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Biomedical subjects

A K Das

Publications and source records attributed to A K Das.

At least 91 records · Page 5Linked to original sources

Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience.

The preliminary experience with 64 patients who have undergone HoLEP combined with intravesical morcellation is presented. The mean preoperative prostate volume was 75.3 cc. The mean laser time was 46.9 minutes and the morcellator time a further 10.5 minutes. A mean total of 35.5 g of tissue was obtained, and 93% of the patients were discharged the day after their surgery without a catheter. The American Urological Association Symptom Score at 1 month was 8.6 and the peak flow rate 23.4 mL/sec. This combination of procedures allows prostate glands of virtually any size to be safely treated transurethrally, and a complete anatomic enucleation of the prostatic adenoma is achieved.

Aged↗

The structure and mechanism of protein phosphatases: insights into catalysis and regulation.

Eukaryotic protein phosphatases are structurally and functionally diverse enzymes that are represented by three distinct gene families. Two of these, the PPP and PPM families, dephosphorylate phosphoserine and phosphothreonine residues, whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine amino acids. A subfamily of the PTPs, the dual-specificity phosphatases, dephosphorylate all three phosphoamino acids. Within each family, the catalytic domains are highly conserved, with functional diversity endowed by regulatory domains and subunits. The protein Ser/Thr phosphatases are metalloenzymes and dephosphorylate their substrates in a single reaction step using a metal-activated nucleophilic water molecule. In contrast, the PTPs catalyze dephosphorylation by use of a cysteinyl-phosphate enzyme intermediate. The crystal structures of a number of protein phosphatases have been determined, enabling us to understand their catalytic mechanisms and the basis for substrate recognition and to begin to provide insights into molecular mechanisms of protein phosphatase regulation.

Animals↗

Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules.

Calcium-channel antagonist drugs are prescribed widely for angina and hypertension. A limiting side effect is edema, which can make heart failure worse. We show that nifedipine, a dihydropyridine-type calcium-channel antagonist, can increase vascular permeability in rat skeletal muscle and skin when injected locally. In nifedipine-injected cremaster muscle, the copper content, used to quantify Monastral blue dye accumulation, was 15.0 +/- 2.4 microgram/g compared with 5.3 +/- 0.7 microgram/g in control preparations (P < 0. 05). The injection of nifedipine in rat skin in vivo increased local plasma leakage in injected sites from 5.5 +/- 1.1 microliter in control sites to 9.9 +/- 2.5, 17.0 +/- 2.4, 24.3 +/- 5.9, and 23.3 +/- 5.4 microliter in sites injected with 10(-10), 10(-9), 10(-8), or 10(-7.2) mol/site, respectively (P < 0.05 in each case compared with control). Vascular labeling techniques using light microscopy, electron microscopy, and microanalysis show that the microvascular site of leakage is not from capillaries but from postcapillary venules of 12-36 micrometer in diameter, the same site that controls the edema response in inflammation. Nifedipine can act within the microcirculation to increase the permeability of the postcapillary venule.

Animals↗

Genetic studies of polymorphisms in ten non-insulin-dependent diabetes mellitus candidate genes in Tamil Indians from Pondichery.

