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Biomedical subjects

A Chaudhary

Publications and source records attributed to A Chaudhary.

At least 37 records · Page 2Linked to original sources
PubMed1998

Specific interaction of Golgi coatomer protein alpha-COP with phosphatidylinositol 3,4,5-trisphosphate.

The phosphoinositide binding selectivity of Golgi coatomer COPI polypeptides was examined using photoaffinity analogs of the soluble inositol polyphosphates Ins(1,4,5)P3, Ins(1,3,4,5)P4, and InsP6, and of the polyphosphoinositides PtdIns(3,4,5)P3, PtdIns(4,5)P2, and PtdIns(3,4)P2. Highly selective Ins(1,3,4,5)P4-displaceable photocovalent modification of the alpha-COP subunit was observed with a p-benzoyldihydrocinnamide (BZDC)-containing probe, [3H]BZDC-Ins(1,3,4,5)P4. A more highly phosphorylated probe, [3H]BZDC-InsP6 probe labeled six of the seven subunits, with only beta, beta', delta, and epsilon-COP showing competitive displacement by excess InsP6. Importantly, [3H]BZDC-triester-PtdIns(3,4,5)P3, the lipid with the same phosphorylation pattern as Ins(1,3,4,5)P4, showed specific, PtdIns(3,4,5)P3-displaceable labeling of only alpha-COP. Labeling by the PtdIns(4,5)P2 and PtdIns(3,4)P2 photoaffinity probes was less intense and showed no discrimination based on PtdInsPn ligand. Thus, both the D-3 and D-5 phosphates are critical for the alpha-COP-PtdIns(3,4,5)P3 interaction, suggesting an important role for this polyphosphoinositide in vesicular trafficking.

Affinity Labels↗
PubMed1998

Probing the phosphoinositide 4,5-bisphosphate binding site of human profilin I.

BACKGROUND: Profilin is a widely and highly expressed 14 kDa protein that binds actin monomers, poly(L-proline) and polyphosphoinositol lipids. It participates in regulating actin-filament dynamics that are essential for many types of cell motility. We sought to investigate the site of interaction of profilin with phosphoinositides. RESULTS: Human profilin I was covalently modified using three tritium-labeled 4-benzoyldihydrocinnamoyl (BZDC)-containing photoaffinity analogs of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). The P-1-tethered D-myoinositol 1,4,5-trisphosphate (Ins(1,4,5)P3) modified profilin I efficiently and specifically; the covalent labeling could be displaced by co-incubation with an excess of PtdIns(4,5)P2 but not with Ins(1,4,5)P3. The acyl-modified PtdIns(4,5)P2 analog showed little protein labeling even at very low concentrations, whereas the head-group-modified PtdIns(4,5)P2 phosphotriester-labeled monomeric and oligomeric profilin. Mass spectroscopic analyses of CNBr digests of [3H]BZDC-Ins(1,4,5)P3-modified recombinant profilin suggested that modification was in the amino-terminal helical CNBr fragment. Edman degradation confirmed Ala1 of profilin I (residue 4 of the recombinant protein) was modified. Molecular models show a minimum energy conformation in which the hydrophobic region of the ligand contacts the amino-terminal helix whereas the 4,5-bisphosphate interacts with Arg135 and Arg136 of the carboxy-terminal helix. CONCLUSIONS: The PtdIns(4,5)P2-binding site of profilin I includes a bisphosphate interaction with a base-rich motif in the carboxy-terminal helix and contact between the lipid moiety of PtdIns(4,5)P2 and a hydrophobic region of the aminoterminal helix of profilin. This is the first direct evidence for a site of interaction of the lipid moiety of a phosphoinositide bisphosphate analog with profilin.

Binding Sites↗
PubMed1998

Bile duct obstruction due to portal biliopathy in extrahepatic portal hypertension: surgical management.

