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Biomedical subjects

B K Sharma

Publications and source records attributed to B K Sharma.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prevalence of serum antibodies to LA-1 oncoprotein, herpes simplex virus type-2 glycoprotein and human papillomavirus type 16 transactivator (E2) protein among Indian women with cervical neoplasia.

Prevalence of serum antibodies to synthetic peptide to oncoprotein of LA-1 known as oncogene of herpes simplex virus type-2, herpes simplex virus type-2 glycoprotein-D as an determinant of viral pathogenicity and human papillomavirus type 16 transactivator E2 protein was studied among 46 Indian women with cervical neoplasia using immunoblot assay for HSV-2 gD glycoprotein and LA-1 antibodies as well as peptide ELISA assay to detect HPV16 E2 antibodies. The seropositivity to LA-1 oncoprotein was found to be high (61%) among patients with invasive cervical carcinoma as compared to 35% in various grades of cervical intraepithelial neoplasia (CIN) and 36% in normal control women. In contrast to this, a uniformly high frequency of antibody to HPV 16 E2 was observed among women with CIN (68%), normal healthy controls (50%) and invasive cervical carcinoma (43%). However, a low frequency of seropositivity (13%) to recombinant vaccinia virus HSV-2 gD protein was found among 15 tested sera each from group of women with various grades of CIN as well as invasive cervical carcinoma as compared to 28% among seven normal healthy control. A negative correlation of LA-1 and HPV16 E2 seropositivity on patient by patient comparison among CIN and invasive cervical carcinoma group was observed which is statistically significant (P = 0.019 for CIN; P = 0.038 for invasive cervical carcinoma). However, a positive correlation (P = 0.144) was found among normal control women. The study has shown a desirable serological marker of cervical neoplasia. This serological marker could be employed as a screening tool in conjunction with cytopathological screening to diagnose women harbouring LA-1 oncogene associated cervical lesions.

Adult↗
PubMed1998

Immunohistochemical co-expression of human papillomavirus type 16/18 transforming (E6) oncoprotein and p53 tumour suppressor gene proteins in oesophageal cancer.

Human papillomaviruses have been widely implicated as important etiologic agents in various squamous cell carcinomas including oesophageal carcinoma. p53 mutant oncoprotein has also been implicated in various tumours. Immunohistochemical analysis was employed to detect the co-expression of HPV and p53 mutant protein in biopsy specimens of patients of cancer oesophagus as well as controls. This analysis revealed a significantly higher immunopositivity (63%) of E6 oncoprotein of HPV 16/18 in carcinoma of the oesophagus. Immunoexpression of E6 oncoprotein of HPV did not alter significantly the degree of differentiation of the tumour. Seventy-seven percent of cases of oesophageal carcinoma showed strong immuno-staining for mutant p53 protein. A higher percentage (89%) of tissues showed immunoexpression of mutant p53 protein in conjunction with E6 oncoprotein of HPV 16/18 indicating a selective degradation of key cellular protein of p53 having regulatory properties which in turn leads to uncontrolled cellular proliferation. Therefore, coexpression of oncoprotein E6 of HPV 16/18 and mutant p53 protein may be considered as a "high risk" factor for progression to oesophageal malignancy.

DNA-Binding Proteins↗
PubMed1998

Paraoxonase polymorphism in northwestern Indians.

OBJECTIVE: The aim of this study was to distinguish paraoxonase phenotypes by dual substrate method. SUBJECTS AND METHODS: 166 unrelated healthy northwestern Indian Punjabis were studied for basal paraoxonase activity (P), in presence of 1 M NaCl (salt-activated) using paraoxon as substrate and arylesterase activity (A) using phenylacetate as substrate. RESULTS: The mean (+ SD) activity of these in population was 70.43 (+/-30.41), 103.11 (+/-42.87) nmol/min/ml plasma and 36.81 (+/- 9.87) micromol/min/ml plasma, respectively, with no significant difference in sexes. Based on the ratio of SAP activity to A activity, 3 distinct phenotypes could be determined with gene frequencies of PON*A and PON*B being 0.845 and 0.155, respectively. Between P and A, and SAP and A in both A and AB phenotypes, significant correlation was observed (A = r 0.34 and 0.62, p < 0.01; B = r 0.31 and 0.81, p > 0.01), suggesting that both enzymes belong to the same group. CONCLUSIONS: Though northwestern Indian Punjabis have trimodal paraoxonase activity, the majority is either low homozygous (AA) or heterozygous (AB) type with enzyme activity lower than Europids.

Adult↗
PubMed1998

Immunoexpression of mutant p53 and human papillomavirus related E6 oncoprotein in anal malignancies.

