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S Aggarwal

Publications and source records attributed to S Aggarwal.

At least 73 records · Page 4Linked to original sources
PubMed1998

A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos.

Several studies have characterized the upstream regulatory region of c-fos, and identified cis-acting elements termed the cyclic AMP (cAMP) response elements (CREs) that are critical for c-fos transcription in response to a variety of extracellular stimuli. Although several transcription factors can bind to CREs in vitro, the identity of the transcription factor(s) that activates the c-fos promoter via the CRE in vivo remains unclear. To help identify the trans-acting factors that regulate stimulus-dependent transcription of c-fos via the CREs, dominant-negative (D-N) inhibitor proteins that function by preventing DNA binding of B-ZIP proteins in a dimerization domain-dependent fashion were developed. A D-N inhibitor of CREB, termed A-CREB, was constructed by fusing a designed acidic amphipathic extension onto the N terminus of the CREB leucine zipper domain. The acidic extension of A-CREB interacts with the basic region of CREB forming a coiled-coil extension of the leucine zipper and thus prevents the basic region of wild-type CREB from binding to DNA. Other D-N inhibitors generated in a similar manner with the dimerization domains of Fos, Jun, C/EBP, ATF-2, or VBP did not block CREB DNA binding activity, nor did they inhibit transcriptional activation of a minimal promoter containing a single CRE in PC12 cells. A-CREB inhibited activation of CRE-mediated transcription evoked by three distinct stimuli: forskolin, which increases intracellular cAMP; membrane depolarization, which promotes Ca2+ influx; and nerve growth factor (NGF). A-CREB completely inhibited cAMP-mediated, but only partially inhibited Ca2+- and NGF-mediated, transcription of a reporter gene containing 750 bp of the native c-fos promoter. Moreover, glutamate induction of c-fos expression in primary cortical neurons was dependent on CREB. In contrast, induction of c-fos transcription by UV light was not inhibited by A-CREB. Lastly, A-CREB attenuated NGF induction of morphological differentiation in PC12 cells. These results suggest that CREB or its closely related family members are general mediators of stimulus-dependent transcription of c-fos and are required for at least some of the long-term actions of NGF.

Amino Acid Sequence↗
PubMed1998

A possible role for multidrug resistance-associated protein in the secretion of basic fibroblast growth factor by osteogenic sarcoma cell line (MG-63).

Basic fibroblast growth factor (bFGF) lacks signal sequence and therefore the mechanism of its secretion is unknown. Multidrug resistance-associated protein (MRP) has been shown to transport a variety of molecules. Therefore, in this study we examined the role of MRP in the secretion of bFGF by osteogenic sarcoma MG-63 cells which spontaneously secrete bFGF. We show that MG-63 cells express MRP both at the protein and at the mRNA level. Furthermore, probenecid (a putative inhibitor of transport activity of MRP), in a concentration-dependent manner, inhibited secretion of bFGF from MG-63 cells with concomitant increase in intracellular contents of bFGF. These results suggest that MRP may have a possible role in the secretion of bFGF.

ATP-Binding Cassette Transporters↗
PubMed1998

Management of teeth with open apices and necrotic pulps with single visit apexification: 3 representative cases.

Apexification is the most widely accepted procedure for the treatment of nonvital immature teeth. Single visit apexification is less time consuming, more economical and an easily acceptable technique with the aim of inducing the formation of a hard tissue barrier, thus allowing proper condensation of gutta percha in the root canal. Factors considered during this procedure are: i. Debridement of root canal minimizing the infection and filling the root canal space with resorbable calcification inducing material i.e. Ca(OH)2. ii. Minimal mechanical intervention to maintain the integrity and vascularity of apical region. Once filled, Ca(OH)2 was not changed again and the treated tooth was examined only radiographically till the desired apical closure was achieved. Three representative cases treated with this single visit apexification technique are discussed here. In all the cases successful apical closure of different types was achieved. Treatment was then concluded with gutta percha obturation in all the cases with successful follow up.

Adolescent↗
PubMed1997

Inhibitors of in vitro mineralization from flexor tendons of rabbits and their role in biological mineralization.

Studies demonstrate that flexor tendons contain loosely associated biomolecules which inhibit its mineralization under physiological conditions. Based upon their molecular weights, these inhibitory biomolecules, could be classified into two categories, having molecular weights less than and greater than 13,000 daltons. The main inhibitory biomolecule was found to be an acidic polypeptide having molecular weight of 12,400 daltons.

Animals↗
PubMed1997

Programmed cell death (apoptosis) in cord blood lymphocytes.

Cord blood lymphocytes are functionally immature and have deficient immune responses. In order to determine whether the process of programmed cell death is distinct between cord blood and peripheral blood lymphocytes, we analyzed the expression of fas and bax (apoptosis promoting genes) and bcl-2 and bcl-xL (apoptosis inhibiting genes) at protein or mRNA levels using flow cytometry and quantitative PCR methods, respectively. The susceptibility of T cell subsets from cord blood and adult peripheral blood to undergo apoptosis following restimulation with anti-CD3 or anti-Fas monoclonal antibodies was also studied. We observed that cord blood T cell subsets expressed lower levels of Fas and Bcl-2, a low bcl-2/bax ratio, and higher bcl-xL compared to peripheral blood. Additionally, upon primary stimulation with anti-CD3, cord blood T cell subsets were more resistant to apoptosis compared to peripheral blood. In contrast, rechallenge of previously stimulated lymphocytes with anti-CD3 monoclonal antibody triggered apoptosis in a larger proportion of T cells from cord blood as compared to peripheral blood, whereas the number of T cells undergoing anti-Fas-induced programmed cell death were lower in cord blood compared to peripheral blood.

