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Biomedical subjects

R Narayanan

Publications and source records attributed to R Narayanan.

At least 127 records · Page 7Linked to original sources

Effect of aldicarb on the growth, respiration and (14C) - glucose metabolism of Axotobacter chroococcum BEIJ.

Aldicarb [2-methyl-2(methyl thio) propionaldehyde-O-methyl carbamoyl oxime], which forms the active ingredient of a systemic oximic carbamate insecticide, at 2 ppm level did not affect the in vitro growth and respiration of Azotobacter chroococcum Beij, while concentrations at 5 ppm and 10 ppm levels were inhibitory. The insecticide treatment at 10 ppm level suppressed the assimilation of (14C) - glucose in the whole cells and in the cellular constitutents viz., cold - TCA soluble, hot TCA soluble fractions and insoluble residue. However, the 14C - incorporation in the alcohol soluble and alcohol-ether soluble fractions was enhanced indicating that aldicarb considerably altered the glucose metabolism of the organism.

Aldicarb↗

Optical coherence tomography in progressive outer retinal necrosis.

A 38-year-old man with human immunodeficiency virus was referred for evaluation of retinal lesions in both eyes. Optical coherence tomography was performed after dilating the pupils. Biomicroscopy of the retina showed an atypical, solitary, yellowish-white lesion in the macula of both eyes with no inflammation of the vitreous. Optical coherence tomography of the lesions showed an area of extremely low reflectivity with well-defined but irregular borders in the outer retina. The surrounding retina showed normal reflectivity and was of normal thickness. Optical coherence tomography showed selective necrosis of the outer layers due to progressive outer retinal necrosis. Optical coherence tomography may serve as a useful tool for the early diagnosis of progressive outer retinal necrosis.

Adult↗

Microarray-based expression profiling in prostate tumors.

High throughput gene expression profiling is increasingly becoming a desirable method for identifying genes differentially expressed in disease versus normal tissues. Microarrays and gene chips containing hundreds to thousands of genes of interest, both known and novel, can be used to establish the expression profile of numerous genes in a single experiment. In order to validate the hits emerging out of such an experiment it is necessary to use an appropriate panel of the cDNA repository. We investigated the usefulness of such a method to identify prostate cancer-specific genes. A microarray containing 588 known genes was analyzed using cDNA probes derived from normal and three independent prostate tumors. At least 19/588 genes were found to be differentially expressed in the tumors in comparison to the normal tissue. Among the nine test genes chosen, one gene, Glutathione-S-transferase theta 1 (GSTT1), showed a correlation with the microarray results when analyzed by RT-PCR. Using a comprehensive panel of normal and tumor tissues and cancer-derived cell lines, we have rapidly validated the expression relevance of GSTT1 in solid tumors. The microarray was also useful in the preliminary identification of androgen-regulated genes in the prostate tumor models. These results indicate that microarray in combination with a relevant cDNA repository can facilitate rapid identification of potential targets for therapy and diagnosis of prostate and other cancers.

Female↗

Relevant genomics of neurotensin receptor in cancer.

The expressed sequence tag (EST) databases are an attractive starting point for gene discovery for diseases like cancer. Validation of gene targets from these sequences (both known and novel) in cancers requires a comprehensive expression profiling. We identified from the Cancer Gene Anatomy Project database (CGAP), a hit called neurotensin receptor (NT-r) that was expressed in the pancreatic cancer cDNA libraries. Neurotensin (NT), a neuroendocrine peptide, exerts trophic effects in vivo and stimulates the growth of cancer-derived cell lines in vitro. High affinity neurotensin receptors (NT-r) are expressed in cancer-derived cell lines and in some primary tumors. To date, a comprehensive expression profile of the NT-r in diverse cancers and normal tissues has not been reported. A cancer-selective expression of NT-r, if demonstrable, may provide a basis for a diagnostic and potential therapeutic utility. We demonstrate that the NT-r is expressed in a variety of cancer-derived cell lines as well as primary tumors, but only in a select few normal tissues. The expression of NT, on the other hand, was detected in many normal tissues, but not in the cancer-derived cell lines. The NT expression however, was detected in the primary tumors. We further demonstrate that NT expression is stimulated by androgen deprivation in the prostate cancer models. These results demonstrate the usefulness of a panel of cDNA repository for rapid validation of potential cancer targets.

