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Biomedical subjects

D R Hunter

Publications and source records attributed to D R Hunter.

At least 19 recordsLinked to original sources
PubMed1997

Bladder dysfunction in schizophrenia.

In schizophrenic patients with incontinence our previous urodynamic studies showed detrusor hyperreflexia in some cases. Many schizophrenic patients have brain abnormalities similar to those associated with urge incontinence and detrusor hyperreflexia in neurological patients. We therefore propose bladder dysfunction and incontinence as previously unrecognized neurobiological correlates of schizophrenia. To clarify this concept our first step, the present study, was a patient survey for urinary problems. Incontinence was more prevalent in schizophrenic patients than in a comparison group of mood disorder patients at the same hospitals. Urge incontinence and leakage of any type were related closely to psychiatric diagnosis. These data, like our pilot urodynamic studies, suggest that incontinence represents detrusor hyperreflexia in a significant subset of schizophrenic patients. Prospective urodynamic studies will be needed to test our proposal directly.

Adult↗
PubMed1995

Preliminary report: detrusor hyperreflexia in schizophrenia.

The object of this study was to demonstrate detrusor hyperreflexia (DH) in schizophrenic patients. Twelve consecutive schizophrenic patients were evaluated by DSM-IIIR diagnostic criteria and other standard psychiatric measures, urological history and examination, and urodynamic study. All were referred for clinical indication, voiding dysfunction, or incontinence. Two patients were excluded for confounding variables, mental retardation and benign prostatic hypertrophy. Of the ten evaluable patients, four had DH. Detrusor hyperreflexia does occur in a subset of schizophrenic patients, even in the absence of other recognized disease to explain the occurrence. This relationship, previously unreported, warrants further investigation.

Adult↗
PubMed1995

Infratentorial cerebral cryptococcosis.

In a nonimmunocompromised patient with cerebral cryptococcosis, unique magnetic resonance findings included abnormalities limited to the posterior fossa and cerebellar hemispheric edema, gyriform enhancement of the vermis and cerebellar hemispheres, and infratentorial plaquelike enhancement. Magnetic resonance findings in central nervous system cryptococcosis are discussed.

Brain Diseases↗
PubMed1994

Aberrant right subclavian artery aneurysm: an analysis of surgical options.

During evaluation of a man for claudication, abnormal chest roentgenographic results were found. Computed tomography documented a 6.5-cm aneurysm of an aberrant retroesophageal right subclavian artery. Interruption of the right subclavian artery with an end-to-side subclavian-carotid anastomosis was performed via a right supraclavicular incision, followed immediately by left transthoracic interruption of the origin of the right subclavian artery using a heparin-bonded shunt. This approach avoids previously reported embolic complications while preserving brachial blood flow and providing safe access to the aorta.

Aged↗
PubMed1991

Control of the Na-Ca exchanger in isolated heart cells. I. Induction of Na-Na exchange in sodium-loaded cells by intracellular calcium.

Isolated adult rat heart cells in suspension were loaded with sodium by incubation with ouabain in the absence of calcium for 30 minutes. Addition of low levels of calcium induced accelerated rates of sodium influx and efflux, as measured with 22Na. The magnitude of calcium-induced 22Na efflux was 50-fold greater than the net rate of calcium uptake and required extracellular sodium, but not extracellular calcium, once some calcium was taken up. Calcium did not induce 86Rb efflux. The accelerated rate of 22Na efflux was prevented by verapamil, but verapamil was ineffective when added after calcium. Addition of EGTA after calcium reversed the effect of calcium, but only after incubation. Dichlorobenzamil, unlike verapamil, both prevented and reversed the induction of sodium fluxes by calcium. We conclude 1) that intracellular calcium induces Na-Na exchange through the Na-Ca exchanger in sodium-loaded cells exposed to calcium; and 2) that Na-Na exchange can be activated by calcium that enters the cell through calcium channels. We propose that this Na-Na exchange reflects the intrinsic activity of the Na-Ca exchanger.

Animals↗
PubMed1987

Inhibition of calcium influx in isolated adult rat heart cells by ATP depletion.

