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P Dhawan

Publications and source records attributed to P Dhawan.

18 recordsLinked to original sources
PubMed2004

Genetic variability of begomoviruses associated with cotton leaf curl disease originating from India.

Cotton leaf curl disease (CLCuD) causing viruses belong to the Begomovirus genus of the family Geminiviridae. Most begomoviruses are bipartite with two molecules of circular single stranded DNA (A and B) encapsidated in icosahedral geminate particles. However, the begomoviruses associated with CLCuD have DNA-beta instead of DNA-B. In this communication we report the complete genomic sequence of DNA-A component of two CLCuD-causing begomoviruses, cotton leaf curl Kokhran virus-Dabawali (CLCuKV-Dab), tomato leaf curl Bangalore virus-Cotton [Fatehabad] (ToLCBV-Cotton [Fat]) and partial sequences of two other isolates cotton leaf curl Rajasthan virus-Bangalore (CLCuRV-Ban) and cotton leaf curl Kokhran virus-Ganganagar (CLCuKV-Gang). A phylogenetic analysis of these isolates along with other related begomoviruses showed that ToLCBV-Cotton [Fat] isolate was closest to the tomato leaf curl Bangalore virus-5 (ToLCBV-Ban5) where as CLCuKV-Dab isolate was close to the cotton leaf curl Kokhran virus-Faisalabad1 (CLCuKV-Fai1), cotton leaf curl Kokhran virus-72b (CLCuKV-72b) and cotton leaf curl Kokhran virus-806b (CLCuKV-806b) isolates from Pakistan. The phylogenetic analysis further showed that the ToLCBV-Cotton [Fat] and CLCuKV-Dab isolates along with CLCuKV-Fai1, CLCuKV-72b and CLCuKV-806b are closer to the ToLCBV, tomato leaf curl Gujarat virus (ToLCGV), tomato leaf curl Gujarat virus-Varanasi (ToLCGV-Var) and tomato leaf curl Sri Lanka virus (ToLCSLV) isolates, where as cotton leaf curl Alabad virus-804a (CLCuAV-804a), cotton leaf curl Multhan virus (CLCuMV) cluster with the isolates from cotton leaf curl Rajasthan virus (CLCuRV) and okra yellow vein mosaic virus (OYVMV). These results demonstrate the extensive variability observed in this group of viruses. The AC4 ORF is the least conserved among these viruses. In order to further asses the variability in the CLCuD-causing begomoviruses, the region showing minimum similarity in the DNA-A sequence was first determined by a comparison of segments of different lengths of the aligned sequences. The results indicated that region 2411-424 (771 nt) was the least conserved. A phylogenetic tree constructed using the sequences of all the CLCuD causing begomoviruses, corresponding to the least conserved region showed that they form two distinct clusters.

DNA, Viral↗
PubMed2003

Vitamin D target proteins: function and regulation.

Recent findings have indicated that calbindin-D(28k), the first known target of vitamin D action, is present in osteoblasts and protects against TNF and glucocorticoid induced apoptosis of osteoblastic cells. Cytokine mediated destruction of pancreatic beta cells, a cause of insulin dependent diabetes, is also inhibited by calbindin-D(28k). In calbindin-D(28k) transfected pancreatic beta cells free radical formation by cytokines is inhibited by calbindin. Thus, besides its role as a facilitator of calcium diffusion, calbindin has a major role in protecting against cellular degeneration in different cell types. Besides calbindin, the other known pronounced effect of 1,25(OH)(2)D(3) in intestine and kidney is increased synthesis of 25(OH)D(3) 24-hydroxylase (24(OH)ase) which is involved in the catabolism of 1,25(OH)(2)D(3). We have noted that CCAAT enhancer binding protein beta (C/EBPbeta) is induced by 1,25(OH)(2)D(3) in kidney and osteoblastic cells and can enhance the transcriptional response of 24(OH)ase to 1,25(OH)(2)D(3). These studies establish C/EBPbeta as a novel 1,25(OH)(2)D(3) target gene and indicate a role for C/EBPbeta in 24(OH)ase transcription. These studies extend our previous studies related to factors that affect vitamin D receptor (VDR) mediated 24(OH)ase transcription (YY1, TFIIB, CBP) and the effect of signaling pathways on 24(OH)ase transcription and cofactor recruitment.