Immunohistochemical expression of mutant p53 protein and human papillomavirus (HPV) 16 and 18 related E6 oncoprotein was studied in 36 biopsy proved anal cancers. Mutant p53 was detected in 61.1% cases. HPV 16 and 18 E6 protein was expressed in 22.2% cases, all of which were squamous cell carcinomas. Coexpression of both mutant p53 and E6 protein was found in only 5 cases (13.8%). In HPV 16/18 positive anal tumors, the degradation of p53 is accelerated by viral E6 oncoprotein. In HPV negative tumors, however, other mutagenic factors probably play a role in carcinogenesis.

Adult↗
PubMed1997

Clinical manifestations of Takayasu arteritis in India and Japan--new classification of angiographic findings.

In this retrospective review 102 Indian and 80 Japanese patients with Takayasu arteritis were compared in regard to their clinical manifestations and angiographic findings. Regardless of nationality, most patients were initially affected in their teens or twenties. Japanese patients were female in a larger ratio compared with the ratio in India. Clinically, the two groups exhibited several different features. More Japanese patients were found to be pulseless (P < 0.01) whereas many Indian patients were hypertensive (P < 0.01). Inflammatory conditions in Japanese patients were more severe (P < 0.01) and tended to be more prolonged than those in the Indians. More Japanese patients suffered from aortic regurgitation (P < 0.01), but Indians suffered from hypertension (P < 0.01). Angiographic findings revealed that the aortic arch and its branches were mainly involved in Japanese patients (type I, IIa) whereas the abdominal aorta and its branches were mainly involved in Indian patients (type IV). However, the diffusely involved type (type V) was the one most commonly found in both countries. From the analyses of vascular lesions in both Indian and Japanese patients, 510 and 396, respectively, different progressions of vasculitis are speculated. In Japanese patients, vasculitis generally occurs in the ascending aorta, the aortic arch, and/or its branches and extends into the thoracic and abdominal aorta, subsequently forming various complicated lesions with prolonged inflammatory activity. On the other hand, in Indian patients, vasculitis generally occurs in the abdominal aorta involving renal arteries, subsequently extending into the thoracic aorta within one or two decades, simple vascular lesions being formed. Data analysis suggests that this morbid condition progresses differently in India and Japan, in spite of some common etiologic factor(s).

Adult↗
PubMed1997

Red cell acetyl cholinesterase and plasma cholinesterase activity and genetic variants of plasma cholinesterase in northwest Indian adults.

The plasma cholinesterase (PChE) and red cell acetyl cholinesterase (AChE) activities are indicators of exposure to organophosphates. We studied their distribution in unexposed Northwest Indian adults by measuring them in 120 men and 111 women by Ellman's and Kalow's method, respectively. We also determined genetic variability of plasma cholinesterase in 193 subjects (male = 111, female = 82). The mean +/- (SD) AChE levels in population, men and women, were 34.97 +/- 13.66, 35.05 +/- 12.42, 34.88 +/- 14.89 nmol/mg Hb/min, whereas PChE was 0.448 +/- 0.173, 0.435 +/- 0.163, 0.462 +/- 0.183 ku/l, respectively. When compared for sex, no significant difference could be found for red cell AChE and PChE activity. However, on 2-way analysis of variance (ANOVA) adjusted for age classification, the levels of both AChE and PChE were significantly higher in groups above the age of 30 years as compared to below 30 years (t = 3.08, p < 0.01, t = 2.82, p < 0.05), respectively. Seven genetic variants of PChE could be detected in males, whereas in females 6 genetic variants were found.

Acetylcholinesterase↗
PubMed1996

Platelet calcium pump activity in essential hypertensives and their first-degree relatives.

Intracellular free Ca2+ concentration has been shown to be elevated in platelets of patients with essential hypertension. This study was designed to characterize Ca(2+)-pump activity of the platelet membranes (surface and intracellular) in these patients A double-blind study was carried out. Untreated and treated (on beta-blockers) essential hypertensives were studied in comparison with normotensive control subjects. First degree blood relatives of essential hypertensives were also studied. The Ca2+ activation kinetics of the enzyme showed a significant decrease in the Vmax (for the plasma- and intracellular membranes) and Km (for the intracellular membranes) in the essential hypertensive patients. Increased platelet membrane cholesterol content was observed in these patients. Lowered Ca2(+)-efflux by Ca2(+)-ATPase may lead to elevated intracellular free Ca2(+)-levels in platelet of essential hypertensives. A lowered Ca2(+) -ATPase activity may emerge as a marker for essential hypertension.

