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Biomedical subjects

Prem Kumar

Publications and source records attributed to Prem Kumar.

At least 19 recordsLinked to original sources
PubMed2006

AMP-activated protein kinase mediates carotid body excitation by hypoxia.

Early detection of an O2 deficit in the bloodstream is essential to initiate corrective changes in the breathing pattern of mammals. Carotid bodies serve an essential role in this respect; their type I cells depolarize when O2 levels fall, causing voltage-gated Ca2+ entry. Subsequent neurosecretion elicits increased afferent chemosensory fiber discharge to induce appropriate changes in respiratory function (1). Although depolarization of type I cells by hypoxia is known to arise from K+ channel inhibition, the identity of the signaling pathway has been contested, and the coupling mechanism is unknown (2). We tested the hypothesis that AMP-activated protein kinase (AMPK) is the effector of hypoxic chemotransduction. AMPK is co-localized at the plasma membrane of type I cells with O2-sensitive K+ channels. In isolated type I cells, activation of AMPK using 5-aminoimidazole-4-carboxamide riboside (AICAR) inhibited O2-sensitive K+ currents (carried by large conductance Ca2+-activated (BKCa) channels and TASK (tandem pore, acid-sensing potassium channel)-like channels, leading to plasma membrane depolarization, Ca2+ influx, and increased chemosensory fiber discharge. Conversely, the AMPK antagonist compound C reversed the effects of hypoxia and AICAR on type I cell and carotid body activation. These results suggest that AMPK activation is both sufficient and necessary for the effects of hypoxia. Furthermore, AMPK activation inhibited currents carried by recombinant BKCa channels, whereas purified AMPK phosphorylated thealpha subunit of the channel in immunoprecipitates, an effect that was stimulated by AMP and inhibited by compound C. Our findings demonstrate a central role for AMPK in stimulus-response coupling by hypoxia and identify for the first time a link between metabolic stress and ion channel regulation in an O2-sensing system.

AMP-Activated Protein Kinases↗
PubMed2006

The 'pitcher pot' ileal neobladder: early experiences.

OBJECTIVE: To analyse initial results of newly designed ileal neobladder-a modification of Studer neobladder METHODS: Twenty-four patients with urinary bladder cancer underwent radical cystoprostatectomy from February 2005 to March 2006. Twenty-one of them had urinary diversion using ileal neobladder in spherical configuration with ileal neourethra (giving the shape of an inverted Indian earthenware container called a 'pitcher pot') to circumvent the problem of short mesentery and construct a low-pressure spherical ileal neobladder. RESULTS: Early post-operative complications occurred in 42% of patients. Late complications occurred in 23% of patients. Most of these complications were minor, mainly as a result of wound infection, urine leak or urinary tract infections and were managed conservatively. No early post-operative mortality was observed. Daytime continence was achieved in 100% of patients who completed the 1 year follow-up. Night-time continence was variable as it depended on timed voiding--75% of patients achieved nocturnal continence by 1 year. The functional neobladder capacity was 426 ml. The mean post-operative residual volume was 36 ml. Three patients required cystoscopic mucus evacuation and catheterization. None of them required clean intermittent catheterization. No significant metabolic disturbance occurred in any patient. CONCLUSIONS: Length of mesentery remains one of the factors in deciding the segment of intestine to be taken for neobladder. Ileal neourethra gives about 2-3 cm extra length to perform tensionless anastomosis, which is a key factor in the smooth recovery after such major surgery and also maintains optimum urodynamic features of neobladder.

Adult↗
PubMed2006

Fiber-based telecom-band degenerate-frequency source of entangled photon pairs.

We demonstrate the generation of polarization-entangled photon pairs of degenerate frequency for the first time, to the best of our knowledge, in standard optical fiber using a novel dual-pump, counterpropagating configuration. Two-photon interference with >97% visibility is obtained. The purity of the photon source, as characterized by the ratio of coincidence to accidental-coincidence counts, is shown to be as high as 116 under suitable operating conditions.

Journal Article↗
PubMed2006

Generation of high-purity telecom-band entangled photon pairs in dispersion-shifted fiber.

We study the purity of correlated photon pairs generated in a dispersion-shifted fiber at various temperatures. The ratio of coincidence to accidental-coincidence counts greater than 100 can be obtained as the fiber is cooled to liquid-nitrogen temperature (77 K). We then generate polarization-entangled photon pairs by using a compact counterpropagating scheme. Two-photon interference with visibility >98% and Bell's inequality violation by >8 standard deviations of measurement uncertainty are observed at 77 K, without subtracting the accidental-coincidence counts due to background Raman photons.

