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Biomedical subjects

B Patel

Publications and source records attributed to B Patel.

At least 127 records · Page 7Linked to original sources
PubMed1992

Mutually exclusive splicing of calcium-binding domain exons in chick alpha-actinin.

We have determined the complete sequence of chick brain alpha-actinin (892 amino acids; 107,644 Da). The sequence differs from that of smooth muscle alpha-actinin only in the region of the first EF-hand calcium-binding motif, where 27 residues in brain alpha-actinin are replaced by just 22 residues in the smooth muscle isoform. This probably accounts for the different calcium sensitivities of the two isoforms with respect to actin binding. Analysis of the gene structure showed that this region of sequence divergence is encoded by two separate exons whose incorporation is mutually exclusive. We have determined the proportion of the two transcripts in various tissues and cell lines using poly(A)+ RNA and a quantitative assay based on the polymerase chain reaction. MRC-5 fibroblasts and HeLa cells express mRNAs encoding both isoforms, whereas Namalwa lymphoblastoid cells, which lack actin stress fibers, express only the non-muscle mRNA. Both isoforms of alpha-actinin became incorporated into stress fibers and cell-matrix junctions when full-length chick alpha-actinin cDNAs were expressed in monkey COS cells. The levels of chick alpha-actinin mRNAs were found to be serum-inducible, suggesting that alpha-actinin may be an early response gene.

Actinin↗
PubMed1992

Does cocaine cause coronary vasospasm in chronic cocaine abusers? A study of coronary and systemic hemodynamics.

The pathogenesis of acute myocardial ischemia or infarction following cocaine abuse is not known. Cocaine causes an increase in circulating catecholamines. Therefore alpha-adrenergic mediated focal or generalized coronary artery spasm has been presumed to be the likely mechanism to induce ischemia. However, coronary vasospasm in chronic cocaine abusers has not been demonstrated angiographically. Moreover, it has been observed that patients commonly manifest ischemic changes hours up to a week after abusing cocaine. In order to evaluate direct effects of cocaine on coronary vasculature, 6 chronic cocaine abusers admitted with prolonged chest pain and electrocardiographic ST- and T-wave changes were studied. Cocaine administered intravenously (maximum 32 mg) produced subjective sensation of central nervous stimulation (the "high") in all patients. However there was no significant change in coronary artery diameter (assessed by computer-assisted quantitative technique), myocardial perfusion (assessed by contrast echocardiography) or left ventricular wall motion (assessed by two-dimensional echocardiography) as compared with the baseline values. Coronary sinus flow (thermodilution) showed an upward trend, a probable reflection of a significant increase in cardiac output (average 62%, p less than 0.007). Despite a significant elevation in heart rate (average 56%, p less than 0.007), mean systemic arterial pressure (average 12%, p less than 0.05) and rate-pressure product (average 69%, p less than 0.005), no symptomatic or acute electrocardiographic changes were observed. It is concluded that recreational doses of cocaine do not cause focal or generalized coronary vasospasm or reduced myocardial perfusion in patients who present with chest pain temporally related to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cadmium effects on bone metabolism: accelerated resorption in ovariectomized, aged beagles.

The purpose of this study was to evaluate, in an animal whose skeleton is comparable to humans, the combined effects of estrogen depletion and Cd exposure on bone resorption by monitoring skeletal release of 45Ca and to determine whether Cd-induced bone resorption occurred independent of osteotropic hormone changes and renal dysfunction. Cd exposure following ovariectomy or sham surgery was for 7 months: 1 month by oral ingestion of capsules (1, 5, 15, 50 ppm) and 6 months via drinking water (15 ppm). Serum and fecal 45Ca were increased at 1 week following ovariectomy (OV) (54 +/- 9% and 122 +/- 40%, respectively), but this response was attenuated by 2 weeks. Five of seven exposed dogs had increased serum and fecal 45Ca during the 50-ppm Cd capsule period (15-40% and 15-190%, respectively). Serum 45Ca levels in OV/+Cd dogs showed a significant and consistent increase within 1 week of initiating each of three separate Cd.H2O exposure cycles. Blood Cd levels increased over time from 2 to 15 micrograms/l, coinciding with the elevated serum 45Ca concentrations. No correlation was observed between serum 45Ca increases and parathyroid hormone, 1,25-(OH)2-vitamin D, or calcitonin. No effects of ovariectomy and/or Cd were observed in total serum Ca, calciotropic hormone concentrations, serum or urinary phosphorus and creatinine, creatinine clearance, or urinary specific gravity. Urinary Cd concentrations ranged from 7 to 50 micrograms/l in exposed dogs but were not detectable in nonexposed dogs. Urinary protein concentrations showed no differences between groups. Cd increased bone resorption (skeletal 45Ca release) in ovariectomized and sham-operated dogs without renal dysfunction or calciotropic hormone interaction. Based on our results, Cd is an exogenous factor which exacerbates bone mineral loss in postmenopausal osteoporosis.