Animals↗
PubMed2001

The role of CDP in the negative regulation of CXCL1 gene expression.

The CXC chemokine, melanoma growth stimulatory activity/growth-regulated protein, CXCL1 is an important modulator of inflammation, wound healing, angiogenesis, and tumorigenesis. Transcription of CXCL1 is regulated through several cis-acting elements including Sp1, NF-kappa B, and an element that lies immediately upstream of the NF-kappa B element, the immediate upstream region (IUR). A transcription element data base search indicated that the IUR element contains a binding site for the transcriptional repressor, human CUT homeodomain protein/CCAAT displacement protein (CDP). It is shown here that in electrophoretic mobility shift assays, complexes obtained with the IUR oligonucleotide probe are supershifted by anti-CDP antibodies and that a CDP polypeptide containing a high affinity DNA binding domain binds to the sequence GGGATCGATC in the IUR element. In Southwestern blot analyses, oligonucleotides containing the wild-type IUR sequence, but not a mutant oligonucleotide with substitutions in the GGGATCGATC sequence, bind a 170--180-kDa protein. Furthermore, overexpression of the CDP protein blocks CXCL1 promoter activity in reporter gene assays, whereas overexpression of an antisense CDP construct leads to a significant increase in CXCL1 promoter activity. Mutations in the IUR element, which map in the putative CDP-binding site, inhibit the binding of CDP to the IUR element and favor increased transcription from the CXCL1 promoter. Based on these results, we propose that transcriptional regulation of the CXCL1 gene is mediated in part by CDP, which could play an important role in inflammatory processes and tumorigenesis.

Base Sequence↗
PubMed2001

YY1 represses vitamin D receptor-mediated 25-hydroxyvitamin D(3)24-hydroxylase transcription: relief of repression by CREB-binding protein.

Ying Yang transcription factor (YY1) can repress or activate transcription. 25-Hydroxyvitamin D(3)-24-hydroxylase [24(OH)ase], an enzyme involved in the catabolism of 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], is up-regulated at the transcriptional level by 1,25-(OH)(2)D(3) to self-induce its deactivation. Here we report that YY1 can repress 1,25-(OH)(2)D(3)-induced 24(OH)ase transcription in CV1 cells transfected with vitamin D receptor (VDR) expression vector or in LLCPK(1) cells that contain VDR endogenously. With increasing amounts of YY1 DNA transfected (500 ng to 2 microg), ligand-dependent VDR activation of 24(OH)ase transcription was steadily repressed (maximum repression was 10-fold). Thus, YY1 may be a key modulator preventing activation at times that do not require the enzyme to be expressed. Relief of YY1 repression was observed in the presence of TFIIB or CBP (CREB binding protein) suggesting that YY1 may exert repression, in part, by sequestering TFIIB/CBP. Glutathione-S-transferase (GST) pull-down assays identified regions in the N and C termini of CBP that can bind YY1. In addition, the N-terminal region of CBP that interacts with YY1 can inhibit YY1 from binding to TFIIB. Thus, CBP may alleviate YY1-mediated repression, in part, by preventing YY1 from binding to TFIIB, which is required for VDR-mediated transcription. In summary, our results suggest that YY1 represses 24(OH)ase transcription, at least in part, by sequestering activator proteins involved in VDR-mediated transcription. In addition, our findings demonstrate a role for CBP in relief of repression of VDR-mediated transcription.

Animals↗
PubMed1999

One-way cross-talk between p38(MAPK) and p42/44(MAPK). Inhibition of p38(MAPK) induces low density lipoprotein receptor expression through activation of the p42/44(MAPK) cascade.

