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Biomedical subjects

D Bose

Publications and source records attributed to D Bose.

At least 19 recordsLinked to original sources
PubMed1995

Intracellular internalization and signaling pathways triggered by the large subunit of HSV-2 ribonucleotide reductase (ICP10).

The large subunit of the HSV-2 ribonucleotide reductase (RR) (ICP10) is a chimera consisting of a serine threonine (Ser/Thr) protein kinase domain at the amino terminus and the RR domain at the carboxy terminus. Transformed human cells that constitutively express ICP10 (JHLa1) were stained with anti-LA-1 antibody (recognizes ICP10 amino acids 13-26) and immunogold-conjugated goat anti-rabbit IgG and were examined by electron microscopy. ICP10-associated gold particles were observed on the cell surface and in structures with ultrastructural characteristics of endocytic vesicles, multivesicular bodies, and lysosomes, consistent with endocytic internalization. ICP10 was also associated with the cytoskeleton fraction of JHLa1 cells and, at least in part, it colocalized with actin filaments. This was evidenced by immunoprecipitation of [35S]methionine-labeled cell fractions and immunofluorescent staining of Triton-treated cells with anti-LA-1 antibody and phalloidin. Endocytic localization of gold particles was not seen in cells that constitutively express the ICP10 transmembrane (TM)-deleted mutant p139TM (JHL15). p139TM did not associate with the cytoskeleton and was almost entirely localized within the cytoplasm. raf and Erk evidenced decreased mobility consistent with an activated state in JHLa1, but not JHL15, cells, and chloramphenicol acetyl transferase (CAT) expression from a c-fos/cat hybrid construct was significantly increased in JHLa1 but not JHL15 cells. The data indicate that effector molecules downstream of ras are activated in JHLa1 cells and the ICP10 TM segment plays a critical role in ICP10 intracellular localization and its ability to activate signaling pathways. This behavior is analogous to that of an activated growth factor receptor kinase.

Actins↗
PubMed1995

Effect of continuous arteriovenous hemofiltration combined with systemic vasopressor therapy on depressed left ventricular contractility and tissue oxygen delivery in canine Escherichia coli sepsis.

BACKGROUND: In a previous study, we showed that continuous arteriovenous hemofiltration (CAVH) reversed the depression in left ventricular (LV) contractility in canine Escherichia coli sepsis by the removal of a circulating substance the molecular weight of which is less than 30,000. Despite the normalization of LV contractility, however, we were unable to demonstrate an improvement in systemic arterial blood pressure (BP), presumably because the mechanisms underlying the depression in LV contractility and the decrease in BP are different in sepsis. In the current study, we examined the effect of combined treatment with CAVH and the alpha-adrenergic agonist phenylephrine on LV mechanics and tissue oxygen delivery in our canine E. coli model. METHODS: Measurements were obtained at baseline (condition B), after 4 h of sepsis (condition S), and after 2 h of CAVH and phenylephrine (condition P) (total of 6 h of sepsis). During P, phenylephrine was infused to restore BP to that found at baseline. The slope of the end-systolic pressure-dimension relation was used as the index of LV contractility; LV anterior-posterior dimensions were measured by sonomicrometry. RESULTS: During combined CAVH and phenylephrine treatment, the decrease in the slope of the end-systolic pressure-dimension relation otherwise observed at S was reversed. The slope (mean +/- SD) was 57.5 +/- 32 mmHg/mm at B versus 22.2 +/- 8 mmHg/mm at S (P < 0.05, B vs. S) versus 62 +/- 37 mmHg at P (P < 0.05 S vs. P) (analysis of variance). Mean BP was restored to that found at B (123 +/- 19 mmHg versus 82 +/- 14 mmHg (P < 0.05 B vs. S) versus 116 +/- 27 mmHg (P < 0.05 S vs. P). Combination treatment with CAVH and phenylephrine also improved stroke volume (39.3 +/- 13.5 versus 32 +/- 8 versus 44 +/- 12 ml) and tissue oxygen delivery during P compared with results obtained when phenylephrine was given alone. CONCLUSIONS: Our study offers a rationale for the combined use of phenylephrine and CAVH in the reversal of cardiac depression and hypotension in sepsis.

Animals↗
PubMed1993

Pharmacological characterization of the activity of endogenous inotropic factor from porcine left ventricle.

