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Biomedical subjects

S R Kumar

Publications and source records attributed to S R Kumar.

At least 19 recordsLinked to original sources
PubMed2006

EphB4 receptor tyrosine kinase is expressed in bladder cancer and provides signals for cell survival.

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.

Base Sequence↗
PubMed2005

Comminuted refracture of the distal femur and condyles in patients with an intramedullary nail: a report of 5 cases.

Patients with in situ intramedullary nails sustaining a second distal femoral fracture following high-velocity trauma are infrequently reported in the literature. We report 5 such patients who sustained a second injury after 6 to 24 months, resulting in another fracture at the nail-tip level. These second fractures severely comminuted the femoral condyles. These patients required removal of the intramedullary nail, reconstruction of the comminuted femoral condyles, and stabilisation using an angled or buttress plate. Four of the 5 patients were followed up for a mean period of 36 months and were evaluated for knee status and outcome using Judet's criteria. Postoperative knee stiffness was common, and further interventions such as manipulation, hardware removal, arthrolysis, and quadricepsplasty were needed. One patient was lost to follow-up. The final results of the knees were good, with more than 100 degrees range of movement. It is important to adhere to established internal fixation protocols in the treatment of these complex nail tip fractures.

Accidents, Traffic↗
PubMed2004

Unrecognised tuberculosis in HIV-infected patients: sputum culture is a useful tool.

Diagnosis of tuberculosis is challenging, especially in human immunodeficiency virus (HIV) positive persons who may have atypical clinical and radiographic features. We report the isolation of Mycobacterium tuberculosis from sputum samples of 10 (4%) HIV-positive persons who were asymptomatic with normal chest radiographs and negative sputum smears for acid-fast bacilli. Six of them had strongly positive tuberculin reactions while four were severely immunosuppressed. Our observation highlights the utility of routine sputum culture in the diagnosis of tuberculosis in high-risk individuals.

Adult↗
PubMed2001

Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke.

BACKGROUND: Activated protein C (APC) contributes to systemic anticoagulant and anti-inflammatory activities. APC may reduce organ damage by inhibiting thrombin generation and leukocyte activation. Neutrophils and cerebrovascular thrombosis contribute to ischemic neuronal injury, suggesting that APC may be a potential protective agent for stroke. METHODS AND RESULTS: We examined the effects of APC in a murine model of focal ischemia. After middle cerebral artery occlusion/reperfusion, the average survival time in controls was 13.6 hours. Animals that received purified human plasma-derived APC 2 mg/kg IV either 15 minutes before or 10 minutes after stroke induction survived 24 hours and were killed for neuropathological analysis. APC 2 mg/kg given before or after onset of ischemia restored cerebral blood flow, reduced brain infarct volume (59% to 69%; P:<0.003) and brain edema (50% to 61%; P:<0.05), eliminated brain infiltration with neutrophils, and reduced the number of fibrin-positive cerebral vessels by 57% (P:<0.05) and 25% (nonsignificant), respectively. The neuroprotective effect of APC was dose-dependent and associated with significant inhibition of ICAM-1 expression on ischemic cerebral blood vessels (eg, 61% inhibition with 2 mg/kg APC). Intracerebral bleeding was not observed with APC. CONCLUSIONS: APC exerts anti-inflammatory, antithrombotic, and neuroprotective effects in stroke. Central effects of APC are likely to be related to improved maintenance of the blood-brain barrier to neutrophils and to reduced microvascular obstructions and fibrin deposition.

Animals↗
PubMed2001

Cervical vascular injuries: carotid and jugular venous injuries.

This article explores the management of carotid arterial injuries, detailing the historical evolution for the management of these injuries and delineating techniques for cerebral perfusion and preservation with shunts. It discusses the role of autogenous versus synthetic grafts in the management of these injuries and the issue of vascular complications and potential pitfalls. Jugular venous injuries are addressed also, with emphasis on the controversies of primary repair versus ligation.

Carotid Artery Injuries↗
PubMed2001

Severity-of-illness scoring systems and models: neurological and neurosurgical intensive care units.

Predicting the outcome of critically ill patients admitted to intensive care units (ICU) has undergone considerable evolution over the last two decades. Various general purpose severity-of-illness scoring systems, Acute Physiology and Chronic Health Evaluation score (APACHE II, APACHE III), Mortality Predicting Model (MPM II), and Simplified Acute Physiology Score (SAPS II), have been extensively validated for large groups of critical care patients with mixed diagnoses and found to correlate well with observed outcome in general. The general hypothesis underlying the use of severity-of-illness scoring systems is that clinical variables that can be assessed on ICU admission and subsequent days of stay in the ICU predict survival and other outcomes of critically ill patients. Variables included in severity-of-illness scoring systems measure specific clinical and physiological functions that are major determinants of mortality. These scoring systems may be used alone within a single disease category or any other independently defined patient group to perform relative risk stratification. Variation in death rates by disease reflects the nature of the underlying process. There is a need for using these scoring systems in specialized ICUs like neurological and neurosurgical ICU as they allow, in addition to predicting outcome, evaluation of new therapies, monitoring of resource utilization and quality assessment of intensive care units.

