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Biomedical subjects

D Gupta

Publications and source records attributed to D Gupta.

At least 73 records · Page 4Linked to original sources

Analysis of static pulmonary mechanics helps to identify functional defects in survivors of acute respiratory distress syndrome.

OBJECTIVE: To assess the utility of static lung pressure-volume measurements in identifying and categorizing pulmonary function test defects in survivors of acute respiratory distress syndrome (ARDS). DESIGN: Cross-sectional. SETTING: Pulmonary function laboratory at a tertiary referral hospital in northern India. PATIENTS: Six survivors of ARDS reporting for their first follow-up visit after discharge. MEASUREMENTS AND MAIN RESULTS: Spirometry and whole body plethysmography were performed to evaluate lung volumes and to collect static lung pressure-volume data; the latter were subjected to monoexponential analysis. Three patients had a restrictive ventilatory defect as evidenced by diminished vital capacity and total lung capacity, but only one had reduced static lung compliance. The other two patients had reduced recoil pressure at total lung capacity, suggestive of respiratory muscle weakness. Two other patients with normal lung volumes had reduced static lung compliance. Exponential analysis of pressure-volume data in the three patients with reduced static lung compliance was consistent with reduced distensibility and loss of lung units in one patient each. Additionally, two patients had high values for shape constant of the exponential curve, indicative of air space distention. CONCLUSIONS: Detailed analysis of static pressure-volume data can identify pulmonary function abnormality and categorize the dominant mechanism responsible for restrictive ventilatory defects in survivors of ARDS, even in patients with normal lung volumes. In addition to lung fibrosis, neuromuscular weakness also contributes to decline in pulmonary function.

Adolescent↗

Sarcoidosis in developing countries.

Sarcoidosis is seen in different parts of India and other developing countries with almost similar frequency as in the West. It was largely due to lack of awareness and non-availability of investigations for diagnosis that the disease was reported to be rare in the past. A combination of clinical, radiologic, and histologic criteria are used to diagnose sarcoidosis. A confident exclusion of other causes of granuloma formation, especially tuberculosis, is required. Absence of mycobacteria and of caseation in the histologic specimens and presence of skin anergy to tuberculin help make a diagnosis. Transbronchial lung biopsy obtained with the help of fiberoptic bronchoscopy is positive in about 80% of patients. Corticosteroids are used to treat patients with symptoms and those showing active organ involvement. Aggressive treatment is required for patients with acute and severe pulmonary, cardiac, ocular, or neurologic involvements.

Adult↗

Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: structural requirements differ from those for responses to lipopolysaccharide.

The purpose of this study was to identify the functional significance of the binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to compare the structural requirements of sCD14 for the binding to PGN and lipopolysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS-induced cell responses. sCD14 did not facilitate the responses of membrane CD14 (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the responses of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells to PGN. sCD14 enhanced mCD14-mediated cell activation by both PGN and LPS, but only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein. Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region of sCD14 were needed for binding to both PGN and LPS and for enhancement of cell activation by both PGN and LPS. However, deletions of individual sequences had different effects on the ability of sCD14 to bind to PGN and to LPS and on the ability to enhance the responses to PGN and to LPS. Thus, there are different structural requirements of sCD14 for binding to PGN and to LPS and for the enhancement of PGN- and LPS-induced cell activation.

Acute-Phase Proteins↗

Epidemiology of pneumothorax in England.

BACKGROUND: Little is known of the epidemiology of pneumothorax. Routinely available data on pneumothorax in England are described. METHODS: Patients consulting in primary care with a diagnosis of pneumothorax in each year from 1991 to 1995 inclusive were identified from the General Practice Research Database (GPRD). Emergency hospital admissions for pneumothorax were identified for the years 1991-4 from the Hospital Episode Statistics (HES) data. Mortality data for England & Wales were obtained for 1950-97. Analyses of pneumothorax rates by age and sex were performed for all data sources. Seasonal and geographical analyses were carried out for the HES data. RESULTS: The overall person consulting rate for pneumothorax (primary and secondary combined) in the GPRD was 24. 0/100 000 each year for men and 9.8/100 000 each year for women. Hospital admissions for pneumothorax as a primary diagnosis occurred at an overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and women, respectively. Mortality rates were 1. 26/million per year for men and 0.62/million per year for women. The age distribution in both men and women showed a biphasic distribution for both GP consultations and hospital admissions. Deaths showed a single peak with highest rates in the elderly. There was an urban-rural trend observed for hospital admissions in the older age group (55+ years) with admission rates in the conurbations significantly higher than in the rural areas. Analysis for trends in mortality data for 1950-97 showed a striking increase in the death rate for pneumothorax in those aged 55+ years between 1960 and 1990, with a steep decline in the 1990s. Mortality in the younger age group (15-34 years) remained low and constant. CONCLUSION: There is evidence of two epidemiologically distinct forms of spontaneous pneumothorax in England. The explanation for the rise and fall in mortality for secondary pneumothorax is obscure.