Using 45Ca, indo1, and quin2, calcium uptake was measured in isolated quiescent adult rat heart cells under different metabolic conditions. Exposure of cells in a medium containing 1 mM CaCl2 to rotenone and uncoupler resulted in adenosine triphosphate (ATP) depletion from 17.08 +/- 2.26 to 0.63 +/- 0.11 nmol/mg within 8 minutes, and the cells went into contracture. In this time, the cells lost 1.65 +/- 0.1 nmol Ca/mg of total rapidly exchangeable cellular calcium, and the level of free cytosolic calcium as measured by indo1 rose from 47.4 +/- 16.3 nM to 79.8 +/- 27.6 nM. The subsequent rate of rise of intracellular free calcium concentration was just 4 nM/min for at least 40 minutes. Therefore, we investigated the effect of ATP depletion on the rate of calcium entry. In cells loaded with sodium by ouabain treatment without calcium, the initial rate of calcium influx on calcium addition was inhibited by 82-84% when cellular ATP was depleted, as measured by 45Ca or indo1. Quin2 also showed a strong inhibition of calcium influx by ATP depletion, but itself also caused a strong inhibition of calcium influx. The rate of calcium influx declined even further in ATP-depleted cells after the initial influx: Between 1 and 12 minutes after calcium addition, the residual 45Ca uptake rate of the first minute was inhibited by an additional 90%. We conclude that ATP depletion per se does not quickly elevate cytoplasmic free calcium and that such an elevation is prevented by a very strong inhibition of the rate of calcium entry.

Adenosine Triphosphate↗
PubMed1986

Control of thallium and sodium fluxes in isolated adult rat heart cells by anthopleurin-A, verapamil and magnesium.

Anthopleurin-A stimulated the initial rate of 201thallium uptake by isolated adult rat heart cells by a factor of 3.41 +/- 0.56, and induced a unique pattern of spontaneous beating activity. Ouabain inhibited the basal uptake rate by 58 +/- 11% and all the anthopleurin-A stimulated rate. The Km for thallium uptake was 0.95 +/- 0.26 mM, and was not changed by anthopleurin-A. Accumulated thallium was quickly released from cells by EDTA addition. Such release was inhibited 87 +/- 10% by verapamil. Thallium reuptake was initiated by restoration of magnesium to the medium. Reuptake was mostly inhibited by ouabain, but the residual ouabain-insensitive uptake remained. The ouabain-insensitive uptake was inhibited by ATP depletion. Anthopleurin-A stimulated the rate of 22Na entry into cells by a factor of 3.17 +/- 1.65, and EDTA stimulated the rate of entry by a factor of 29.5 +/- 13.0. The EDTA-induced 22Na entry was inhibited 86 +/- 11% by verapamil. From this we draw three conclusions: The major pathway for thallium uptake is the Na-K pump. The rate of uptake by this route, like the rate of K+ uptake, is governed by the rate of cellular sodium influx; A residual ouabain-insensitive uptake route also exists which appears to require ATP but not a monovalent ion gradient; Removal of Mg and Ca induces a verapamil-sensitive monovalent channel activity which is both massive and reversible.

Animals↗
PubMed1985

Modulation of uncoupler-induced sugar uptake in isolated adult rat heart cells by isoproterenol.

When cells (2.4 mg/ml) in the presence of glucose were exposed to 0.15 microM p-trifluoromethoxyphenylhydrazone (FCCP), the time until 50% of the rod-shaped cells had undergone contracture was more than twice as long for cells without isoproterenol as for cells with isoproterenol. The cause of this large effect was revealed in experiments without glucose where 3-O-methylglucose entry, ATP levels, and cellular configuration were measured simultaneously. It was found that the onset of contracture was almost coincident with the decline in total measured ATP, suggesting that, in any cell, contracture was accompanied by a sudden and total ATP loss. In control cells, FCCP stimulated 3-O-methylglucose entry at or before the time this ATP catastrophe occurred. In cells exposed to isoproterenol, however, the stimulation of 3-O-methylglucose entry by FCCP did not occur until after the ATP catastrophe, and the extent of stimulation was reduced. This suggests that, when glucose was present, the FCCP-induced glucose influx was sufficient to significantly delay the onset of contracture in control cells but not in cells treated with isoproterenol. This conclusion was borne out by the observation that the effect of isoproterenol on contracture could be overcome with insulin.