Journal Article↗
PubMed2006

AMP-activated protein kinase couples mitochondrial inhibition by hypoxia to cell-specific Ca2+ signalling mechanisms in oxygen-sensing cells.

It is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation in O2-sensing cells, and thereby mediates, in part, cell activation. However, the mechanism by which this process is coupled to discrete, cell-specific Ca2+ signalling mechanisms remains elusive. We considered the possibility that hypoxia may increase the cellular ATP/AMP ratio, increase the activity of AMP-activated protein kinase (AMPK) and thereby evoke Ca2+ signals in O2-sensing cells. Co-immunoprecipitation identified alpha1beta2gamma1 as the primary AMPK isozyme in pulmonary arterial smooth muscle, whilst the tissue-specific distribution of AMPK activities and their activation by hypoxia suggested that the AMPK-alpha1 catalytic subunit isoform is key to the regulation of O2-sensing cells. Strikingly, 3D reconstruction of immunofluorescence images showed AMPK-alpha1 to be located throughout the cytoplasm of pulmonary arterial smooth muscle cells and, by contrast, targeted to the plasma membrane in carotid body glomus cells. Consistent with these observations Ca2+ imaging, tension recording and electrophysiology demonstrated that AMPK, like hypoxia, activates each cell type via discrete Ca2+ signalling mechanisms: cyclic ADP-ribose-dependent Ca2+ mobilization from the sarcoplasmic reticulum via ryanodine receptors in pulmonary arterial smooth muscle cells and voltage-gated Ca2+ influx into carotid body glomus cells. Thus, metabolic-sensing by AMPK underpins the cell-specific response of O2-sensing cells to hypoxia.

AMP-Activated Protein Kinases↗
PubMed2005

Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?

Specialized O2-sensing cells exhibit a particularly low threshold to regulation by O2 supply and function to maintain arterial pO2 within physiological limits. For example, hypoxic pulmonary vasoconstriction optimizes ventilation-perfusion matching in the lung, whereas carotid body excitation elicits corrective cardio-respiratory reflexes. It is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation in O2-sensing cells, thereby mediating, in part, cell activation. However, the mechanism by which this process couples to Ca2+ signaling mechanisms remains elusive, and investigation of previous hypotheses has generated contrary data and failed to unite the field. We propose that a rise in the cellular AMP/ATP ratio activates AMP-activated protein kinase and thereby evokes Ca2+ signals in O2-sensing cells. Co-immunoprecipitation identified three possible AMP-activated protein kinase subunit isoform combinations in pulmonary arterial myocytes, with alpha1 beta2 gamma1 predominant. Furthermore, their tissue-specific distribution suggested that the AMP-activated protein kinase-alpha1 catalytic isoform may contribute, via amplification of the metabolic signal, to the pulmonary selectivity required for hypoxic pulmonary vasoconstriction. Immunocytochemistry showed AMP-activated protein kinase-alpha1 to be located throughout the cytoplasm of pulmonary arterial myocytes. In contrast, it was targeted to the plasma membrane in carotid body glomus cells. Consistent with these observations and the effects of hypoxia, stimulation of AMP-activated protein kinase by phenformin or 5-aminoimidazole-4-carboxamide-riboside elicited discrete Ca2+ signaling mechanisms in each cell type, namely cyclic ADP-ribose-dependent Ca2+ mobilization from the sarcoplasmic reticulum via ryanodine receptors in pulmonary arterial myocytes and transmembrane Ca2+ influx into carotid body glomus cells. Thus, metabolic sensing by AMP-activated protein kinase may mediate chemotransduction by hypoxia.

AMP-Activated Protein Kinases↗
PubMed2005

Storage and long-distance distribution of telecommunications-band polarization entanglement generated in an optical fiber.

We demonstrate storage of polarization-entangled photons for 125 micros, a record storage time to date, in a 25-km-long fiber spool, using a telecommunications-band fiber-based source of entanglement. With this source we also demonstrate distribution of polarization entanglement over 50 km by separating the two photons of an entangled pair and transmitting them individually over separate 25-km fibers. The measured two-photon fringe visibilities were 82% in the storage experiment and 86% in the distribution experiment. Preservation of polarization entanglement over such long-distance transmission demonstrates the viability of all-fiber sources for use in quantum memories and quantum logic gates.

Journal Article↗
PubMed2005

10-GHz dispersion-managed soliton fiber-optical parametric oscillator using regenerative mode locking.

