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P Arora

Publications and source records attributed to P Arora.

At least 19 recordsLinked to original sources
PubMed1998

The role of actin-binding protein 280 in integrin-dependent mechanoprotection.

To survive in a mechanically active environment, cells must adapt to variations of applied membrane tension. A collagen-coated magnetic bead model was used to apply forces directly to the actin cytoskeleton through integrin receptors. We demonstrate here that by a calcium-dependent mechanism, human fibroblasts reinforce locally their connection with extracellular adhesion sites by inducing actin assembly and by recruiting actin-binding protein 280 (ABP-280) into cortical adhesion complexes. ABP-280 was phosphorylated on serine residues as a result of force application. This phosphorylation and the force-induced actin reorganization were largely abrogated by inhibitors of protein kinase C. In a human melanoma cell line that does not express ABP-280, actin accumulation could not be induced by force, whereas in stable transfectants expressing ABP-280, force-induced actin accumulation was similar to human fibroblasts. Cortical actin assembly played a role in regulating the activity of stretch-activated, calcium-permeable channels (SAC) since sustained force application desensitized SAC to subsequent force applications, and the decrease in stretch sensitivity was reversed after treatment with cytochalasin D. ABP-280-deficient cells showed a > 90% increase in cell death compared with ABP-280 +ve cells after force application. We conclude that ABP-280 plays an important role in mechanoprotection by reinforcing the membrane cortex and desensitizing SACs.

Actins↗
PubMed1998

Total body nitrogen predicts long-term mortality in haemodialysis patients--a single-centre experience.

BACKGROUND: It has been estimated that 30-50% of adult haemodialysis patients have moderate to severe malnutrition. We have previously shown that estimation of total body nitrogen, expressed as a nitrogen index (NI) by in vivo neutron activation analysis (IVNAA) is an accurate tool for estimating total body protein in dialysis patients. It is not clear whether the nitrogen index is predictive of mortality and morbidity in dialysis patients. METHODS: We studied the long-term predictive value of nutritional assessment by IVNAA and serum albumin on mortality and morbidity (including infection episodes requiring hospital admission, ischaemic heart disease (IHD), cerebrovascular or peripheral vascular disease (PVD). Seventy-six chronic haemodialysis patients were initially studied between 1989 and 1991, with a minimum follow-up of 5 years. The mean age of the patients was 48.3 years (range 21-76). Patients were divided into two groups, group I, n = 22, had a NI < or = 0.8 (NI < or = 0.8 represents protein malnutrition) and group II, n = 54, had a NI > 0.8. RESULTS: Fifteen patients in group II died in the follow-up period compared to nine from group I (P < 0.05), but NI < or = 0.8 did not predict vascular or infective morbidity. Serum albumins < or = 35 g/day did predict over all mortality (P < 0.05) as well as infection episodes (P < 0.001). When patients above the age of 50 years were analysed, NI did predict mortality (P < 0.05) but serum albumin did not, while the age of> 50 itself was a strong predictor of mortality (P < 0.001). CONCLUSION: We conclude that NI < or = 0.8 is predictive of long-term mortality. This reinforces the view that low body protein stores are predictive of increased mortality in dialysis patients and that the serum albumin is predictive of mortality because of its reflection of protein stores.

Adult↗
PubMed1997

Single cell analysis of intracellular osteopontin in osteogenic cultures of fetal rat calvarial cells.

