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Biomedical subjects

B K Sharma

Publications and source records attributed to B K Sharma.

At least 19 recordsLinked to original sources

Role of calcium and protein kinase C in the activation of T cells in Takayasu's arteritis.

The roles of protein kinase C and calcium in the T cells of patients suffering from Takayasu's arteritis (TA) in response to the mitogens phorbol-myristate acetate (PMA) and streptococcal antigens have been studied. In TA there was an increased basal activity of protein kinase C (1.074 +/- 0.223 nmoles/mg protein/min) as compared with that of controls (0.570 +/- .12) (p < 0.001). There was 75% translocation from the cytosol to membrane fraction in response to PMA. Intracellular calcium levels showed increased basal levels in TA (177.07 +/- 12.56 nmoles) compared with the controls (112.83 +/- 10.6 nmoles) (p < 0.001) and there was a further rise on stimulation, indicating the T cells were in an activated state. There was a positive correlation between the calcium levels and the activity of protein kinase C (r = 0.71, p < 0.05). Unlike the situation in patients with rheumatic fever, T cells in TA showed no stimulation in response to streptococcal antigens. The low level of cAMP (1.12 +/- 0.169 pmoles/million cells) compared with that of controls (1.4 +/- 0.03) further supports the role of PKC-calcium in the T cell activation process. These findings suggest activation of the PKC-calcium pathway in TA.

Adolescent

Effect of dietary energy restriction on the expression of insulin-like growth factor-I in liver and corpus luteum of heifers.

The effects of energy balance on the corpus luteum may be mediated by IGF-I. Our objective was to determine whether negative energy balance decreases expression of IGF-I mRNA in the liver or corpus luteum of heifers. For four consecutive estrous cycles, 14 Holstein heifers were maintained in negative or positive energy balance to lose 510 g/d of BW or gain 560 g/d of BW, respectively. The liver was biopsied and the corpus luteum was collected 7 d after fourth estrus. Heifers fed below maintenance had a smaller corpus luteum than did control heifers. Compared with that of controls, negative energy balance increased growth hormone in serum but decreased IGF-I in serum and the abundance of mRNA for growth hormone receptor and IGF-I in liver. In contrast, diet did not affect the abundance of mRNA for the growth hormone receptor or IGF-I in luteal tissue. Negative energy balance increased IGF binding protein-2 in serum but did not affect IGF binding protein-3. We conclude that negative energy balance of cattle decreases IGF-I mRNA abundance in the liver but not in the 7-d corpus luteum. If decreased IGF-I mediates the adverse effect of negative energy balance on luteal growth, the mode of action is likely endocrine, not autocrine or paracrine.

Animals

Long-term somatotropic and galactopoietic effects of a (1-30) ethyl amide analog of growth hormone-releasing factor.

Thirty-five lactating Holstein cows (165 +/- 8 DIM) received the following treatments for 96 d: uninfused controls; i.v. infusion of .9, 2.7, or 8.1 mg/d of Ile2, Ser8.28, Ala15, Leu27, Hse30-bovine growth hormone-releasing factor (1-30) ethyl amide; or i.v. infusion of 12 mg/d of recombinant Leu27, Hse45-bovine growth hormone-releasing factor (1-45) lactone. Concentrations of somatotropin in serum and SCM yield of cows infused with 1-30 releasing factor increased quadratically as the dose increased. Responses for somatotropin and SCM yield were quantitatively similar for cows infused with 2.7 and 8.1 mg of 1-30 or 12 mg of 1-45. While concurrently infused with the 1-30 or 1-45 as described, cows retained their ability to release somatotropin following an acute i.v. injection of 10 nmol/100 kg of BW of either growth hormone-releasing factor 1-30 or 1-45. Mean concentrations of IGF-I in serum increased similarly in magnitude for cows infused at all doses of 1-30 or 1-45. The 1-30 releasing factor generally increased IGF-binding protein-3, but had little effect on IGF-binding protein-2. The 1-45 releasing factor did not significantly affect either binding protein. Yield of SCM was correlated with serum concentrations of somatotropin, but not with IGF-I. Concentrations of NEFA in serum were elevated through 36 and 50 d in response to the highest doses of 1-30 and 1-45, respectively. Treatment did not affect DMI, BW, or body condition score.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Takayasu arteritis may be underdiagnosed in North America.