We demonstrate a regeneratively mode-locked fiber-optical parametric oscillator that utilizes intracavity dispersion compensation to generate pulses at a 10-GHz repetition rate in both soliton and nonsoliton regimes. At the threshold pump power the generated pulses are close to fundamental solitons. At higher pump powers we found a significant deviation of the pulses from the sech2 shape. In addition, the use of an ultralow-jitter self-starting pump-pulse source in a regenerative feedback loop allows for a significant reduction of the signal's timing jitter and amplitude noise.

Journal Article↗
PubMed2005

Optical-fiber source of polarization-entangled photons in the 1550 nm telecom band.

We present a fiber-based source of polarization-entangled photons that is well suited for quantum communication applications in the 1550 nm band of standard fiber-optic telecommunications. Polarization entanglement is created by pumping a nonlinear-fiber Sagnac interferometer with two time-delayed orthogonally polarized pump pulses and subsequently removing the time distinguishability by passing the parametrically scattered signal and idler photon pairs through a piece of birefringent fiber. Coincidence detection of the signal and idler photons yields biphoton interference with visibility greater than 90%, while no interference is observed in direct detection of either signal or idler photons. All four Bell states can be prepared with our setup and we demonstrate violations of the Clauser-Horne-Shimony-Holt form of Bell's inequality by up to 10 standard deviations of measurement uncertainty.

Journal Article↗
PubMed2004

Noise-figure limit of fiber-optical parametric amplifiers and wavelength converters: experimental investigation.

Recent theoretical work predicts that the quantum-limited noise figure of a x(3)-based fiber-optical parametric amplifier operating as a phase-insensitive in-line amplifier or as a wavelength converter exceeds the standard 3-dB limit at high gain. The degradation of the noise figure is caused by the excess noise added by the unavoidable Raman gain and loss occurring at the signal and the converted wavelengths. We present detailed experimental evidence in support of this theory through measurements of the gain and noise-figure spectra for phase-insensitive parametric amplification and wavelength conversion in a continuous-wave amplifier made from 4.4 km of dispersion-shifted fiber. The theory is also extended to include the effect of distributed linear loss on the noise figure of such a long-length parametric amplifier and wavelength converter.

Journal Article↗
PubMed2004

Acidosis abolishes the effect of repeated applications of ATP on pulmonary artery force and [Ca2+]i.

The purine nucleotide, ATP, can cause receptor-mediated desensitizing contractions of smooth muscle that may be modulated by pH. We investigated in the rat the effect of acidosis upon the contractile and Ca2+ responses induced by ATP upon intrapulmonary artery (PA) smooth muscle. Four successive applications of ATP (300 microM) at pH 7.4 induced desensitising contractile responses that showed progressively decreasing peak amplitudes that correlated with decreases of [Ca2+]i. Acidosis significantly reduced the peak contractile response to the first application of ATP without modifying the rate or degree of desensitisation in response to ATP and without decreasing the [Ca2+]i. Successive applications of ATP did not further reduce contractile force nor [Ca2+]i. These results demonstrated that acidosis abolishes the effect of repeat applications of ATP on pulmonary artery force and [Ca2+]i via alteration in the desensitization-resensitisation characteristics of ATP receptor. This suggest a potentially important physiological role for changes in external pH in the regulation of ATP-mediated control of the pulmonary circulation.

Acidosis↗
PubMed2004

Raman-noise-induced noise-figure limit for chi(3) parametric amplifiers.

The nonzero response time of the Kerr [chi(3)] nonlinearity determines the quantum-limited noise figure of chi(3) parametric amplifiers. This nonzero response time of the nonlinearity requires coupling of the parametric amplification process to a molecular-vibration phonon bath, causing the addition of excess noise through Raman gain or loss at temperatures above 0 K. The effect of this excess noise on the noise figure can be surprisingly significant. We derive analytical expressions for this quantum-limited noise figure for phase-insensitive operation of a chi(3) amplifier and show good agreement with published noise-figure measurements.

Journal Article↗
PubMed2004

Kidney transplantation: the evolving challenges.

Kidney transplantation is the treatment of choice for patients with end stage renal disease. Kidney transplantation not only improves the quality of life but also prolongs life. Over the last decade, the short-term allograft survival rate has been improved dramatically. Chronic allograft nephropathy and death from cardiovascular diseases become predominant causes of later graft loss. Prevention and treatment of these disease processes require a comprehensive approach. The ever-increasing shortage of organ supply becomes the greatest challenge for the transplant community and modern medicine. More and more patients are waiting for organs; many of them are dying while waiting. Xenotransplantation and organ engineering and cloning are promising techniques and can potentially provide organs for transplantation in the future.

Animals↗