Search PubMed⌕ Search

Biomedical subjects

S Ginsburg

Publications and source records attributed to S Ginsburg.

At least 19 recordsLinked to original sources
PubMed1999

Ion channels in presynaptic nerve terminals and control of transmitter release.

The primary function of the presynaptic nerve terminal is to release transmitter quanta and thus activate the postsynaptic target cell. In almost every step leading to the release of transmitter quanta, there is a substantial involvement of ion channels. In this review, the multitude of ion channels in the presynaptic terminal are surveyed. There are at least 12 different major categories of ion channels representing several tens of different ion channel types; the number of different ion channel molecules at presynaptic nerve terminals is many hundreds. We describe the different ion channel molecules at the surface membrane and inside the nerve terminal in the context of their possible role in the process of transmitter release. Frequently, a number of different ion channel molecules, with the same basic function, are present at the same nerve terminal. This is especially evident in the cases of calcium channels and potassium channels. This abundance of ion channels allows for a physiological and pharmacological fine tuning of the process of transmitter release and thus of synaptic transmission.

Animals↗
PubMed1998

Development of a quantitative vancomycin immunoassay for the Abbott AxSYM analyzer.

A novel fluorescence polarization immunoassay for vancomycin on Abbott AxSYM analyzer is described. The immunoassay allows for the accurate quantification of vancomycin in the presence of the crystalline degradation product (CDP). It displays dilution linearity from 1.0 microg/ml to 100.0 microg/ml, coefficients of variation ranging from 2.94% to 4.26%, recovery from 98% to 105%, and a sensitivity of <2.0 microg/ml. The assay demonstrates no cross-reactivity to crystalline degradation product, and to commonly-prescribed and over-the-counter drugs, as well as a minimum interference from endogenous substances.

Animals↗
PubMed1996

How plants dispose of chlorophyll catabolites. Directly energized uptake of tetrapyrrolic breakdown products into isolated vacuoles.

During the yellowing of leaves the porphyrin moiety of chlorophyll is cleaved into colorless linear tetrapyrrolic catabolites, which eventually are deposited in the central vacuoles of mesophyll cells. In senescent cotyledons of rape, Brassica napus, three nonfluorescent chlorophyll catabolites (NCCs), accounting for practically all the chlorophyll broken down, were found to be located in the vacuoles (vacuoplasts) prepared from protoplasts. Transport of catabolites across the tonoplast was studied with vacuoles isolated from barley mesophyll protoplasts in conjunction with a radiolabeled NCC, Bn-NCC-1, prepared from senescent rape cotyledons. The uptake of Bn-NCC-1 into vacuoles was against a concentration gradient and strictly dependent on MgATP and it followed saturation kinetics with a Km of approximately 100 microM. Although the hydrolysis of ATP was required, transport was apparently independent of the vacuolar proton pumps: accumulation of the NCC occurred both in the presence of the H+-ATPase inhibitor bafilomycin and after destroying the DeltapH between the vacuolar sap and the medium. ATP could be replaced by GTP or UTP, and the transport was inhibited in the presence of vanadate. Chlorophyll catabolites isolated from senescent barley leaves competed with the rape-specific substrate for uptake into the vacuoles. Compounds such as the glutathione conjugate of N-ethylmaleimide and taurocholate, which are known to be transported across the tonoplast in a primary active mode, did not significantly inhibit uptake of Bn-NCC-1. Although the heme catabolites biliverdin and bilirubin inhibited the uptake of the NCC, this effect is caused by unspecific binding to the vacuolar membrane rather than to the specific inhibition of carrier-mediated transport. Taken together, the results demonstrate that barley mesophyll vacuoles are constitutively equipped with a directly energized carrier that transports tetrapyrrolic catabolites of chlorophyll into the vacuole.

Biological Transport↗
PubMed1996

Evaluation in the Health Resources and Services Administration. Improving program performance.

The mission of the Health Resources and Services Administration (HRSA) in the U.S. Department of Health and Human Services is to improve the health of the nation by assuring quality health care to underserved and vulnerable populations and by promoting a primary care and public health workforce. This article provides an overview of HRSA's prior work in performance measurement and highlights a current initiative designed to help the agency improve its performance measurement efforts in the context of the Government Performance and Results Act. This initiative began with an agencywide assessment of capacity to measure performance at program, bureau, and agency levels. Based on the findings, HRSA is moving forward both with technical assistance to individual bureaus in developing performance indicators and data sources and with activities to coordinate performance measurement for the agency as a whole.

Budgets↗
PubMed1995

The difference in shape of spontaneous and uniquantal evoked synaptic potentials in frog muscle.