Aging↗
PubMed1992

The effect of SK&F 95654, a novel phosphodiesterase inhibitor, on cardiovascular, respiratory and platelet function.

1. SK&F 95654 inhibited the guanosine 3':5'-cyclic monophosphate (cyclic GMP)-inhibited phosphodiesterase (cGI-PDE) with an IC50 value of 0.7 microM. The IC50 values were greater than 100 microM for the other four phosphodiesterase isoenzymes tested. The R-enantiomer of SK&F 95654 (IC50 = 0.35 microM) was a more potent inhibitor of cGI-PDE than was the S-enantiomer (IC50 = 5.3 microM). 2. In the guinea-pig working heart, SK&F 95654 produced a positive inotropic response without altering heart rate. 3. Oral administration of SK&F 95654 to conscious dogs caused dose-dependent increases in left ventricular dp/dtmax in the range 10-50 micrograms kg-1. These positive inotropic responses were maintained for 3 h without simultaneous changes in heart rate or blood pressure. The peak effects on left ventricular dp/dtmax were similar for orally and intravenously administered compound, indicating good oral bioavailability. 4. SK&F 95654 caused a potent inhibition of U46619-induced aggregation in both a human washed platelet suspension (WPS) (IC50 = 70 nM) and in human platelet-rich plasma (PRP) (IC50 = 60 nM), indicating that the compound shows negligible plasma binding. 5. The R-enantiomer of SK&F 95654 was twenty fold more potent as an inhibitor of platelet aggregation than was the S-enantiomer. The similarity of this ratio to that obtained on the cGI-PDE suggests that SK&F 95654 inhibits platelet aggregation via its effects on cGI-PDE. This was also indicated by studies which showed that SK&F 95654 increased adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels and activated cyclic AMP-dependent protein kinase in human platelets. 6. Collagen-induced aggregation of rat PRP was also inhibited by SK&F 95654 (ICso = 65 nM). The effects of SK&F 95654, administered intravenously, on ex vivo platelet aggregation were studied in the conscious rat. At 1 mg kg-', SK&F 95654 inhibited aggregation for at least 4 h post dose and was more potent than the two other cGI-PDE inhibitors studied (siguazodan and SK&F 94120).7. In contrast to its potent effects on heart and platelets, SK&F 95654 caused only a modest relaxation of histamine- or U46619-induced bronchoconstriction in the anaesthetized, ventilated guinea-pig.8. Taken together, these results indicate that SK&F 95654 may be a suitable agent for the treatment of congestive heart failure.

Administration, Oral↗
PubMed1991

Substantial quantities of the high energy derivative oligophosphoglyceroyl-ATP are located in mitochondria in rat liver.

Perfusion with [8-14C]adenosine demonstrated the likely existence in rat liver of oligophosphoglyceroyl-ATP (OPG-ATP). Purification followed by assay with a new specific 3' phosphodiesterase confirmed this. The quantities present were 5-10-fold those found previously and comparable to total soluble nucleotides. OPG-ATP was also purified from the mitochondrial fraction, shown to co-distribute with succinate dehydrogenase and can be co-purified with an enzyme confined to intermembrane space.

Adenosine Triphosphate↗
PubMed1991

The characterization of a new enzyme from rat liver mitochondria, oligophosphoglyceroyl-ATP 3'-phosphodiesterase.

By using an assay based on the precipitation of intact 14C-labelled substrate, an activity has been located in the mitochondrial fraction of rat liver which selectively hydrolyses the 3' ester link in the fairly recently discovered oligomeric tetraphosphate derivative of ATP and glyceric acid for which the structure 3-phospho[glyceroyl-gamma-triphospho-5'-adenosine-3'-3-phospho]n-glyceroyl- gamma-triphospho-5'-adenosine has been proposed [Hutchinson, Morris & Mowbray (1986) Biochem. J. 234, 623-627]. This enzyme activity (Mr 85,000) has been purified approx. 30-fold from washed mitochondria by (NH4)2SO4 precipitation and f.p.l.c. The apparent Km for substrate (adenosine equivalents) is around 35 microM. The recovery of total activity is about 20%, and this, allied to the relatively low Vmax. found in contrast with the rapid turnover of oligomer seen in post-ischaemic tissues, suggests that some activating factors have been lost in purification. Percoll-gradient studies confirm that the activity is mitochondrial and not lysosomal or endoplasmic-reticular. The activity is latent in intact mitochondria; it is not, however, associated with intact inner-membrane vesicles but released during their preparation, implying an intermembrane-space location. The product of the enzyme is proposed to be the monomeric unit 3-phosphoglyceroyl-gamma-triphospho-5'-adenosine, from which digestion with snake-venom phosphodiesterase releases ADP.

Animals↗
PubMed1991

Community-acquired acute renal failure.