Osteopontin (OPN), a major component of the bone matrix, is expressed at different stages of bone formation. To determine possible relationships between OPN expression and stages of osteogenic cell differentiation, we have performed single cell analyses of intracellular OPN in early (proliferating), subconfluent (differentiating), and mature (mineralizing) cultures of fetal rat calvarial cells (FRCC) using a combination of flow cytometry and confocal microscopy. At each culture stage, a high proportion (60-98%) of cells were immunoreactive for OPN (OPN+ve). Each of these populations also included a small proportion of OPN-ve cells which were characterized by their small size, low granularity, high proliferative capacity, and enhanced osteogenic potential. The OPN+ve cells displayed two distinct patterns of intracellular immunostaining: a perinuclear distribution typical of secreted proteins and a perimembrane distribution in which patches of OPN were concentrated at the cell surface. Perimembranous staining predominated in migrant cells, which contained greater than tenfold higher levels of OPN than nonmigrant cells as separated in a Boyden chamber. When cell proliferation was high (day 2), most cells were OPN + ve. At all culture stages the intensity of OPN staining was increased as cells progressed through the cell cycle. As cells differentiated and started to form matrix (days 4 and 6), the mean cell expression of OPN was also increased (fourfold), independent of changes in total cell protein. However, despite the association of OPN with osteogenic cells, we were surprised to find that a high proportion (60%) of fetal skin fibroblasts were also immunoreactive for OPN. The expression of OPN by these cell populations was confirmed by RT-PCR, and a strong correlation was observed between the quantitative flow cytometry data and Western blot analysis of cell extracts in which the high and low phosphorylated isoforms of OPN were observed. These studies, therefore, have identified several phenotypes in FRCC cultures that are based on OPN expression: small OPN-ve cell populations enriched in osteogenic precursors, differentiating osteogenic cells that synthesize and secrete OPN, and migrating stromal cells characterized by a perimembranous OPN staining pattern.

Animals↗
PubMed1997

Prognosis of acute renal failure in children: a multivariate analysis.

Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P < 0.05) and associated with cardiac surgery (90.9%, P < 0.01). Anuria (67.6% vs. 43.5%, P < 0.05), need for dialysis (85.3% vs. 56.5%, P < 0.05), neurological complications (50% vs. 6.3%, P < 0.01), and respiratory complications (35.2% vs. 2.1%, P < 0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors.

Acute Kidney Injury↗
PubMed1997

Tuberculosis in childhood nephrotic syndrome in India.

We studied the prevalence, clinical features, and impact of tuberculosis (TB) on children with nephrotic syndrome (NS). Of the 300 children with NS, 28 (9.3%) were diagnosed as having TB. This occurred following the initiation of immunosuppressive therapy in 27 children, and in 1 child it preceded the onset of NS. Pulmonary involvement was the commonest (22/28), followed by tubercular lymphadenitis (2/28), meningitis (2/28), and occult TB (2/28). Of the various diagnostic criteria, history of previous cough, fever, or exposure to a case of TB (23/28) and chest skiagram (21/28) were the most useful. The occurrence of TB did not induce a relapse or affect the subsequent response to steroid therapy (as is often seen with other infections) or have a deleterious effect on renal function. Patients who received higher doses of steroids (frequent relapsers, steroid dependent, initial non-responders, and subsequent non-responders) had a significantly higher prevalence of TB (19/148) than those who received lower doses (infrequent relapsers 8/151) (P = 0.04). We thus found TB to be an important complication of children with NS in our country. The conventional diagnostic tests, such as Mantoux and acid-fast bacilli isolation, are often unhelpful in these children, and a high index of suspicion is required, especially in children who require frequent courses of steroid therapy.

Adolescent↗
PubMed1997

Renal artery stenosis in aortoarteritis: spectrum of disease in children and adults.

Nonspecific aortoarteritis is the commonest cause of renovascular hypertension (RVH) accounting for 87% of the patients in the present study. We compared the clinical and radiographic features and outcome in children (n = 16) and adult (n = 24) patients with aortoarteritis. Children have a shorter duration of disease and present more commonly with constitutional symptoms. All the patients were hypertensive; however, malignant hypertension and hypertensive encephalopathy were more common in children. Abdominal bruit and asymmetry of pulses were present only in 75 and 35% of the patients, respectively. Asymmetric kidney size on ultrasound was present in 15 of 24 adults, whereas 9 of 16 children had equal sized kidneys. Captopril renography had a better sensitivity for detection of RVH in children (13 of 16 in children vs. 12 of 24 in adults showing positive results). On intra-arterial digital substraction angiography, abdominal aortic involvement was invariable, whereas the thoracic aorta was involved less frequently in both age groups. Angiographic scores for the severity of vascular involvement was significantly lesser in children (6.87+/-4.8) as compared to adults (11.32+/-4.5). Thirteen of the 15 children were found suitable for revascularization, whereas 12 of 24 adults were not considered for revascularization as their kidneys were small and contributed to less than 10% of total function. Six of the adult patients underwent nephrectomy for the control of blood pressure. Results of angioplasty were also better in children than adults. We conclude that children present earlier with less severe vascular disease and respond better to revascularization, as compared to adults.