Adolescent↗
PubMed1996

Prevalence of serum antibodies to synthetic peptides to HPV16 epitopes among Indian women with cervical neoplasia.

Serum samples from 38 Indian women with cervical intraepithelial neoplasia (CIN) and cancer along with 20 control women were analysed for IgG antibodies against a panel of four synthetic peptides derived from early and late gene open reading frames of HPV16. The cervical tissue samples from these patients were also subjected to PCR in order to detect the presence of human papilloma viruses (HPVs) type 6, 11 and 16 DNA, using a set of primers for the E6 open reading frames in order to establish the acquisition of HPV infection. E2, E6 and L1 peptides of HPV16 were found to be highly reactive with the patients' sera, and a significant prevalence of antibodies to E6, E2 and L1 (P < 0.01) was observed among women with CIN, while antibodies to E6 peptide were only significantly elevated (P < 0.01) among women with cervical invasive carcinoma. Furthermore, there was good agreement between the development of the E6 antibody response and the presence of HPV16 E6 DNA among women with CIN and cervical invasive carcinoma as shown by high values of the kappa coefficient (0.7-1.0). The study clearly revealed a strong agreement between two assay methods defining unambiguous immunogenic B-cell epitopes on synthetic peptides to early and late gene open reading frames of HPV16 which could be used in HPV peptide serology. As such, single or combination of peptides in HPV peptide serology can be used as a screening tool to identify HPV-associated cervical lesions.

Amino Acid Sequence↗
PubMed1996

Direct role of HLA-B5 in influencing susceptibility to Takayasu aortoarteritis.

To investigate genetic factors involved in the pathogenesis of Takayasu arteritis (TA), North Indian patients belonging to the states of Punjab, Haryana, Uttar Pradesh and Delhi were examined for HLA-class I and class II antigens and the data compared with healthy controls from the same ethnic group. Additionally, DNA typing was performed using polymerase chain reaction/sequence specific oligonucleotide probe (PCR-SSOP) technique to evaluate the distribution of molecular alleles in the healthy Indian population as compared to orientals and Western caucasoids. The frequency of HLA-B5 was significantly increased in patients as compared to controls (chi 2 = 32.5, corrected P value, Pc = 3 x 10(-6), relative risk = 4.3). Serological splitting of B5 into B51 and B52 did not reveal an association with any of the two subtypes. Weak association was also noticed with DR8 in the patient group (chi 2 = 8.2, Pc = 0.05). Distribution of the molecular subtypes of various HLA-B and DR alleles indicated that although the Indian population is essentially caucasoid, it comprises of an admixture of both caucasoid as well as oriental alleles/haplotypes. The observations clearly suggest that (a) HLA-linked genes are involved in the development of Takayasu arteritis, and (b) rather than a subtype of B5, the whole molecule or its closely linked gene(s) influence susceptibility to TA.

Adolescent↗
PubMed1996

Current status of Takayasu arteritis in India.

The clinical features of 106 patients of Takayasu arteritis (TA) seen over a period of 16 years are documented (65 females and 41 males). The mean age was 27.3 +/- 9.2 years. Hypertension was the commonest mode of presentation (51.3%) and was detected in 82 patients (77.4%) at the time of presentation. Vascular bruits were heard in 72 patients (67.9%) and 13 patients (12.3%) were in congestive heart failure. Aortography was performed in 95 patients. Based on the extent of involvement, Type I (branches of aortic arch) was seen in 7 (6.6%) patients, Type II (aortic arch, its branches and descending thoracic aorta) in 7 (6.6%) patients, Type III (descending thoracic aorta and abdominal aorta) in 4 (3.8%) patients, Type IV (abdominal aorta only) in 29 (27.3%) patients and Type V (aortic arch, descending thoracic aorta and abdominal aorta) in 59 (55.7%) patients. Therapeutic modalities included antihypertensive drug therapy in 81 patients, antitubercular drugs in 8 patients, steroids in 16 patients and cyclophosphamide in one patient. Response to steroids was satisfactory in 5 of these 16 patients while the lesions of vasculitis healed in the patient who was treated with cyclophosphamide. Surgical interventions included nephrectomy and autotransplantation of kidney in 3 patients each and revascularization in 4 patients and angioplasty in 4 patients. In the area of pathogenesis of this disease, a high activity of protein kinase C(PKC), an increased intracellular calcium and inositol 1,4,5 triphosphate in both unstimulated and stimulated T cells of TA was observed. These findings suggest an activation of PKC-calcium pathway in TA.

Adolescent↗
PubMed1996

Diagnostic criteria for Takayasu arteritis.