In this paper, we report that SB202190 alone, a specific inhibitor of p38(MAPK), induces low density lipoprotein (LDL) receptor expression (6-8-fold) in a sterol-sensitive manner in HepG2 cells. Consistent with this finding, selective activation of the p38(MAPK) signaling pathway by expression of MKK6b(E), a constitutive activator of p38(MAPK), significantly reduced LDL receptor promoter activity. Expression of the p38(MAPK) alpha-isoform had a similar effect, whereas expression of the p38(MAPK) betaII-isoform had no significant effect on LDL receptor promoter activity. SB202190-dependent increase in LDL receptor expression was accompanied by induction of p42/44(MAPK), and inhibition of this pathway completely prevented SB202190-induced LDL receptor expression, suggesting that p38(MAPK) negatively regulates the p42/44(MAPK) cascade and the responses mediated by this kinase. Cross-talk between these kinases appears to be one-way because modulation of p42/44(MAPK) activity did not affect p38(MAPK) activation by a variety of stress inducers. Taken together, these findings reveal a hitherto unrecognized one-way communication that exists between p38(MAPK) and p42/44(MAPK) and provide the first evidence that through the p42/44(MAPK) signaling cascade, the p38(MAPK) alpha-isoform negatively regulates LDL receptor expression, thus representing a novel mechanism of fine tuning cellular levels of cholesterol in response to a diverse set of environmental cues.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Critical role of p42/44(MAPK) activation in anisomycin and hepatocyte growth factor-induced LDL receptor expression: activation of Raf-1/Mek-1/p42/44(MAPK) cascade alone is sufficient to induce LDL receptor expression.

The protein synthesis inhibitor anisomycin activates stress-related mitogen-activated protein kinases (MAPKs), namely, c-jun NH(2)-terminal kinase (p46/54(JNK)) and p38(MAPK) in mammalian cells. In this paper, we show that although exposure to anisomycin resulted in rapid and strong activation of p46/54(JNK) and p38(MAPK), with a delayed low level dual-phosphorylation of mitogen/extracellular protein kinase (p42/44(MAPK)), low density lipoprotein (LDL) receptor induction depends solely on the mild activation of p42/44(MAPK) signaling cascade in HepG2 cells. Unlike hepatocyte growth factor (HGF) which caused LDL receptor induction via rapid, strong, and Ras-dependent p42/44(MAPK) activation, anisomycin-induced p42/44(MAPK) activity and increased LDL receptor expression in a Ras-independent manner. Finally, we examined the role of the p42/44(MAPK) signaling cascade in LDL receptor induction by activating this kinase independently of anisomycin or HGF. By using estrogen-dependent human Raf-1 protein kinase in transient transfection assays, we show that the exclusive activation of the Raf-1/MEK-1/p42/44(MAPK) signaling cascade with antiestrogen ICI 182, 780 caused induction of LDL receptor expression to the same level as observed with either HGF or anisomycin. Consistent with the role of p42/44(MAPK), induction was strongly inhibited by pretreatment with the MEK-1/2 inhibitor PD98059. Our observation that anisomycin can use p42/44(MAPK) signaling cascade is a departure from established thinking, and the results presented shows that activation of the p42/44(MAPK) alone is sufficient to fully induce LDL receptor transcription.

Anisomycin↗
PubMed1998

Genetic complexity of the human geranylgeranyltransferase I beta-subunit gene: a multigene family of pseudogenes derived from mis-spliced transcripts.

