Biomedical subjects

Prem Gurnani

Publications and source records attributed to Prem Gurnani.

5 recordsLinked to original sources

PubMed2005

Regulation of oxidative stress by the anti-aging hormone klotho.

klotho is an aging suppressor gene and extends life span when overexpressed in mice. Klotho protein was recently demonstrated to function as a hormone that inhibits insulin/insulin-like growth factor-1 (IGF-1) signaling. Here we show that Klotho protein increases resistance to oxidative stress at the cellular and organismal level in mammals. Klotho protein activates the FoxO forkhead transcription factors that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance. Thus, Klotho-induced inhibition of insulin/IGF-1 signaling is associated with increased resistance to oxidative stress, which potentially contributes to the anti-aging properties of klotho.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Suppression of aging in mice by the hormone Klotho.

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

Aging↗

PubMed2005

Diagnosis of early relapse in ovarian cancer using serum proteomic profiling.

Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry data has been increasingly analyzed for identifying biomarkers to help early detection of the disease. Ovarian cancer commonly recurs at the rate of 75% within a few months or several years later after standard treatment. Since recurrent ovarian cancer is relatively difficult to be diagnosed and small tumors generally respond better to treatment, new methods for the detection of early relapse in ovarian cancer are urgently needed. Here, we propose a new algorithm SVM-MB/RFE (SVM-Markov Blanket/Recursive Feature Elimination) based on SVM-RFE, which identifies biomarkers for predicting the early recurrence of ovarian cancer. In this approach, we first apply t-test for feature pruning and then binning using 5-fold cross validation. Finally, 58 peaks are obtained from 27,000 of the raw data. Such dramatically reduced features relax the computational burden in the next step of our algorithm. We compare the performance of three feature selection algorithms and demonstrate that SVM-MB/RFE outperforms other methods.

Algorithms↗

PubMed2003

Validation of a near-infrared probe for detection of thin intracranial white matter structures.

OBJECT: The authors have developed an intracranial near-infrared (NIR) probe that analyzes the scattering of light emitted from its tip to measure the optical properties of cerebral tissue. Despite its success in distinguishing graymatter from white matter in humans during stereotactic surgery, the limits of this instrument's resolution remain unclear. In this study, the authors determined the spatial resolution of this new probe by using a rodent model supplemented with phantom measurements and computer simulation. METHODS: A phantom consisting of Intralipid and gelatin was constructed to resemble a layer of white matter overlying a layer of gray matter. Near-infrared measurements were obtained as the probe was inserted through the gray-white matter transition. A computer simulation of NIR measurements through a gray-white matter transition was also performed using Monte Carlo techniques. The NIR probe was then used to study 19 tracks from the cortical surface through the corpus callosum in an in vivo rodent preparation. The animals were killed and histological sections through the tracks were obtained. Data from the phantom models and computer simulations showed that the NIR probe samples a volume of tissue extending 1 to 1.5 mm in front of the probe tip (this distance is termed the "lookthrough" distance). Measurements obtained from an NIR probe passing through a thin layer of white matter consisted of an initial segment of increasing values, a maximum (peak) value, and a trailing segment of decreasing values. The length of the initial segment is the lookthrough distance, the position of the peak indicates the location of the superficial white matter boundary, and the length of the trailing segment is the thickness of the layer. These considerations were confirmed in experiments with rodents. All tracks passed through the corpus callosum, which was demonstrated as a broad peak on each NIR graph. The position of the dorsal boundary of the corpus callosum and its width (based on histological measurements) correlated well with the peak of the NIR curve and its trailing segment, respectively. The initial segments correlated well with estimates of the lookthrough distance. Five of the tracks transected the smaller anterior commissure (diameter 0.2 mm), producing a narrow NIR peak at the correct depth. CONCLUSIONS: Data in this study confirm that the NIR probe can reliably detect and measure the thickness of layers of white matter as thin as 0.2 mm. Such resolution should be adequate to detect larger structures of interest encountered during stereotactic surgery in humans.

Animals↗

PubMedDate not supplied

Pegylated, steptavidin-conjugated quantum dots are effective detection elements for reverse-phase protein microarrays.

Protein microarray technologies provide a means of investigating the proteomic content of clinical biopsy specimens in order to determine the relative activity of key nodes within cellular signaling pathways. A particular kind of protein microarray, the reverse-phase microarray, is being evaluated in clinical trials because of its potential to utilize limited amounts of cellular material obtained through biopsy. Using this approach, cellular lysates are arrayed in dilution curves on nitrocellulose substrates for subsequent probing with antibodies. To improve the sensitivity and utility of reverse-phase microarrays, we tested whether a new reporter technology as well as a new detection instrument could enhance microarray performance. We describe the use of an inorganic fluorescent nanoparticle conjugated to streptavidin, Qdot 655 Sav, in a reverse-phase protein microarray format for signal pathway profiling. Moreover, a pegylated form of this bioconjugate, Qdot 655 Sav, is found to have superior detection characteristics in assays performed on cellular protein extracts over the nonpegylated form of the bioconjugate. Hyperspectral imaging of the quantum dot microarray enabled unamplified detection of signaling proteins within defined cellular lysates, which indicates that this approach may be amenable to multiplexed, high-throughput reverse-phase protein microarrays in which numerous analytes are measured in parallel within a single spot.

Calibration↗