Hepatitis B and pupil-sparing oculomotor nerve paresis.
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Biomedical subjects
Publications and source records attributed to D Gupta.
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Management of interstitial lung disease, especially idiopathic pulmonary fibrosis, is both difficult and unsatisfactory. In many patients, only supportive therapy can be instituted. Attempts have been made to use anti-inflammatory therapy to reverse inflammation, provide symptomatic relief, stop disease progression, and prolong survival; the results of such treatment have varied from no improvement to significant prolongation of survival. Corticosteroids are the most frequently used anti-inflammatory agents. Cytotoxic drugs, such as oral azathioprine or intermittent intravenous cyclophosphamide, have also been shown to be effective both alone and in combination with low-dose oral corticosteroids. Of the other antifibrotic drugs that have been used, colchicine seems to provide some benefit. It is especially useful in aged persons and those with corticosteroid-induced problems or concomitant illnesses that are likely to be worsened by steroids. Anti-inflammatory therapy is costly to administer and monitor, particularly in the developing world. It is therefore important to consider these issues before instituting treatment. Younger patients and patients with less-severe disease of recent onset are most likely to respond to treatment. Similarly, patients with lymphocytic alveolitis or desquamative interstitial pneumonia respond better. Despite the use of newer strategies for treatment, the overall prognosis for patients with interstitial lung disease has not really changed, and the median population survival remains almost the same as it was about 30 years ago.
STUDY OBJECTIVE: To evaluate if direct substitution of arm span for height during interpretation of spirometry data leads to any significant statistical or clinical differences in Indian adults, and to compare this method with the use of height estimated indirectly from arm span. DESIGN: Cross-sectional. SETTING: Respiratory laboratory of a tertiary referral hospital in North India. PARTICIPANTS: Two hundred twenty-eight subjects referred for spirometry. MEASUREMENTS AND RESULTS: Standing height and arm span were measured for all subjects. Spirometry measurements included FVC, FEV1, FEV1/FVC, peak expiratory flow, and maximal midexpiratory flow. Predicted values for each parameter were calculated separately for height, arm span, and height estimated from fixed height:arm span ratio. Results were classified into normal, obstructive, and restrictive defects for each height, arm span, and estimated height measurement, and any abnormality was categorized as mild, moderate, or severe. Arm span exceeded height in 182 (79.82%) subjects. Thirty-seven (16.2%) and 32 (14.0%) results were classified or categorized incorrectly when arm span and estimated height were substituted respectively, for actual height, with a kappa estimate of agreement 0.779 and 0.808, respectively; 17.4% and 11.0% normal results were classified, respectively, as restrictive defects using arm span and estimated height. Limits of agreement, which were almost equally wide for both sets of data, were more than the permissible intraindividual variability for FVC and FEV1. CONCLUSIONS: The substitution of arm span for height introduces statistically significant changes in spirometry results. Use of height estimated from arm span using fixed ratio also leads to misclassification of data, though less than that caused by use of arm span alone. Height estimated from arm span can be substituted for actual height in patients in whom height cannot be measured reliably. Where racial/ethnic norms for height and arm span correlation are not available, arm span is a reasonable surrogate for standing height.
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Conformational flexibility of tuftsin molecule is studied using all-atom based atom-atom potential and systematic search, simulated annealing molecular dynamics (SAMD) and molecular dynamics (MD) techniques. Latter was carried out for 650 pico seconds (ps) using AMBER 4.0 with explicit water in TIP3P model. Number of inter-atomic distances and torsional angles were monitored during SAMD and MD simulation. We found that tuftsin molecule, irrespective of any starting conformation, assumes highly folded structure with strong electrostatic interaction between Lys-2 NH3 and Arg-4 carboxylic group and weak hydrogen bond between Lys-2 CO and Arg-4 NH atoms. It had distorted but stable conformation close to inverse gamma turn.
The activity of glyoxalase I from the soluble fraction of diabetic rat liver was found to decrease as compared to the control. Sodium orthovanadate in drinking water and Trigonella foenum graecum seed powder when administered to these diabetic animals were found to reverse the activity of glyoxalase I to control values. A combination of the above two antidiabetic compounds showed a better reversal. Vanadate and Trigonella seed powder treatment separately to diabetic rats also normalized hyperglycemia together with glyoxalase I activity. A combination of vanadate and Trigonella seed powder also restored the other general parameters of the diabetic animals.