Diagnosis of Takayasu arteritis (TA) is often delayed because of a non-specific clinical presentation. Ishikawa's criteria (1988) has been widely used for the diagnosis of this disease. Few modifications have been proposed in Ishikawa's criteria for the diagnosis of TA. The proposed modifications include: (a) removal of the obligatory criteria of age less than 40 years; (b) inclusion of characteristic signs and symptoms as a major criteria; (c) removal of age in defining hypertension; (d) deletion of the absence of aorto-iliac lesion, in defining abdominal aortic lesion; and (e) an addition of coronary artery lesion in absence of risk factors. The criteria proposed consists of three major criteria including left and right mid subclavian artery lesions and characteristic signs and symptoms of at least one month duration and ten minor criteria-a high erythrocyte sedimentation rate, carotid artery tenderness, hypertension, aortic regurgitation or annuloaortic ectasia, pulmonary artery lesion, left mid common carotid lesion, distal brachiocephalic trunk lesion, descending thoracic aorta lesion, abdominal aorta lesion and coronary artery lesion. Presence of two major or one major and two minor criteria or four minor criteria suggests a high probability of TA. When applied to 106 Indian patients of angiographically proven TA and 20 control subjects, it had a sensitivity of 92.5% and specificity of 95% that was higher than that of Ishikawa's criteria (sensitivity 60.4%, specificity 95%) and American college of Rheumatology criteria (sensitivity 77.4%, specificity 95%). Similarly, this criteria had a 96% sensitivity and 96% specificity in 79 Japanese patients of TA and 79 control subjects. Adoption of these criteria is expected to prevent the possibility of an under diagnosis of TA.

Adult↗
PubMed1996

Systemic manifestations of Takayasu arteritis: the expanding spectrum.

Takayasu arteritis (TA) is a chronic inflammatory and obliterative disease of large vessels particularly the aorta and its major branches. Recently, the disease has been shown to involve the parenchyma of various organs. Specific glomerular lesions reported in patients with TA are mesangial proliferative, membrano-proliferative, crescentic glomerulonephritis and amyloidosis. Dermatological manifestations of this disease are erythema nodosum, facial lupus rash and erythema induratum. Dilated cardiomyopathy, myocarditis and pericarditis have been reported in TA. Rarely, interstitial lung disease, pneumonic consolidation, idiopathic ulcerative colitis, rheumatoid arthritis and polymyositis have been described in association with TA. In this report, five patients of TA with primary parenchymatous involvement of kidneys, skin, heart and gastrointestinal tract have been described. An association of primary parenchymatous organ involvement and TA suggests an autosensitization to an unidentified antigen in the pathogenesis of TA.

Adolescent↗
PubMed1996

Reactive oxygen species-mediated tissue injury in experimental ascending pyelonephritis.

Pyelonephritis is the most common urinary tract infection in females, but the pathogenetic mechanisms are not well understood. Reactive oxygen species (ROS) have been implicated as cause of injury in several renal diseases. In this study, we have demonstrated the role of ROS in pathogenesis of pyelonephritis in Balb/c mice. A clear correlation between extent of ROS generation and subsequent lipid peroxidation and DNA damage in kidneys was observed during the course of infection, from 2 to 14 days. Activities of brush border membrane marker enzymes were also significantly altered. Administration of antioxidants, superoxide dismutase, catalase and dimethylsulfoxide significantly reversed the histopathological changes, reduced the extent of lipid peroxidation in renal brush border membrane, and also reversed the altered enzyme activities to near normal situation. These results clearly suggest that interaction of ROS with various cellular organelles in kidneys has a significant deleterious effect, and this could be the underlying mechanism for renal dysfunction in pyelonephritis.

Animals↗
PubMed1996

Oxygen-dependent and -independent mechanisms of renal injury in experimental ascending pyelonephritis.

Pyelonephritis is the most common urinary tract infection affecting females of all age groups. Despite concerted efforts the mechanism of renal injury in pyelonephritis is not clearly understood. In the present study we have made an attempt to characterise the mediators of inflammatory insult in an experimental model of ascending pyelonephritis. Mice infected with Escherichia coli O6:K13:H1 were sacrificed at 2, 7 and 14 days post-infection. Luminol-dependent chemiluminescence response, NADPH oxidase, acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase activities were monitored in circulating as well as renal phagocytic cells in order to determine the role of reactive oxygen species and lysosomal enzymes in genesis of renal injury. We have demonstrated that reactive oxygen species are generated at the initiation of infection and the levels increase progressively during the course of infection. While intracellular release of lysosomal enzymes was seen in all groups, extracellular release was primarily observed at 7 and 14 days post-infection only. The results indicate that while reactive oxygen species play a significant role in tissue injury during all stages of infection, lysosomal enzyme release in extracellular milieu augments tissue destruction at later stages only.