Breast Neoplasms↗

HER-2/neu expression in archival non-small cell lung carcinomas using FDA-approved Hercep test.

HER-2/neu is a 185 kDa glycoprotein related to the epidermal growth factor receptor. Overexpressed in 25-30% of primary breast carcinomas, HER-2/neu is associated with a poor clinical outcome. Recently the FDA approved an antibody to HER-2/neu, trastuzumab (Herceptin), for the treatment of HER-2/neu overexpressing metastatic breast cancers. Relatively little is known about HER-2/neu status and lung cancers. We reasoned that if HER-2/neu status could be ascertained in non-small cell lung carcinomas (NSCLCs), and a clinical correlation can be established, a rationale for the use of Herceptin in this tumor type could be established. Using a FDA-approved standardized diagnostic kit, HercepTest, for detection of HER-2/neu in clinical specimens, we examined the expression of HER-2/neu in NSCLCs in archival paraffin-embedded specimens (N = 81). In normal epithelium, HER-2/neu expression was not detected in a majority of samples (74/81). HER-2/neu overexpression was detected in 27% of the tumors of different histological types including adenocarcinomas, large cell carcinomas, and squamous cell carcinomas. Poor to moderately differentiated, but not well differentiated tumors showed overexpression of HER-2/neu. The specificity of HercepTest was further increased (from 27% to 21%) when the expression in the few normal tissues was subtracted from the tumor score. HER-2/neu may offer an attractive predictive and prognostic factor for NSCLC.

Adenocarcinoma↗

Antisense therapy of cancer.

Binding sites for the NF-kappa B transcription factor complex, composed of two subunits, p50 (NFKB1) and p65 (rel A), are present in many cell adhesion molecules, cytokines, and growth-factor receptors. Antisense techniques were used to establish the role of NF-kappa B in cell growth. Surprisingly, antisense phosphorothioate oligomers to the rel A subunit of NF-kappa B caused a pronounced block of cellular adhesion. Since adhesion plays an important role in diseases including cancer and inflammation, this chance observation was extended to various in vitro and in vivo models. Our results establish the in vivo efficacy of phosphorothioate oligomers.

Animals↗

A DNA motif present in alpha V integrin promoter exhibits dual binding preference to distinct transcription factors.

Antisense inhibition of the RelA subunit but not the NFKB1 subunit of NK-kappa B transcription factor results in a block of cellular adhesion and inhibition of tumor cell growth in vitro and in vivo. Studies aimed at dissecting the molecular mechanism of antisense relA action led to our identification of a kappa B-like motif present in aV integrin promoter. The alpha V/kappa B motif is closely related to RelA/c-Rel-binding sequences, such as 65-2 and TF-1. However, unlike these two kappa Blike motifs, the alpha V/kappa B motif detected a nuclear Sp1 activity distinct from kappa B activity, which was subsequently confirmed to be derived from Sp1. In comparison to the conventional GC box-containing Sp1 motif, the alpha V/kappa B motif also binds in vitro to c-Rel and RelA but not to NFKB1. Antisense inhibition of RelA inhibited the alpha V/kappa B activity. Direct in vivo competition of alpha V/kappa B-binding activity by a decoy approach also resulted in inhibition of alpha V/kappa B activity in intact cells. A variant of the alpha V/kappa B motif was found to retain the dual ability to detect Sp1 and the NF-kappa B complex in the nuclear and cytoplasmic extracts. Such dual interacting ability of a DNA motif offers yet another way of gene regulation in vivo and hence can affect cellular growth. Our results identify alpha V integrin as one of the molecular targets for relA/NF-kappa B and may explain growth inhibition by antisense relA.

Animals↗