BACKGROUND: Varices can develop in and around the bile duct in the presence of portal hypertension, especially when it is caused by extrahepatic portal vein thrombosis. The term 'portal biliopathy' is used to describe changes in the bile duct due to these varices, which may cause bile duct obstruction. This paper reviews experience of the surgical management of patients with symptomatic portal biliopathy. METHODS: Nine patients with extrahepatic portal vein obstruction with symptomatic portal biliopathy. were reviewed retrospectively. RESULTS: Eight patients presented with jaundice, two had abdominal pain and one had recurrent cholangitis. Endoscopic retrograde cholangiography revealed abnormality of the bile duct wall, with stricture in eight patients and bile duct calculi in two. Portasystemic shunting relieved jaundice in five of seven patients, and in two a second-stage hepaticojejunostomy was required. CONCLUSION: Symptomatic biliary obstruction in patients with extrahepatic portal hypertension may be relieved by a portasystemic shunt. Rarely biliary bypass may be required and is rendered safer by previous portasystemic shunting to decompress the pericholedochal varices. A direct approach to the biliary tract without a preliminary shunt may be hazardous and is frequently unnecessary.

Adolescent↗
PubMed1998

Indoor air quality and acute lower respiratory infection in Indian urban slums.

The present prospective study was conducted at two urban slums of Delhi, Kusumpur Pahari and Kathputly Colony, in the peak winter season from November 1994 through February 1995. We studied 642 infants to determine the incidence of acute lower respiratory infection (ALRI) and its relationship to indoor air pollution due to fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317 children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene), there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p < 0.05). Controls were children without ALRI and were used as controls in different groups. The demographic data and risk factors, namely, nutritional and immunization status, were comparable in ALRI cases and controls in both study areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur Colony. Only one case of croup was reported from Kusumpur Pahari among wood users. The duration of illness was longer in the Kusumpur Pahari due to poor compliance, feeding, and child rearing habits. In conclusion, a higher incidence of ALRI was reported in kerosene users in Kathputly Colony, a high pollution area; however, the reasons for the differences observed need further elucidation.

Acute Disease↗
PubMed1997

Phosphoinositide binding specificity among phospholipase C isozymes as determined by photo-cross-linking to novel substrate and product analogs.

We tested for the presence of high-affinity phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 binding sites in four phospholipase C (PLC) isozymes (delta1, beta1, beta2, and beta3), by probing these proteins with analogs of inositol phosphates, D-Ins(1,4,5)P3, D-Ins(1,3,4,5)P4, and InsP6, and polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3, which contain a photoactivatable benzoyldihydrocinnamide moiety. Only PLC-delta1 was specifically radiolabeled. More than 90% of the label was found in tryptic and chymotryptic fragments which reacted with antisera against the pleckstrin homology (PH) domain, whereas less than 5% was recovered in fragments that encompassed the catalytic core. In separate experiments, the isolated delta1-PH domain was also specifically labeled. Equilibrium binding of D-Ins(1,4,5)P3 to PLC-delta1 indicated the presence of a single, high-affinity binding site; binding of D-Ins(1,4,5)P3 to PLC-beta1, -beta2, or -beta3 was not detected. The catalytic activity of PLC-delta1 was inhibited by the product D-Ins(1,4,5)P3, whereas no inhibition of PLC-beta1, -beta2, or -beta3 activity was observed. These results demonstrate that the PH domain is the sole high-affinity PI(4,5)P2 binding site of PLC-delta1 and that a similar site is not present in PLC-beta1, -beta2, or -beta3. The data are consistent with the idea that the PH domain of PLC-delta1, but not the beta isozymes, directs the catalytic core to membranes enriched in PI(4,5)P2 and is subject to product inhibition.

Benzophenones↗
PubMed1997

Selective photoaffinity labeling of the inositol polyphosphate binding C2B domains of synaptotagmins.