Adolescent↗

Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-negative and Gram-positive bacteria and activation of chemokine genes.

MD-2 is associated with TLR4 on the cell surface and enables TLR4 to respond to LPS. TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS, ReLPS, and lipid A. MD-2 enables TLR2 to respond to non-activating LPS, ReLPS, and lipid A, and enhances TLR2-mediated responses to Gram-negative and Gram-positive bacteria, protein-containing LPS, peptidoglycan, and lipoteichoic acid. MD-2 enables TLR4 to respond to a wide variety of endotoxic LPS partial structures, Gram-negative bacteria, and Gram-positive lipoteichoic acid, but not to Gram-positive bacteria, peptidoglycan, and lipopeptide. MD-2 physically associates with both TLR4 and TLR2, but the association with TLR2 is weaker than with TLR4. Also, MD-2 and TLR2 and TLR4 enhance each other's expression. The highest induced genes in human monocytes stimulated with Gram-positive and Gram-negative bacterial cell wall components are chemokine genes, and IL-8 is the highest induced chemokine. Both Gram-positive and Gram-negative bacteria activate TLR2-->MyD88-->IRAK-->TRAF-->NIK-->IKK-->NF-->kappaB signal transduction pathway that induces transcription of the IL-8 gene. Therefore, TLR2 is a functional receptor for both Gram-positive and Gram-negative bacteria and it induces activation of IL-8.

Animals↗

Study of the prevalence of asthma in adults in North India using a standardized field questionnaire.

Prevalence of asthma was calculated using a Hindi adaptation of the International Union Against Tuberculosis and Lung Disease (IUATLD)-1984 questionnaire. The questionnaire was administered to patients with and without asthma to select specific items to define asthma. Questionnaire validity was tested against physician-diagnosed asthma in 753 individuals in the field, with sensitivity and specificity of 63.1% and 98.8%, respectively. The field prevalence study was conducted among 958 men and 1158 women. True population prevalence, calculated from the observed prevalence using specificity and sensitivity of the questionnaire, was 3.94% in urban men, 3.99% in rural men, and 1.27% in both urban and rural women.

Adolescent↗

Primary bilateral mucosa-associated lymphoid tissue lymphoma of the breast with atypical ductal hyperplasia and localized amyloidosis. A case report and review of the literature.

Primary non-Hodgkin lymphoma of the breast is a rare disease. Primary mucosa-associated lymphoid tissue lymphoma is even rarer, and bilateral involvement is exceptional. We describe a case of primary bilateral breast mucosa-associated lymphoid tissue lymphoma with bilateral atypical ductal hyperplasia and bilateral localized amyloidosis in a 64-year-old woman with a history of arthritis and systemic lupus erythematosus and its clinical, histologic, and immunohistochemical features. Microscopic examination of the breast lesion showed dense periductal and perilobular small and plasmacytoid lymphocytes with eosinophilic amyloid in the vessels and the stroma. Bilateral single foci of atypical ductal hyperplasia were also noted. Fine needle aspiration showed small and large lymphocytes and plasma cells. Molecular analysis demonstrated a heavy chain immunoglobulin H gene rearrangement. Flow cytometry studies showed an abnormal B-cell population. The combined histologic, paraffin immunohistochemistry, flow cytometry, and molecular results were considered diagnostic for low-grade mucosa-associated lymphoid tissue lymphoma. The patient underwent bilateral local breast radiation without other organ or site involvement.

Amyloidosis↗

Cloning, sequencing, and expression of the hepatitis E virus (HEV) nonstructural open reading frame 1 (ORF1).

Hepatitis E virus (HEV) causes enterically transmitted epidemic and sporadic viral hepatitis affecting millions of people in the developing world. Different geographical isolates of HEV show a high degree of homology at the nucleotide and amino acid levels. The approximately 7.2 kb RNA genome has three open reading frames of which ORF1 is predicted to code for the viral nonstructural polyprotein. The expression, processing and properties of the nonstructural ORF1 polyprotein have not been reported so far. In this study, the complete HEV ORF1 was reconstructed from overlapping fragments amplified by polymerase chain reaction (PCR) of total RNA isolated from the bile fluid of a rhesus monkey experimentally infected with HEV isolate from an epidemic. The complete assembled ORF1 was sequenced using HEV specific primers. The ORF1 polyprotein was expressed in E. coli, in a cell free translation system and in HepG2 cells, and was characterized by western blotting and immunoprecipitation using acute phase patient serum as well as polyclonal antibodies raised against defined parts of the ORF1 polyprotein. The nonstructural polyprotein of HEV was expressed as a 186 kDa protein. No processing was observed into discrete units, either in-vitro based on a kinetic analysis, or in HepG2 cells based on immunoprecipitation.