Geranylgeranyltransferase I controls the function of a variety of cellular proteins by attaching a geranylgeranyl group to the carboxy-terminus of proteins. The purified enzyme from rat brain is comprised of two polypeptides, a catalytic alpha-subunit (GGTalpha) and a substrate-binding beta-subunit (GGTbeta). The present paper demonstrates the existence of a GGTbeta multigene family in humans by describing the presence and characterization of at least 13 pseudogenes related to this protein. Sequencing of numerous PCR-derived clones, obtained following amplification of human genomic DNA, revealed multiple, distinct but highly related sequences. All clones had a common deletion of 99-bp that conforms to the GT-AG rule of splicing in eukaryotes, and differed from the human GGTbeta cDNA sequence by multiple nucleotide substitutions. PCR amplification from mRNA, however, yielded only the sequence expected for the expressed GGTbeta protein. This apparent paradox was resolved by cloning and sequencing a complete GGTbeta-specific pseudogene. Multiple features of the cloned gene, in particular the absence of introns, presence of flanking direct repeats, and the lack of sequence similarity with the untranscribed region of the gene, indicate that this clone represents a processed pseudogene possibly resulting from a mis-spliced transcript. Multiple GGTbeta-specific pseudogenes appear to have resulted from more than one retroposition event. These results suggest a potential role for mis-splicing in the evolutionary diversity of pseudogenes.

Alkyl and Aryl Transferases↗
PubMed1997

Identification of essential nucleotides of the FP1 element responsible for enhancement of low density lipoprotein receptor gene transcription.

Low density lipoprotein (LDL) receptor gene is regulated at the transcriptional level by the intracellular level of sterols in animal cells. We have recently identified a 20 bp long region (-145 to -126), designated Footprint 1 (FP1), participating in maximal expression of the human LDL receptor gene in the absence of sterols in HepG2 cells [Mehta, K. D., Chang, R., Underwood, J., Wise, J. and Kumar, A. (1996) J. Biol. Chem ., 271, 33616-33622]. To determine the minimal FP1 sequence and to define the critical nucleotides required for function, a series of single nucleotide substitutions were introduced in the FP1 region. Twenty-three independent mutations were analyzed by transfection into HepG2 cells. These studies localize the regulatory region to 14 bp and demonstrate the requirement for essential guanine nucleotides at positions -135 and -136 for FP1 function. Furthermore, transfection studies suggest that the FP1-dependent increase in reporter gene expression is possibly mediated through interaction with the sterol-regulatory element. UV cross-linking and Southwestern blot analysis identified FP1-binding factors of approximately 50 and 125 kDa, which we have denoted p50 and p125. Mutations of the critical guanine residues (-135/-136) decreased the formation of the specific protein-DNA complex with the FP1 sequence and abolished its binding to the p125. We conclude that direct interaction of the p125 factor with these nucleotides of the FP1 element potentially contributes to FP1-dependent induction of LDL receptor gene expression.

Animals↗
PubMed1997

Detection of anti-PPD IgG antibody and PPD-induced delayed type hypersensitivity in anterior uveitis patients.

Present study relates to the results of anti-PPD IgG, anti-A60 and antinuclear antibodies and PPD-induced delayed type hypersensitivity (DTH) in 17 anterior uveitis, (AU) patients. Results of anti-PPD IgG assay revealed detection of higher mean antibody level (O.D. 0.11 +/- 0.06) compared to healthy controls (O.D. 0.04 +/- 0.03), other eye disease controls (O.D. 0.05 +/- 0.003) and leprosy controls (O.D. 0.03 +/- 0.03). Anti-A60 IgM antibody assay revealed insignificant differences in mean antibody levels between various groups. Four of 17(23.5%) AU patients and 1(5.8%) subject each, belonging to other eye disease and healthy control groups had raised anti-nuclear antibody index. Findings of PPD skin test revealed detection of moderate to strong (2 to 4+) reactivity in 14 (82%). AU patients. Conversely, 13(76%) healthy controls and 8(47%) other eye disease controls gave mild (1+) reactivity. Results of this study suggested possible role of hypersensitivity to mycobacterial antigens in pathogenesis of anterior uveitis.

Antibodies, Antinuclear↗
PubMed1996

Alpha-subunit of farnesyltransferase is phosphorylated in vivo: effect of protein phosphatase-1 on enzymatic activity.