Synaptotagmin (Syt) II, a synaptic vesicle protein containing two copies of highly conserved protein kinase C homology regions known as the C2A and C2B domains, acts as a Ca2+ sensor and provides both phospholipid and inositol polyphosphate (IPn) recognition domains important in endo- and exocytosis. Four photoaffinity analogues of IP3, IP4, and IP6 containing a P-1- or P-2-linked 4-benzoyldihydrocinnamidyl (BZDC) photophore were used to label glutathione S-transferase (GST) fusion constructs of the Syt II-C2A and C2B domains. The P-2-linked [3H]BZDC-IP6 showed efficient, IP6-displaceable labeling of the GST-Syt II-C2B. The rank order of photocovalent modification paralleled the order of competitive displacement: IP6 (P-2-linked) > IP4 > IP3. The P-1-linked [3H]BZDC-IP6 failed to label the C2B domains. The GST-Syt III-C2B domain, which lacks IP6 binding affinity, also failed to undergo labeling by P-2-linked [3H]BZDC-IP6. When mixtures of the 32-amino acid basic peptide corresponding to the essential IPn binding region of the Syt II-C2B domain and GST-Syt II-C2B were labeled by a stoichiometric amount of P-2-linked [3H]BZDC-IP6, the two polypeptides showed equivalent affinity for the photolabel. Although the CD spectrum of this 32-mer at two pH values showed a random coil, the photoaffinity analogue of IP6 appeared to induce a binding-compatible structure in the short peptide.

Affinity Labels↗
PubMed1997

Surgical management of pancreatic necrosis presenting with locoregional complications.

BACKGROUND: Local complications of pancreatic necrosis may occur after surgery, but when they occur spontaneously render surgical treatment more hazardous and impair prognosis. METHODS: A retrospective review was carried out of 83 patients who underwent surgery for pancreatic necrosis from 1988 to 1995, to determine the incidence, type, treatment and outcome of locoregional complications caused by pancreatic necrosis associated with acute pancreatitis. RESULTS: Seventeen patients (20 per cent) were identified to have intra-abdominal complications with pancreatic necrosis either before operation or at the time of surgery. The majority of patients had a delay in intervention (mean 46 days). At presentation ten of the 17 patients had one or more organ system failures. Fourteen patients had gastrointestinal tract involvement, two had involvement of the biliary tract and one patient had a splenic rupture. Six patients died. CONCLUSIONS: In patients with pancreatic necrosis, development of locoregional complications is associated with a high mortality rate. The presence of gastrointestinal bleeding, peritonitis, jaundice or pneumoperitoneum in such patients suggests the presence of a complication of the necrotic process and should prompt early intervention. Early referral of patients with severe acute pancreatitis to specialized units may reduce the risk of locoregional complications.

Acute Disease↗
PubMed1997

Segment III cholangiojejunostomy for carcinoma of the gallbladder.

Jaundice in patients of advanced carcinoma of the gallbladder requires palliation for the distressing symptoms of pruritus and cholangitis. Intrahepatic segment III duct cholangiojejunostomy is a means for alleviating the obstruction with malignant porta block. The authors reviewed their experience with this procedure in 48 patients of carcinoma of the gallbladder. All patients had jaundice; pruritus was present in 44 (92%) and cholangitis in 14 (29%). The level of obstruction was determined preoperatively by percutaneous transhepatic cholangiography. In 32 patients the block was below the level of the bifurcation of the right and left ducts, and 16 patients had a block involving the confluence, isolating the two lobes of the liver. Following segment III cholangiojejunostomy, pruritus was relieved in all and cholangitis in 86% of patients. At the end of 6 weeks a significant fall in serum bilirubin and alkaline phosphatase levels was seen with both types of hilar obstruction. Varying degrees of pain relief was also noted in 75% of patients. Segment III biliary bypass is an effective, one-time, reliable means of palliation for carcinoma of the gallbladder with hilar obstruction. Its efficacy appears to depend on the duration and depth of the jaundice and on the anatomy of the biliary ductal system in the left hemiliver rather than on the type of hilar obstruction.

Adult↗
PubMed1997

Benzophenone photoprobes for phosphoinositides, peptides and drugs.

