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R Rubinstein

Publications and source records attributed to R Rubinstein.

At least 55 records · Page 3Linked to original sources
PubMed1990

Distinct muscarinic receptor subtypes differentially modulate acetylcholine release from corticocerebral synaptosomes.

The effect of McN-A-343 and oxotremorine on acetylcholine (ACh) release and choline (Ch) transport was studied in corticocerebral synaptosomes of the guinea pig. The synaptosomes were preloaded with [3H]Ch after treatment with the irreversible cholinesterase inhibitor, diisopropyl fluorophosphate, and then tested for their ability to release isotope-labeled ACh and Ch in the presence and absence of these agents. The kinetics of release were determined at the resting state (basal release) and in the presence of 50 mM K+. Under either condition, McN-A-343 enhanced the release of isotope-labeled ACh, whereas oxotremorine inhibited the K(+)-evoked release but had no effect on the basal release. The enhancing effect of McN-A-343 on basal ACh release was fully blocked by the selective M1 muscarinic antagonist, pirenzepine (100 nM). In contrast to its enhancing effect on ACh release, McN-A-343 potently inhibited Ch efflux as well as Ch influx. These effects were not blocked by atropine, a nonselective muscarinic antagonist. Oxotremorine had no effect on Ch transport. Binding studies showed that McN-A-343 was 3.6-fold more potent in displacing radiolabeled quinuclidinyl benzilate from cerebral cortex muscarinic receptors (mostly M1 subtype) than from cerebellar receptors (mostly M2 subtype), whereas oxotremorine was 2.6-fold more potent in the cerebellum. The displacements of radio-labeled pirenzepine and cis-dioxolane confirmed the M1 subtype preference of McN-A-343 and the M2 subtype preference of oxotremorine.(ABSTRACT TRUNCATED AT 250 WORDS)

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1989

BK virus DNA cloned directly from human urine confirms an archetypal structure for the transcriptional control region.

A BK virus isolate cloned from the urine of an immunosuppressed patient was identified as the WW strain. Fine mapping using four base-pair restriction enzymes identified a number of small deletions and insertions relative to prototype BK. The finding of a transcriptional control region with a structure similar to that of a previous isolate cloned in a similar way demonstrates that this is a reproducible finding and reinforces the hypothesis that the structure is the archetypal form, found when cloned directly from urine, but generally altered when passaged in cell culture. BK virus is a human papovavirus first identified in the urine of a renal allograft patient by Gardner. Several BK strains have been studied in detail by restriction endonuclease mapping or sequencing. Two of these, the Dunlop and the MM strains, have been sequenced in their entirety, and a 400 to 500 base-pair region concerned with the control of transcription and replication has been sequenced in a number of others. All of these BK virus isolates were amplified by passage in cell culture before being characterized, although it often takes many weeks in culture before plaques can be identified and it has been reported that genome changes can occur on passage. Previous to the present isolate, we have identified BK virus in the urine of three local patients, and limited restriction endonuclease analysis of DNA prepared directly from the urine showed that they were similar and represented a new strain (BK-WW).(ABSTRACT TRUNCATED AT 250 WORDS)

BK Virus↗
PubMed1989

Cytoplasmic polyhedrosis virus classification by electropherotype; validation by serological analyses and agarose gel electrophoresis.

Serological analyses of several different cytoplasmic polyhedrosis viruses (CPVs), including two type 1 CPVs from Bombyx mori, type 1 CPV from Dendrolimus spectabilis, type 12 CPV from Autographa gamma, type 2 CPV from Inachis io, type 5 CPV from Orgyia pseudotsugata and type 5 CPV from Heliothis armigera, demonstrated a close correlation between the antigenic properties of the polyhedrin or virus particle structural proteins and the genomic dsRNA electropherotypes. The dsRNAs of these viruses were analysed by electrophoresis in 3% and 10% polyacrylamide gels with a discontinuous Tris-HCl/Tris-glycine buffer system or by 1% agarose gel electrophoresis using a continuous Tris-acetate-EDTA buffer system. Electrophoretic analysis in agarose gels was found to be the most suitable for the classification of CPV isolates into electropherotypes, and the results obtained showed a close correlation with the observed antigenic relationships between different virus isolates. However, electrophoretic analysis in 10% polyacrylamide gels was most sensitive for the detection of intra-type variation and the presence of mixed virus isolates.