Farnesyltransferase is a heterodimer consisting of a 49 kDa alpha-subunit and a 46 kDa beta-subunit. In this report, we demonstrate that the endogenous heterodimeric farnesyltransferase protein is phosphorylated at the alpha-subunit in vivo and phosphorylation plays a role in the regulation of farnesyltransferase activity. In vivo 32P-labeling of PC-12 cells followed by immunoprecipitation with specific anti rat alpha-subunit IgG showed a labeled alpha-subunit protein band at an expected molecular mass of 49 kDa. Treatment of PC-12 cells with protein phosphatase inhibitor, Calyculin A, resulted in a decrease in FTase activity, and phophoserine/phosphothreonine-specific protein phosphatase-1 treatment of PC-12 and GM37 cell extracts resulted in 100% and 375% increase in farnesyltransferase activity, respectively, compared to untreated extracts.

Alkyl and Aryl Transferases↗
PubMed1995

Polytuftsin: its possible effects and mechanism during macrophage activation.

Polytuftsin (PT) a 35-40 repeat unit of tuftsin (TKPR), when administered as a conjugate with the malarial peptide, ring-infected erythrocyte surface antigen (RESA), enhanced antigen-induced lymphoproliferation and antibody levels in mice as compared to RESA alone. This enhancement was unrelated to the H-2 background of the animals. The present study was undertaken with a view to understanding the mechanism(s) responsible for this immune enhancement. Peritoneal adherent cells (PAC) from H-2b and H-2d mice were incubated with RESA alone, PT-conjugated RESA, a physical mixture of RESA + PT and PT alone. They were subsequently evaluated for I-A expression using monoclonal antibodies and flow cytometry as well as cell-ELISA. Significant increase in I-A expression on PAC was observed in all 4 groups as compared to untreated cells. Whereas cells treated with PT-conjugated RESA showed highly significant increase in I-A (P < 0.001), the other groups showed moderate increase (P < 0.05). This enhancement was attributable to increase in the number of I-A-positive cells rather than I-A molecules per cell. Moreover, IL-1 release, as assayed by bioassay, was significantly higher in cells treated with conjugated RESA as compared to cells treated with RESA or PT alone (P < 0.05). Thus, it would appear that PT-conjugated RESA peptide of the malarial antigen selectively enhances major histocompatibility complex (MHC) class II molecules on antigen-presenting cells (APC) and may therefore improve immune functions by stimulating better antigen presentation and proliferation of T cells.

Adjuvants, Immunologic↗
PubMed1994

Role of routine estimation of creatinine clearance in patients with liver cirrhosis.

BACKGROUND: Frequent occurrence of renal dysfunction without azotemia in patients with decompensated cirrhosis, and its prognostic and therapeutic importance, are not well appreciated. METHODS: Creatinine clearance (CrCl), 24-hour urinary sodium excretion, fractional excretion of sodium, and urine flow were estimated in 68 non-azotemic uncomplicated cirrhosis patients; all these patients were followed up for a period of 6 months. Eighteen patients with ascites and edema were treated with large volume paracentesis without colloid replacement and renal function was evaluated before, and 48 hours and 7 days later. Eight patients with abnormal CrCl were treated with 10 mg of enalapril daily and CrCl estimated at the end of 7 days. RESULTS: Of 68 patients, 22 had CrCl > 80 mL/min (Group I), 21 had CrCl of 50-80 mL/min (Group II) and 25 had CrCl < 50 mL/min (Group III). Renal dysfunction correlated with Child's class. During a mean follow up period of 180 days, patients in Groups II and III had higher mortality rates than those in Group I (23.8% and 36.0% vs 9.1%; p < 0.001). Following large volume paracentesis, CrCl decreased at 48 h and continued to be low at the end of 7 days even though blood urea nitrogen and serum creatinine remained normal. CrCl improved with 10 mg enalapril at 7 days (46.5 +/- 15.4 to 73.2 +/- 19.7 mL/min; p < 0.05). CONCLUSION: More than two-thirds of patients with advanced cirrhosis have abnormal CrCl despite normal blood urea nitrogen and serum creatinine; they also have a higher mortality as compared with patients with normal CrCl. CrCl decreases after large volume paracentesis even though blood urea nitrogen and serum creatinine remain unchanged. Enalapril improves CrCl in patients with liver cirrhosis but its exact clinical utility needs further evaluation.