Acetylglucosaminidase↗
PubMed1996

Effect of energy balance and somatotropin on insulin-like growth factor I in serum and on weight and progesterone of corpus luteum in heifers.

Holstein heifers (approximately 1 yr old) were fed to be in negative energy balance (n = 14; NEB) or positive energy balance (n = 15; PEB) during four estrous cycles. Each heifer was given PGF2 alpha to control the timing of fourth estrus. From 1 d after PGF2 alpha injection until 10 d after estrus, half of the heifers were injected daily with 14 mg of somatotropin (bST), and the corpus luteum (CL) was collected on d 10. Heifers in NEB had less IGF-I in serum (P < .01), smaller CL (P < .01), and less progesterone in CL (P < .01) than heifers in PEB. Exogenous bST increased (P < .01) IGF-I in serum, but this increase was greater in heifers in PEB than those in NEB (P < .01 for interaction of energy balance and bST). Nonetheless, bST did not alter weight or progesterone content of the CL in either energy balance group. In addition, serum IGF-I during the first 10 d after estrus was not correlated to luteal weight and only weakly correlated (r = .3) with luteal progesterone content. We conclude that exogenous bST given during luteal development does not alter growth or progesterone content of the CL in heifers. Reduced concentration of IGF-I in serum during luteal development does not account for suppressed luteal growth and progesterone synthesis of heifers in NEB.

Animals↗
PubMed1996

Aluminum phosphide ingestion--a clinico-pathologic study.

BACKGROUND: Aluminum phosphide is widely used in India as a fumigant to protect stored grain from pests and rodents. It is marketed in India as 3 g tablets under several brand names as Celphos, Phostek, Quickphos, and Phosphume. If ingested, it is acutely toxic with a high mortality. The present study was undertaken to define any factors which could predict the outcome after an ingestion. METHODS: Between March 1989 and March 1994, 195 patients with aluminum phosphide ingestion were admitted to Nehru Hospital of the Postgraduate Institute of Medical Education and Research, Chandigarh in Northwest India. The information regarding demography, time elapsed between ingestion and arrival in the hospital, nature of ingestion, dose ingested, symptoms and signs at admission and course during hospital stay was recorded on a proforma. RESULTS: Of 195 patients, 115 died. The deaths could be related to the dose ingested but not to the time elapsed between ingestion and arrival at the hospital. The nonsurvivors had more severe hypotension and metabolic acidosis than the survivors who had more severe vomiting. Autopsies conducted in 115 subjects revealed congestion of liver, spleen, kidneys, adrenals, gastrointestinal tract and brain that correlated with the severity of hypotension. Histopathology did not reveal any specific changes beyond visceral congestion and patchy necrosis of the liver. CONCLUSION: Aluminum phosphide when ingested is highly toxic with fatal dose as low as 1.5 g. The dominant clinical feature is severe hypotension refractory to dopamine.

Adolescent↗
PubMed1996

Alteration of peripheral blood lymphocyte subsets in essential hypertension.

OBJECTIVE: To assess lymphocytic subpopulation by labelled monoclonal antibody technique in a small group of patients with untreated essential hypertension (EH) and to detect any alteration with control of blood pressure. DESIGN: Prospective study with phenotypic estimation of lymphocytes at presentation and a minimum of two weeks after the control of blood pressure. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, normotensive controls (n = 10); group 2, mild to moderate essential hypertension (n = 10); group 3, severe (accelerated/malignant) hypertension (n = 10). All the secondary causes of hypertension were ruled out by a thorough history, physical examination and appropriate radiological and biochemical investigations. TESTS: Venous blood samples, taken at entry and a minimum of two weeks after control of blood pressure, were analyzed by alkaline phosphatase antialkaline phosphatase (APAAP) antibody technique for CD4, CD3, CD8 and CD22. Peripheral lymphocytes were separated and cocultured with phytohemagglutinin (PHA) for 72 h and assayed for CD25 by the APAAP technique. MAIN RESULTS: In untreated patients with EH (groups 2 and 3), there was a significant down regulation of CD3, and CD4 lymphocytes whereas the proportion of mature CD22 cells increased. In group 3 there was a significant down regulation of CD25 with PHA stimulation. A negative correlation was observed between CD25 and diastolic pressure upon pooling the results of groups 2 and 3. No significant alteration in these parameters was observed following control of blood pressure with drugs for up to two weeks. CONCLUSION: In this small group of patients with untreated EH, a significant alteration in the lymphocytic repertoire was observed. Whether this will be found in large groups of hypertensives remains to be seen.

Adult↗