Acute renal failure usually occurs during hospitalization, but may also be present on admission to the hospital. To define the causes and outcomes of community-acquired acute renal failure, we undertook a prospective study of patients admitted to the hospital with acute elevations in serum creatinine concentrations. Over a 17-month period, all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L (2 mg/dL). These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital. One hundred patients were entered into the study, with an overall incidence of 1% of hospital admissions. Seventy percent of the patients had prerenal azotemia, 11% had intrinsic acute renal failure, 17% had obstruction, and 2% could not be classified. Mean peak serum creatinine (318 +/- 18 mumol/L [3.6 +/- 0.2 mg/dL]) and mortality (7%) was lowest in the group with prerenal azotemia. In this group, volume contraction due to vomiting, decreased fluid intake, diarrhea, fever, glucosuria, or diuretics was the most common underlying cause. The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality (55%). Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure, this etiology was seen in only one patient. Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure. Obstructive renal failure had a mortality of 24% and was most commonly due to benign prostatic hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1991

Needle holder for use with a biopsy gun.

The authors designed and constructed a simple needle holder device for maintaining the position of the trocar and cannula before performance of computed tomography (CT)- and ultrasonography-guided biopsies with a biopsy gun. The holder can be removed before attachment of the biopsy gun and routine obtaining of tissue. Use of the holder facilitated quicker and easier CT-guided biopsies of the liver (n = 3), pancreas (n = 1), and adrenal gland (n = 1) and of a chest wall tumor.

Biopsy, Needle↗
PubMed1991

Potential use of selective phosphodiesterase inhibitors in the treatment of asthma.

Selective inhibitors of the cyclic nucleotide phosphodiesterase (PDE) isoenzymes have been studied to assess the potential for such agents in the treatment of asthma. A novel selective PDE V inhibitor, SK&F 96231, reversed the bronchoconstriction induced in anaesthetised guinea pigs by histamine, a thromboxane-mimetic or by ovalbumin challenge. There was no effect of SK&F 96231 on heart rate or blood pressure in conscious dogs. Siguazodan (SK&F 94836, a selective PDE III inhibitor) caused bronchodilation but also had cardiovascular effects in conscious dogs. Studies on the PDE profile of various inflammatory cells have indicated that inhibition of PDE IV would be beneficial in the treatment of the inflammatory aspects of asthma and this is briefly reviewed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Autonomic and haemodynamic responses to SK & F 101468 (ropinirole), a DA2 agonist, in anaesthetised cats.

The haemodynamic and autonomic nervous system effects of the DA2 agonist, SK & F 101468, have been studied in anaesthetised cats. SK & F 101468 inhibited the tachycardia response to cardiac accelerans nerve stimulation. The inhibition, reversed by L-sulpiride a selective DA2 receptor antagonist, was dose-dependent over the dose range 10-50 micrograms.kg-1 and there was proportionally greater inhibition of the responses to low rather than high frequency stimulation. There was evidence that SK & F 101468-A inhibited sympathetically mediated reflexes, but even at high doses, of up to 500 micrograms.kg-1, there was no inhibition of end-organ responsiveness to noradrenaline, isoprenaline or acetylcholine nor of the bradycardia caused by vagus nerve stimulation. SK & F 101468-A produced falls in blood pressure and heart rate at 50 and 500 micrograms.kg-1, but stroke volume, aortic blood flow and total peripheral resistance, were only slightly affected. These effects of SK & F 101468 in the intact cardiovascular system are consistent with an action on presynaptic receptors at sympathetic nerve endings to reduce transmitter release and thereby selectively reduce responses to sympathetic nerve stimulation.

Acetylcholine↗
PubMed1990

Induced expression of a monocytoid B lymphocyte antigen phenotype on the REH cell line.

A human common acute lymphoblastic leukemia (ALL) cell line, REH, was treated in vitro with gamma-interferon (gamma-IFN) or 12-O-tetradecanoylphorbol 13-acetate (TPA). Untreated (control) and treated cells were analyzed for changes in growth patterns, morphology, cytochemistry, surface phenotype, and terminal transferase (TdT) activity. TPA but not gamma-IFN induced further maturation of REH cells along the B-cell lineage. There was a dramatic decrease in CALLA expression, loss of TdT activity, induction of Leu M5, and increase in Leu 14 expression. TPA also induced monocytoid morphological features on REH cells. Enzymatically, the induced cells strongly expressed acid phosphatase (tartrate sensitive), alpha-naphthol acetate esterase (NAE), and periodic acid Schiff (PAS). We conclude that TPA induced monocytoid B-lymphocyte features on REH cells within the B-cell lineage, which should not be confused with monocytes/macrophage. The phenotype of cells in this stage is Leu 14+, Leu M5+, BL1+, Leu 12+, AcP+, PAS+, NAE+, CALLA-, TdT-, MO1-, and MO2-.

Antigens, Neoplasm↗