We report some of the unique pharmacological properties of a semipurified endogenous inotropic factor (EIF) present in the extract of the porcine left ventricle. EIF produced the following effects: (a) increase in isometric contractile force developed by electrically driven canine right ventricular trabecula, reaching a maximum with 60-100 microliters/ml concentration; (b) inhibition of Na-pump activity in canine portal vein; (c) no digitalis-like cardiac toxicity, e.g., increased diastolic tension or spontaneous diastolic mechanical oscillatory activity, despite inhibition of the sodium pump; (d) a small increase in sarcoplasmic reticular Ca release from the heart but a large increase in transsarcolemmal Ca influx as seen in biphasic contractions, an action similar to that produced by digitalis-like substances; and (e) prolongation of the action potential duration and refractory period of the canine isolated trabeculae. This latter action may confer a unique antiarrhythmic property to EIF.

Action Potentials↗
PubMed1992

A computer-based decision support system for diagnostic histopathology of the breast.

Accurate histological diagnosis of breast lesions is essential for the appropriate management of the patient. However, the technique of histological typing is problematic due to the large number of histological patterns, often of a complex and variable nature, which occur in breast disease. The introduction of the Breast Screening Programme has increased the burden on pathologists, and emphasised the need for training. Problems arise because mammographic screening detects a greater proportion of special histological types, with their attendant difficulties of identification, when compared to clinically palpable lesions. A computer-based decision support tool has been developed to assist pathologists in the histological diagnosis of breast disease. Unlike conventional expert systems, which seek to recreate the problem-solving processes of an expert, this system has been designed to act as an intelligent assistant to the pathologist. The system represents knowledge in the form of 'disease profiles', and utilises a novel inference model based upon the mathematical technique of hypergraphs. Initial trials with this system have demonstrated that a high level of diagnostic accuracy can be achieved.

Breast Diseases↗
PubMed1992

Contribution of sarcolemmal sodium-calcium exchange and intracellular calcium release to force development in isolated canine ventricular muscle.

The aim of this work was to determine the relationship between peak twitch amplitude and sarcoplasmic reticulum (SR) Ca2+ content during changes of stimulation frequency in isolated canine ventricle, and to estimate the extent to which these changes were dependent upon sarcolemmal Na(+)-Ca2+ exchange. In physiological [Na+]o, increased stimulation frequency in the 0.2-2-Hz range resulted in a positive inotropic effect characterized by an increase in peak twitch amplitude and a decrease in the duration of contraction, measured as changes in isometric force development or unloaded cell shortening in intact muscle and isolated single cells, respectively. Action potentials recorded from single cells indicated that the inotropic effect was associated with a progressive decrease of action potential duration and a marked reduction in average time spent by the cell near the resting potential during the stimulus train. The frequency-dependent increase of peak twitch force was correlated with an increase of Ca2+ uptake into and release from the SR. This was estimated indirectly using the phasic contractile response to rapid (less than 1 s) lowering of perfusate temperature from 37 degrees C to 0-2 degrees C and changes of twitch amplitude resulting from perturbations in the pattern of electrical stimulation. Lowering [Na+]o from 140 to 70 mM resulted in an increase of contractile strength, which was accompanied by a similar increase of apparent SR Ca2+ content, both of which could be abolished by exposure to ryanodine (1 x 10(-8) M), caffeine (3 x 10(-3) M), or nifedipine (2 x 10(-6) M). Increased stimulation frequency in 70 mM [Na+]o resulted in a negative contractile staircase, characterized by a graded decrease of peak isometric force development or unloaded cell shortening. SR Ca2+ content estimated under identical conditions remained unaltered. Rate constants derived from mechanical restitution studies implied that the depressant effect of increased stimulation frequency in 70 mM [Na+]o was not a consequence of a decreased rate of refilling of a releasable pool of Ca2+ within the cell. These results demonstrate that frequency-dependent changes of contractile strength and intracellular Ca2+ loading in 140 mM [Na+]o require the presence of a functional sarcolemmal Na(+)-Ca2+ exchange process. The possibility that the negative staircase in 70 mM [Na+]o is related to inhibition of Ca(2+)-induced release of Ca2+ from the SR by various cellular mechanisms is discussed.

Animals↗
PubMed1991

Mechanism of hypoxia-induced alteration in cerebral arteriolar tone in rats.