OBJECTIVES: To summarize some of the literature about Takayasu arteritis, a nonspecific chronic inflammatory disease involving the aorta and its main branches, and to analyze the criteria for its diagnosis. The pulmonary artery and its branches, as well as the coronary arteries, may also be involved. DATA ANALYSIS: Although Takayasu arteritis has been commonly reported in Asian countries such as Japan, India, China and Korea, case reports from other parts of the world describing symptoms of this disease are also available. Because of nonspecific pathology, a rather nonspecific initial clinical presentation and an obligatory criterion of age (40 years or younger) it is possible that the disease may be underdiagnosed in Europe and North America. The cause of this disease remains obscure. Various infections have been blamed but genetic and immunological disturbances seem to play a major role in bringing Takayasu arteritis into the list of autoimmune disease. INTERVENTIONS: Takayasu arteritis responds well to glucocorticoids/cyclophosphamide in the acute (prepulseless) phase. In the chronic fibrotic phase, treatment of hypertension and various angioplastic and surgical interventions are required. CONCLUSIONS: Adoption of improved diagnostic criteria may change the prevailing view that Takayasu arteritis is an Asian disease. Understanding of the pathogenesis at cellular and molecular levels is needed. Creation of an animal model would be a desirable tool in that direction.

Adult

Evaluation of three serological tests for detection of anti-candidal antibodies in diagnosis of invasive candidiasis.

Immunoblot detection of antibody against 47 KD cytoplasmic antigen of Candida albicans was evaluated in diagnosis of invasive candidiasis and compared to whole cell agglutination and gel diffusion tests for detection of anticandidal antibody in 64 patients. The patients included 17 with culture proved candidemia, 34 with significant candiduria (more than 10,000 colony forming units per ml of urine) and 13 with nonsignificant candiduria. Antibody against 47 KD antigen was found to be the best indicator for diagnosis of invasive candidiasis even in patients with malignancy. The sensitivity of this procedure was 82.4%, specificity 86.7%, positive predictive value 77.8%, negative predictive value 89.7% and efficacy 85.1%. The gel diffusion procedure lacked in sensitivity whereas whole cell agglutination lacked in specificity. Detection of antibody against 47 KD antigen proved to be a valuable adjunct in the diagnosis of invasive candidiasis.

Agglutination Tests

Evaluation of Salmonella porins as a broad spectrum vaccine candidate.

Porins were prepared from smooth strain of Salmonella typhi 0-901 and chemotype of rough mutant of S. typhimurium Ra-30. Mice were immunized with both the porin preparations in different groups and challenged with S. typhimurium LT2-71 and S. enteritidis SH-1269. Porin immunized mice showed significant protection (P < 0.01) against challenge with homologous as well as heterologous strains. Hence, the use of porins may be attempted in future to protect against salmonellosis.

Animals

Stimulation of macrophage oxygen free radical production and lymphocyte blastogenic response by immunization with porins.

Porins were prepared from smooth strain of Salmonella typhi 0-901 and chemotype rough mutant of S. typhimurium Ra-30. Porins could significantly stimulate the immune systems of mice. Immunization of mice with the porins provoked synthesis of anti-porin antibodies. Macrophages from the immunized mice showed increased capacity to generate oxygen free radicals, and lymphocytes from these mice showed proliferative response to the porins. Thus porins may play a role in providing protection from salmonellosis by stimulating the antibody production and increasing the capacity of macrophages to generate oxygen free radicals along with stimulation of lymphocytes.

Animals

Malignant hypertension in north west India. A hospital based study.

One hundred and thirty-five patients with malignant hypertension seen over a period of 11 years (1979 to 1989) at a referral hospital were analyzed to characterize the clinical features and etiology of this disease. Ninety male and 45 female patients with an average age of 38.2 +/- 1.4 years were studied. Malignant hypertension was the presenting feature in 68 patients. The etiology included essential hypertension in 88 patients and a secondary cause in 47 patients. Secondary causes included a renovascular etiology in 20 patients, renal parenchymal disease in 19, pheochromocytoma in 6 and Conn's syndrome and adrenal carcinoma in one patient each. Among the 20 patients with renovascular hypertension, Takayasu's arteritis was seen in 15 (75%). The mean age of patients with essential hypertension was 41.7 + 1.14 years while the mean age in patients with secondary hypertension was 33.2 + 1.96 years. Duration of preexisting hypertension was longer in essential hypertensives (2.42 + 0.45 years) than in patients with secondary hypertension (1.27 + 0.41 years, p < 0.05). Raised serum creatinine was seen in 93 patients. Seventy-seven patients had left ventricular hypertrophy on ECG. Ninety-six patients were followed for a period ranging from 18 months to 10 years (mean 32 months). Sixteen patients died during hospital stay while 6 patients died during the follow-up period. The deaths were related to the effects of uncontrolled hypertension including, renal failure (11), stroke (6), congestive cardiac failure (3) and myocardial infarction (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Expression of insulin-like growth factor-I in cows at different stages of lactation and in late lactation cows treated with somatotropin.

