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Biomedical subjects

S Bhagat

Publications and source records attributed to S Bhagat.

At least 19 recordsLinked to original sources
PubMed2006

An unusual cause of locking.

This case report describes the discovery of a plastic foreign body in a patient's knee joint 21 years from the initial injury. The patient was thoroughly investigated radiologically with plain X-rays both immediately after the initial injury and years later in orthopaedic outpatients. He also subsequently received an MRI. All these were reported as normal. The patient's symptoms persisted and an arthroscopy was performed. At this procedure the presence of the foreign body was confirmed and the offending plastic was safely removed. The patient's symptoms of intermittent locking resolved. This experience stresses this importance of clinical suspicion despite apparently normal radiology.

Adult↗
PubMed2003

A comparative evaluation of C-reactive protein as a short-term prognostic marker in severe unstable angina--a preliminary study.

OBJECTIVE: The present study was done to evaluate the short-term prognostic significance of C-reactive protein (CRP) in unstable angina (UA) and to compare it with other known prognostic markers of UA, as there is a paucity of data from our country. METHODOLOGY: This prospective study comprised of 44 UA patients (Braunwald Class II A, B) with age < 65 years, along with 40 age and sex matched healthy controls. Patients with h/o myocardial infarction (MI) in the preceding 1-month and evidence of infection, inflammation or neoplasm were excluded from the study. Complete clinical evaluation was done and presence of any prognostic variables of UA was noted (including Brauriwald high-risk variables). Apart from biochemical investigations and ECG, CRP was measured at the time of admission in the study group and controls using Microwell ELISA assay. Standard treatment protocol was followed for all patients and they were closely monitored during hospital stay and subsequently for 4 weeks for occurrence of any adverse cardiac events. RESULTS: There was a statistically significant difference in the mean level of CRP between study group (6.12 +/- 6.134 mg/L) and controls (1.52 +/- 0.751 mg/L); p = 0.000. Among the 44 patients, 19 (43%) experienced any one or more outcome measures. Of the three variables (i.e. ongoing chest pain, ST depression > or = 1 mm and CRP > or = 4 mg/L) which showed statistical significance on univariate analysis with respect to adverse outcome measures (p = 0.001, 0.027 and 0.000 respectively), only CRP > or = 4 mg/L and ST depression > or = 1 mm showed independent prognostic significance on multiple logistic regression analysis (p = 0.000 and 0.002 respectively). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and relative risk (RR) for CRP > or = 4 mg/L were 78.9%, 96%, 93.75%, 85.74% and 6.56 (95% CI; 2.62 - 16.4) and that for ST depression > or = 1 mm were 89.47%, 64%, 65.38%, 88.89% and 5.88% (95% CI: 1.54 - 22.38), respectively. Trop T could be done in eight patients only. CONCLUSION: CRP > or = 4 mg/L by ELISA is an independent predictor of adverse cardiac outcome in severe UA in the short-term follow up and, hence, is useful for risk stratification of these patients. CRP has a higher specificity, PPV and overall RR for prediction of an outcome than ST segment depression, although it is less sensitive.

Adult↗
PubMed2001

Bacterial RNA polymerase subunit omega and eukaryotic RNA polymerase subunit RPB6 are sequence, structural, and functional homologs and promote RNA polymerase assembly.

Bacterial DNA-dependent RNA polymerase (RNAP) has subunit composition beta'betaalpha(I)alpha(II)omega. The role of omega has been unclear. We show that omega is homologous in sequence and structure to RPB6, an essential subunit shared in eukaryotic RNAP I, II, and III. In Escherichia coli, overproduction of omega suppresses the assembly defect caused by substitution of residue 1362 of the largest subunit of RNAP, beta'. In yeast, overproduction of RPB6 suppresses the assembly defect caused by the equivalent substitution in the largest subunit of RNAP II, RPB1. High-resolution structural analysis of the omega-beta' interface in bacterial RNAP, and comparison with the RPB6-RPB1 interface in yeast RNAP II, confirms the structural relationship and suggests a "latching" mechanism for the role of omega and RPB6 in promoting RNAP assembly.

