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S Das

Publications and source records attributed to S Das.

At least 577 records · Page 32Linked to original sources

Selective proliferation of brain kappa opiate receptors in spontaneously hypertensive rats.

The binding of tritiated ligands for various opiate receptor subtypes to brain membranes prepared from spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was determined. The density (Bmax) or the apparent dissociation constant (Kd) for the binding of the mu-ligand (naltrexone) and delta-ligand (Tyr-D-Ser-Gly-Phe-Leu-Thr) to brain membranes of hypertensive and normotensive rats did not differ. However, the Bmax for the binding of kappa-ligand (ethylketocyclazocine, EKC) to brain membranes after the suppression of mu and delta-sites by 100 nM each of unlabeled D-Ala2-MePhe4-Gly-ol5-enkephalin and D-Ala2-D-Leu5-enkephalin, respectively, was significantly greater in hypertensive rats compared to normotensive rats. The Kd values for the binding of 3H-EKC in the two groups did not differ. The binding of 3H-EKC in brain regions was in the order: hypothalamus greater than midbrain greater than striatum greater than cortex greater than pons + medulla. The increase in the binding of 3H-EKC in the brain of hypertensive rats compared to normotensive rats was due to increased binding in the hypothalamus and cortex. These results provide for the first time evidence of selective proliferation of kappa-opiate receptors in the brain of hypertensive rats, and suggest that brain kappa-opiate receptors may play an important role in the pathophysiology of hypertension.

Animals↗

A cyclic nucleotide-independent protein kinase in Leishmania donovani.

Leishmania donovani promastigotes labelled for 2 h with 32Pi incorporated radioactivity into at least 21 different proteins, as determined by SDS/polyacrylamide-gel electrophoresis. Pulse-chase studies with 32Pi demonstrated that the labelled proteins were in a dynamic state: some radiolabelled proteins rapidly disappeared and others appeared after the chase. The possibility of an ectokinase on the parasite was examined; incubation of intact parasites for 10 min at 25 degrees C in an osmotically buffered medium containing [gamma-32P]ATP, but not [alpha-32P]ATP, resulted in the labelling of 10 different protozoal proteins, presumably localized to the surface of the organism's plasma membrane. Intact promastigotes also catalysed the transfer of 32P from [gamma-32P]ATP to histones. The histone-dependent kinase was solubilized by repeated freezing and thawing, and sonication, and purified 118-fold by chromatographing the high-speed (200,000 g, 1 h) supernatant fraction on QAE-Sephadex, Sephadex G-150 and hydroxyapatite columns. The kinase eluted as a single activity peak from all three columns. The partially purified histone-dependent kinase had the following properties: pH optimum, 7.0; optimum temperature, 37 degrees C; Km for mixed calf thymus histone, 0.15 mM; Km for ATP, 0.8 mM; preferred fractionated histone acceptors, H2b greater than H4 greater than H2a greater than H3 (H1 does not serve as an acceptor); optimum activity required 10-20 mM-Mg2+; inhibited 50-80% by 0.01 mM- and 1 mM-Ca2+; activity was not stimulated by calmodulin, cyclic AMP (1 mM) or cyclic GMP (1 mM) nor inhibited by a cyclic AMP-dependent protein kinase inhibitor (50 micrograms/assay); apparent Mr 75,000, as determined by Sephadex G-150 gel filtration chromatography; phosphorylated exclusively serine residues. Protein kinase activity was low in the early exponential phase of the growth curve and increased 6-fold upon entry into the stationary phase.

Animals↗

Modification by diacylglycerol of the structure and interaction of various phospholipid bilayer membranes.

The effects of incorporating diacylglycerol (DG) derived from egg phosphatidylcholine (PC) into PC, egg phosphatidylethanolamine (PE), and bovine phosphatidylserine (PS) have been measured. In excess solution DG induces a multilamellar-to-hexagonal (L-H) structural transition in PE and PC that is temperature dependent. At 37 degrees C it begins at about 3 and 30 mol%, respectively. In PC at lower DG concentrations a modified lamellar phase is formed; at about 70 mol% DG a single primitive cubic phase forms. An L-H transition induced by 20-30 mol% DG in PS is dependent on ionic strength and degree of lipid hydration, with the appearance of crystalline acyl chains at the higher DG levels. Calcium precipitates of DG/PS (1/1) mixtures have melted chains. Structural parameters were derived for the lamellar phases at subtransition levels of DG in PE and PC. The area per polar group is increased, but by contrast with cholesterol, the polar group spreading is not accompanied by an increase in bilayer thickness. DG does not affect the equilibrium separation of PC or PE bilayers. Measured interbilayer forces as they vary with bilayer separation show that DG at 20 mol% does not effect closer apposition of PC bilayers at any separation. Spreading the polar groups may effect the binding of protein kinase C or the activation of phospholipases; the nonlamellar phases may be linked to the biochemical production of DG in cellular processes involving membrane fusion.