We report a study of 10 candidate genes presumably involved in diabetes or insulin resistance or obesity among Pondicherian Tamil Indians, an isolated population with a high prevalence of diabetes. Forty-nine families with at least two affected patients in the sibship (567 individuals) were selected and tested by PCR-RFLP techniques for reported mutations in 10 diabetes or obesity candidate genes: glucagon receptor, insulin receptor substrate 1, insulin receptor, human beta 3 adrenergic receptor, fatty acid binding protein 2, mitochondrial tRNA(Leu(UUR)), sulphonylurea receptor, human uncoupling protein and the glycogen-associated regulatory subunit of protein phosphatase-1. Glucokinase gene was also screened for mutations. No mutations were found in glucokinase, glucagon receptor and mitochondrial genes in any of the 49 probands. Frequencies of polymorphisms at other loci were similar to those reported in Caucasian populations, except for 4 of the loci at which a higher frequency of variants was observed: human beta 3 adrenergic receptor, human uncoupling type 1 protein, fatty acid binding protein 2 and the glycogen-associated regulatory subunit of protein phosphatase-1. However, no evidence of association between any of these gene variants and non-insulin-dependent diabetes mellitus (NIDDM) or quantitative traits related to NIDDM (including body mass index, waist/hip ratio, insulinaemia, glycaemia, triglycerides and total cholesterol) was found in our sample. These results suggest that none of these gene variants commonly found in the Pondicherian Tamil population of South India is a major NIDDM predisposing locus, although it cannot be excluded that they may contribute to the polygenic background of the metabolic syndrome in Pondichery.

Adult↗

A fibroblast cell line defective in alkyl-dihydroxyacetone phosphate synthase: a novel defect in plasmalogen biosynthesis.

Using fluorescence-activated cytotoxicity selection, followed by colony autoradiographic screening of the surviving population, we have isolated a unique plasmalogen-deficient Chinese hamster ovary (CHO) cell line. The mutant, NZel-1, showed a dramatic (90%) reduction in the rate of biosynthesis and levels of plasmalogens, as determined using short- and long-term labeling with 32Pi. Enzymatic assays and lipid supplementation studies showed that NZel-1 was defective in a single step in the biosynthetic pathway for plasmalogens. This step, catalyzed by the peroxisomal enzyme, alkyl-dihydroxyacetone phosphate (DHAP) synthase, is responsible for the introduction of the ether bond found in plasmalogens. The activity of alkyl-DHAP synthase was reduced in whole-cell homogenates from NZel-1 to 18% of wild-type values. Unlike previously described plasmalogen-deficient mutants, NZel-1 contained peroxisomes, as confirmed by immunofluorescence microscopy and catalase release by digitonin. Peroxisomal functions, including the breakdown of very long-chain (>20 carbons) fatty acids, phytanic acid oxidation, and the acylation of DHAP, were normal. Cell fusion studies revealed that the mutation is recessive and belongs to a new complementation group. To our knowledge this is the first report describing the isolation and characterization of a mutant CHO cell line defective in plasmalogen biosynthesis which contains intact, functional peroxisomes. These cells will allow us to examine the role of ether lipids in cellular functions without complications associated with peroxisome deficiency.

Alkyl and Aryl Transferases↗

Purification and biochemical characterization of a protein-palmitoyl acyltransferase from human erythrocytes.

Protein palmitoylation involves the post-translational attachment of palmitate in thioester linkage to cysteine residues of proteins. The labile nature of the thioester linkage makes possible the palmitoylation-depalmitoylation cycles that have emerged in recent times as additions to the repertoire of cellular control mechanisms. However, detailed understanding of these cycles has been limited by the lack of knowledge of the transferases and thioesterases likely to be involved. Here, we describe the purification of a protein-palmitoyl acyltransferase (PAT) from human erythrocytes. PAT behaved as a peripheral membrane protein and catalyzed the attachment of palmitate in thioester linkage to the beta-subunit of spectrin. On SDS-polyacrylamide gel electrophoresis, PAT appeared as a 70-kDa polypeptide. Antibody against this polypeptide could immunodeplete PAT activity from the crude extract, confirming the assignment of the 70-kDa polypeptide as PAT. PAT-mediated spectrin palmitoylation could be inhibited by nonradioactive palmitoyl-, myristoyl-, or stearoyl-CoA. The apparent Km for palmitoyl-CoA was 16 microM.

Acylation↗

The crystal and molecular structure of (HgL2)n (L = 4,6-dimethylpyrimidine-2-thiolate)--an unusual helical supramolecular assembly in solid phase: in search of a new antidote to mercury poisoning.