Amino Acid Sequence↗
PubMed2001

Neurological manifestations of HIV disease.

We report the results of neurological evaluation of 1,527 HIV positive subjects. Neurological complications were seen in 457 patients (481 neurological events). The prevalence was 20.24% of patients attending the out-patient clinic and in 44.57% of in-patients. Involvement of all levels of neuraxes was documented. The commonest manifestations were neuropathies, including herpes zoster (28.27%), meningitis (17.88%) and mass lesions (16%). Cryptococcal meningitis was clearly commoner than tubercular meningitis (67.44% vs 18.60% of all cases of meningitis, respectivelv). Amongst mass lesions, 14/24 single lesions and 27/38 multiple lesions responded to anti-toxoplasma treatment and were diagnosed as CNS toxoplasmosis. In abscence of biopsy, it would be prudent to initiate empirical anti-toxoplasma treatment for all HIV patients with mass lesions and assess clinical and radiological response. To our knowledge this is the largest series of neurological manifestations of HIV disease documented in Indian literature.

Adult↗
PubMed1999

Corneal epithelial toxic effects and inflammatory response to perfluorocarbon liquid.

We report an unusual case of corneal epithelial toxic effects associated with perfluorocarbon liquids (PFCLs). The clinical and histopathologic findings are described. An elderly man underwent vitreoretinal surgery for a complicated retinal detachment. Perfluorodecalin was used to repair the retina. It was left in situ for 8 weeks and removed via the pars plana. One month after removal of heavy liquids the patient developed a nonhealing corneal epithelial defect associated with limbitis. Perfluorodecalin was found under the superior conjunctiva. A conjunctival biopsy revealed the presence of vacuoles in the conjunctival stroma surrounded by an inflammatory response that consisted of lymphocytes, macrophages, and giant cells. On surgical removal of the PFCL from the subconjunctival space, the epithelial defect healed. The histopathologic and clinical evidence suggest that the inflammatory response and corneal epithelial ulceration were caused by the prolonged presence of PFCL in the subconjunctival space. To the best of our knowledge, PFCLs have not previously been reported to cause corneal epithelial defects or incite an inflammatory response in the human eye.

Aged↗
PubMed1999

Increased lower denture security using the Myoloc system.

PURPOSE OF THE STUDY: To assess whether the Myoloc System. Improves the stability of the mandibular complete denture. METHOD: Unstable dentures move during function causing pain and discomfort to patients resulting in decreased denture security. Improvement in patients' perceived denture security was used to assess if the Myoloc System improved the stability of the mandibular complete denture. Complete dentures were constructed for 27 patients (20 female and seven male) by conventional methods. Patients were asked to mark a point on a visual analogue scale to indicate their denture security. Following this, copies of the mandibular dentures were made and Myoloc wings added to the dentures. Denture security was recorded once again. The two responses were statistically analysed for significant improvement. RESULT: A statistically significant improvement in denture security was found to occur after addition of the Myoloc wings to the mandibular denture. CONCLUSION: The Myoloc System improves the stability of the mandibular complete denture and may prove useful when conventional methods fail to provide adequate denture stability and the patient is not a candidate for surgery.

Aged↗
PubMed1998

P-glycoprotein shows strong catalytic cooperativity between the two nucleotide sites.