Animals↗

Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage.

Twenty five patients with post operative ischaemic deficits, following clipping of intracranial aneurysms, were studied. Hypertensive-hypervolaemic-haemodilution (triple H) therapy was given to all patients using colloids and crystalloids. CVP was used to monitor the fluid therapy. Dopamine was needed in 22 patients to elevate the systemic blood pressure. Vasospasm was confirmed in 20 patients with transcranial doppler studies (TCD). 20 (80%) patients survived, 10 (40%) with good outcome, 7 (28%) with fair, 2 (8%) with poor outcome and 1 (4%) with vegetative state. There were 5 (20%) deaths, 4 of which occurred due to infarct. All these patients had poor Hunt and Hess grade at admission, high Fisher grade haemorrhages in the initial CT scan and/or required prolonged temporary clipping at surgery. One death occurred due to central venous line induced septicaemia. The duration of 'triple H therapy' amongst the survivors varied from 2-7 days with an average of 4.6 days. The complications of 'triple H therapy' included hypokalaemia (3 patients), haemorrhagic infarct (1 patient) and septicaemia (1 patient). It is concluded that 'triple H therapy' is useful in treating vasospasm induced ischaemic deficits. It worsens brain oedema in presence of acute infarcts and hence is contraindicated in such patients. A further study involving a larger number of patients with strict haemodynamic and ICP monitoring is suggested to determine the usefulness of individual components of 'triple H therapy'.

Adolescent↗

Statistical estimation of height from arm span in north Indian subjects.

We measured height and arm span of 400 males and 231 female subjects between 16-83 years of age. Arm span exceeded height in 82.6% subjects. Mean height to arm span ratio was 0.9711 and 0.9816 in males and females respectively, and was not significantly correlated with age. Linear regression equations were generated for both sexes for prediction of height from arm span and age. The use of height to arm span ratio was found to be a less suitable method than the use of regression equations in estimating height from arm span.

Adolescent↗

Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal pheochromocytomas.

No reliable pathologic criteria have been identified that predict clinical behavior in adrenal and extra-adrenal pheochromocytomas (PHEOs). Reliable prognostic markers for the prediction of clinical outcome are needed to assign optimal treatment for potentially malignant tumors. In this report, we evaluated several molecular markers (topoisomerase II alpha, E-cadherin, HER-2/neu, and retinoblastoma (RB) gene protein) that have not been previously studied in PHEOs. Paraffin-embedded, formalin-fixed tissue blocks from 50 cases of PHEO (30 benign and 20 malignant, 31 adrenal and 19 extra-adrenal) were obtained from University of Utah Health Sciences Center, Salt Lake City, and the Medical College of Wisconsin, Milwaukee. Gross (tumor size, weight, local extension, cyst formation, hemorrhage, necrosis), microscopic (pleomorphism, hyaline globules, intranuclear inclusion, mitotic count, capsular and vascular invasion, ganglionic/neuronal differentiation), and immunohistochemical features (topoisomerase II alpha, p53, MIB-1, E-cadherin, RB, and HER-2/neu) were studied. With the exception of vascular invasion (P = 0.025), there were no unequivocal gross or microscopic characteristics that distinguished benign from malignant lesions (P approximately = 0.11-0.71). Topoisomerase III and MIB-1 indices in malignant lesions were significantly higher than those observed in benign lesions (P = 0.012 and 0.019). Differences in p53 expression were not statistically significant (P = 0.082). Loss in RB protein product expression was significantly more common in malignant lesions (P = 0.001), E-cadherin loss and HER-2/-neu overexpression were not observed in any of the benign or malignant lesions. We studied the immunohistochemical expression of topoisomerase II alpha, MIB-1, p53, RB gene protein product, E-cadherin, and HER-2/neu in a series of adrenal and extra-adrenal PHEOs. Overexpression of topoisomerase II alpha and MIB-1 and loss of RB protein product were more common in malignant lesions, whereas p53, E-cadherin, and HER-2/neu do not seem to have diagnostic utility in the prediction of biologic behavior in these neoplasms.

