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Biomedical subjects

G B Weiss

Publications and source records attributed to G B Weiss.

At least 19 recordsLinked to original sources
PubMed1995

Evidence that BKCa channel activation contributes to K+ channel opener induced relaxation of the porcine coronary artery.

The rank order of potency of a series of benzopyran and cyanoguanidine K+ channel openers (KCOs) for causing relaxation of the PGF2 alpha-precontracted porcine coronary artery was determined. Glyburide, an inhibitor of KATP channels, showed an apparent competitive inhibition of the vasorelaxant activity of the KCOs. The pA2 values of glyburide when cromakalim and CGP 14877 (P1060) were used as vasorelaxants were 7.66 and 7.83, respectively. Charybdotoxin (40 nM), an inhibitor of BKCa channels, also caused a significant inhibition of the cromakalim mediated relaxation of the porcine coronary artery. In order to clarify the site of action of these KCOs, we identified a K+ channel current in single porcine coronary arterial cells and measured channel activity in the presence of these compounds. The prominent K+ ion current in these cells had characteristics typical of the conventional large Ca(2+)-activated K+ channel (BKCa) present in other smooth muscle cells. Using symmetrical K+ concentrations, the channel had a conductance of 214 pS and was found to be sensitive to [Ca2+]i and membrane potential. The KCOs were found to reversibly increase the open probability (P(o)) of the channel without changing channel conductance. The potency of the KCOs to increase K+ channel opening was similar to the potency of these compounds to cause coronary artery relaxation. These results indicate that the porcine coronary artery contains the BKCa channel and that this channel, along with other types of K+ channels (KATP), mediate the vasorelaxant effects of K+ channel openers.

Animals↗
PubMed1995

Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline.

CDP-choline, supplied exogenously as citicoline, has beneficial physiological actions on cellular function that have been extensively studied and characterized in numerous model systems. As the product of the rate-limiting step in the synthesis of phosphatidylcholine from choline, CDP-choline and its hydrolysis products (cytidine and choline) play important roles in generation of phospholipids involved in membrane formation and repair. They also contribute to such critical metabolic functions as formation of nucleic acids, proteins, and acetylcholine. Orally-administered citicoline is hydrolyzed in the intestine, absorbed rapidly as choline and cytidine, resynthesized in liver and other tissues, and subsequently mobilized in CDP-choline synthetic pathways. Citicoline is efficiently utilized in brain cells for membrane lipid synthesis where it not only increases phospholipid synthesis but also inhibits phospholipid degradation. Exogenously administered citicoline prevents, reduces, or reverses effects of ischemia and/or hypoxia in most animal and cellular models studied, and acts in head trauma models to decrease and limit nerve cell membrane damage, restore intracellular regulatory enzyme sensitivity and function, and limit edema. Thus, considerable accumulated evidence supports use of citicoline to enhance membrane maintenance, membrane repair, and neuronal function in conditions such as ischemic and traumatic injuries. Beneficial effects of exogenous citicoline also have been postulated and/or reported in experimental models for dyskinesia, Parkinson's disease, cardiovascular disease, aging, Alzheimer's disease, learning and memory, and cholinergic stimulation.

Animals↗
PubMed1993

Rapid reversal of angiotensin I-induced contractions in rat carotid arteries after acute and chronic treatment with the angiotensin-converting enzyme inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo- 3S-1H-1-benzazepena-1-acetic acid (CGS 16617).

The purpose of these experiments was to determine whether, in carotid arteries obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) a correlation exists between access of the angiotensin-converting enzyme (ACE) inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo-3S- 1H-benzazepena-1-acetic acid (CGS 16617), to tissue sites and the corresponding responsiveness of these tissues to the contractile effect of angiotensin I (ANG I). In carotid arteries isolated from SHR and WKY, the magnitude of [14C]CGS 16617 uptake was slightly greater than the [14C]sucrose uptake (the extracellular space), and the percentages of [14C]CGS 16617 and [14C]sucrose in fast and slow desaturation components were similar. Addition of high concentrations of nonradioactive CGS 16617 (10(-5)M during uptakes or washouts of [14C]CGS 16617 did not change uptake amounts or efflux rates. The dose-response curves of contractions obtained with ANG I or ANG II as well as the dose-dependent inhibition of ANG I-induced responses in the presence of CGS 16617 were similar for carotids taken from both WKY and SHR. Responses to ANG I were restored as early as 5 min after incubation solutions containing inhibitory concentrations of CGS 16617 were removed. Similarly, normal responsiveness to the contractile effects of ANG I were observed with carotid arteries removed from SHR with decreased blood pressure and plasma ACE activity after 5 weeks exposure to CGS 16617. In contrast, however, responses to norepinephrine were decreased in carotid arteries obtained from CGS 16617-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1992

Cellular Mg++ accumulation is altered by extracellular Na+ and directly affects agonist-induced mobilization of Ca++ in vascular smooth muscle.

