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Search Results: 1 - 10 of 325861 matches for " Karnam S Murthy "
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Distinctive G Protein-Dependent Signaling by Protease-Activated Receptor 2 (PAR2) in Smooth Muscle: Feedback Inhibition of RhoA by cAMP-Independent PKA
Wimolpak Sriwai, Sunila Mahavadi, Othman Al-Shboul, John R. Grider, Karnam S. Murthy
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066743
Abstract: We examined expression of protease-activated receptors 2 (PAR2) and characterized their signaling pathways in rabbit gastric muscle cells. The PAR2 activating peptide SLIGRL (PAR2-AP) stimulated Gq, G13, Gi1, PI hydrolysis, and Rho kinase activity, and inhibited cAMP formation. Stimulation of PI hydrolysis was partly inhibited in cells expressing PAR2 siRNA, Gaq or Gai minigene and in cells treated with pertussis toxin, and augmented by expression of dominant negative regulator of G protein signaling (RGS4(N88S)). Stimulation of Rho kinase activity was abolished by PAR-2 or Ga13 siRNA, and by Ga13 minigene. PAR2-AP induced a biphasic contraction; initial contraction was selectively blocked by the inhibitor of PI hydrolysis (U73122) or MLC kinase (ML-9), whereas sustained contraction was selectively blocked by the Rho kinase inhibitor (Y27632). PAR2-AP induced phosphorylation of MLC20, MYPT1 but not CPI-17. PAR2-AP also caused a decrease in the association of NF-kB and PKA catalytic subunit: the effect of PAR2-AP was blocked by PAR2 siRNA or phosphorylation-deficient RhoA (RhoA(S188A)). PAR2-AP-induced degradation of IkBa and activation of NF-kB were abolished by the blockade of RhoA activity by Clostridium botulinum C3 exoenzyme suggesting RhoA-dependent activation of NF-kB. PAR2-AP-stimulated Rho kinase activity was significantly augmented by the inhibitors of PKA (myristoylated PKI), IKK2 (IKKIV) or NF-kB (MG132), and in cells expressing dominant negative mutants of IKK (IKK(K44A), IkBa (IkBa (S32A/S36A)) or RhoA(S188A), suggesting feedback inhibition of Rho kinase activity via PKA derived from NF-kB pathway. PAR2-AP induced phosphorylation of RhoA and the phosphorylation was attenuated in cells expressing phosphorylation-deficient RhoA(S188A). Our results identified signaling pathways activated by PAR2 to mediate smooth muscle contraction and a novel pathway for feedback inhibition of PAR2-stimulated RhoA. The pathway involves activation of the NF-kB to release catalytic subunit of PKA from its binding to IkBa and phosphorylation of RhoA at Ser188.
MEKK1-MKK4-JNK-AP1 Pathway Negatively Regulates Rgs4 Expression in Colonic Smooth Muscle Cells
Yonggang Zhang, Fang Li, Shu Liu, Hong Wang, Sunila Mahavadi, Karnam S. Murthy, Kamel Khalili, Wenhui Hu
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035646
Abstract: Background Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1β is mediated by the activation of NFκB signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. Here we investigate the effect of the c-Jun N-terminal kinase (JNK) pathway on Rgs4 expression in rabbit colonic smooth muscle cells. Methodology/Principal Findings Cultured cells at first passage were treated with or without IL-1β (10 ng/ml) in the presence or absence of the selective JNK inhibitor (SP600125) or JNK small hairpin RNA (shRNA). The expression levels of Rgs4 mRNA and protein were determined by real-time RT-PCR and Western blot respectively. SP600125 or JNK shRNA increased Rgs4 expression in the absence or presence of IL-1β stimulation. Overexpression of MEKK1, the key upstream kinase of JNK, inhibited Rgs4 expression, which was reversed by co-expression of JNK shRNA or dominant-negative mutants for MKK4 or JNK. Both constitutive and inducible upregulation of Rgs4 expression by SP600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin D. Dual reporter assay showed that pretreatment with SP600125 sensitized the promoter activity of Rgs4 in response to IL-1β. Mutation of the AP1-binding site within Rgs4 promoter increased the promoter activity. Western blot analysis confirmed that IL-1β treatment increased the phosphorylation of JNK, ATF-2 and c-Jun. Gel shift and chromatin immunoprecipitation assays validated that IL-1β increased the in vitro and ex vivo binding activities of AP1 within rabbit Rgs4 promoter. Conclusion/Significance Activation of MEKK1-MKK4-JNK-AP1 signal pathway plays a tonic inhibitory role in regulating Rgs4 transcription in rabbit colonic smooth muscle cells. This negative regulation may aid in maintaining the transient level of RGS4 expression.
Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat
Chun-Mei Xia, Melisa A Gulick, Sharon J Yu, John R Grider, Karnam S Murthy, John F Kuemmerle, Hamid I Akbarali, Li-Ya Qiao
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-30
Abstract: Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p < 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.Clinical evidence has shown sensory cross-sensitization between the urinary bladder and the distal colon [1-5]. Patients with inflammatory bowel disease (IBD) are more l
Hypopigmented pityriasis versicolor developing on a pre-existing Becker′s naevus
Murthy S
Indian Journal of Dermatology, Venereology and Leprology , 2002,
Zosteriform lesion over abdomen
Murthy S
Indian Journal of Dermatology, Venereology and Leprology , 2006,
Skin Sparing Mastectomy in Locally Advanced Breast Cancer: A Possibility?  [PDF]
Vijayashree Murthy, K. S. Gopinath, Anand Krishna
Surgical Science (SS) , 2012, DOI: 10.4236/ss.2012.34044
Abstract: Breast cancer is the second most common cause of cancer death in women in India in spite of advances in the adjuvant treatment of breast cancer. Locally advanced breast cancer (LABC) still represents the major presenting picture in many urban and rural institutions in our country. Skin Sparing Mastectomy (SSM) and primary reconstruction is a popular option for patients with breast cancer. There are similar local and distant recurrences in SSM compared to the traditional non-skin sparing mastectomy. A 57-year-old lady presented with a locally advanced left breast cancer. After undergoing neoadjuvant chemotherapy and a PET-CT to accurately detect residual disease in breast and axilla, she underwent skin sparing mastectomy with nipple-areola complex preservation and primary reconstruction with silicon prosthesis implant over a latissimus dorsi myocutaneous flap for primary reconstruction. SSM in LABC has not been reported in the literature so far. This patient is disease free for the past 24 months.
Characterization of Esterases of Tamarindus indica Seeds  [PDF]
S. Kantharaju, K. R. Siddalinga Murthy
Journal of Biosciences and Medicines (JBM) , 2014, DOI: 10.4236/jbm.2014.24009