Critical Care↗
PubMed2000

Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model.

Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.

Animals↗
PubMed2000

Central pontine myelinolysis: delayed changes on neuroimaging.

The authors report two cases, a 44-year-old woman and a 6-year-old girl who had mental status changes and hyponatremia. Serum sodium levels in both of these cases were corrected quickly with further decline in their mental status, and the patients became quadriparetic. Magnetic resonance imaging (MRI) studies performed then did not reveal any abnormalities, whereas a repeat imaging study performed 10-14 days after the shift in serum sodium revealed evidence for central pontine myelinolysis and extrapontine demyelination. The clinical manifestations and distribution of lesions seen on the imaging studies demonstrated that the above presentation of neurologic illness is the result of hyponatremia and its correction. The authors conclude that imaging studies performed early during the illness may be unremarkable, but still a diagnosis of central pontine myelinolysis should be suspected and, most importantly, a repeat imaging study might be required in 10-14 days to establish the diagnosis of central pontine myelinolysis.

Adult↗
PubMed2000

Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier.

Elimination of amyloid-ss peptide (Ass) from the brain is poorly understood. After intracerebral microinjections in young mice, (125)I-Ass(1-40) was rapidly removed from the brain (t(1/2) </= 25 minutes), mainly by vascular transport across the blood-brain barrier (BBB). The efflux transport system for Ass(1-40) at the BBB was half saturated at 15.3 nM, and the maximal transport capacity was reached between 70 nM and 100 nM. Ass(1-40) clearance was substantially inhibited by the receptor-associated protein, and by antibodies against LDL receptor-related protein-1 (LRP-1) and alpha(2)-macroglobulin (alpha(2)M). As compared to adult wild-type mice, clearance was significantly reduced in young and old apolipoprotein E (apoE) knockout mice, and in old wild-type mice. There was no evidence that Ass was metabolized in brain interstitial fluid and degraded to smaller peptide fragments and amino acids before its transport across the BBB into the circulation. LRP-1, although abundant in brain microvessels in young mice, was downregulated in older animals, and this downregulation correlated with regional Ass accumulation in brains of Alzheimer's disease (AD) patients. We conclude that the BBB removes Ass from the brain largely via age-dependent, LRP-1-mediated transport that is influenced by alpha(2)M and/or apoE, and may be impaired in AD.

Aging↗
PubMed1999

High efficiency in vitro gene transfer into vascular tissues using a pseudotyped retroviral vector without pseudotransduction.

Murine leukemia virus (MuLV)-derived retroviral vectors have had limited application in vascular gene therapy because of low transduction efficiency of vascular tissues, both in vitro and in vivo. In this study, we compared the gene transfer efficiency of two retroviral vectors: amphotropic MuLV and a MuLV vector pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) envelope. Target vascular tissues included human endothelial cells (EC), smooth muscle cells (SMC) and saphenous veins (SV). Transduction efficiency of human EC and SMC was significantly higher for VSV-G pseudotyped MuLV vector (90%) than for Amphotropic MuLV (20%). Luminal surface en face analysis of transduced cultured SV showed a six- to 10-fold greater transduction efficiency with VSV-G pseudotyped MuLV. The tissue plasminogen activator (tPA) gene was transduced into EC using each vector. Four days following transduction, a 12-fold higher tPA antigen concentration and a 38-fold higher tPA enzymatic activity was measured from cells transduced with the VSV-G pseudotyped vectors as compared with the amphotropic MuLV. There was no detectable pseudotransduction (protein transfer) associated with the VSV-G MuLV vector. Both AZT inhibition of reverse transcriptase and cell division arrest by gamma irradiation inhibited transduction, indicating that viral transduction correlated with RNA reverse transcription and cell proliferation. MuLV pseudotyped with the VSV-G envelope glycoprotein is an effective retroviral vector for vascular gene therapy.

Cell Division↗
PubMed1996

Argyrophilic nuclear organizer regions (AgNORs) in pediatric acute lymphoblastic leukemia.