Effects of altered Na+, Ca++ and Mg++ concentrations on 45Ca and 28Mg distribution and binding as well as of changes in cellular Mg++ on mobilization of Ca++ by added norepinephrine (NE) were examined in the rabbit aortic media-intimal layer. Uptake of 45Ca at cellular high affinity sites was decreased by Mg++ much more than 28Mg uptake was altered by Ca++. Substitution of Na+ affects 45Ca uptake primarily at extracellular (La( )-accessible) binding sites. Muscles were pre-loaded with Mg++ by incubation in a low-Na+ solution (75% Na+ replaced isosmotically with sucrose) for 30 min followed by a 90 min exposure to a similar solution also containing 15 mM MgCl2. These tissues, upon examination in normal (154 mM) Na(+)-containing solution, indicated decreased retention of that cellular, high-affinity Ca++ fraction important for NE-induced contractile response. Accordingly, release of 45Ca from this site and associated tension responses to added NE were attenuated in these muscles. These results suggest that variations in extracellular Na+ concentration modulate binding and subsequent mobilization of activator Ca++ by agonists through alterations in cellular Mg++ content in vascular smooth muscle.

Animals↗
PubMed1992

Asymptomatic unilateral papilledema in pseudotumor cerebri.

A 32-year-old asymptomatic woman was found to have unilateral papilledema on routine ophthalmological examination. Subsequent visual field, neuroimaging, and cerebrospinal fluid examinations were consistent with the diagnosis of pseudotumor cerebri. This case demonstrates that pseudotumor cerebri may present as unilateral papilledema in any asymptomatic patient and illustrates the need for thorough neuro-ophthalmological evaluations to allow early detection of cases with atypical presentations to increase the efficacy of therapeutic intervention and prevent progressive visual loss.

Acetazolamide↗
PubMed1991

Comparative effects of a selective adenosine A2 receptor agonist, CGS 21680, and nitroprusside in vascular smooth muscle.

CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethyolcarboxamidoa denosine) is an adenosine agonist that has been reported recently to bind selectively to adenosine A2 receptors in rat brain. This adenosine agonist, and the parent compound NECA (5'-N-ethylcarboxamidoadenosine), were found to be potent vasorelaxants of prostaglandin F2 alpha (PGF2 alpha) precontracted porcine coronary smooth muscle with EC50s of 4.5 and 9.7 nM, respectively. Schild analysis of the inhibition of CGS 21680, NECA and 2-chloroadenosine induced relaxation of the porcine coronary artery by CGS 15943 (9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-C]quinazolin-5-amine), an A2 receptor antagonist, yielded identical pA2 values for the antagonist (approximately 9.3). This indicates that the same receptor mediates the effects of these three adenosine agonists. NECA and CGS 21680 were equipotent in most vascular preparations except in the canine coronary artery. Porcine coronary arterial rings contracted with PGF2 alpha were relaxed by NECA or CGS 21680 as well as by nitroprusside; those contracted with KCl (40 mM) were relaxed only by nitroprusside. In rabbit aorta, contractions induced by phenylephrine or PGF2 alpha were inhibited by nitroprusside but not by NECA or CGS 21680. Thus, the adenosine A2 receptor agonists, NECA and CGS 21680, are potent vasorelaxants that display regional vascular and species variations that differ from those of nitroprusside.

Adenosine↗
PubMed1990

Effects of potassium or potassium/magnesium supplementation on potassium content of body tissues and fluids in furosemide-treated rats on magnesium-deficient or magnesium-sufficient diet.

Persistent Mg2+ deficiency may interfere with restoration of normal tissue K+ levels. This study examined: a) the effects of chronic furosemide treatment on K+ of sartorius, aorta and ventricle of rats fed Mg2(+)-deficient (100 ppm) or Mg2(+)-sufficient (400 ppm) diet and deionized water; b) whether normal tissue K+ is restored by oral K+ or K+/Mg2+ supplementation with continued furosemide therapy. Levels of Mg2+ were also measured. Furosemide (20 mg/kg i.p.) decreased K+ in sartorius, aorta and ventricle by 5.5, 4.3 and 19.9 microEq/gm (p less than .05), respectively, in rats fed 100 ppm Mg2+ diet. Furosemide did not alter K+ levels in rats fed 400 ppm Mg2+ diet. K+ supplementation (1 mEq/kg for 7 days) restored K+ to normal in sartorius but the addition of Mg2+ supplementation was necessary to restore K+ levels to normal in ventricle and aorta. These data indicate that furosemide can decrease tissue K+ in rats on a Mg2(+)-deficient diet. This decrease can be reversed during diuretic administration by K+ supplementation in sartorius, or K+ plus Mg2+ supplementation in ventricle and aorta.