P-Glycoprotein (Pgp) (also known as multidrug-resistance protein) contains two nucleotide binding sites, both of which are catalytic ATPase sites. The covalent reagent 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) reacts in catalytic sites, and full inactivation of ATPase activity occurs at a reaction stoichiometry of 1 mol of NBD-Cl/mol of Pgp. We show that, at reaction stoichiometry of < or = 1 mol/mol, both nucleotide sites become labeled in relatively nonselective fashion. There is therefore strong interaction between the two nucleotide sites because (a) reaction of one site with NBD-Cl severely impedes reaction of reagent with the other site, and (b) reaction of one site inhibits steady-state ATPase, i.e. both sites are inhibited. Vanadate-trapping experiments revealed that when one nucleotide site was reacted with NBD-Cl, not even a single ATPase turnover event could occur in the other, intact, nucleotide site. The data demonstrate therefore that catalytic cooperativity between the two nucleotide sites in Pgp is extremely strong and mandatory for catalysis.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Photoaffinity labelling of P-glycoprotein catalytic sites.

Photoaffinity labelling of hamster P-glycoprotein was carried out after trapping of radioactive Mg-8-azido-ADP in the catalytic sites by vanadate or beryllium fluoride. With either trapping agent the same labelled peptide was obtained in homogeneous form, with the sequence -FNEVVFNxPTRPDI-, corresponding to residues 1034-1037 in the C-terminal nucleotide binding site. The missing residue 'x' corresponds to Tyr-1041, which is therefore a primary reaction target of 8-azido-ADP. This tyrosine is conserved in all hamster, mouse and human P-glycoproteins. A second major labelled peptide fraction was also identified. The major sequence in this fraction was -NIHFSxPSR-, corresponding to residues 393-401 of hamster P-glycoprotein, where 'x' corresponds to Tyr-398 in the N-terminal nucleotide binding site. Therefore Tyr-398, which is also conserved in other P-glycoproteins, is also a reaction target for 8-azido-ADP. In sequence alignment of the two nucleotide binding sites, Tyr-398 exactly corresponds to Tyr-1041. The data indicate that these two tyrosines lie close to the adenine ring of bound substrate MgATP in the respective catalytic sites of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Inhibition of P-glycoprotein ATPase activity by beryllium fluoride.

ATPase activity of P-glycoprotein (multidrug-resistance protein) was found to be potently inhibited by beryllium fluoride (BeFx) in combination with MgATP, MgADP, or corresponding Mg-8-azido-nucleotides. Inhibition was due to trapping of nucleoside diphosphate at catalytic sites. Full inhibition was achieved on trapping of 1 mol of nucleotide per mol of Pgp. Reactivation was slow (t(1/2) = 32 min at 37 degrees C), and release of trapped nucleotide correlated with recovery of ATPase. Trapping of 8-azido-ADP followed by UV irradiation yielded permanent inactivation and specific labeling of Pgp in plasma membranes. Both N- and C-terminal nucleotide binding sites were labeled. These findings give strong confirmation of the concepts that in intact Pgp both nucleotide sites are active in MgATP hydrolysis, and that they interact strongly. The characteristics of inhibition by BeFx were similar in general to those seen with vanadate. However, PPi gave strong protection against BeFx inhibition, and in this respect, inhibition by BeFx was clearly different from vanadate inhibition.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Inhibition of P-glycoprotein ATPase activity by procedures involving trapping of nucleotide in catalytic sites.

Fluoroaluminate in combination with nucleotide inhibited ATPase activity of P-glycoprotein (Pgp) in plasma membranes and in pure reconstituted form. Low nucleotide concentrations were effective, e.g., half-maximal inhibition was obtained with 10 microM MgATP. With MgATP or MgADP, reactivation occurred with t1/2 = 7 min at 37 degrees C. With 8-azido-ATP, UV irradiation of inhibited Pgp gave specific photolabeling of both nucleotide sites. Fluoroaluminate therefore provides a valuable tool for functional and structural characterization of P-glycoprotein and probably of other ABC transporters. 2-Azido-ATP, in combination with vanadate, fluoroaluminate, or beryllium fluoride, inhibited Pgp ATPase activity. Low concentrations of 2-azido-ATP were effective. However, after UV irradiation of the inhibited Pgp species, in no case was there evidence of covalent labeling of nucleotide sites. Therefore in the Pgp catalytic sites, under conditions of nucleotide trapping, there is no suitable amino acid side chain adjacent to the photoactivated 2-position of bound 2-azido-nucleotide, and 8-azido-ATP is the preferred photolabeling analog.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Both P-glycoprotein nucleotide-binding sites are catalytically active.