Germinating seeds of Tamarindus indica synthesizes various enzymes which are required for the degradation of seed reserves such as xyloglucans, fatty acid esters and proteins. Among these, esterases, belonging to a group of hydrolytic enzymes catalyze the hydrolysis of various types of esters. They play an important role in cell expansion as well as detoxification of xenobiotics and many agrochemicals and insecticides. The esterases are extracted from the germinating tamarind seeds using 50 mM phosphate buffer, pH 7. The Km with α-naphthyl acetate as the substrate is 19.23 μM and the enzymes are optimally active at pH 7.0 to 7.5 and are stable between pH 5.0 to 9.0. The optimum temperature of esterase activity of tamarind seed is between 37?C - 50?C and is stable up to 40?C. The activity declined by 30% at 60?C and about 90% at 70?C. Highest esterase activity and specific activity are observed on the 21st day of germination. The polyacrylamide gel electrophoresis (PAGE) indicated the presence of nine isozymes of esterases. Band numbers 1, 5 and 6 are the major esterolytic bands present throughout the germination period while band numbers 2 & 3 are minor bands present only during the latter period of the germination. Based on substrate and inhibitor specificity in conjunction with electrophoresis, the esterases 1 to 8 have been classified as carboxylesterases sensitive to organophosphate inhibitor (OP) and PCMB (p-chloromercuribenzoate) while esterase 9 is classified as carboxylesterase sensitive to OP. These esterases are unaffected by carbamate inhibitor, eserine sulphate.

Males at High Risk for Breast Cancer: Who Are They and How Should We Screen Them?  [PDF]
Natalie Swergold, Vijayashree Murthy, Ronald S. Chamberlain
Surgical Science (SS) , 2014, DOI: 10.4236/ss.2014.57054