Adolescent↗
PubMed1997

Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching.

The actin-dependent sensory and response elements of stromal cells that are involved in mechanical signal transduction are poorly understood. To study mechanotransduction we have described previously a collagen-magnetic bead model in which application of well-defined forces to integrins induces an immediate (< 1 second) calcium influx. In this report we used the model to determine the role of calcium ions and tyrosine-phosphorylation in the regulation of force-mediated actin assembly and the resulting change in membrane rigidity. Collagen-beads were bound to cells through the focal adhesion-associated proteins talin, vinculin, alpha 2-integrin and beta-actin, indicating that force application was mediated through cytoskeletal elements. When force (2 N/m2) was applied to collagen beads, confocal microscopy showed a marked vertical extension of the cell which was counteracted by an actin-mediated retraction. Immunoblotting showed that force application induced F-actin accumulation at the bead-membrane complex but vinculin, talin and alpha 2-integrin remained unchanged. Atomic force microscopy showed that membrane rigidity increased 6-fold in the vicinity of beads which had been exposed to force. Force also induced tyrosine phosphorylation of several cytoplasmic proteins including paxillin. The force-induced actin accumulation was blocked in cells loaded with BAPTA/AM or in cells preincubated with genistein, an inhibitor of tyrosine phosphorylation. Repeated force application progressively inhibited the amplitude of force-induced calcium ion flux. As force-induced actin reorganization was dependent on calcium and tyrosine phosphorylation, and as progressive increases of filamentous actin in the submembrane cortex were correlated with increased membrane rigidity and dampened calcium influx, we suggest that cortical actin regulates stretch-activated cation permeable channel activity and provides a desensitization mechanism for cells exposed to repeated long-term mechanical stimuli. The actin response may be cytoprotective since it counteracts the initial force-mediated membrane extension and potentially strengthens cytoskeletal integrity at force-transfer points.

Actins↗
PubMed1997

Chronic renal failure in India.

A prospective study of all new cases of chronic renal failure (CRF) including inservice referrals was done at our hospital over a period of 1 year from May 1994 to April 1995. The diagnosis of CRF was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. The patients were subdivided into various etiologic groups of primary renal disease according to standard criteria. There were a total of 835 cases of CRF with a median age of 43 years (range 10 days to 90 years); 67.8% of them were men. Glomerulonephritis (28.6%), diabetic nephropathy (23.2%), and interstitial nephritis (16.5%) were the most common causes of CRF, followed by obstructive nephropathy (6.4%), benign nephrosclerosis (4.1%), and polycystic kidney disease (2%). However, in patients more than 40 years of age, diabetic nephropathy was the most common cause (36.8%). The cause of CRF was unknown in 16.2% of the cases. One hundred twenty-one patients (14.5%) had an acute deterioration of their underlying renal dysfunction at presentation. This was most commonly due to accelerated hypertension (26.1%), infection (22.4%), volume depletion (20.1%), and drugs (14.9%). Anti-inflammatory drugs were the most common drugs responsible for the acute decline in renal function. One year after their initial presentation, of the 512 patients (61.3%) with end stage renal disease, 12.5% had died, 17% had received a kidney allograft, 12.7% were on some form of maintenance dialysis, and 295 patients were lost to follow-up. Of the 323 patients with less severe illness, 7 died, 209 were on outpatient treatment, and 107 patients were lost to follow-up. We conclude that the pattern of CRF in India does not differ greatly from that in the developed countries. However, it carries a poorer prognosis due to late referral and limited availability and affordability of renal replacement therapy in India.