Benzophenones (BP) and related aryl ketone photophores have become established as the photoactivatable group of choice for high-efficiency covalent modification of hydrophobic regions of binding proteins, including enzymes and receptors that recognize peptide hormones, (oligo) nucleotides and nucleosides, phosphoinositides, inositol polyphosphates and a wide variety of therapeutic molecules. This review presents the advantages of BP as photoaffinity labels and provides specific examples from the last 3 years of applications of BP-containing ligands used in biochemistry.

Affinity Labels↗
PubMed1997

Reoperative surgery for choledochal cysts.

BACKGROUND: Complications often follow if a choledochal cyst is treated simply by drainage, either internal or external. This study reviews 17 patients who had had previous cystoenterostomy (n = 9) or external drainage (n = 8) and who required reoperation and cyst excision. METHODS: The study was a retrospective review including ten women and seven men managed over 9 years. The indications for reoperation were stone formation (10 patients), pancreatitis (three), portal hypertension (two) and hepatic abscess (one); two patients were asymptomatic. RESULTS: Definitive surgery with cyst excision was possible in all patients who had previously had external cyst drainage and in seven of nine who had had previous cystoenterostomy. There were no deaths. Two postoperative biliary leaks and two duodenal fistulas resolved spontaneously. CONCLUSION: Excision of a choledochal cyst is possible and desirable even after a previous drainage operation. In severely ill patients with a complication of choledochal cyst, external drainage may be a preferable initial manoeuvre.

Adolescent↗
PubMed1996

Purification and properties of levanase from Rhodotorula sp.

Levanase, a slime dissolving enzyme of Rhodotorula sp., was purified to approx. 26-fold by ammonium sulphate precipitation, DEAE and gel filtration (Sephacryl S-200) chromatography. The molecular mass of the enzyme was 39 kDa. The purified levanase showed maximum activity at pH 6.0 and 40 degrees C. Enzyme was quite stable at 4 degrees C and at pH 5.5 to 6.5. Hg2+ at a level of 10 mM completely inhibited the levanase activity, while 2-mercaptoethanol at the same concentration showed a 2.93-times increase in activity. In addition to levan, the enzyme also showed substrate specificity towards inulin.

Ammonium Sulfate↗
PubMed1996

Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta 2.1 subunits.

The voltage-sensitive currents observed following hKv1.5 alpha subunit expression in HEK 293 and mouse L-cells differ in the kinetics and voltage dependence of activation and slow inactivation. Molecular cloning, immunopurification, and Western blot analysis demonstrated that an endogenous L-cell Kv beta 2.1 subunit assembled with transfected hKv 1.5 protein. In contrast, both mRNA and protein analysis failed to detect a beta subunit in the HEK 293 cells, suggesting that functional differences observed between these two systems are due to endogenous L-cell Kv beta 2.1 expression. In the absence of Kv beta 2.1, midpoints for activation and inactivation of hKv1.5 in HEK 293 cells were -0.2 +/- 2.0 and -9.6 +/- 1.8 mV, respectively. In the presence of Kv beta 2.1 these values were -14.1 +/- 1.8 and -22.1 +/- 3.7 mV, respectively. The beta subunit also caused a 1.5-fold increase in the extent of slow inactivation at 50 mV, thus completely reconstituting the L-cell current phenotype in the HEK 293 cells. These results indicate that 1) the Kv beta 2.1 subunit can alter Kv1.5 alpha subunit function, 2) beta subunits are not required for alpha subunit expression, and 3) endogenous beta subunits are expressed in heterologous expression systems used to study K+ channel function.

Amino Acid Sequence↗
PubMed1996

Diagnosis and outcome of isolated rectal tuberculosis.