1. Spontaneous and stimulation-induced uniquantal synaptic activity at the frog cutaneous pectoris muscle, treated with neostigmine, was recorded by focal extracellular microelectrodes. A monoexponential curve was fitted to the decay of each synaptic response. 2. A highly significant positive relationship was found between the amplitude and the decay time constant of spontaneous extracellular miniature endplate potentials (MEPPs(o)), whereas the relationship displayed by evoked uniquantal extracellular endplate potentials (EPPs(o)) was only slightly greater than zero. 3. The difference did not stem from changes in the muscle membrane conductance or from inclusion of outstanding MEPPs(o) formed as a result of the block of acetylcholinesterase. 4. The dependence of the rise time on the amplitude was also stronger in MEPPs(o) than in EPPs(o). 5. In the absence of neostigmine, MEPPs(o) exhibited a positive correlation between decay time constant and amplitude, while EPPs(o) did not show such a correlation. 6. In view of previously published models of transmitter release, it is suggested that spontaneous secretion of quanta occurs both within and outside the active zones facing postsynaptic areas of variable receptor density.

Acetylcholinesterase↗
PubMed1995

Oscillations in the activity of a potassium channel at the presynaptic nerve terminal.

1. Periodic oscillations were detected in the activity of single macromolecules: potassium channels. 2. When potassium channels are repeatedly activated in isolated patches from fused synaptosomes of Torpedo electric organ, their behavior exhibits a departure from random activation. 3. The departure from random behavior is demonstrated by the runs test and by the lack of fit to Poisson distribution. 4. Under appropriate experimental conditions, the channels display periodic oscillations with a periodicity of approximately 20 s when activated at a rate of 1.25 Hz. 5. The oscillations do not arise from sampling, recording, or computational artifacts. 6. It is conceivable that single-channel oscillations play a role in the generation of membrane oscillations and thus may contribute to the oscillatory behavior of the nervous system.

Animals↗
PubMed1992

A long closed state of the synaptosomal bursting potassium channel confers a statistical memory.

1. The statistical properties of the bursting potassium channel from fused Torpedo synaptosomes were studied by using patch-clamp recording and time series analysis. 2. Voltage steps produce channel openings; the number of channels opening fluctuates from trial to trial. The maximal current observed in each trial is strongly dependent on the previous history of the membrane patch. Trials with no activity are frequently clumped together and so are trials with intense activity. 3. Autocorrelation analysis reveals a strong interdependence of successive responses, which is voltage dependent. 4. We propose that the strong statistical interdependence of responses to successive depolarizing pulses (the statistical "memory") is a manifestation of a long lived closed state. We speculate that this statistical memory may be of significance in frequency modulation of transmitter release.

Animals↗
PubMed1991

A bursting potassium channel in isolated cholinergic synaptosomes of Torpedo electric organ.

1. Pinched-off cholinergic nerve terminals (synaptosomes) prepared from the electric organ of Torpedo ocelata were fused into large structures (greater than 20 microns) using dimethyl sulphoxide and polyethylene glycol 1500, as previously described for synaptic vesicles from the same organ. 2. The giant fused synaptosomes were easily amenable to the patch clamp technique and 293 seals with a resistance greater than 4 G omega were obtained in the 'cell-attached' configuration. In a large fraction of the experiments, an 'inside-out' patch configuration was achieved. 3. Several types of unitary ionic currents were observed. This study describes the most frequently observed single-channel activity which was found in 247 out of the 293 membrane patches (84.3%). 4. The single-channel current-voltage relation was linear between -60 and 20 mV and showed a slope conductance of 23.8 +/- 1.3 pS when the pipette contained 350-390 mM-Na+ and the bath facing the inside of the synaptosomal membrane contained 390 mM-K+. 5. From extrapolated reversal potential measurements, it was concluded that this channel has a large selectivity for K+ over Na+ (70.4 +/- 11.5, mean +/- S.E.M.). Chloride ions are not transported significantly through this potassium channel. 6. This potassium channel has a low probability of opening. The probability of being in the open state increases upon depolarization and reaches about 1% when the inside of the patch is 20 mV positive compared to the pipette side. 7. The mean channel open time increases with depolarization; thus the product current x time (= charge) also increases upon depolarization, showing properties of an outward rectifier. 8. The potassium channel in the giant synaptosome membrane has a bursting behaviour. Open-time distribution, closed-time distribution and a Poisson analysis indicate that the minimal kinetic scheme requires one open state and three closed states.

Animals↗
PubMed1990

Studies on new, centrally active and reversible acetylcholinesterase inhibitors.