An X-ray crystallographic study reveals that in solid phase, 4,6-dimethylpyrimidine-2-thiol (4,6Me2 Pm2SH) forms a multinuclear complex with mercury, containing an open HgN3S2 core and exhibiting a helix-like polymerization through repetitive distant Hg(sp3d) ... N(sp2) interactions along the b axis of the lattice. The complex, therefore, exemplifies a supramolecular assembly, generated by successive vacant ligand site promoted self-associations. It crystallizes in the monoclinic space group P2(1)/c, a = 11.808(2), b = 9.198(2), and c = 14.702(3) A, beta = 112.19(3)0, Z = 4 (monomers). Such self-associative distant interactions are absent in solution phase, as observed from the 1H NMR spectrum (acetone-d6, TMS). A preliminary toxicological study of the pyrimidinethiol ligand reveals a high toxicity at substantially higher doses and appreciably low toxic effects at lower doses. The ligand is also highly potent in inhibiting all common gram negative bacteria (except the acid fast group, which was not tested) and this property may endow it with some side therapeutic uses when considered as an antidote to mercury poisoning following some functional modifications in order to reduce the toxic effects, even when administered at higher doses.

Animals↗

Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit.

Tadenan (Debat Laboratories, France) is a plant extract used in Europe for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction observed after 2 weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan therapy following the creation of partial outlet obstruction. Two sets of experiments were performed: one with mild and the other with severe outlet obstruction. For both sets of experiments, male New Zealand rabbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each rabbit in groups 1 and 2 was obstructed using standard methodology. Rabbits in group 3 served as controls and did not receive any surgery. After 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/kg/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil). After 3 weeks of treatment (5 weeks after partial outlet obstruction), rabbits were anesthetized and cystometries were performed. Immediately after cystometry, the rabbits were euthanized, the bladder rapidly removed, and 4 longitudinal strips prepared and mounted in individual baths for contractile studies. The contractile responses to field stimulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium chloride (KCl) were determined, as follows: (1) Bladder mass approximately doubled in the mildly obstructed groups. Bladder mass increased significantly (3-5-fold) in the severely obstructed groups. (2) Cystometrograms from the mildly obstructed rabbits treated with peanut oil showed low compliance, whereas those of the mildly obstructed rabbits treated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstruction caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No changes were noted in response to bethanechol, ATP, and KCl stimulation. (4) Severe obstruction caused significant decreases in the response of bladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-frequency field stimulation and a substantial improvement in the response to bethanechol (response equal to control). No changes were noted in response to ATP and KCl stimulation. In conclusion, Tadenan treatment reversed the bladder dysfunctions induced by mild partial outlet obstruction, and resulted in improved bladder function in the severe model of outlet obstruction. These studies are consistent with previous studies showing that Tadenan pretreatment protects the bladder against the development of contractile dysfunctions.

Animals↗

Coincidence of true and false left ventricular aneurysm.

Coincidence of true and false left ventricular aneurysm is very rare. To date 6 cases have been reported in the world literature. We present a case of false aneurysm emanating from a posterior true aneurysm of the left ventricle. These findings were demonstrated preoperatively by transesophageal echocardiography and were confirmed at operation. The aneurysms were successfully resected and the ventricle repaired.

Aged↗

Erythrophagocytosis and its relation to band 3 clustering in chronic myelogenous leukemia.

Band 3, a major erythrocyte membrane glycoprotein, undergoes topographic redistribution leading to enhanced clustering, in chronic myelogenous leukemia (CML). This is probably due to the binding of heme compounds to the CML erythrocyte membrane resulting from depletion of cellular levels of reduced glutathione (GSH). Band 3 clustering appears to be one of the factors associated with increased erythrophagocytosis in CML.

Anion Exchange Protein 1, Erythrocyte↗

A trace metal (zinc and iron) study on low dose x-radiation response in rat skin.