We studied the changes in pial arteriolar diameter during hypoxia and 60 and 120 min after restoration of normoxia, using the closed cranial window technique in artificially ventilated and normocapnic rats. Pial arteriolar diameter increased 16 +/- 4% during hypoxia (PaO2 less than 25 mm Hg, lasting 10 min). Although blood pressure (BP), heart rate (HR), and blood gases returned to prehypoxic level when measured at 60 and 120 min after hypoxia, pial arterial diameter decreased significantly (13 +/- 5 and 16 +/- 6% below control levels, respectively). This posthypoxic vasoconstriction was reversed by treatment of the brain surface with L-660,711 (10(-5) M), a specific leukotriene D4 receptor antagonist. These data suggest that leukotrienes may be involved in delayed cerebral vasoconstriction that follows a brief period of hypoxia.

Animals↗
PubMed1991

Possible role of leukotrienes in hypoxic contraction of canine isolated basilar artery.

1. Hypoxia reversibly increased isometric tension in unstimulated canine isolated basilar artery rings. 2. Nordihydroguaiaretic acid (NDGA; 5 x 10(-6) M), an inhibitor of lipoxygenase and quinacrine (10(-5) M), which blocks the release of arachidonic acid from phospholipids by inhibiting the enzyme phospholipase A2, blocked hypoxia-induced contractions. 3. The preferential leukotriene D4 (LTD4) antagonist, L-660,711, also inhibited the hypoxia-induced contractions in concentrations ranging from 10(-8) M to 10(-5) M. The effects seen were statistically significant (P less than 0.05). Two components of inhibition were seen. 4. Arachidonic acid (5 micrograms ml-1) caused contraction of the isolated basilar artery rings. This response was inhibited by NDGA (5 x 10(-6) M) and L-660,711 (10(-5) M). 5. The LTD4 (10(-8) M-10(-7) M)-induced contraction was relaxed by L-660,711 in a dose-dependent manner. Both the contraction caused by LTD4 as well as that caused by hypoxia were relaxed by 5 x 10(-6) M adenosine. 6. Leukotriene(s) may be involved in hypoxia-induced contraction of canine isolated basilar artery. However, they may not be the sole mediator(s).

Animals↗
PubMed1991

Knowledge-based computer system to aid in the histopathological diagnosis of breast disease.

A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of "disease profiles" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged "correct" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing "decision support" in histopathology.

Breast↗
PubMed1991

Inhibition of the acetylcholine-induced relaxation of canine isolated basilar artery by potassium-conductance blockers.

Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1-0.5 microM) relaxed in the presence of acetylcholine (25-100 microM), sodium nitroprusside (0.1 microM), or stimulation of the electrogenic sodium pump by restoration of extracellular K+ (4.5 mM) after K(+)-deprivation. Acetylcholine-induced relaxation is believed to be caused by the release of endothelium-derived relaxing factor (EDRF) and is prevented by mechanical removal of the endothelium, while relaxations induced by sodium nitroprusside or restarting of the sodium pump are endothelium-independent. Acetylcholine-induced relaxation was selectively blocked by pretreatment of the tissue with the nonselective K+ conductance inhibitors, 4-aminopyridine (4-AP, 3 mM), Ba2+ (1 mM), and tetraethylammonium (20 mM), 4-AP also blocked ACh-mediated relaxation in muscles contracted with elevated external K+. Relaxation of 5-hydroxytryptamine-induced contraction by sodium nitroprusside, or by addition of K+ to K(+)-deprived muscle, was not affected by 4-AP. Relaxation of basilar artery with acidified sodium nitrite solution (containing nitric oxide) was reduced by 4-AP. These results suggest that 4-AP and possibly Ba2+ inhibit acetylcholine-induced endothelium-dependent relaxation by inhibition of the action of EDRF on the smooth muscle rather than through inhibition of release of EDRF. The increase in K+ conductance involved in acetylcholine-induced relaxation is not due to ATP-inhibited K+ channels, as it is not blocked by glyburide (10(-6) M). Endothelium-derived relaxant factor(s) may relax smooth muscle by mode(s) of action different from that of sodium nitroprusside or by hyperpolarization due to the electrogenic sodium pumping.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1991

Influence of experimental diabetes on sarcoplasmic reticulum function in rat ventricular muscle.