Adolescent↗
PubMed1996

Lazaroids inhibit proliferation of cultured human astrocytoma cells.

Lazaroids (or 21-aminosteroids) are potent lipid peroxidation inhibitors and are more potent antioxidants than steroids which have been shown to suppress tumor proliferation. The effects of two lazaroid compounds (U-75389G and U-83836E) were tested on the proliferation of a human brain astrocytoma cell line U-373MG. Both lazaroids had dose-dependent growth-inhibitory effects on the proliferation of U-373MG. For purposes of comparison, two steroids (methylprednisolone and dexamethasone) and a highly potent antioxidant (alpha-tocopherol) were tested under similar experimental conditions and were found to have antiproliferative effects as well, although at higher dose ranges. As cell growth-inhibitors, lazaroids are more effective than alpha-tocopherol while they are advantageous over glucocorticoids for their actions are devoid of the usual glucocorticoid side-effects.

Antineoplastic Agents↗
PubMed1996

Role of captopril renography in the diagnosis of renovascular hypertension.

Eighty-six hypertensive patients with clinical suspicion of renovascular hypertension (RVH) were evaluated by captopril renal scintigraphy (CRS) and intra-arterial digital subtraction angiography (IADSA) to determine the usefulness of CRS in the diagnosis of RVH and to predict the outcome of revascularization procedures. Technetium 99m-diethlenetriaminepentaacetic acid (DTPA) renal scintigraphy was performed on 2 consecutive days before and after captopril administration. Captopril renal scintigraphy was considered positive if there were changes in the time activity curve according to the criteria specified by the American Society of Hypertension working group. Captopril renal scintigraphy data were compared with presence or absence of anatomic renal artery stenosis (RAS). Of 86 hypertensive patients investigated, 45 had RAS. Aortoarteritis was the cause of RAS in 40 (89%) patients. Revascularization was done in 25 patients, and response to revascularization was compared with that of captopril renography. Compared with IADSA, CRS showed a sensitivity of 82.8% and a specificity of 98.2%. Fourteen patients had bilateral RAS on IADSA. In these patients, CRS was suggestive of bilateral disease in seven patients, unilateral in four, and negative in three. Comparison of CRS with the results of revascularization showed a sensitivity and specificity in detecting curable RAS (RVH) of 95% and 100%, respectively (positive predictive value, 100%; negative predictive value, 85%). In conclusion, we found CRS to be useful in the diagnosis of RVH due to aortoarteritis.

Adolescent↗
PubMed1996

Urinary tract infection in nephrotic syndrome.

BACKGROUND: The aim was to study the frequency, etiology and predisposing factors of urinary tract infection (UTI) in children with nephrotic syndrome. METHODS: A retrospective analysis of all children with nephrotic syndrome was made to determine the occurrence of infectious complications. RESULTS: UTI was found to be the most common infection (40.26%); 49 episodes of culture-positive UTI were observed in 37 children. All 49 episodes occurred in patients who were initially considered to be steroid nonresponders or in relapse. Fourteen of the 49 episodes (28.6%) were asymptomatic. One child had Grade IV reflux and another had a ureteric calculus. The majority of the children had no underlying urinary tract malformations. The children with UTI had significantly lower serum albumin (P < 0.05) and higher serum cholesterol (P < 0.001) concentrations than the group of 206 children without infections. Non-Escherichia coli organisms accounted for 39% of the culture isolates. CONCLUSIONS: We believe that UTI is an important but often underdiagnosed infection in children with nephrotic syndrome.

Adolescent↗
PubMed1996

Visceral leishmaniasis in a renal transplant recipient: diagnostic and therapeutic problems.

Visceral leishmaniasis is infrequently reported in renal transplant recipients. A 40-year-old renal transplant recipient developed hepatosplenomegaly and pyrexia of unknown origin 5 months after transplantation. Visceral leishmaniasis was confirmed on bone marrow examination. The usual dose of antiparasitic therapy with stibogluconate sodium failed to eradicate Leishmania donovani. High-dose conventional therapy with stibogluconate sodium for an extended period of time was successful in the treatment of a relapse of leishmaniasis.