The effects of insulin, sodium orthovanadate and a hypoglycemic plant material, Trigonella foenum graecum (fenugreek) seed powder were studied on the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in diabetic liver and kidney. The significantly increased activities of the two enzymes during diabetes in liver and kidney were found to be lowered to almost control values by the use of the antidiabetic compounds. Diabetic liver exhibited a much greater increase in the activities of the two enzymes than diabetic kidney. The highest percentage of reversal to normal values was seen using the combination of vanadate and Trigonella seed powder. The lowered rate of growth of the animals as well as the increased blood sugar were reversed almost to the control levels by the Trigonella seed powder and vanadate treatment. The inclusion of the Trigonella seed powder overcame the toxicity of vanadium encountered when it was given alone as insulin mimetic agent. Much lower levels of vanadate were needed when it was given in combination with Trigonella seed powder. Their combined effects were better at restoring the above parameters than those induced by insulin administration.
Secreted epithelial mucins are extremely large and heterogeneous glycoproteins. We report the 5 kilobase DNA sequence of a second gene, BSM2, which encodes bovine submaxillary mucin. The determined nucleotide and deduced amino acid sequences of BSM2 are 95.2% and 92. 2% identical, respectively, to those of the previously described BSM1 gene isolated from the same cow. Further, the five predicted protein domains of the two genes are 100%, 94%, 93%, 77%, and 88% identical. Based on the above results, we propose that expression of multiple homologous core proteins from a single animal is a factor in generating diversity of saccharides in mucins and in providing resistance of the molecules to proteolysis. In addition, this work raises several important issues in mucin cloning such as assembling sequences from seemingly overlapping clones and deducing consensus sequences for nearly identical tandem repeats.
Hepatitis C virus (HCV) protease NS3 and its protein activator NS4A participate in the processing of the viral polyprotein into its constituent nonstructural proteins. The NS3/4A complex is thus an attractive target for antiviral therapy against HCV. We expressed the full-length NS3 and NS4A in insect cells as a soluble fusion protein with an N-terminal polyhistidine tag and purified the two proteins to homogeneity. Cleavage at the junction between HisNS3 and NS4A occurs during expression, producing a noncovalent complex between HisNS3 and NS4A with a subnanomolar dissociation constant. We purified the HisNS3/4A complex by detergent extraction of cell lysate and by metal chelate chromatography. We removed the His tag by thrombin cleavage and then further purified the complex by gel filtration. The purified NS3/4A complex is active in a protease assay using a synthetic peptide substrate derived from the NS5A-NS5B junction, with kcat/K(m) of 3700 (+/- 600) M-1 s-1, an order of magnitude above those previously reported for NS3 expressed by other strategies. This high protease activity implies that the full-length sequences of NS3 and NS4A are required for optimal activity of the NS3 protease domain. We examined the dependence of the NS3/4A protease activity on buffer conditions, temperature, and the presence of detergents. We find that, under most conditions, NS3 protease activity is dependent on the aggregation state of the NS3/4A complex. The monodisperse, soluble form of the NS3/4A complex is associated with the highest protease activity.
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PURPOSE: To evaluate the diagnostic yield of CT-guided (CTNAB) and fluoroscopy-guided transbronchial (TBNA) fine-needle aspiration cytology in pulmonary nodules and to compare their complications. MATERIAL AND METHODS: Thirty patients with pulmonary nodules not abutting upon the chest wall and inaccessible to bronchoscopy were randomised for CTNAB or TBNA. Eighteen patients underwent CTNAB and 16 TBNA. Four patients underwent both procedures. RESULTS: In the CTNAB group, a definitive diagnosis could be made in 14 (78%) out of 18 patients whereas in the TBNA group, a definitive diagnosis was made in 11 (69%) out of 16 patients. This difference was not statistically significant (p > 0.05). The final diagnosis in 29 out of 30 patients comprised primary bronchogenic carcinoma in 14 patients, metastases in 5 patients, and benign lesions in 10 patients (34%) of which 3 lesions (30%) were of tuberculous aetiology. There were 2 asymptomatic pneumothoraces in the CTNAB group and no complication was observed in the TBNA group. CONCLUSION: Both techniques were safe and effective in the diagnosis of peripheral pulmonary lesions. TBNA was best suited for lesions larger than 3 cm and located in the middle and lower lobes while CTNAB could be used for any lesions.
Peptidoglycan (PGN) activates macrophages through membrane CD14 (an endotoxin receptor) and binds to both soluble and membrane CD14. Since soluble CD14-lipopolysaccharide (LPS) complexes activate CD14-negative endothelial and epithelial cells, this study tested whether soluble CD14-PGN complexes activate human umbilical vein endothelial cells and epithelial-like U373 cells to secrete interleukin (IL)-6, express vascular cellular adhesion molecule-1, and translocate nuclear factor-kappaB. In contrast to LPS, endothelial, epithelial, and other cells of non-hemopoietic origin were unresponsive to PGN through soluble or membrane-bound CD14, whereas cells of hemopoietic origin were responsive to both PGN and LPS. PGN, similarly to LPS, activated endothelial and epithelial cells indirectly in the presence of 2%-4% blood, by inducing secretion of both tumor necrosis factor-alpha and IL-1 from monocytes. These results reveal different mechanisms of CD14 function and cell activation for LPS and PGN and also demonstrate strong indirect activation of endothelial and epithelial cells by both PGN and LPS.