Animals↗
PubMed1990

The calcium-related basis of action of adenosine in rabbit aortic smooth muscle.

1. In rabbit aortic smooth muscle, adenosine inhibited the increase induced by norepinephrine (NE) in 45Ca uptake in the presence of KCl (under low affinity Ca2+ uptake conditions) and the NE-induced decrease in 45Ca uptake (under high affinity Ca2+ uptake conditions). Basal 45Ca uptake and KCl-stimulated 45Ca uptake were not altered by adenosine. 2. Adenosine blocked the NE-induced contraction (in high K+) and inhibited both the tonic and phasic components of the NE-induced contraction. 3. Thus, adenosine selectively inhibits release of the intracellular Ca2+ store important for the phasic response to NE and that Ca2+ uptake component important for the NE-induced tonic response.

Adenosine↗
PubMed1990

Concurrent chemotherapy/radiotherapy for limited small-cell lung carcinoma: a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) has conducted a phase II study to explore the efficacy and toxicity of initial, concurrent use of radiation therapy with cisplatin, etoposide (VP-16), and vincristine in limited-stage small-cell carcinoma of the lung. Two courses of cisplatin, VP-16, and vincristine chemotherapy were given with concurrent radiotherapy (XRT) to the primary tumor to a total dose of 4,500 cGy. Elective brain XRT was given to all patients concurrent with a third course of cisplatin/VP-16 therapy. Consolidation chemotherapy consisting of vincristine, methotrexate, and VP-16 alternating with Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide, was given for 12 weeks following the initial induction chemotherapy/XRT program. Patients with a complete response had all therapy discontinued. Among 154 eligible patients treated, the complete response rate was 56%, with a partial response rate of 27%. The median survival is 17.5 months with an estimated 30% survival rate at 4 years from initiation of treatment. Combined modality toxicities were acceptable with the predominant toxicity being moderate to severe leukopenia and mild radiation esophagitis. The results of this treatment program appear superior to any previously reported by our group and compare favorably to those in the literature at large.

Adult↗
PubMed1990

Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein.

Effects of the K+ channel blocking agent, glyburide, on the actions of two K+ channel openers, BRL 34915 (cromakalim) and P 1060 (Leo), a potent pinacidil derivative (N-(t-butyl)-N"-cyano-N'-3-pyridyl-guanidine), were ascertained. Tension responses and 86Rb fluxes in rat portal vein strips and single channel electrophysiological recordings in enzymatically dissociated rat portal vein cells were obtained. Glyburide (0.3 microM) increased spontaneous contractile activity and caused concentration-dependent shifts in the relaxation responses to BRL 34915 and P 1060. Increases in 86Rb efflux were obtained only at much higher concentrations of BRL 34915 or P 1060, and these increases were blocked only at higher concentrations of glyburide (5.0 microM). BRL 34915 and P 1060 specifically increase the open-state probability of the Ca+(+)-activated K+ (maxi-K+) channel, and these actions are blocked by glyburide and also by charybdotoxin. Changes in single channel activity and contractile responsiveness occur at similar concentrations of agonists and antagonists. Thus, the membrane channel in rat portal vein affected by glyburide, BRL 34915 and P 1060 appears to be the Ca+(+)-activated maxi-K+ channel (that does not show ATP dependence under the conditions of these experiments). Concentrations of agonists and antagonists effective on maxi-K+ channel activity correspond to those affecting contractile responsiveness and are lower than those eliciting changes in 86Rb flux.

Animals↗
PubMed1989

Effects of pH and anion substitution on magnesium accumulation in rabbit aortic smooth muscle.

The effects of anion substitution, pH and extracellular Mg2+ concentration on 28Mg accumulation were examined in rabbit aortic smooth muscle. Accumulation of 28Mg (expressed as a 28Mg/Mg2+ ratio) was not changed when the concentration of added, nonradioactive MgCl2 was increased from 1.5 to 15.0 mM. The 28Mg efflux rate was increased by added MgCl2 (0.15, 0.5 or 1.5 mM) in a dose-related manner after a similar delay of 5-10 min. Addition of 1.5 mM MgCl2, MgSO4 or magnesium aspartate hydrochloride enhanced 28Mg efflux and inhibited accumulation of 28Mg to the same extent. An increase or decrease in extracellular pH correspondingly increased or decreased 28Mg accumulation. However, the 28Mg efflux rate was not altered when extracellular pH was decreased. Efflux of 28Mg was increased by added 1.5 mM MgCl2 at pH 7.4 but not at pH 5.8. Thus, the net uptake of Mg2+ appears to be proportional to the concentration of extracellular Mg2+ in rabbit aorta. Low external pH decreases 28Mg retention in rabbit aorta by inhibiting the uptake of 28Mg rather than by increasing 28Mg efflux. Effects of added Mg2+ on transmembrane movements of 28Mg are not altered by changes in the associated anion. Extracellular Mg2+ appears to enter the cell and exchange with an intracellularly located pool of 28Mg in the same manner, regardless of whether the accompanying anion is sulfate, chloride or monoaspartate hydrochloride.