Background: It is estimated that 2240 males in the United States will develop invasive breast cancer (BC) in 2013, resulting in 410 deaths. Overall, male breast cancers (MBCs) are diagnosed with larger tumor size, more frequent lymphatic invasion, and advanced tumor stage compared to their female counterparts. Several risk factors have been elucidated for the development of MBC, and this paper aims to critically review the existing literature on at-risk populations and provide screening recommendations. Methods: A comprehensive search for all published studies on populations at risk for MBC using PubMed, EBSCOhost, and Google Scholar was performed (1982- 2013). The search focused specifically on genetic and epidemiologic risk factors, and screening for MBC. Keywords searched included “male breast cancer risk factors”, “male breast cancer epidemiology”, and “male breast cancer genetics”. A total of 34 studies involving 4,865,819 patients were identified. Results: Five studies (N = 327,667) focused primarily on family history of breast cancer as a risk factor for MBC. 15% - 20% of men with BC have a family history of breast or ovarian cancer, and a family history of BC among first-degree relatives confers a 2-to 3-fold increase in MBC risk (odds ratio = 3.3). Seventeen studies (N = 5451) analyzed associations between several heritable genes and MBC. Lifetime MBC risk among BRCA1 mutation carriers is 1% - 5%, while MBC risk in BRCA2 mutation carriers is higher and varies between 4% - 40%. Less clear associations between MBC and PALB2, Androgen Receptor gene, CYP17, and CHEK2 mutations have also been documented. Five studies (N = 16,667) have addressed occupational risk factors for MBC. An 8-fold increase in MBC is reported in males working in the cosmetic cream manufacturing, and the motor vehicle industries. A meta-analysis of 18 trials also identified electromagnetic field exposure as a potential MBC risk, though causation remains undocumented. Eleven studies (N = 4,843,598) analyzed the role of abnormalities in the androgen-to-estrogen ratio as a risk factor for MBC. Conditions associated with increased MBC risk include Klinefelter’s syndrome (relative risk, RR = 29.64), obesity (RR = 1.98), orchitis/epididymitis (RR = 1.84), and gynecomastia (RR = 5.86). Conclusion: Routine screening for MBC should be considered in all high risk male populations, including those with a prior history of breast carcinoma, a strong family history of BC

Studies on Xyloglucanase during the Germination of Seeds of Tamarindus indica  [PDF]
K. R. Siddalinga Murthy, S. Kantharaju
Journal of Biosciences and Medicines (JBM) , 2014, DOI: 10.4236/jbm.2014.24007

Germinating seeds of Tamarindus indica contain endo-β-1, 4-xyloglucanases which degrade tamarind xyloglucan, but not carboxymethylcellulose (CMC). The xyloglucanases are isolated from the germinating tamarind seeds using 50 mM acetate buffer, pH 5.5 containing 0.5 M NaCl. The Km value is 0.667 g/liter and the enzyme is optimally active at pH 5.5 and stable between pH 4 - 6.5. The optimum temperature is 45?C and is quite stable upto 50?C. The activity declined by 50% at 60?C and is completely inactivated at 70?C. Highest xyloglucanase activity and specific activity are observed on the 23rd day of germination. The polyacrylamide gel electrophoresis (PAGE) indicated the presence of five isozymes of xyloglucanases which are visualized by activity staining separately with congo red and grams iodine. Isozyme 2 is the major xyloglucanase present throughout the germination period.

Additional Space Dimension in Bound Spaces Created by a Central Object  [PDF]
T. V. B. S. Satyanarayana Murthy
Journal of Applied Mathematics and Physics (JAMP) , 2015, DOI: 10.4236/jamp.2015.32019
Abstract: Space is a common entity in any static or dynamic system of objects whether the system is a bound system or an open system. Space is described by either measured or abstract dimensions. All motions, momentum and energy transfers take place in space in any given system of objects. By understanding space we understand many physical phenomena happening in space. One method is to observe similarities among phenomena, deduce possible relations and validate the relations through known results. De Broglie wavelength for matter waves is a typical theorized abstract dimension existence of which is established through experiments later. In this paper, the author studies two bound spaces in two bound systems, namely, atomic bound systems and gravitationally bound systems. Both these bound systems have similar characteristics; they have inertial masses in motion with constant kinetic energies for a given orbital distance around the respective central object. In atomic bound space, the central object is the central positive charge which plays the role of creating the bound space around it. In gravitationally bound space, it is the central mass that plays the same role. Thus for these two bound systems a common constitutive relation between the energies of inertial masses in kinetic state, their distance from central object could be present. By noticing the similarities of the two systems, the author proposes such a relation through introduction of an additional space dimension. The existence of the proposed additional dimension is proved in this paper by considering hydrogen atom for atomic bound space and by considering any gravitational system for gravitationally bound space. Though the magnitude of the additional space dimension is different in both the situations, the additional space dimension exists. It is observed that in hydrogen atom the additional space dimension is a constant for the given positive charge of hydrogen atom when electron is in any energy state having principal quantum number of any value from 1 to 5 and with the orbital quantum number zero. For other quantum numbers additional space dimension exists. In the case of gravitational bound space, the additional space dimension is constant for a given mass of the central object for any energy of orbiting inertial mass. The author concludes that total mass energy of an inertial mass having a constant kinetic energy in any bound space is related to an additional space dimension defined by the constitutional property of the central object creating
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