PURPOSE: Segmental colonic tuberculosis commonly involves the ascending, transverse, or sigmoid colon. Rectal involvement in tuberculosis is uncommon and poorly characterized. This study describes the clinical presentation, endoscopic features, and outcome of isolated rectal tuberculosis. METHODS: Isolated rectal tuberculosis was defined as focal lesions of the rectum in the absence of radiologically demonstrable lesions in the small and large bowel on barium contrast studies. Diagnosis of rectal tuberculosis was based on characteristic endoscopic appearance of lesions, histopathologic features of tuberculosis in biopsy/ resected material, and response to antitubercular therapy. RESULTS: Eight patients with rectal tuberculosis were seen during a four-year period at our hospital. Hematochezia was the most common presenting feature (88 percent), followed by constitutional symptoms (75 percent) and constipation (37 percent). Rectal examination revealed a tight stricture within 10 cm of the anal verge in seven patients. Barium enema showed stricture of variable length, with focal areas of deep mucosal ulceration and increase in presacral space. Proctoscopic findings were tight stricture (7), nodularity with ulceration (6), and multiple aphthous ulcers (1). Granulomatous infiltration was detected in seven of eight patients in biopsy material obtained at endoscopy (6) or surgery (1). Cessation of hematochezia, resolution of constitutional symptoms, and weight gain were seen in all patients following treatment with antitubercular drugs. CONCLUSION: Our data suggest that tubercular involvement of rectum, although uncommon, is an important cause of rectal strictures in India. Response to antitubercular chemotherapy is uniformly good, and surgery is seldom required in these patients.

Adolescent↗
PubMed1996

Coeliac artery aneurysm: a case report.

Coeliac artery aneurysms are rare. A case of coeliac artery aneurysm treated successfully by endoaneurysmorrhaphy is presented. Although excision with arterial reconstruction is usually recommended, endoaneurysmorrhaphy can also be considered in selected cases.

Aneurysm↗
PubMed1996

Endoscopic biliary endoprosthesis for palliation of gallbladder carcinoma.

BACKGROUND: Carcinoma of the gallbladder is a major cause of malignant obstructive jaundice in India. It usually presents at an advanced stage and endoscopic palliation is the mainstay of treatment. We prospectively studied our results with endoscopic stenting in patients with carcinoma of the gallbladder. METHODS: Patients unfit for surgery were included in the study. Straight 10F plastic prostheses were placed endoscopically. Patients were assessed for procedure success, early and late complications, and stent patency. RESULTS: The success rate of stent placement was 84% (27 of 32). The five failures were caused by an inability to pass the guide wire across the stricture. Relief of pruritus and reduction in jaundice was seen in 25 of 27 (92%) patients. Double stents were placed in three patients. Four patients (11%) developed cholangitis in the first 30 days. Stent occlusion was detected in four patients after longer follow-up. The 30-day mortality was 5 of 27 (18%). There were no procedure-related deaths. CONCLUSION: Endoscopic endoprosthesis is a safe and relatively effective palliative measure for the majority of patients with unresectable carcinoma of the gallbladder.

Adult↗
PubMed1996

Internal pancreatic fistulae with serous effusions in chronic pancreatitis.

BACKGROUND: Serous effusions in chronic pancreatitis are infrequent but persistent. These occur usually as a consequence of internal pancreatic fistulae and commonly involve the pleural cavity or peritoneum. METHODS: To assess strategies in operative management, the records of 12 patients who underwent surgery for internal pancreatic fistula with underlying chronic pancreatitis were reviewed retrospectively. Seven patients had pancreatic ductal calculi. Three cases underwent external drainage. Three cases with leaking pseudocysts underwent cystojejunostomy-en-Y. Three cases with ductal dilatation or calculi underwent lateral pancreaticojejunostomy and three patients had caudal pancreatectomy for distal disease. RESULTS: Eight patients were completely controlled of all symptoms, with no sequelae. One case each had recurrent pancreatitis and ascites but did not require re-operation. There were two deaths: one with massive haematemesis and one with pre-existent multi-organ failure and sepsis. CONCLUSIONS: Pancreatic duct stones may be causally associated with internal pancreatic fistulae. Delineation of ductal anatomy and pathological aberrations of the pancreas, including determination of the leak site, was of paramount importance in planning surgery. Peroperative ductography proved the most useful in this regard.

Adolescent↗