Surface structures of bacteria contribute to the microbial pathogenic potential and are capable of causing local and generalized inflammatory reactions. Among these factors, endotoxin and peptidoglycan are of particular medical importance. Both toxic bacterial polymers are now recognized to interact with the same cellular receptor, the CD14 molecule, which is expressed on different types of immune cells, in particular, monocytes/macrophages. The interaction between these bacterial activators and CD14 leads to the production of endogenous mediators such as tumor necrosis factor alpha, interleukin 1 (IL-1), and IL-6, which are ultimately responsible for phlogistic responses. The fact that CD14 recognizes not only endotoxin and peptidoglycan but also other glycosyl-based microbial polymers suggests that this cellular surface molecule represents a lectin.
An algorithm for diagnosis of pulmonary fibrosis in the tropical countries has been developed on the basis of the common causes of fibrosis, and the availability and feasibility of different diagnostic techniques in those countries. First, it is important to exclude common diseases such as the atypical or occult forms of bronchiectasis, pulmonary tuberculosis, and chronic bronchitis, which often overshadow interstitial pulmonary fibrosis. A good history and physical examination supplemented with chest radiography and simple lung function tests are generally enough to narrow down the list of causes of diffuse lung disease to interstitial pulmonary fibrosis. The real difficulty lies in identifying the idiopathic or "lone" forms from the secondary forms of pulmonary fibrosis. High-resolution CT is helpful in a large number of patients. Transbronchial lung biopsy is performed in a select population of patients. Open surgical or thoracoscopy guided biopsy is the gold standard, but is rarely required.
OBJECTIVE: Our objective was to assess the technical feasibility, safety, and accuracy of sonographically guided fine-needle aspiration biopsy of superior mediastinal masses by the suprasternal route. CONCLUSION: Sonographically guided biopsy through the suprasternal route is safe and effective for lesions in the pretracheal, right paratracheal, and prevascular compartments of the superior mediastinum. This procedure is especially useful for lesions with an acoustic window too small for parasternal biopsy under sonographic guidance.
We have built a model for Ca2+ channel using amino acid sequence from S3 helix of the fourth internal repeat of alpha 1 subunit of dihydropyridine sensitive calcium channel from rabbit skeletal muscle, on the basis of X-ray crystallographic data on four helix bundle. The assembling of the geometry of the pore was achieved using a sixteen residues peptide fragment from short SSI/II loop (residues 1010-1025) which had F1013 and E1014 residues, considered to be important for the drug induced activity of the channel. This had hairpin bend between F1013 to W1016. The drug 2,6-dimethyl 3,5-dicarbomethoxy-4 (2-nitrobenzyl) 1,4 dihydropyridine (DHP) (nifedipine), which is a calcium channel inhibitor used in the treatment of cardiovascular diseases, was introduced, interacting with these two residues via Ca2+ ion. Two more Ca2+ ions were introduced in the pore. The model was incorporated in the bilayer of 36 dimyristoyl phosphatidyl choline (DMPC) molecules with 1201 water molecules and simulated for 200 picoseconds (ps) after equilibration for 120 ps. We also simulated the channel model in vacuum and in aqueous environment for comparison. The latter was unstable after 120 ps. The geometric parameters of the pore are analysed by MOLMOL, PCURVE 3.1 and a special program ANHELIX developed by us. Stability of the pore dimensions during simulations is discussed in this paper.
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Role of Parthenium hysterophorous as an allergen evoking bronchial hyper-responsiveness was assessed in twenty five adult patients with stable asthma and ten healthy controls. Assessment was made with the help of skin prick and bronchial provocation tests (BPT) using a commercially available Pathenium extract. Eleven patients (44%) of the study group had a positive skin reaction and 4 (16%) showed a significant fall in FEV1 and PEFR (p < 0.05) on bronchial provocation. In the control group only one patient (10%) had a positive skin test while there was none with a positive bronchial challenge. There was a significant fall in the mean values of FEV1 and PEFR over base line after the BPT in patients of asthma than controls. It is concluded that a significant proportion of bronchial asthma patients are sensitized to Parthenium hysterophorous and it may act as a cofactor in seasonal exacerbation of their symptoms.