There is no reliable bio-dosimeter regarding low dose radiation effects in mammalian systems. In this study, chronic low dose (< 1 cGy) whole body x-irradiated rat skin have shown altered trace metal (zinc and iron) content which clearly indicated the redistribution of these metals in the integumentary system. The decreased zinc to iron ratios suggested enhanced oxidative stress of the tissue. Changes in trace metal content in irradiated rat skin, as a biological response to low dose radiation, were non-linear. Moreover, the lowered zinc content of E2, E3, E4 and E5 dose groups suggested a different steady state, compared to the control. The Zn: Fe ratio decreased with increasing radiation dose.

Animals↗

Experimental apexigenesis in baboons.

Apexification with calcium hydroxide is a routine procedure. However, some clinical reports suggest that root completion can occur by controlling the infection without use of a catalyst. The present study investigated the use of tetracycline treatment (in root canals) on root growth in immature teeth, rendered non-vital experimentally. Incisors in 3 young baboons were exposed and canals were left open. After 2 months all canals were cleaned and treated with either tetracycline or formocresol. Some canals in each group were filed. Animals were sacrificed after 6 months. Bacterial evaluations were done before placing medications, one week later and six months after that. The number of bacteria were reduced in all treatment groups. Root growth almost near completion was observed in more teeth treated with tetracycline than in the formocresol group.

Animals↗

Cariostatic effect of aspartame in rats.

This study examined the effects of aspartame (APM) on caries and the Streptococcus sobrinus population. Six groups of rats (20 in each group) colonized with S. sobrinus were fed varying amounts of sucrose (SU) and APM in their diets as follows: 1-0.15% APM, 2-0.30% APM, 3-30% SU, 4-30% SU + 0.15% APM, 5-50% SU and 6-50% + 0.15% APM. Ten from each group were sacrificed at 6 weeks and 10 at 12 weeks. S. sobrinus populations at both intervals were negligible in groups 1 and 2 and had no differences between groups 3, 4, 5 and 6. No caries were found in groups 1 and 2 Animals fed SU plus APM had significantly lower caries than animals fed the same amounts of SU (p = 0.001-0.0002). We conclude that APM is noncariogenic and anticariogenic.

Analysis of Variance↗

A foundational model of time for heterogeneous clinical databases.

Differences among the database representations of clinical data are a major barrier to the integration of databases and to the sharing of decision-support applications across databases. Prior research on resolving data heterogeneity has not addressed specifically the types of mismatches found in various timestamping approaches for clinical data. Such temporal mismatches, which include time-unit differences among timestamps, must be overcome before many applications can use these data to reason about diagnosis, therapy, or prognosis. In this paper, we present an analysis of the types of temporal mismatches that exist in databases. To formalize these various approaches to timestamping, we provide a foundational model of time. This model gives us the semantics necessary to encode the temporal dimensions of clinical data in legacy databases and to transform such heterogeneous data into a uniform temporal representation suitable for decision support. We have implemented this foundational model as an extension to our Chronus system, which provides clinical decision-support applications the ability to match temporal patterns in clinical databases. We discuss the uniqueness of our approach in comparison with other research on representing and querying clinical data with varying timestamp representations.

Databases as Topic↗

A temporal database mediator for protocol-based decision support.

To meet the data-processing requirements for protocol-based decision support, a clinical data-management system must be capable of creating high-level summaries of time-oriented patient data, and of retrieving those summaries in a temporally meaningful fashion. We previously described a temporal-abstraction module (RESUME) and a temporal-querying module (Chronus) that can be used together to perform these tasks. These modules had to be coordinated by individual applications, however, to resolve the temporal queries of protocol planners. In this paper, we present a new module that integrates the previous two modules and that provides for their coordination automatically. The new module can be used as a standalone system for retrieving both primitive and abstracted time-oriented data, or can be embedded in a larger computational framework for protocol-based reasoning.

Artificial Intelligence↗