fits the experimental data.

Animals↗