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Biomedical subjects

Deepak Agrawal

Publications and source records attributed to Deepak Agrawal.

11 recordsLinked to original sources
PubMed2003

Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells.

The microenvironment has been shown to influence tumor cell phenotype with respect to growth, metastasis, and response to chemotherapy. We have utilized oligonucleotide microarray analysis to identify signal transduction pathways and gene products altered by the interaction of myeloma tumor cells with the extracellular matrix component fibronectin that may contribute to the antiapoptotic phenotype conferred by the microenvironment. Genes with altered expression associated with fibronectin cell adhesion, either induced or repressed, were numerically ranked by fold change. FN adhesion repressed the expression of 469 gene products, while 53 genes with known coding sequences were induced by twofold or more. Of these 53 genes with two fold, or greater increase in expression, 11 have been reported to be regulated by the nuclear factor-kappa B (NF-kappa B) family of transcription factors. EMSA analysis demonstrated NF-kappa B binding activity significantly increased in cells adhered to fibronectin compared to cells in suspension. This DNA binding activity consisted primarily of RelB-p50 heterodimers, which was distinct from the NF-kappa B activation of TNF alpha. These data demonstrate the selectivity of signal transduction from the microenvironment that may contribute to tumor cell resistance to programmed cell death.

Cell Adhesion↗
PubMed2003

Pituitary apoplexy and inappropriate ADH secretion.

Pituitary apoplexy may be associated with visual deterioration that may be severe in some cases. Misdiagnosis of this condition is not uncommon, resulting in delayed treatment, which may adversely affect the outcome and visual prognosis. We present a case of pituitary apoplexy, who presented with features of syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and monocular blindness. He had remarkable improvement to normal vision along with normalisation of serum sodium following emergency trans-sphenoidal surgery.

Decompression, Surgical↗
PubMed2003

Primary excision of pediatric posterior fossa abscesses--towards zero mortality? A series of nine cases and review.

Nine children with infratentorial brain abscesses were treated at our institution over a 3-year period. Seven of them were boys and two were girls. In five cases, the abscesses were otogenic, and in two cases, the cause was tubercular (including one case of tubercular otitis). There were three cases of abscess formation in dermoids. All cases were managed with primary excision of the abscess. The average hospital stay was 12 days, and there was no mortality. The most common complication was hydrocephalus, noticed in three patients, of whom one eventually required shunt placement. Our policy of primary excision of these abscesses has yielded gratifying results. This approach also resulted in minimal morbidity and a substantially shortened hospital stay. Moreover, primary excision yields definitive histopathology of the lesion, especially in cases of tubercular and dermoid etiologies.

Adolescent↗
PubMed2002

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.

Amino Acid Sequence↗
PubMed2002

The effect of age on immunologic response to recombinant hepatitis B vaccine: a meta-analysis.

Hepatitis B vaccine is a key tool for the prevention of hepatitis B infection. Age-associated changes in immune function may contribute to decreased vaccine efficacy in older individuals, although research related to this topic has yielded contradictory findings. We performed a meta-analysis of 24 published trials and studies that evaluated the association of age with response to hepatitis B vaccine, using a random-effects model. Pooling of study results suggested a significantly increased risk of nonresponse to hepatitis B vaccine among older individuals (relative risk [RR], 1.76; 95% confidence interval [CI], 1.48-2.10). An elevated risk of nonresponse persisted even after exclusion of poor-quality studies (RR, 1.63; 95% CI, 1.23-2.15) and adjustment for publication bias (RR, 1.52; 95% CI, 1.26-1.83), and it was present even when "older" individuals were defined as being as young as 30 years. These findings have important implications for individuals at risk for hepatitis B infection, including health care workers and travelers.

Adult↗
PubMed2002

Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling.

BACKGROUND: New tumor markers and markers of tumor progression are needed for improved staging and for better assessment of treatment of many cancers. Gene expression profiling techniques offer the opportunity to discover such markers. We investigated the feasibility of sample pooling strategy in combination with a novel analysis algorithm to identify markers. METHODS: Total RNA from human colon tumors (n = 60) of multiple stages (adenomas; cancers with modified Astler Collier stages B, C, and D; and liver metastases) were pooled within stages and compared with pooled normal mucosal specimens (n = 10) by using oligonucleotide expression arrays. Genes that showed consistent increases or decreases in their expression through tumor progression were identified. Northern blot analysis was used to validate the findings. All statistical tests were two-sided. RESULTS: More than 300 candidate tumor markers and more than 100 markers of tumor progression were identified. Northern analysis of 11 candidate tumor markers confirmed the gene expression changes. The gene for the secreted integrin-binding protein osteopontin was most consistently differentially expressed in conjunction with tumor progression. Its potential as a progression marker was validated (Spearman's rho = 0.903; P<.001) with northern blot analysis using RNA from an independent set of 10 normal and 43 tumor samples representing all stages. Moreover, a statistically significant correlation between osteopontin protein expression and advancing tumor stage was identified with the use of 303 additional specimens (human cancer = 185, adenomas = 67, and normal mucosal specimens = 51) (Spearman's rho = 0.667; P<.001). CONCLUSIONS: Sample pooling can be a powerful, cost-effective, and rapid means of identifying the most common changes in a gene expression profile. We identified osteopontin as a clinically useful marker of tumor progression by use of gene expression profiling on pooled samples.

Adenoma↗
PubMed2002

Delivery of exogenous protein antigens to major histocompatibility complex class I pathway in cytosol.

A fragment of anthrax lethal factor possesses the interesting function of delivering recombinant protein antigens through the classical major histocompatibility complex (MHC) class I pathway. This region of the lethal factor lacks the domain associated with anthrax cytotoxicity and functions independently of its binary partner, protective antigen. Experiments that used inhibitors at different steps of the MHC class I pathway supported this hypothesis. Application of this discovery to current T cell assays allows for the measurement of cytotoxic T lymphocyte function without resorting to live vectors and provides a useful new tool to design and test T cell-dependent vaccines.

Antigen Presentation↗
PubMed2002

Intramedullary neurenteric cyst presenting as infantile paraplegia: a case and review.

The authors report a case of a 3-month-old male child with paraplegia in whom magnetic resonance imaging (MRI) revealed a nonenhancing intramedullary cystic lesion extending from the level of D1 to D7 without any other associated anomaly. Intraoperatively, these findings were confirmed and the spinal cord was found to have splayed circumferentially into a papery thin rim. The patient underwent marsupialization of the cyst with subtotal excision of the cyst wall. Histopathological examination revealed ciliated pseudostratified columnar epithelium consistent with the diagnosis of a neurenteric cyst. Intramedullary neurenteric cysts are rare developmental malformations, and out of the 13 previously reported cases, only 3 were evaluated by MRI. This is the first case report in the literature of an intramedullary neurenteric cyst presenting as infantile paraplegia. In the present report, the embryology, etiopathogenesis, radiological imaging and management of this rare clinical entity are discussed and a detailed literature review is presented.

Diagnosis, Differential↗
PubMed2002

Vasospasm.

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Delayed-Action Preparations↗