Animals↗
PubMed1988

Effect of phase-encoding direction upon magnetic resonance image quality of the heart.

In order to optimize overall cardiac image quality on MR images experienced observers were asked to rank and rate MR images of the heart. The effect of phase-encoding direction and use of cardiac triggering with and without respiratory gating was examined in three orthogonal imaging planes. Results indicate that use of both respiratory and cardiac gating yields the best images. Adequate images of the heart can be obtained without respiratory gating. The quality of images of the heart can be optimized by proper selection of the direction of the phase-encoding gradient. These are improved by using horizontal phase encoding in the sagittal plane and vertical phase encoding in transverse and coronal planes.

Heart↗
PubMed1987

Acetylcholine mediation of the contractile response to histamine in human bladder detrusor muscle.

In Krebs solution, histamine evokes in human bladder detrusor muscle strips a dose-dependent contractile response which consists of two pharmacologically distinct responses: a high-sensitivity response evoked at 0.4-2 microM histamine, which is potentiated by neostigmine (0.1 microM) or blocked by atropine (0.1 microM) or ranitidine (1 microM); a low-sensitivity response evoked at 4-40 microM histamine and blocked by dimethindene or diphenhydramine. These findings suggest that the contractile response to low doses of histamine is mediated by acetylcholine released from a site proximal to the muscle. This effect of histamine seems to be mediated by a site which is insensitive to the H1 antagonists dimethindene and diphenhydramine but blocked by the H2 antagonist ranitidine.

Acetylcholine↗
PubMed1987

A comparative study of the affinities of some tricyclic antidepressants for the muscarinic cholinergic receptor in human and guinea-pig bladder, ileum and brain in relation to differential drug potency.

Following a report that nortriptyline was found useful in the control of enuresis in adults, presumably as an anticholinergic, its likely mechanism of action and apparent bladder specificity have now been investigated in vitro. The ratios of anticholinergic potencies (reciprocal of dissociation contents, Ki) for four different tricyclic antidepressants, derived from competitive binding assays with (-)[3H]QNB in tissue homogenates, in the order (human) detrusor muscle/ileal longitudinal muscle/caudate, are as follows: Nortriptyline, 5/4/7; desipramine, 2/1/5/; clomipramine, 4/3/27; amitriptyline, 25/14/56. The apparent selective effect of nortriptyline on the bladder cannot be ascribed to its higher affinity to bladder receptors. Still, this drug is the least discriminatory of the four. Hence, at a given concentration, it is expected to affect tissue embodying a low density receptor pool sooner than tissue having a large receptor reserve. The ratios of the densities of (-)[3H]QNB binding sites in the order detrusor muscle/ileal muscle/cortex is 1/3/5, supporting the present contention. In the guinea-pig, the ratios of the anticholinergic potency in the order bladder/proximal ileum/distal ileum/cortex are as follows: Nortriptyline, 25/5/6/33; desipramine, 8/2/2/14; amitriptyline, 100/14/20/100; clomipramine, 17/3/5/33. Also, the ratios of the densities of binding sites are 1/6/5/2. Hence, data derived from assays in the guinea-pig are not representative of those derived from human tissue.

Animals↗
PubMed1987

Structure and function of the transcriptional control region of nonpassaged BK virus.

We compared the nucleotide sequence in the transcriptional control region of BK virus isolates cloned directly from human urine (BK-WW) with that of prototype BK virus. BK-WW was found to have a 63-base-pair insertion and only one of the 68-base-pair enhancer repeat elements. In transient expression assays, BK-WW enhancer showed approximately one-half the activity given by the prototype enhancer.