Nuclear organizer regions (NORs) code for ribosomal RNA and are associated with non-histone nucleoproteins which can be identified by silver staining (AgNORs). AgNORs have been correlated to proliferative activity of tumors and hence may be prognosis-related. The present study evaluates the possible prognostic importance of the AgNORs in tumor cells of patients with pediatric acute lymphoblastic leukemia (ALL). A significant increase in AgNOR counts was observed in ALL patients as compared to normal controls. Further, a significant positive correlation was observed between AgNOR counts and total WBC count at diagnosis. A negative correlation was also observed between AgNOR counts and age of the patients. Logistic regression analysis revealed further correlation between AgNOR counts and disease with an odds ratio of 1.29 (P = 0.03) as compared to normal controls. These results therefore suggest that AgNOR counts may be significant in the evaluation of pediatric ALL.

Case-Control Studies↗
PubMed1996

Renal collecting duct carcinoma in an 8-year-old child.

A fatal collecting duct carcinoma, presenting with pleural metastases, arose from the right kidney in an 8-year-old child. A distal nephron origin of the tumor is supported by positive tumor staining with Ulex europaeus and Arachis hypogaea, and a lack of staining with Tetragonolobus lotus. The ultrastructural features of short stubby microvilli, smooth basal cell membranes, and lateral membrane infoldings also support a distal nephron origin (inner most inner medullary collecting duct). This rare childhood renal neoplasm behaved similarly to that reported in adults with metastatic disease at presentation and a short fatal clinical course.

Carcinoma↗
PubMed1996

Chemotherapy in Hodgkin's disease.

OBJECTIVE: To assess the efficacy of primary chemotherapy in patients with clinically staged Hodgkin's disease. DESIGN: Non randomized study. SETTING: Pediatric Oncology Division of Regional Cancer Center. SUBJECTS: Twenty nine children with Hodgkin's disease. INTERVENTIONS: Chemotherapy was given to 21 patients whose parents agreed for the same. Sixteen children received COPP regimen and 5 received MOPP regimen. RESULTS: Complete remission was achieved in 19 patients. The relapse free survival and overall survival in these patients were 76% and 86%, respectively at 5 years. There was no death related to chemotherapy toxicity. CONCLUSION: Combination chemotherapy is an effective modality of treatment for children with Hodgkin's disease.

Adolescent↗
PubMed1994

Human T-cell lymphotropic virus type I-associated retinal lymphoma. A clinicopathologic report.

Human T-cell lymphotropic virus type I has been associated with a wide range of ocular conditions, including neoplastic, infectious, and inflammatory lesions. We studied a patient infected with human T-cell lymphotrophic virus type I who presented with deep retinal and subretinal infiltrates but without cells in the vitreous. The differential diagnosis included intraocular lymphoma and fungus infection. A chorioretinal biopsy specimen obtained for tissue diagnosis disclosed large atypical mononuclear cells located primarily at the level of the retinal pigment epithelium but focally involving overlying retina. Electron microscopy of this infiltrate showed features consistent with adult T-cell lymphoma/leukemia. Infection by human T-cell lymphotropic virus type I was verified by polymerase chain reaction studies conducted on peripheral-blood mononuclear cells. This case emphasizes the occurrence of intraocular lesions in adult T-cell lymphoma/leukemia that clinically show some features similar to those of the usual ocular lymphoma (reticulum cell sarcoma); diagnosis can be established by chorioretinal biopsy, thereby allowing appropriate therapy.

Adult↗
PubMed1994

Unusual clinical course of chronic myelogenous leukemia. A case report.

We describe an 8-year-old boy with chronic myeloid leukemia (CML), in lymphoid blast crisis at presentation. Ph chromosome was negative and he remained in complete continuous remission for 3 years. At 10 months from cessation of treatment he presented with involvement of both testes, and bone marrow examination at that time was consistent with CML. Lymphoid blast crisis occurred again after 6 months. No further treatment was given, as parents refused permission.

Blast Crisis↗
PubMed1991

Cystoid macular edema, retinal detachment, and glaucoma after Nd:YAG laser posterior capsulotomy.

A series of 897 Nd:YAG laser posterior capsulotomies were reviewed for the complications of cystoid macular edema, retinal detachment, new onset of glaucoma, and worsened preexisting glaucoma. After Nd:YAG capsulotomy, 11 patients (1.23%; 95% confidence interval, 0.51% to 1.95%) developed cystoid macular edema and eight patients (0.89%; 95% confidence interval, 0.28% to 1.5%) developed a retinal detachment. The new onset of glaucoma was observed in seven patients (0.78%; 95% confidence interval, 0.20% to 1.36%). Five patients (0.56%; 95% confidence interval, 0.07% to 1.05%) with preexisting glaucoma had persistent worsening of their glaucoma. Most patients with a complication had no identifiable risk factors in common. The numbers of laser pulses and energy delivered were not risk factors. Retinal detachment and cystoid macular edema developed most often many months after capsulotomy and many months to years after the cataract surgery. Patients undergoing Nd:YAG laser capsulotomy therefore require ongoing medical observation to detect and treat these serious complications.

Cataract Extraction↗