Animals↗
PubMed1988

Calcium release in smooth muscle.

In smooth muscle, maintenance of the contractile response is due to Ca2+ influx through two types of Ca2+ channel, a voltage-dependent Ca2+ channel and a receptor-linked Ca2+ channel. However, a more transient contraction can be obtained by release of Ca2+ from a cellular store, possibly the sarcoplasmic reticulum. In spike generating smooth muscle (e.g., guinea-pig taenia caeci), spike discharges may trigger the release of cellular Ca2+ by activating a Ca2+-induced Ca2+ release mechanism. Caffeine directly activates this mechanism in the absence of a triggered Ca2+ influx. In contrast to this, maintained depolarization may not only release but also refill the Ca2+ store. Drug-receptor interactions also release Ca2+ from a cellular store. This release may be elicited with inositol trisphosphate produced by receptor-linked phosphoinositide turnover. In non-spike generating smooth muscle (e.g., rabbit thoracic aorta), maintained membrane depolarization does not release but, instead, fills the Ca2+ store. However, caffeine and receptor-agonists release the Ca2+ store - possibly by activating the Ca2+-induced Ca2+ release mechanism and phosphoinositide turnover, respectively. The Ca2+ store in smooth muscle is filled by Ca2+ entry through voltage dependent Ca2+ channels and also by resting Ca2+ influx in the absence of receptor-agonists. The Ca2+ entering the cells through these pathways may be accumulated by the Ca2+ store and may activate the contractile filaments.

Animals↗
PubMed1988

Concurrent chemotherapy and radiation therapy for limited unresectable non-small cell carcinoma of the lung. A phase I study.

We treated nine patients diagnosed as inoperable, but localized non-small cell lung cancer with aggressive high-dose radiation therapy and two cycles of concomitant cisplatin and 5-fluorouracil (5-FU) to determine the feasibility of this approach for this disease. This combined modality program was well tolerated by seven of our nine patients. One who had a poor initial performance status died of sepsis. Another could not tolerate the nausea and vomiting. Only one patient has suffered a local failure inside the irradiated areas. Eight have died, and 5 of 9 survived at least 1 year. The survival is at least consistent with that associated with radiation therapy alone.

Adult↗
PubMed1988

Alterations in 28Mg distribution and movements in rabbit aortic smooth muscle.

The distribution and transmembrane fluxes of 28Mg were examined in the isolated media-intimal layer of rabbit aorta. Accumulation of 28Mg was slow and not complete after a 3-hr incubation. The major portion of the cellular Mg++ is not exchangeable. The 28Mg efflux rate was increased by 1.5 mM nonradioactive Mg++ after a time lag of 5 to 10 min; this increase was blocked reversibly by decreasing bathing solution temperature to 4 degrees C. A rapid and sustained increase in 28Mg efflux rate was elicited with added EDTA. Accumulation of 28Mg by rabbit aorta was increased more than 5-fold by substituting sucrose for NaCl in the bathing solution. Q10 values obtained for Mg++ accumulation in rabbit aorta incubated at different temperatures either in normal solution or low-Na+ solution ranged from 1.3 to 2.0. Uptake of 28Mg was inhibited substantially by 60 mM added K+, 1.5 or 15.0 mM La , 7 mM neomycin or 1 microgram/ml of antimycin A. These ions and drugs did not significantly increase 28Mg efflux when added during the slow component phase of the washout. Thus, the major portion of slowly accumulated Mg++ appears to be stored and exchanged intracellularly. The transmembrane movements of Mg++ depend upon simple diffusion, Mg++-Mg++ exchange and a transport process that is increased when Na+ is decreased. The EDTA-induced increase in 28Mg efflux rate may result from nonspecific membrane permeability increases, whereas ions and drugs decrease cellular Mg++ content by reducing uptake rather than increasing loss.

Animals↗
PubMed1987

Dissociation of actions of BRL 34915 in the rat portal vein.

In rat portal vein, 0.5 and 5.0 microM BRL 34915 [(+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl++ +)-2H- benzo[b]pyran-3-ol] abolished spontaneous rhythmic movements and norepinephrine (NE)-induced tension responses, respectively. Only the higher (5 microM) concentration of BRL 34915 increased 42K efflux and inhibited the NE-induced increase in 42K efflux. These results suggest that BRL 34915 inhibits spontaneous rhythmic movements and NE-induced tension responses by differing mechanisms of action and that only the block of the NE-induced tension response is related to K+ permeability or conductance changes.

Animals↗