BK Virus↗
PubMed1986

A study of the contractile response to acetylcholine in human ileal and detrusor muscle: origin of the low efficacy of acetylcholine.

In Krebs solution (3.36 mM Ca2+), the maximal contractile response of human ileal and urinary bladder detrusor muscle to acetylcholine (ACh) was 40-60% that to carbachol (CCh). The maximum response to ACh was reached at a bath concentration of about 1 microM and was maintained throughout a range extending to 100 microM. In the presence of neostigmine (0.1 microM), the maximum response to ACh reached the level of that of CCh. However, bioassay of bath concentrations of ACh at various points of the maximal response in the absence of neostigmine revealed only slight to insignificant diminution of the applied concentration of ACh. Joint application of ACh and CCh generated a dose-response profile consistent with a model of competitive antagonism between a full agonist (CCh) and a partial one (ACh). Also, choline (100 microM) reduced the maximum response to ACh in the presence of neostigmine and that to CCh to 60-80% of control. These observations are consistent with a mechanism whereby intact cholinesterase together with its substrate ACh and possibly a breakdown product of ACh constitute a filter or diffusional barrier regulating the flow of agonist from the enzyme compartment to the receptor compartment.

Acetylcholine↗
PubMed1986

Preliminary report on the use of the Percluder occluding aortic balloon in human beings.

Management of massive exsanguinating hemorrhage is a major challenge in acute trauma care. The value of military antishock trousers (MAST) in this setting is controversial. In selected instances, thoracotomy with aortic cross-clamping may be effective and often is used as the "gold standard" to which new experimental therapy is compared. Previous animal research with an occluding aortic balloon catheter (Percluder) has shown this technique to be physiologically similar to aortic cross clamping. The Percluder was more effective than the MAST plus volume replacement in controlling hemorrhage and prolonging four-hour survival from blunt splenic trauma in an animal model. We have used the Percluder in 23 patients with life-threatening hemorrhage. There were 15 trauma cases, five cases of ruptured abdominal aortic aneurysm, and three others. Only nine of 23 patients (39%) had vital signs when the balloon was inserted; all showed an increase in arterial blood pressure of about 50% to 100% (P less than .0001). Two of 15 trauma victims (13%) and four aneurysm patients in whom the balloon was used were long-term survivors. One trauma victim lived for two weeks before dying of ischemic complications after 90 minutes of balloon aortic occlusion. Overall survival rate was 26%. This study was uncontrolled and occlusion therapy was not randomized. Eleven of 12 attempts to place the catheter by femoral cutdown were successful. Seven of 12 attempts (58%) to place the catheter percutaneously were successful. The six insertion failures were due to an inadequately small introducer, inability to identify arterial pulses in moribund patients, or difficulty in cannulating the femoral artery because of proximal occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Aneurysm↗
PubMed1986

Selective effect of nortriptyline on smooth muscle as an anticholinergic drug: a pharmacological and clinical study.

The anticholinergic potency of nortriptyline was studied on muscle strips from human bladder and ileum. Concurrently the effect of nortriptyline low dosage therapy was studied in 21 women suffering from motor or sensory urgency and urge incontinence. Analysis of the results by the dose ratio method showed a significant difference in the affinity of the anticholinergic receptors to the antagonist. The Ki values were 0.298 microM for the bladder and 0.938 microM for the ileum. In the clinical study, the condition of 15 (71.4%) women treated with notriptyline improved considerably. The higher affinity of the drug to the receptors in the bladder than to those in the ileum may explain the positive therapeutic effect of a relatively low dose of nortriptyline in over 70% of the patients treated.

Bethanechol Compounds↗
PubMed1985

Antihistaminic properties of AF-14, an experimental quinuclidine derivative: discrimination between two histaminergic sites in both guinea-pig ileum and bladder.