3-O-Methylglucose↗
PubMed1985

Evidence for two distinct intracellular pools of inorganic sulfate in Penicillium notatum.

A strain of Penicillium notatum unable to metabolize inorganic sulfate can accumulate sulfate internally to an apparent equilibrium concentration 10(5) greater than that remaining in the medium. The apparent Keq is near constant at all initial external sulfate concentrations below that which would eventually exceed the internal capacity of the cells. Under equilibrium conditions of zero net flux, external 35SO42- exchanges with internal, unlabeled SO42- at a rate consistent with the kinetic constants with the sulfate transport system. Efflux experiments demonstrated that sulfate occupies two distinct intracellular pools. Pool 1 is characterized by the rapid release of 35SO42- when the suspension of preloaded cells is adjusted to 10 mM azide at pH 8.4 (t 1/2, 0.38 min). 35SO42- in pool 1 also rapidly exchanges with unlabeled medium sulfate. Pool 2 is characterized by the slow release of 35SO42- induced by azide at pH 8.4 or unlabeled sulfate (t 1/2, 32 to 49 min). Early in the 35SO42- accumulation process, up to 78% of the total transported substrate is found in pool 1. At equilibrium, pool 1 accounts for only about 2% of the total accumulated 35SO42-. The kinetics of 35SO42- accumulation is consistent with the following sequential process: medium----pool 1----pool 2. Monensin (33 microns) accelerates the transfer of 35SO42- from pool 1 to pool 2. Valinomycin (0.2 microM) and tetraphenylboron- (1 mM) retard the transfer of 35SO42- from pool 1 to pool 2. At the concentrations used, neither of the ionophores nor tetraphenylboron- affect total 35SO42- uptake. Pool 2 may reside in a vacuole or other intracellular organelle. A model for the transfer of sulfate from pool 1 to pool 2 is presented.

Azides↗
PubMed1984

Heterogeneous response of isolated adult rat heart cells to insulin.

3-O-Methylglucose uptake by Ca2+-resistant adult rat heart cells in suspension was measured, free of artifactual inhibitor-insensitive uptake, and with an accuracy of +/- 1.9% pellet water. (Ca2+-resistant cells are cells which retain their original rod-shaped morphology in the presence of physiological levels of Ca2+.) High levels of insulin (10(-6) M) stimulated the rate of 3-O-methylglucose uptake approximately 10-fold. In the presence of low levels of insulin (3 X 10(-11) M, 10(-10) M) uptake was biphasic; it could not be described by a single exponential function within experimental error, but required the sum of two exponentials. Deviation from a single exponential function was not so great with high levels of insulin (10(-6) M) or no insulin. Cell sugar uptake was also investigated using autoradiography of cells which had accumulated [2-14C]deoxyglucose under similar conditions. This showed considerable heterogeneity of 2-deoxyglucose uptake by cells treated with low levels of insulin, but significantly less heterogeneity of 2-deoxyglucose uptake by cells treated with high levels of insulin. It is concluded that the deviation of 3-O-methylglucose uptake from a single exponential observed at low insulin levels can be accounted for in terms of a heterogeneous response of cells to insulin.

3-O-Methylglucose↗
PubMed1984

Cellular lithium uptake as a probe of sodium channels in the rat heart: modulation of lithium uptake by tetrodotoxin, verapamil, anthopleurin-A, isoproterenol and external stimulation.

Since the initial rate of sodium influx by the perfused rat heart is too rapid to measure accurately, lithium was used as an analogue for sodium. 10 mM lithium was added to the perfusate, and the rate of cellular lithium uptake was found to be linear for 5 min and was equal to 1.29 +/- 0.26 mumol/5 min/g wet wt heart. The cell took up lithium ions 36% as fast as sodium ions, but after 30 min the cellular/perfusate ratio of lithium reached nine times the cellular/perfusate ratio of sodium. Lithium uptake was inhibited 43% by 1 microM tetrodotoxin (TTX) (P greater than 0.05) and 47% by 1.4 microM verapamil (P less than 0.05). External stimulation abolished the inhibition by TTX. Anthopleurin-A (60 nM) stimulated TTX-sensitive lithium uptake by 118% (P less than 0.01) and stimulated verapamil-sensitive lithium uptake by 213% (P less than 0.01) but did not stimulate verapamil-sensitive manganese uptake. Anthopleurin-A also increased dP/dt by 164% (P less than 0.01). Isoproterenol (150 nM) stimulated both verapamil-sensitive lithium uptake (72%, P less than 0.01) and verapamil-sensitive manganese uptake (128%, P less than 0.01). This suggests that there are both TTX-sensitive and verapamil-sensitive sodium channels in the rat heart.