We have synthesized the tertiary amines of pyridostigmine and neostigmine, 3-pyridinol dimethylcarbamate (norpyridostigmine) and 3-dimethylaminophenol dimethylcarbamate (norneostigmine) respectively, and we have tested their abilities to cross the blood-brain barrier and inhibit mouse brain AChE activity. The in vivo inhibition of AChE activity by norpyridostigmine reaches 72% at 10 minutes which is comparable to that seen with physostigmine (73% at 10 minutes). Inhibition by norneostigmine is less effective (50% at 10 minutes) and approaches that obtained with tetrahydroaminoacridine (57% at 10 minutes). These data show that both norpyridostigmine and norneostigmine cross the blood-brain barrier and that they are effective inhibitors of mouse brain AChE activity. These drugs could be useful in the treatment of memory impairment associated with Alzheimer's disease, and other memory disorders.

Acetylcholinesterase↗
PubMed1989

Ionic channels in synaptic vesicles: are they involved in transmitter release?

Synaptic vesicles were isolated from the nerve terminals of Torpedo electric organ. After fusion, 'giant' vesicles were formed which could be examined by the patch clamp technique. One of the cationic channels, the P channel, shows a small preference for K+ compared to Na+ and has multiple conductance levels. Its rate of opening is voltage and calcium dependent. Fractal analysis of the P channels reveals that its behaviour does not seem to be fractal in nature. At voltages where only one conductance level is observed, fractal analysis shows at least one discrete open state and at least two discrete closed states. There are considerable similarities between the P channel and channels found in granules from the hypophysis. These channels resemble, in turn, the channels found in gap junctions. Therefore, it is not unwarranted to speculate that a gap-junction-like communication between the secretory vesicle and the extracellular space may occur during exocytosis.

Animals↗
PubMed1989

Modulation of effect of extracellular calcium buffering in cardiac muscle.

The buffering of extracellular calcium by citrate, with identical free calcium levels in the buffered and unbuffered medium, was previously found to markedly reduce tension in frog and guinea pig atria. We now report the following results. 1) In guinea pig, postest contractions are not reduced by citrate. 2) In frog the negative inotropic effect of citrate is greatly attenuated by partially replacing extracellular sodium concentration ([Na+]o) with lithium or sucrose. In contrast, in low [Na+]o, sodium salts of weak acids (which cause intracellular acidosis) still reduce tension. These findings strongly support the suggestion that citrate does not reduce tension directly, e.g., by causing intracellular acidosis or by reducing voltage-dependent calcium currents. 3) Higher stimulation rates also decrease the effect of citrate. 4) Treatment with neuraminidase or phospholipase D, both of which alter sarcolemmal calcium binding, dose not change the effect of citrate. 5) The positive inotropic effect of strophanthidin is reversibly lost in the presence of citrate. Our results provide a different, novel approach to support earlier suggestions that the extracellular matrix and/or the sarcolemma contain abundant calcium-binding sites that supply some of the calcium for contraction. Citrate presumably binds calcium more strongly, thereby "trapping" calcium released from the extracellular "stores," so that less calcium is made available for contraction. The inotropic effect of cardiac glycosides may also depend on the calcium that is bound to these stores.

Animals↗
PubMed1988

Catabolites of chlorophyll in senescing barley leaves are localized in the vacuoles of mesophyll cells.

Senescing barley leaves accumulate a series of pink pigments with the chemical properties of catabolites derived from chlorophyll. Levels of the major component of this group of pigments were quantified by HPLC and shown to be maximal in tissues exhibiting maximal rates of chlorophyll degradation. Protoplasts were isolated from senescent leaf tissue and fractionated to yield intact vacuoles and plastids. Although small but significant proportions both of total catabolites and of the dominant component of the series were recovered from the plastid fraction, the vast bulk of these compounds could be assigned to the vacuole. These observations suggest a role for the vacuole in the later stages of chlorophyll breakdown during senescence.

Journal Article↗
PubMed1987

Negative inotropic effect of extracellular calcium buffering in cardiac muscle.

Heart muscle contracts more vigorously when calcium levels are raised. A transient depletion of calcium from restricted extracellular spaces occurs with each contraction. We decided to maintain the concentration of this ion at a constant level by using an external calcium buffering system. It was found that buffering calcium at a millimolar level (using citrate as a buffer) caused a decrease, rather than an increase in the strength of contraction. The mean reduction in peak tension was by 27% in guinea pig and by 50.5% in frog atrium. This finding is analyzed; its most plausible explanation is the hypothesis that the buffer dissipates a calcium inhomogeneity, consisting of a higher calcium concentration adjacent to the membrane. Alternative interpretations such as intracellular acidosis, were tested experimentally and ruled out.

Animals↗
PubMed1984

Use of covalently bound cord factor analog to increase tumor immunogenicity.

Mice were immunized in vitro and in vivo against the tumor-associated antigens of a methylcholanthrene-induced tumor, using immunogen cells coupled to a cord factor analog (trehalosedihemisuccinatemonohexadecylamide). Immune activity was measured with a short-term 51Cr-release assay. The cord factor analog potentiated immunity induced by adjuvant peptide.

Acetylmuramyl-Alanyl-Isoglutamine↗