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Biomedical subjects

D Choudhury

Publications and source records attributed to D Choudhury.

At least 19 recordsLinked to original sources

Digestive enzymes and metabolic profile of Labeo rohita fingerlings fed diets with different crude protein levels.

Labeo rohita, commonly called rohu is one of the most important fish species for aquaculture in India. Digestive enzyme response and metabolic profile of fingerling L. rohita to different dietary crude protein (CP) levels (viz. 25, 30, 35 and 40%) were studied in an attempt to optimize a practical diet formulation for this species. After 45 days of feeding, activity of digestive enzymes and metabolite concentrations were assayed. Amylase, lipase and alkaline phosphatase (ALP) activities were not influenced by the dietary protein, but proteolytic and acid phosphatase (ACP) activities varied (P<0.05) between the treatments. Proteolytic activity showed a second order polynomial relationship with dietary crude protein (CP) as Y = 0.0734X(2) + 4.937X - 68.37, r(2)=0.97. A positive correlation was observed between dietary CP and amylase (r(2)=0.78). All the metabolites except muscle glucose showed significant change corresponding to the dietary protein levels. Glucose and glycogen levels corresponded to the dietary carbohydrate levels. Muscle and plasma pyruvic acid increased as the crude protein in the diet increased, whereas liver pyruvic acid showed the opposite trend. Muscle protein content was not affected by dietary CP. Protein fractions in plasma (total protein, albumin and globulin) showed maximum values in 30% CP fed group. It is concluded that proteolytic activity and ACP are the major digestive enzymes responsive to dietary CP in L. rohita fingerlings. Considering the cost effectiveness of the diet, and based on liver and plasma free amino acid levels and plasma protein fractions, 30% crude protein is recommended as the optimal dietary protein for L. rohita fingerlings.

Animal Feed↗

Substrate binding site of naphthalene 1,2-dioxygenase: functional implications of indole binding.

The three-dimensional structure of the aromatic hydroxylating enzyme naphthalene dioxygenase (NDO) from Pseudomonas sp. NCIB 9816-4 was recently determined. The refinement of the structure together with cyclic averaging showed that in the active site of the enzyme there is electron density for a flat aromatic compound. This compound appears to be an indole adduct, which in Escherichia coli is derived from tryptophan present in the rich culture medium. An indole-dioxygen adduct has been built which fits the electron density convincingly. Support for this interpretation was obtained from crystals of the enzyme purified from cells grown in the absence of tryptophan which had an empty substrate pocket. These types of crystals were soaked in indole solutions and the position of indole in this complex was similar to the corresponding part in the modelled indole-oxygen adduct. This suggests that a peroxide bound to iron end-on attacks the substrate and forms this intermediate. The substrate position has implications for the substrate specificity of the enzyme. Docking studies with indole, naphthalene and biphenyl inside the substrate pocket of NDO suggest the presence of subpockets where the one close to the active site iron is reserved for the binding of the aromatic ring which is hydroxylated upon catalysis. The plausible location for the binding of dioxygen is between this pocket and the catalytic iron. This is in accordance with the enantiospecificity of the products.

Amino Acid Sequence↗

Advanced glycation end products: a Nephrologist's perspective.

Advanced glycation end products (AGEs) are a heterogeneous group of molecules that accumulate in plasma and tissues with advancing age, diabetes, and renal failure. There is emerging evidence that AGEs are potential uremic toxins and may have a role in the pathogenesis of vascular and renal complications associated with diabetes and aging. AGEs are formed when a carbonyl of a reducing sugar condenses with a reactive amino group in target protein. These toxic molecules interact with specific receptors and elicit pleiotropic responses. AGEs accelerate atherosclerosis through cross-linking of proteins, modification of matrix components, platelet aggregation, defective vascular relaxation, and abnormal lipoprotein metabolism. In vivo and in vitro studies indicate that AGEs have a vital role in the pathogenesis of diabetic nephropathy and the progression of renal failure. The complications of normal aging, such as loss of renal function, Alzheimer's disease, skin changes, and cataracts, may also be mediated by progressive glycation of long-lived proteins. AGEs accumulate in renal failure as a result of decreased excretion and increased generation resulting from oxidative and carbonyl stress of uremia. AGE-modified beta(2)-microglobulin is the principal pathogenic component of dialysis-related amyloidosis in patients undergoing dialysis. Available dialytic modalities are not capable of normalizing AGE levels in patients with end-stage renal disease. A number of reports indicated that restoration of euglycemia with islet-cell transplantation normalized and prevented further glycosylation of proteins. Aminoguanidine (AGN), a nucleophilic compound, not only decreases the formation of AGEs but also inhibits their action. A number of studies have shown that treatment with AGN improves neuropathy and delays the onset of retinopathy and nephropathy. N-Phenacylthiazolium bromide is a prototype AGE cross-link breaker that reacts with and can cleave covalent AGE-derived protein cross-links. Thus, there is an exciting possibility that the complications of diabetes, uremia, and aging may be prevented with these novel agents.