We examined whether the decrease in cardiac contractility in streptozotocin-induced diabetes in the rat is accompanied by reduced or excessive loading of the sarcoplasmic reticulum (SR) with Ca2+. Pooled SR Ca2+ content and fractional release on stimulation were estimated with rapid cooling contracture (RCC) and twitch height measurements, respectively. Interval-force relation was studied to assess the ability of diabetic tissue to alter the relative contribution of SR Ca2+ for contraction. Two months after injection with streptozotocin, peak isometric contraction and steady-state RCC decreased in parallel to approximately 50% of control values. The time to peak force development and complete relaxation was prolonged to 156 and 161% in diabetes in the presence of 1.25 and 2.5 mM extracellular Ca2+ concentration [Ca2+]o, respectively. A stepwise increase in the rate of stimulation from 0.2 to 0.5 and 1.0 Hz resulted in a negative force staircase, the slope of which was identical in control and diabetic animals in each [Ca2+]o tested. Postrest contractions and RCC, after variable test intervals, were significantly depressed after 0.2 and 0.5 Hz stimulation in diabetic muscles at 1.25 mM [Ca2+]o. This defect of SR Ca2+ availability was reversed by increasing the stimulation frequency to 1.0 Hz or by elevating [Ca2+]o to 2.5 mM. The results suggest that the marked reduction of developed tension in diabetic tissues was a consequence of depleted SR Ca2+ stores, rather than a result of chronic SR Ca2+ overloading. The maintained integrity of the interval-force relation in the presence of diabetes implies that the cellular mechanisms responsible for frequency- and time-dependent alterations in SR Ca2+ availability are not disturbed at this stage of disease.

Animals↗
PubMed1991

Does pentobarbital anesthesia depress left ventricular contractility in dogs?

Although pentobarbital sodium (NP) anesthesia has been shown to depress left ventricular (LV) contractility in dogs, measurements of LV contractility in previous studies have been made soon after a bolus of NP was given when serum concentrations would be extremely high. In this study, we compared indexes of LV contractility during awake and anesthetized conditions. During anesthesia, measurements were obtained 1 h after an intravenous bolus of NP was given when serum concentrations were approximately 25 mg/l and above that reported to abolish pain. In 13 dogs, subendocardial ultrasonic crystal transducers and a high-fidelity pressure transducer were implanted into the LV. Measurements were obtained with and without prior treatment with propranolol to produce beta-adrenergic blockade. LV contractility was assessed by ejection fraction and the end-systolic pressure-volume relationship. The effect of NP on ventricular myocardium was also examined in an in vitro canine right trabecular preparation to compare in vivo and in vitro effects. In the in vivo study, the results showed no decrease in LV contractility during anesthesia regardless of whether propranolol was administered. The in vitro preparation showed only a minimal decrease in isometric tension at the concentrations used in the in vivo study. We conclude that NP anesthesia does not depress LV contractility when concentrations are maintained at approximately 25 mg/l.

Analysis of Variance↗
PubMed1991

Masseter muscle spasm in children: implications of continuing the triggering anesthetic.

This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique.

Anesthesia, Inhalation↗
PubMed1990

The influence of calcium, sodium, and the Na+/Ca2+ antiport on susceptibility to cytolysin/perforin-mediated cytolysis.

In NK cell-mediated cytolysis, the degranulation of the NK cell, and the binding and polymerization of its effector molecule cytolysin/perforin, are Ca2+ dependent. To determine if increases in the target cell free intracellular Ca2+ concentration ([Ca2+]i) are also important for cytotoxicity, we examined the effects of Ca2+ substitutes, promotors of Ca2+ influx; and inhibitors of Ca2+ efflux on the cytolysis mediated by purified cytolysin. Ca2+ promoted cytolysin-mediated cytolysis but could also inactivate cytolysin on preincubation in the absence of target cells. Ba2+ and Sr2+ could not alone promote cytolysin-mediated cytolysis but did enhance Ca2(+)-driven cytolysis. Preincubation with Ba2+ and Sr2+ did not inactivate cytolysin. One interpretation which these results suggested was that neither Ba2+ nor Sr2+ were involved in cytolysin polymerization and pore formation, but could act intracellularly as Ca2+ analogs once pore formation had occurred. The synergistic interaction of cytolysin and the Ca2+ ionophore A23187 further supported a role for increased [Ca2+]i in cytolysis. Inhibitors of Na+/Ca2+ exchange, namely low Na+ medium, ouabain, and the amiloride analogs 2',4'-dimethylbenzamil, 5-(N-4-chlorobenzyl)-2',4'dimethylbenzamil, and alpha-phenylbenzamil all markedly enhanced cytolysin-mediated cytolysis. These results support the hypothesis that the Ca2+ dependency of NK cell- and cytolysin-mediated cytolysis is related to increases in target cell [Ca2+]i. Furthermore, they indicate that Na+/Ca2+ exchange is an important counterlytic mechanism.