The technique of vanadate trapping of nucleotide was used to study catalytic sites of P-glycoprotein (Pgp) in plasma membranes from multidrug-resistant Chinese hamster ovary cells. Vanadate trapping of Mg- or Co-8-azido-nucleotide (1 mol/mol of Pgp) caused complete inhibition of Pgp ATPase activity, with reactivation rates at 37 degrees C of 1.4 x 10(-3) s-1 (t1/2 = 8 min) or 3.3 x 10(-4) s-1 (t1/2 = 35 min), respectively. UV irradiation of the inhibited Pgp yielded permanent inactivation of ATPase activity and specific photolabeling of Pgp. Mild trypsin digestion showed that the two nucleotide sites were labeled in equal proportion. The results show that both nucleotide sites in Pgp are capable of nucleotide hydrolysis, that vanadate trapping of nucleotide at either site completely prevents hydrolysis at both sites, and that vanadate trapping of nucleotide in the N- or C-terminal nucleotide sites occurs non-selectively. A minimal scheme is presented to explain inhibition by vanadate trapping of nucleotide and to describe the normal catalytic pathway. The inhibited Pgp-Mg-nucleotide.vanadate complex is probably an analog of the catalytic transition state, implying that when one nucleotide site assumes the catalytic transition state conformation the other site cannot do so and suggesting that the two sites may alternate in catalysis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody.

BACKGROUND/AIMS: Extraintestinal manifestations of inflammatory bowel disease include involvement of the eye and joint. However, the pathogenesis of ocular and joint complications is unknown. The aim of the current study is to examine the presence of cross-reactive peptide in the colon and ocular and joint tissue. METHODS: Using a murine monoclonal antibody (7E12H12; immunoglobulin M isotype) developed against a colon epithelial protein, various parts of the eyes (n = 10) and joints (n = 8) were examined. A sensitive immunoperoxidase assay was used. RESULTS: In the ocular and joint tissues, the reactivity of 7E12H12 monoclonal antibody was exclusively present in the nonpigmented epithelial cells of the ciliary processes and chondrocytes, respectively. Other structures of the eyeball, such as the sclera, cornea, iris, and retina, and the synovium of the joints did not react with 7E12H12 monoclonal antibody. Colonic epithelial cells examined in parallel also reacted with the monoclonal antibody. CONCLUSIONS: The colon epithelial cells share a unique peptide with the nonpigmented ciliary epithelial cells and chondrocytes. Future studies of the peptide(s) expressing this common epitope shared by the colon and extracolonic organs known to be involved in colitis may provide further understanding of the pathogenesis of extraintestinal complications in patients with ulcerative colitis.

Antibodies, Monoclonal↗
PubMed1978

The effect of extraction of the intrafascicular contents of peripheral nerve trunks on perineurial structure.

The intrafascicular contents have been extracted from the tibial nerve of the rabbit through perineurial incisions. Within 6--8 days following this procedure, the perineurial cells separate from one another, become dissociated from their basement membranes and assume a fibroblast-like appearance. The intrafascicular space becomes populated with endoneurial fibroblasts. With the ingrowth of regenerating axons, bundles of axons and associated Schwann cells become surrounded by cells of fibroblastic appearance which undergo perineurial transformation resulting in the development of multiple small fascicles. The cells of the surrounding perineurium appear to reassume a lamellar organization and to reestablish contacts with each other with the formation of junctional complexes. It is therefore suggested that neural structures may be responsible for the development and maintenance of the structural organization of the perineurium.

Animals↗