Aging↗

Chaperone-assisted pilus assembly and bacterial attachment.

Bacterial pili assembled by the chaperone-usher pathway can mediate microbial attachment, an early step in the establishment of an infection, by binding specifically to sugars present in host tissues. Recent work has begun to reveal the structural basis both of chaperone function in the biogenesis of these pili and of bacterial attachment.

Adhesins, Bacterial↗

Bacterial adhesins: structural studies reveal chaperone function and pilus biogenesis.

During the past year, remarkable progress has been made in understanding how periplasmic chaperones fold and protect protein modules that are destined for assembly into adhesive pili in Gram-negative bacteria. The first two three-dimensional structures of complexes of periplasmic chaperones with substrate pilus subunits have revealed much about the structural basis for chaperone-mediated folding and aggregation prevention, and have provided insight into the structure of adhesive pili.

Adhesins, Bacterial↗

Pseudo-symmetry characterization and refinement of a trigonal crystal form of naphthalene 1,2-dioxygenase.

Two trigonal crystal structures of naphthalene 1,2-dioxygenase from Pseudomonas sp. NCIB 9816-4 have been refined at 2.6 A resolution. The space group is R3, with four heterodimers in the asymmetric unit. The crystallographic threefold axis coincides with the symmetry axis of the active molecule, a mushroom-shaped alpha(3)beta(3) hexamer. The crystal is formed by symmetrical contacts between the hexamers on three different interaction surfaces, one on the beta-subunit and the other two on the alpha--subunits. Nickel ions mediate one of the alpha-subunit interactions. The two other types of packing contacts sustain two interlaced and almost independent crystal patterns with significantly different temperature factors. The space group of the individual crystal patterns is R32, with the corresponding twofold axes parallel to each other. The interactions between the crystal patterns separate the two parallel twofolds, eliminating the twofold symmetry for the whole crystal. The differences in temperature factors among the molecules in the asymmetric unit have been refined and are different for the two refined structures. An analysis of the structure factors of the pseudo-equivalent reflections showed that their differences lie in their phases and not in their amplitudes, suggesting that R(merge) is not an appropriate indicator for revealing the correct point group.

Bacterial Proteins↗

Stereoisomeric selectivity of human deoxyribonucleoside kinases.

Deoxynucleoside kinases catalyze the 5'-phosphorylation of 2'-deoxyribonucleosides with nucleoside triphosphates as phosphate donors. One of the cellular kinases, deoxycytidine kinase (dCK), has been shown to phosphorylate several L-nucleosides that are efficient antiviral agents. In this study we investigated the potentials of stereoisomers of the natural deoxyribonucleoside to serve as substrates for the recombinant cellular deoxynucleoside kinases. The cytosolic thymidine kinase exhibited a strict selectivity and phosphorylated only beta-D-Thd, while the mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK) as well as dCK all had broad substrate specificities. TK2 phosphorylated Thd and dCyd stereoisomers in the order: beta-D- > or = beta-L- >> alpha-D- > or = alpha-L-isomer. dCK activated both enantiomers of beta-dCyd, beta-dGuo, and beta-dAdo with similar efficiencies, and alpha-D-dCyd also served as a substrate. dGK phosphorylated the beta-dGuo enantiomers with no preference for the ribose configuration; alpha-L-dGuo was also phosphorylated, and beta-L-dAdo and beta-L-dCyd were substrates but showed reduced efficiencies. The anomers of the 2',3'-dideoxy-D-nucleosides (ddNs) were tested, and TK2 and dCK retained their low selectivities. Unexpectedly, alpha-dideoxycytidine (ddC) was a 3-fold better substrate for dCK than beta-ddC. Similarly, alpha-dideoxythymidine (ddT) was a better substrate for TK2 than beta-ddT. dGK did not accept any D-ddNs. Thus, TK2, dCK, and dGK, similar to herpes simplex virus type 1 thymidine kinase (HSV-1 TK), showed relaxed stereoselectivities, and these results substantiate the functional similarities within this enzyme family. Docking simulations with the Thd isomers and the active site of HSV-1 TK showed that the viral enzyme may in some respects serve as a model for studying the substrate specificities of the cellular enzymes.

Binding Sites↗

X-ray structure of the FimC-FimH chaperone-adhesin complex from uropathogenic Escherichia coli.

Type 1 pili-adhesive fibers expressed in most members of the Enterobacteriaceae family-mediate binding to mannose receptors on host cells through the FimH adhesin. Pilus biogenesis proceeds by way of the chaperone/usher pathway. The x-ray structure of the FimC-FimH chaperone-adhesin complex from uropathogenic Escherichia coli at 2.5 angstrom resolution reveals the basis for carbohydrate recognition and for pilus assembly. The carboxyl-terminal pilin domain of FimH has an immunoglobulin-like fold, except that the seventh strand is missing, leaving part of the hydrophobic core exposed. A donor strand complementation mechanism in which the chaperone donates a strand to complete the pilin domain explains the basis for both chaperone function and pilus biogenesis.