Amiloride↗
PubMed1990

hemofiltration reverses left ventricular dysfunction during sepsis in dogs.

Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration.

Animals↗
PubMed1990

Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle.

1. We previously isolated an extract from porcine left ventricle that possessed digitalis-like properties such as inhibition of cardiac and kidney Na+, K(+)-ATPase, displacement of [3H]-ouabain from its binding sites and cross reactivity with digoxin antibodies. The extract also had a positive inotropic effect on the guinea-pig heart. 2. In the present study the positive inotropic response of the extract was characterized in canine right ventricular trabeculae. Maximum inotropic response (501 +/- 20%) was produced by 300 microliters and the half maximal increase occurred with 125 microliters of the extract. 3. Ouabagenin produced aftercontractions in rapidly paced trabeculae. Equipotent and even greater amounts of the extract did not produce aftercontractions. 4. The extract increased the amplitude of the delayed component (P2) of biphasic contractions produced by replacing about 92-96% of the external Ca with Sr. A smaller increase in the size of the early component (P1) was also seen. 5. The extract decreased post-rest potentiation after rest for 30s and 2 min. After 8 min of rest, post-rest potentiation was converted to post-rest depression. 6. The extract (20 microliters) produced a decrease in the amplitude of the post-rest rapid cooling contracture (RCC) at all rest intervals. The steady state RCC, although greater than that in the control muscle, was increased to a lesser extent than the size of the steady state electrically driven contractions. 7. It is suggested that the extract from porcine left ventricle produces a positive inotropic response by increasing the trans-sarcolemmal influx of Ca. It also has additional effect(s) on the sarcoplasmic reticulum in that it may facilitate the loss of Ca from the sarcoplasmic reticulum and/or inhibit the uptake of Ca by the organelle.

Animals↗
PubMed1989

Cardiac glycoside-like structure and function of 5 beta,14 beta-pregnanes.

5 beta-Reduction and 14 beta-substitution convert the planar progesterone molecule to the cardiac glycoside configuration--A and D rings of the steroid moiety are bent toward the alpha-face relative to the B and C rings. Potency of the 5 beta,14 beta-derivative in a [3H]ouabain binding assay or its ability to inhibit the sodium pump in red blood cells is enhanced by 3 beta-hydroxylation, 20 beta-hydroxylation, and 3 beta-glycosidation. Synthesis of 14,20 beta-dihydroxy-3 beta-(beta-D-glucopyranosyloxy)- 5 beta,14 beta-pregnane from digitoxin is described. The glucoside is 1/20 as potent as ouabain and elicits prominent, sustained, positive inotropy in isolated cardiac muscle.

Animals↗
PubMed1989

Role of endothelium in hypoxic contraction of canine basilar artery.

1. Reversible contraction of canine basilar artery, produced by hypoxia, persisted after mechanical and chemical removal of the endothelium. The removal of endothelium was confirmed by scanning electron microscopy as well as by the abolition or reversal of the relaxant response to acetylcholine or arginine8-vasopressin. 2. Hydroquinone, believed to block selectively endothelium-mediated relaxation, also preferentially attenuated hypoxic contractions even in the absence of endothelium but did not reduce responses to 5-hydroxytryptamine (5-HT) or high external potassium. 3. Contractions induced by red blood cell haemolysate, which occur independently of the endothelium, were also selectively attenuated by hydroquinone. 4. Contractions caused by hypoxia were inhibited by pretreatment with adenosine or by its application after contraction had developed. 5. Hypoxic contraction in canine basilar artery may result partly from a direct effect on smooth muscle as well as through the endothelium. 6. Hydroquinone may have an additional locus of action in smooth muscle cells besides its well known effect on the endothelium.

Adenosine↗