Adolescent↗

Incidence of tuberculosis among patients receiving treatment with oral corticosteroids.

OBJECTIVES: To study the incidence and pattern of tuberculosis in patients taking systemic corticosteroids (CS). METHODS: Seventy seven patients taking oral CS for various respiratory diseases and eighty patients suffering from similar diseases but not receiving steroids were followed up for one year to study the incidence of tuberculosis. RESULTS: Five patients (6.5%) receiving CS developed tuberculosis as against none amongst the controls (p < 0.05). Of these, three patients had sputum positive pulmonary tuberculosis and one each had sputum negative pulmonary tuberculosis and tubercular meningitis. All patients were treated with standard anti-tubercular therapy; four patients improved whereas one died due to complications of disease. CONCLUSION: Systemic CS therapy causes a significant increase in incidence of tuberculosis.

Administration, Oral↗

Familial aggregation of cancer in patients with bronchogenic carcinoma.

History of cancer among first degree relatives was obtained in 124 patients with bronchogenic carcinoma [probands] and 248 controls, and differences in familial aggregation evaluated by calculation of odds ratio [OR] and their 95 percent confidence intervals [95% CI]. Probands were more likely than controls to have relatives with cancers [OR 1.27, 95% CI 0.49-3.10], both among smokers and nonsmokers [OR 1.31, 95% CI 0.27-6.79 and OR 1.21, 95% CI 0.12-6.16 respectively]. Sisters of probands were particularly at a higher risk [OR 8.72, 95% CI 0.85-430.08]. A genetic component, possibly independent of smoking habits, may be important in the causation of lung cancer.

Adenocarcinoma↗

Hypothalamo-pituitary-adrenal axis function in asthmatics taking low dose inhaled beclomethasone dipropionate.

OBJECTIVES: Anti-inflammatory drugs, particularly inhaled corticosteroids remain the mainstay of treatment of bronchial asthma. However, these drugs have potential side effects. This study was undertaken to evaluate the effects of inhaled beclomethasone dipropionate (400 and 800 micrograms) over a period of six months on the hypothalamo-pituitary-adrenal axis (HPA) suppression. METHODS: Assessment of the hypothalamo-pituitary-adrenal axis function was carried out by tetracosactrin test at time zero, (before start of treatment), three months, and six months. The baseline values served as the controls for each patient. Serum cortisol was estimated by radioimmuno assay. The response to short tetracosactrin test was classified as normal if serum cortisol levels rose at least 200 nmol/L to a minimum of 500 nmol/L. RESULTS: There were seven patients who were inhaling beclomethasone dipropionate in a dose of 400 micrograms/day and another seven patients were taking the same drug in a dose of 800 micrograms/day. There was no side effect of the drug in any patient except in one patient who had dysphonia. The mean basal cortisol levels were normal in all the subjects at 0, 3 and 6 months of therapy. Tetracosactrin stimulation test was also normal in all patients at all the times who were receiving the dose of 400 micrograms/day. However, one patient (14%) receiving 800 micrograms/day had HPA axis suppression at six months. Two patients in this group also had low basal cortisol levels. There was no clinical evidence of such suppression/deficiency. CONCLUSION: Beclomethasone dipropionate in a dose of 800 micrograms/day may suppress the hypothalamo-pituitary-adrenal axis if used for long periods (six months). However, this may not have any clinical significance.

Administration, Inhalation↗

Structure of the carbonic anhydrase VI (CA6) gene: evidence for two distinct groups within the alpha-CA gene family.

The secreted carbonic anhydrase (CA VI) is believed to be one of the oldest mammalian CAs in evolutionary terms. To elucidate its gene structure and compare it with other members of the alpha-CA family, we cloned genomic fragments encoding the bovine CA6 gene and determined its exon/intron organization. The gene spans approx. 25 kb and consists of eight exons and seven introns. Exon 1 encodes the 5' untranslated region, the signal peptide and the N-terminus of the mature enzyme. Exon 8 encodes the 3' untranslated region and the C-terminal extension that is unique to CA VI. Exons 2-7 encode the CA domain, which shows significant sequence similarity to other CAs. Two distinct groups exist in the alpha-CA family on the basis of a comparison of the known gene structures. One group consists of the cytoplasmic (CA I, II, III and VII) and mitochondrial (CA V) members. The other group consists of the membrane-bound (CA IV and IX) and secreted (CA VI) members. In particular, the seven exon/intron boundaries in the CA domain of the CA6 gene are conserved in the CA9 gene, which encodes the multidomain protein CA IX that is overexpressed in tumours and has transforming potential.

Amino Acid Sequence↗