Adhesins, Bacterial↗

Percutaneous cuffed catheter insertion by nephrologists.

The use of Dacron cuff double-lumen permanent catheters for hemodialysis has become more common in the dialysis unit as patients await for creation or maturation of a permanent hemoaccess for various reasons. Placement of these catheters is often done by surgeons. Nephrologists skilled in the placement of temporary central vein accesses can extend their skill to placement of cuff catheters with the current available peel-away insertion technique. Data are presented on the percutaneous placement of 77 Dacron cuff permanent catheters by 4 nephrologists in two medical centers in a nonoperating room setting with minimal complications.

Adult↗

A conserved structural element in horse and mouse IGF2 genes binds a methylation sensitive factor.

The equine IGF2 gene has been cloned and characterised. It spans a 9 kb region, which is substantially less than the corresponding human gene. Three coding exons and three untranslated leader exons, all highly homologous to those in other species, were identified. Downstream of the polyadenylation site in exon 6, a dinucleotide repeat sequence was identified. Three putative promoters (P1-P3) were localised in the 5' region of the gene. RNase protection analysis revealed two active promoters in fetal tissues, P2 and P3, whereas P3 was the only promoter active in adult tissues. This represents a transcriptional pattern different from that in humans or rodents. A novel structural element, an inverted repeat, is predicted in the 3' region of the IGF2 gene. This repeat is conserved between species and located in a region which is differentially methylated in the human and mouse genes and might therefore be involved in the imprinting mechanism. The inverted repeat acquires a stem-loop structure in vitro with a hybrid A/B-DNA conformation in the stem area. Both in horse and mouse, a methylation-sensitive protein binds this structure with a strong requirement for the loop area. Furthermore, the protein might be developmentally regulated.

Animals↗

Drug-induced nephrotoxicity.

Drug-induced renal dysfunction is not an uncommon event, which can cause significant morbidity and can be easily overlooked. Many medications can lead to renal dysfunction through various mechanisms. The most common medications or classes of medications along with their clinical presentations are discussed in this article. As can be noted, many drugs can cause nephropathy in more than one way. Because it is difficult to discuss nephrotoxicities of every reported medication, Tables 1, 2, and 3 are provided; although these tables are by no means comprehensive, they may serve as further reference. This article is intended to provide a broad overview of the spectrum of presentation associated with drug-induced nephrotoxicity to guide the clinician to familiarity with this entity.

Acute Kidney Injury↗

IgA multiple myeloma presenting as Henoch-Schönlein purpura/polyarteritis nodosa overlap syndrome.

We report the unusual case of a man with a 5-year history of relapsing Henoch-Schonlein purpura (HSP) and macroscopic polyarteritis nodosa (PAN) as early manifestations of IgA kappa multiple myeloma. The glomeruli contained monoclonal IgA kappa deposits, without other immunoglobulins or lambda light chains. Glomerular deposits lacked the usual electron density but could be demonstrated by immunoelectron microscopy. Multisystem large vessel vasculitis (antineutrophil cytoplasmic antibody negative) produced aneurysms of renal and hepatic arteries, whereas small vessel vasculitis affected the skin and glomeruli, producing a symptom complex of HSP with dermal and glomerular deposits of IgA. We conclude that HSP/overlap syndrome may be the initial manifestation of IgA myeloma and should be considered within the spectrum of monoclonal IgA deposition disease.

Humans↗

Correlation of venography, venous pressure, and hemoaccess function.

We analyzed the anatomic features of both grafts and fistulas and correlated these features with access function. We also attempted to determine venous pressures predicting access dysfunction (critical venous pressures) at various blood flow rates (BFRs). Therefore, accesses of 46 chronic hemodialysis patients were studied by venography in a prospective fashion. We defined the incidences of various lesions and the effects of venous collaterals on graft function, and determined critical venous pressures at various BFRs. Eighty-three percent of the accesses had outflow obstruction. Five types of anatomic lesions were identified. The incidences were venous stenosis of the draining vein immediately proximal to the venous anastomosis, 36.4%; central vein, 23.6%; venous anastomosis, 25.5%; arterial anastomosis, 10.9%; and intragraft hyperplasia, 3.6%. Twelve patients had multiple lesions. When the homogenous polytetrafluoroethylene arm graft population was studied for the effect of venous collaterals, we found that venous collaterals conferred protection but did not prevent graft failure. Venous pressure measurements were good predictors of access failure at the lower BFRs. Venous pressures increased with increasing BFRs. A critical venous pressure of 145 mm Hg was found for a BFR of 250 mL/min. At a BFR of 300 mL/min, the critical venous pressure was 170 mm Hg. A critical venous pressure could not be found for a BFR of 400 mL/min.

Arteriovenous Shunt, Surgical↗