Adult↗
PubMed1993

Pancreatic ascites.

Pancreatic ascites is rarely considered in the differential diagnosis of exudative ascites, and is in fact missed in a majority of patients. Eleven cases of pancreatic ascites are described. 63.6% were chronic alcoholics. The clinical diagnosis was cirrhosis of liver (5/11), tuberculous peritonitis (5/11) or malignant peritonitis (1/11). In all patients ascites was exudative and the ascitic fluid amylase was markedly elevated (mean +/- SD: 7815 +/- 6507 SU/dl). Endoscopic retrograde pancreatography (ERP) performed in 4 patients demonstrated the site of leak in 3. Laparoscopy performed in 8 patients helped in the diagnosis of pancreatic ascites in all, which was confirmed on histology. Laparoscopy ruled out other causes of exudative ascites in all. We conclude that pancreatic ascites should be suspected in any patient with exudative ascites, especially chronic alcoholics and that ascitic fluid amylase should be routinely performed in all such cases. High ascitic fluid content is virtually diagnostic of pancreatic ascites. ERP is essential in preoperative assessment or planning endoscopic treatment. Laparoscopy is an invaluable investigation to rule out other conditions such as tuberculous or malignant peritonitis and cirrhosis of liver.

Adolescent↗
PubMed1993

Alternate-day therapy with omeprazole for duodenal ulcer.

BACKGROUND: Maximal acid suppression produced by a single dose of 20 mg omeprazole has been reported to persist for over 24 hours, with acid secretion returning to normal after 2 days. OBJECTIVES: (i) To study the effect of single oral dose of 20 mg omeprazole on maximal acid output (MAO) and peak acid output (PAO) in duodenal ulcer patients and healthy volunteers. (ii) To compare the efficacy of omeprazole 20 mg daily versus 20 mg on alternate days in the treatment of duodenal ulcer. STUDY DESIGN: Open randomized comparative trial. METHODS: MAO and PAO were estimated in five duodenal ulcer patients and five healthy volunteers before, and 24 hours and 48 hours after, a single 20 mg oral dose of omeprazole. Fifty eight consecutive uncomplicated duodenal ulcer patients were randomized to receive omeprazole 20 mg either daily (n = 30) or on alternate days (n = 28) for four weeks. The two groups were matched for age, sex, duration of ulcer symptoms, smoking, NSAID use, and ulcer size at entry. Symptom scores using a pre-defined scoring system and endoscopic ulcer healing rates were evaluated at 2 and 4 weeks. RESULTS: MAO and PAO showed significant reduction in both duodenal ulcer patients and healthy controls 24 hours after 20 mg omeprazole. Reduction at 48 hours was significant in duodenal ulcer patients but not in controls. Endoscopic healing rates of duodenal ulcer at 2 and 4 weeks were 80% and 93.3% respectively in the daily treatment group and 71.4% and 85.7% respectively in the alternate-day treatment group. These differences were not statistically significant. CONCLUSION: 20 mg omeprazole on alternate days is as effective as 20 mg daily (i) in suppressing MAO and PAO and (ii) in the treatment of duodenal ulcer.

Adult↗
PubMedDate not supplied

Laparoscopic gastropexy for chronic intermittent gastric volvulus.

The traditional surgical treatment of chronic gastric volvulus involves laparotomy for derotation of the stomach and its fixation to the patients. We describe a 36-year-old man with organoaxial gastric volvulus who was treated successfully with laparoscopic gastropexy. He is asymptomatic four months later.

Adult↗