Animals↗
PubMed1983

Metabolic cost of the stimulated beating of isolated adult rat heart cells in suspension.

Heart cells from adult rats were induced to beat in suspension by electric field stimulation. We have gained evidence that all the rod-shaped cells in suspension were indeed beating, and that the beat had dynamic characteristics similar to those of intact heart muscle contracting under zero load. The cells were undamaged in the process, as judged by maintenance of ATP levels, morphology, and ability to beat. In gaining such evidence, we also measured the metabolic cost to the cells of beating under zero load. In cells with oxidative phosphorylation inhibited by rotenone plus oligomycin (termed anaerobic), the rate of beat-dependent lactate production suggested an equivalent rate of ATP utilization of 0.126 +/- 0.013 nmol ATP/beat per mg protein (plus isoproterenol), and 0.058 +/- 0.005 nmol ATP/beat per mg protein (minus isoproterenol). In respiring cells, the rate of beat-dependent oligomycin-sensitive oxygen consumption gave an equivalent rate of ATP utilization of 0.198 +/- 0.009 nmol ATP/beat per mg protein (plus isoproterenol), and 0.126 +/- 0.013 nmol ATP/beat per mg protein (minus isoproterenol). The cells beat with the same approximate maximum velocity whether isoproterenol was present or not. We calculate that--in the case of anaerobic cells without isoproterenol--this rate of ATP utilization can account for only about a 15% degree of activation of the contractile proteins. In addition, we have found an oligomycin-insensitive beat-dependent mitochondrial respiration of 0.023 +/- 0.006 nanoatom O/beat per mg. The cause of this respiration is not known. The total rate of oxygen consumption of cells and also the rate per beat was comparable to that measured in nonworking whole hearts.

Adenosine Triphosphate↗
PubMed1983

Modulation of cellular calcium stores in the perfused rat heart by isoproterenol and ryanodine.

The inhibitory action of procaine on cellular calcium release was utilized to define a new cellular calcium pool which, under physiological conditions, is present only during catecholamine stimulation. Rat hearts labeled with 45Ca++ were perfused with medium containing procaine and EGTA at 23 degrees C to remove extracellular calcium, and then cellular calcium was released by removal of procaine and restoration of calcium. By this method we have identified a cellular calcium pool (pool C) whose release is inhibited by procaine, but which does not require extracellular calcium for its release. Release of pool C can also be triggered by caffeine. [We have previously identified a cellular calcium pool (pool A) whose release is triggered by caffeine, inhibited by procaine, and which does require extracellular calcium for its release.] When hearts were labeled for 3 minutes with perfusate containing 1 mM 45Ca++, 48 +/- 6 nmol Ca++/g wet weight was found in pool A, but only 3 +/- 1 nmol Ca++/g in pool C. However, if isoproterenol was present during labeling, the hearts contained 72 +/- 5 nmol Ca++/g in pool A and 42 +/- 6 nmol Ca++/g in pool C. When calcium concentration in the labeling perfusate was varied, with and without isoproterenol, it was found that pool C does not begin to fill until pool A is almost full. The same effect was seen when excess cellular calcium uptake was induced by removing sodium from the perfusate. Ryanodine (0.2 microM) induced contractile failure (t1/2 = 3.4 +/- 0.4 min) and depleted pool A in control hearts by 85%. Ryanodine also similarly depleted pools A and C in isoproterenol-treated hearts. When contractility was monitored at the same time as the hearts were labeled, a linear relationship between dP/dt and the sum of pools A and C was observed over a wide range of conditions. Pools A and C both selected strongly for calcium over barium. These observations suggest that both pools A and C are located in the sarcoplasmic reticulum and are intimately involved in the regulation of contractility.

Alkaloids↗