Animals↗

Evidence for opiate action at the brain receptors for thyrotropin-releasing hormone.

The effect of drugs acting on mu-, delta-, kappa- and sigma-opiate receptors on the binding of [3H-3-MeHis2]thyrotropin releasing hormone ([3H-Me]TRH) to rat brain membranes was determined. The drugs used included morphine and naloxone (mu-ligands), N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154, 129, delta-ligand), ethylketocyclazocine (EKC, kappa-ligand), and N-allylnormetazocine (SKF-10,047, sigma-ligand). [3H-Me]TRH bound specifically to brain membranes at a single high-affinity site with a Bmax value of 50 fmol/mg protein and a Kd of 5 nM. A concentration of 2 nM of [3H-Me]TRH was used for in vitro interaction studies. The binding of [3H-Me]-TRH was unaffected by morphine or naloxone up to and including 1 mM concentration, but was inhibited by ICI 154,129 (IC50, 8 X 10(-5) M), EKC (IC50, 3 X 10(-4) M), SKF 10,047 (IC50, 1 mM), and TRH (IC50, 2 X 10(-7) M). In the presence of an IC25 concentration of IDI 154, 129 or EKC, there was a 25% decrease in the Bmax values of [3H-Me]TRH but the apparent dissociation constant, Kd value did not change. The results demonstrate for the first time that ligands acting at the delta- and kappa-opiate receptors interact with the brain TRH receptors; sigma-receptor ligands have weak interaction and mu-receptor ligands do not interact with brain TRH receptors. These results may help in explaining the observed pharmacological interactions between opiates and TRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurohumoral activation during exercise in congestive heart failure.

Neurohumoral factors were assessed in 14 subjects with chronic, stable New York Heart Association functional class II or III congestive heart failure and nine comparably aged normal subjects at rest and during moderate (50 W) and strenuous (100 W) upright exercise. Heart failure was associated with elevated plasma renin activity and plasma antidiuretic hormone (ADH) concentrations at rest. However, plasma renin activity almost doubled (from 4.7 +/- 0.6 to 8.4 +/- 1.1 ng/ml per hour) during strenuous exercise in subjects with heart failure, and changed only minimally in normal control subjects. Plasma ADH concentration did not change during exercise in the presence of heart failure, but rose in normal subjects during strenuous exercise to levels comparable to those of subjects with heart failure. Similar plasma osmolality values were present in both groups. Circulating norepinephrine concentrations were insignificantly elevated by heart failure both at rest and during exercise, and plasma epinephrine concentrations were similar. These findings suggest independent neurohumoral activation during exercise in the presence of congestive heart failure, with predominant activation of the renin-angiotensin-aldosterone axis.

Adult↗

Endometrial carcinoma of prostate.

In the rare group of atypical adenocarcinomas of the prostate gland, endometrial carcinoma arising from the prostatic utricle can be perplexing to diagnose because of its histologic similarity with other ductal carcinomas and frequent simultaneous admixture of microacinar adenocarcinomas. Two cases of endometrial carcinoma of the prostate are detailed, and the therapeutic implications of such histologic diagnosis are reviewed.

Adenocarcinoma↗

Prophylactic antibiotics in transurethral resection of bladder tumors: are they necessary?

In a double-blind study, 30 patients having transurethral surgery for bladder tumors were randomly assigned to receive prophylactic carbenicillin indanyl sodium or a placebo perioperatively. Only one patient in the carbenicillin group had a postoperative urinary infection due to carbenicillin-resistant Klebsiella oxytoca organisms. Thus, no advantage from the prophylactic use of antibiotics was evident in this uninfected group of patients.

Adult↗

Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani.

Leishmania donovani promastigotes contain intense tartrate-resistant cell surface acid phosphatase (ACP1) which blocks superoxide anion production by activated human neutrophils [A.T. Remaley et al. (1984) J. Biol. Chem, 259, 11173-11175]. An extensively purified preparation of ACP1 dephosphorylates several phosphoproteins which are phosphorylated at serine residues; these include: pyruvate kinase (Km 1.6 microM; Vmax 71.4 U (mg protein)-1), phosphorylase kinase (Km 0.076 microM; Vmax 5.4 U (mg protein)-1) and histones (Km 4.86 microM; Vmax 2.2 U (mg protein)-1). However, the specific activity of the leishmanial phosphatase on these phosphoproteins is very low as compared to other phosphoprotein phosphatases. The phosphatase activity of ACP1 was also low on phosphohistone phosphorylated at tyrosine residues. Phosphatidylinositol-4,5-diphosphate (PIP2) and inositoltriphosphate (IP3) were also tested as ACP1 substrates. PIP2 was hydrolyzed rapidly by ACP1. The rate of hydrolysis of PIP2 was higher at pH 6.8 (Km 2.35 microM; Vmax 107 X 10(3) U (mg protein)-1) than at pH 5.5 (Km 4.16 microM; Vmax 71 X 10(3) U (mg protein)-1). 32P-labeled IP3 was also a substrate for ACP1; the hydrolysis products consisted of a mixture of inositoldiphosphate and inositolmonophosphate. ACP1 and ten other phosphatases were tested for their ability to dephosphorylate proteins and to inhibit O2- production by stimulated human neutrophils. There was no correlation between the protein phosphatase activity of the acid- and alkaline phosphatases and their ability to block neutrophil O2- production. The results indicate that ACP1 probably blocks the production of reduced oxygen intermediates by a mechanism that does not involve dephosphorylation of phosphoproteins; however, the possibility that the parasite's phosphatase affects phagocyte metabolism by degrading PIP2 or IP3 should be considered.