AF-14 (1-aza-4-phenyltricyclo[6.2.2.0(2,7)]dodecan-5-one), a selective antimuscarinic agent, was shown to block the histamine-induced contractile response in Krebs solution in guinea-pig ileum and bladder. Careful linear regression analyses of the concentration-response relationship revealed that AF-14 antagonism consisted of two sequential and distinct phases, corresponding to an early phase and a late phase of the contractile response to histamine. In the late phase, the action of AF-14 was consistent with competitive antagonism, its pA2 (95% confidence limits) being 5.80-6.06 (ileum) and 5.66-5.80 (bladder). In the early phase, AF-14 almost completely blocked the contractile response at a concentration of 100-300 nM, which was much less than required to block the late phase or cholinergic contractions of the ileum or bladder. It is concluded that AF-14 discriminates between two histamine-sensitive sites that mediate muscle contraction in each of the two organs.

Animals↗
PubMed1985

Histamine-mediated acetylcholine release in the guinea-pig ileum.

The isometric contraction induced by histamine in guinea-pig ileum longitudinal muscle was biphasic in Krebs ([Ca]: 3.36 mM) but monophasic in Tyrode solution ([Ca]: 1.80 mM). The late phase (histamine: 20-400 nM) was common to the two solutions but the early phase (histamine: 2-20 nM) was observed only in Krebs solution. This early phase could be blocked with atropine (0.01-0.2 microM), morphine (0.1, 1 microM), adenosine (5, 20 microM) and tetrodotoxin (0.3 microM) without affecting the late phase. Washout of morphine or adenosine was fast. Neostigmine (100 nM) greatly potentiated the effect of histamine (4 nM) in the early phase, the muscle undergoing almost maximum contraction but also reversible desensitization to doses of histamine less than or equal to 20 nM for as long as 40 min after washout. Beyond this concentration, the preparation responded to increasing doses of histamine as observed in the late phase. It is concluded that low concentrations of histamine that have no observable direct effect on muscle contractility release acetylcholine in the presence of [Ca] 3.36 mM, the early phase being entirely due to release of endogenous acetylcholine.

Acetylcholine↗
PubMed1984

Affinity of nortriptyline to muscarinic receptors in the bladder and ileum of man and guinea-pig.

The antagonism by nortriptyline of carbachol- or urecholine-induced contractions was studied in strips of ileum and bladder derived from man and guinea-pig. Analyses of the results by the dose ratio method (Schild plots) showed significant differences in the affinities of the relevant muscarinic receptors to the antagonist: The Ki values in microM were as follows: Human ileum, 0.938; human bladder, 0.298; guinea-pig ileum, 0.159; guinea-pig bladder, 0.333 and 0.453. In man, the higher affinity of the drug to the receptors in the bladder than to those in the ileum may be of consequence in its therapeutic application as an antienuretic agent.

Animals↗
PubMed1983

Midgut and viral associated proteases of Heliothis armigera.

The role played by the gut juice of insects in the infective process of insect viruses was examined. Analysis of larval gut extract of Heliothis armigera by SDS-PAGE revealed protease activity associated with components of molecular weights 48,000 and 94,000. Proteases were found to be associated with occlusion bodies and virions of both nuclear polyhedrosis virus (NPV) and cytoplasmic polyhedrosis virus (CPV) infecting H. armigera. CPV occlusion bodies were dissolved by gut juice extract at pH 8.0, trypsin and chymotrypsin at pH 8.0, and carbonate-chloride solution at pH 10.5. Trypsin treatment was selective for occlusion bodies of CPV at pH 8.0, whereas solutions more alkaline than pH 10.0 without added enzymes were adequate to digest NPV occlusion bodies. This property was used to identify and separate the two types of viruses from a mixed infection. Gut extract proteases have characteristics similar to those of trypsin.

Animals↗