Adult↗
PubMed1996

Evaluation of clinical and histological prognostic markers in drug-induced acute interstitial nephritis.

We analyzed the case records of 19 patients diagnosed to have drug-induced acute interstitial nephritis to assess the clinical profile and role of steroids in renal recovery, and to correlate histological features to outcome. Patients with underlying glomerular diseases, malignancy, obstructive nephropathy, or systemic infections were excluded. Nonsteroidal anti-inflammatory drugs alone accounted for 6 cases (group A), whereas antibiotics were the major offender in the remaining patients (group B). In 13/19 (69%) cases, renal failure was severe enough to require dialytic support. Overall 14/19 (74%) of the patients recovered normal renal function within 6 weeks of withdrawal of the offending drugs. Neither the extent of renal recovery nor the time required for it was altered by oral steroids. Tubular atrophy and interstitial fibrosis adversely affected renal recovery. Oliguria, tubular necrosis, interstitial edema, and the density/distribution of interstitial infiltrate did not have any effect on the rate/extent of renal recovery.

Acute Disease↗
PubMed1996

Malignant hypertension in children in India.

BACKGROUND: Malignant hypertension is now an uncommon entity in the western world but still remains a significant problem in India. Therefore we studied the aetiological spectrum, management, and outcome of these patients. METHODS: Forty consecutive children (<16 years) with malignant hypertension were admitted and investigated to exclude or confirm the secondary causes of hypertension. For acute control of blood pressure sublingual nifedipine was used in dosage of 0.3-0.6 mg/kg, failing which intravenous nitroglycerin was used. In patients with aortoarteritis with active disease, steroids were used. Angioplasty was carried out for renal artery stenosis whenever possible. RESULTS: Renoparenchymal disease was the commonest cause of malignant hypertension, and was seen in 25 cases, renovascular hypertension in 13 cases (11 aortoarteritis and two fibromuscular dysplasia) and two had essential hypertension. For acute control of severe hypertension, sublingual nifedipine was effective in 92.5% of patients. Of the patients with renoparenchymal disease five became normotensive with treatment of the underlying disease, four received renal allograft, seven died, and nine are stable on antihypertensive drugs. Renal angioplasty was carried out in seven patients with renovascular hypertension (4 cured, 3 improved) and six are controlled on drugs. CONCLUSIONS: We conclude that apart from renoparenchymal disease, aortoarteritis is a common cause of malignant hypertension in children. Sublingual nifedipine is effective for the rapid control of severe hypertension, and angioplasty is effective in aortoarteritis for short-term preservation of renal function and control of hypertension.

Adolescent↗
PubMed1995

Spectrum of infections in Indian children with nephrotic syndrome.

We conducted a retrospective analysis of infections in 154 children (114 boys, 40 girls) with nephrotic syndrome who satisfied the International Study of Kidney Disease in Children criteria. Their mean age at onset of symptoms was 6.2 years (range 6 months to 16 years) and the mean duration of follow-up was 32 months (range 6-55 months). One or more infectious complications were observed in 59 of the 154 children (38%), with urinary tract infection being the commonest (13.7%), followed by pulmonary tuberculosis (10.4%), peritonitis (9.1%), skin infections (5.2%), upper respiratory infections (5.2%), lower respiratory tract infections (3.9%) and pyomeningitis (0.6%). There were 3 deaths, the mortality in 2 patients being attributable to infections. There was no significant difference between children who developed infection and those who didn't in terms of age of onset, sex, duration of disease, serum creatinine, blood urea nitrogen and 24-h proteinuria. However, the children who developed infectious complications had significantly higher serum cholesterol levels (P < 0.01) and lower serum albumin levels (P < 0.02). The frequency of infections was higher in children who were frequent relapsers, steroid dependent and subsequent non-responders (28/60) compared with infrequent relapsers and initial non-responders (29/94).

Adolescent↗