Acid Phosphatase↗

Effect of acute and chronic morphine administration on brain cholinergic muscarinic receptors.

The binding of [3H]quinuclidinyl benzilate (QNB) to various brain regions was determined in rats after acute or chronic treatment with morphine. Morphine and naloxone, in vitro, inhibited the binding of [3H]QNB to striatal membranes only at high concentrations. Thirty minutes after a single injection, morphine (5 or 40 mg/kg s.c.) did not alter the Bmax or Kd values for [3H]QNB binding to striatal receptors. The binding of [3H]QNB to membranes of different brain regions was not changed in morphine tolerant-dependent rats or rats undergoing abrupt or naloxone precipitated withdrawal. The results suggest that central cholinergic muscarinic receptors are unaffected by acute or chronic treatment with morphine, or during abstinence.

Animals↗

Vesical diverticulum associated with bladder carcinoma: therapeutic implications.

Of 146 patients with bladder diverticula during a 15-year period 9 had associated transitional cell carcinoma of the bladder: 3 (2 per cent of all patients with diverticula) in the diverticulum, 3 adjacent to the ostium of the diverticulum and 3 remote from the diverticulum. All 3 patients with carcinoma in the diverticulum died of metastases, whereas the other 6 patients survived more than 5 years. We propose aggressive treatment for patients with carcinoma in the diverticulum but we do not recommend routine diverticulectomy in cases of asymptomatic and uncomplicated diverticula.

Aged↗

Abdominal transposition of the female urethra.

Abdominal transposition of the female urethra, a rational choice for the surgical treatment of reflex neurogenic incontinence, has been used infrequently to date. We present a case to illustrate the steps in the surgical technique of transposition, emphasizing the principles we believe necessary to create a continent urethrovesical valve. If proper attention is given to surgical details the patient can achieve continence and require intermittent self-catheterization only.

Abdomen↗

Benign intrascrotal neoplasms.

We analyzed the surgical and pathological records of 90 patients who underwent surgical exploration of solid scrotal masses during a 5-year period. Sixteen patients had benign lesions, including 10 adenomatoid tumors, 3 fibrous pseudotumors, 2 fibromas and 1 dermoid cyst. Twelve patients with benign lesions were treated by local excision and 4 by orchiectomy. Identification of benign intrascrotal lesions, aided by examination of frozen sections and combined with an understanding of the lesions, allows the intraoperative decision for local excision and the avoidance of needless orchiectomy.

Adenoma↗

Demonstration of various acid hydrolases and preliminary characterization of acid phosphatase in Naegleria fowleri.

Extracts of the pathogenic ameba Naegleria fowleri, prepared by freeze-thawing and sonication, were analyzed for their content of various hydrolytic enzymes that have acid pH optima. The organism is rich in acid phosphatase activity as well as a variety of glycosidases which include beta-glucosidase, beta-galactosidase, beta-fucosidase, alpha-mannosidase, hexosaminidase, arylsulfatase A, and beta-glucuronidase. The crude extract contained only negligible levels of sphingomyelinase, neuraminidase, or arylsulfatase B. All of the hydrolases exhibited higher activity at pH 5.5 than at 7.0, indicating that they are truly "acid" hydrolases. In general, after centrifugation (100,000 g, 1 h), except for arylsulfatase B, more than half of the activity of each of the various hydrolases was recovered in the supernatant fraction. The acid phosphatase in the high-speed supernatant was purified 45-fold (32% yield) by chromatography on QAE-Sephadex and Sephadex G-200 and shown to have the following properties: pH optima, 5.5; Km (4-methylumbelliferyl phosphate), 0.60 mM; molecular weight (estimated by gel filtration chromatography), 92,000; inhibited by heteropolymolybdate complexes but not by L(+) sodium tartrate (0.5 mM) or sodium fluoride (0.5 mM). In addition, unlike the tartrate-resistant acid phosphatase of Leishmania donovani, the major acid phosphatase of N. fowleri is less than 5% as effective in inhibiting superoxide anion production by f-Met-Leu-Phe-stimulated human neutrophils. The finding of high levels of a number of acid hydrolases in Naegleria fowleri raises several questions that merit further study: Do the hydrolases perform a housekeeping function in this single cell eukaryote or do they play some role in the pathogenic process that ensues when the organism infects a suitable host?

Acid Phosphatase↗