Relative amounts of IGF-I mRNA were measured in livers of Holstein cows at different stages of lactation (6 early, 6 mid, 6 late lactation, 6 dry) and 6 late lactation cows treated with bST for 1 wk. Milk yield was greater for early lactation cows than for mid and late lactation controls. All cows except those in early lactation were in positive energy balance. Serum IGF-I increased as lactation progressed and was greatest during the dry period. Liver IGF-I mRNA was less in cows in early than in late lactation but greater in lactating than in dry cows. Treatment with bST increased milk yield and concentrations of serum IGF-I, hepatic IGF-I mRNA, and serum IGF-binding protein-3, decreased concentration of serum IGF-binding protein-2, and did not alter abundance of mammary IGF-I mRNA. These parallel changes in serum IGF-I and hepatic IGF-I mRNA suggest that exogenous bST increases IGF-I synthesis in liver of cows during late lactation and that IGF-I synthesis is depressed during early lactation when cows are in negative energy balance. We conclude that IGF-I may play an endocrine role in mediating galactopoietic effects of exogenous bST during late lactation. However, the role of IGF-I during early lactation remains unclear.

Animals

Ocular changes in Takayasu's arteritis in India.

Twenty-seven patients (ages 13-55 years) with Takayasu's arteritis (TA) underwent a detailed ophthalmological examination which included a history of visual symptoms, recording of visual acuity, slit-lamp examination, examination of retina (direct fundoscopy and rapid sequence fluorescein angiography) and estimation of retinal haemodynamics. Arterial hypertension was the commonest (77%) presentation of TA. Sixty-six percent of the patients had one or more ocular change. Sixteen (33%) of the 54 eyes tested had Takayasu's retinopathy (TR), 20 eyes (37%) had hypertensive retinopathy (HR) and the retina was normal (NR) in 18 eyes (33%). Two patients with advanced TR had bilateral cataract. The arm-to-retina circulation time in eyes with TR (16.4 +/- 2.66 seconds) was prolonged as compared to the eyes with HR (10.9 +/- 1.63 seconds, P < 0.01) and NR (9.6 +/- 2.37 seconds, P < 0.01). The arteriovenous filling time in eyes with TR was also significantly prolonged. The intraocular pressure (mmHg) in eyes with TR (9.3 +/- 3.6) was lower (P < 0.001) than that in eyes with HR (14.4 +/- 4.1 mmHg) and NR (14.2 +/- 2.6). Central retinal artery pressure recorded in 8 eyes with TR was less than 35 mmHg in spite of the systemic hypertension. The retinal haemodynamics suggest that the carotid artery involvement leading to diminished retinal blood flow is the pathogenetic mechanism of TR.

Adolescent

Is a hypertensive always a hypertensive?

Forty two patients of uncomplicated essential hypertension with well controlled and stable blood pressure for the last six months have been followed up for 2 years after withdrawal of therapy. Drug therapy was reinstituted if they became hypertensive again. Thirty four (89.9%) and 33 patients remained normotensive at 4 and 8 weeks respectively. At the end of 6 months, 26 (61.9%) patients were drug free, 9 (21.4%) were back on therapy and 7 (16.5%) were lost to follow up. At the end of one year, 18 (42.8%) were drug free, 14 (33.3%) were on drugs and 10 (23.8%) had dropped out. At the end of 2 years, the figures were 14 (drug free), 15 (on drugs) and 13 (drop-outs). No cardiovascular or any other complication was recorded during the period. These observations suggest that there may be a subgroup of mild or moderate hypertensives in whom it may be possible to withdraw therapy under observation. However, there is a risk of substantial drop out rate possibly under a false sense of security. Considering the large number of hypertensives in our country and the world over, its economic and therapeutic implications are obvious.

Adolescent

Oxygen free radicals in essential hypertension.

Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p less than 0.01) in Gp IIC (243.04 +/- 24.9 x 10(3) counts per minute) as compared to Gp IIA (2.80 +/- 1.87), Gp IIB (34.54 +/- 30.24) and Gp I (0.52 +/- 0.15) and SOD was reduced significantly (p less than 0.05) in all EH (Gp IIA 3.9 +/- 0.3 units per mg protein, Gp IIB 3.5 +/- 0.3 and Gp IIC 3.12 +/- 0.3) as compared to controls (4.1 +/- 0.2). Similarly GSH was reduced (p less than 0.05) in EH (Gp IIA 11.2 +/- 1.7 mg per gm protein, Gp IIB 8.5 +/- 1.1 and Gp IIC 6.6 +/- 0.3) as compared to Gp I (13.5 +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Takayasu arteritis in India.

Takayasu arteritis is the commonest cause of renovascular hypertension in India. The clinical and radiological features, complications and course of 83 patients (51 females, 32 males) seen during the period from 1972-1990 are described in this study. The age of the patients ranged from 5 to 53 years with the mean +/- SD of 26.9 +/- 9.7. Hypertension (n = 50) and the related symptom of headache (n = 40), dyspnea (n = 24), and giddiness (n = 20) were common at presentation. Twelve patients were in congestive cardiac failure. The symptoms of activity with fever and arthralgia were present in only 16% contrary to reports from Japan and Mexico. Abnormal arterial pulses and bruit over abdominal (37%) or extra abdominal great arteries (25%) were useful clinical clues to suspect Takayasu arteritis. Rapid sequence intravenous urography was a sensitive screening procedure and predicted correctly the presence of renovascular disease in 80% of the patients. The diagnosis was confirmed on aortography in 72. In the rest, the clinical features and autopsy findings confirmed the same. The four patterns of the disease based on the anatomical extent of involvement were recognised. These were: type I (n = 8) with involvement of aortic arch and its branches, type II (n = 25) descending thoracic and abdominal aorta type III (n = 46) combination of I and II and type IV (n = 4) pulmonary artery in addition to any of the above.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Immunopathogenesis of Takayasu arteritis.

Takayasu arteritis is a common cause of renovascular hypertension in India. Sensitization to infective agents, particularly mycobacterium tuberculosis or autoimmune disturbances have been incriminated in its pathogenesis. Twenty patients of Takayasu arteritis along with groups of normal individuals, patients of essential hypertension, autoimmune disorders, tuberculosis, and healthy tuberculin reactors were studied. Besides detailed immunological profiles including LE cell phenomenon, serum complement C3 levels, antibodies to single (SS) and double stranded (DS) DNA, rheumatoid factor, lymphocyte subsets, blast transformation to antigens including, phytohemagglutinin, PPD, pokeweed, and purified human aortal antigen (PHAA) were examined. Soluble protein from human aorta was fractionated into 9 peaks by DEASE-52 and Sephadex G-75 chromatography, and 25 micrograms of major protein fraction-II was used for blast transformation study. Blast transformation by PHAA was higher in Takayasu arteritis as compared to all other groups (P < 0.05). Blast transformation to PPD showed wide variation in all the groups, and was significantly higher only in tuberculin reactors as compared to controls. These observations support aortal sensitization to PHAA playing a role in pathogenesis of Takayasu arteritis and do not relate tuberculosis to Takayasu arteritis, at least immunologically. In addition, the ratio of CD-4 positive to CD-8 positive lymphocytes changing in favor of the former and the concomitant increase in B lymphocytes favor the presence of autoimmune disturbances in Takayasu arteritis.

Adolescent

Coarctation repair in neonates with subclavian-sparing advancement flap.

A modification of the technique of using the subclavian-sparing advancement flap for severe coarctation of the aorta was successfully used in 7 neonates ranging in age from 3 to 30 days (mean age, 12 days). Four of the 7 patients had associated cardiac defects with congestive heart failure. The procedure was performed through a left thoracotomy incision, and the coarctation repair was performed by advancing the origin of the left subclavian artery as a flap while preserving flow to the left arm. No deaths occurred, and there was patency of the repair in all patients at follow-up ranging from 1 1/2 to 2 1/4 years (mean, 2 years). In 7 of the 8 patients there was no clinically significant gradient either by examination or Doppler echocardiography at follow-up. One patient underwent balloon angioplasty at the time of catheterization to evaluate other cardiac defects 1 year postoperatively, at which time he was noted to have a peak systolic gradient of 30 mm Hg across the repair site. The technique of subclavian-sparing advancement is a reasonable addition to the surgical armamentarium for coarctation repair in neonates. It provides the advantages of subclavian flap aortoplasty without sacrificing the blood supply to the left arm. Because of the unique anatomic variations associated with coarctation of the aorta, we suggest that the choice of repair be individualized for patients with this condition.

Aortic Coarctation