Adult↗
PubMed1997

Altered expression and function of P-glycoprotein (170 kDa), encoded by the MDR 1 gene, in T cell subsets from aging humans.

Aging is associated with progressive T cell-mediated immune deficiency, increased frequency of infections, and autoimmune phenomena. P-glycoprotein (P-gP), a 170-kDa glycoprotein, is a member of a superfamily of ATP-binding cassette transport proteins that has been shown to express on cells of the immune system and suggested to play a role in secretion of certain cytokines and cytotoxic molecules. Because aging is associated with altered secretion of cytokines, in this investigation we examined the expression and function of P-gP in CD4+ and CD8+ T cells and their "memory" and "naïve" subpopulations in peripheral blood from healthy aging and young subjects. P-glycoprotein expression was analyzed at the protein levels by dual- or triple-color flow cytometric analysis, using monoclonal antibodies against P-gP (MRK16), and at the mRNA level by quantitative reverse-transcriptase polymerase chain reaction. The efflux function of P-gP was measured by intracellular accumulation of rhodamine-123 (Rh123; a substrate for P-gP) in the presence or absence of cyclosporin A (which binds to P-gP and inhibits its efflux function). The data show increased expression of P-gP at both the protein and the mRNA levels in aging lymphocytes. Increased P-gP expression, at the protein level, was also observed in naïve cell subpopulations from aging CD4+ and CD8+ T cell subsets compared to those from young controls. An increase in P-gP function, as measured by the ability of T cell subsets to efflux Rh123, was observed in aging CD4+ and CD8+ T cell subsets and their naïve and memory subpopulations. These data suggest that altered P-gP expression and function in aging may play a role in changes in immune response, including cytokine secretion, associated with human aging.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Use of carbidopa-levodopa in a patient with hydrocephalus and frozen movement.

While movement disorders are frequently encountered after brain injuries, and may create a host of complicated problems for the clinician, only a few cases of Parkinsonism associated with hydrocephalus have ever been described in the literature. Parkinsonism-like syndrome complicating hydrocephalus is a rare disorder, especially when associated with nontumoral aqueductal stenosis. Yet as this case report discusses, hdyrocephalus-induced Parkinsonism may be responsive to levodopa-carbidopa administration. This report describes a perplexing case of persistent akinesis following corrective surgery for aqueductal stenosis and the subsequent response to levodopa-carbidopa administration. We present the case of a 28-year-old male with a history of non-tumoral aqueductal stenosis diagnosed at age 12. As a child, he underwent a ventriculo-peritoneal shunt placement for obstructive hydrocephalus followed by multiple shunt revisions over the next several years. Sixteen years after his initial shunt placement, the patient presented with a decline in mental status. A third ventriculocisternostomy was performed rather than another shunt revision. Following surgery, the patient remained obtunded, and displayed profound hypokinesis, best described as freezing in movement. Upon admission to a rehabilitation unit 2 weeks later, he had made only minimal progress. A SPECT (single-photon emission computed tomography) brain scan revealed decreased basal ganglia perfusion. Levodopa/carbidopa therapy was initiated and within 2 weeks, the patient showed improvement in speed of movement, facial expression and verbal output. Eight weeks later, the patient could independently complete his basic activities of daily living and demonstrated little, if any, disordered movement. This report illustrates how dopaminergic agents may be useful in cases of hypokinesis following corrective surgery for aqueductal stenosis. SPECT may further aid in the diagnosis and management of Parkinsonism-like syndromes in brain injuries.

Adult↗
PubMed1997

Spontaneous rupture of normal spleen.

Spontaneous rupture of a normal spleen is very rare. We report a case where multiple episodes of spontaneous bleeding from the spleen gave an 'onion skin' appearance on CT scan.

Humans↗
PubMed1996

Abnormal expression of a 170-kilodalton P-glycoprotein encoded by MDR1 gene, a metabolically active efflux pump, in CD4+ and CD8+ T cells from patients with human immunodeficiency virus type 1 infection.

Peripheral blood CD4+ and CD8+ T cells from 16 patients with HIV-1 infection, 8 each with CD4+ T cell counts of > 200/mm3 (group I) and with CD4+ T cell counts of < 200/mm3 (group II), and 8 age- and sex-matched controls, were examined for the expression of P-glycoprotein (P-gp), a 170-kDa phosphoglycoprotein encoded by the MDR1 gene, using dual-color flow cytometric analysis. The function of P-glycoprotein was assessed by the accumulation of rhodamine-123 (Rh123) dye in the presence or absence of cyclosporin A (which inhibits Rh123 efflux). A significantly increased proportion of CD4+ T cells from patients with HIV-1 infection expressed P-glycoprotein as compared to controls, resulting in a significantly increased ratio of the proportions of CD4+P-gp+/CD8+P-gp+ cells. The ratio of CD4+P-gp+/CD8+P-gp+ in group II patients was significantly higher (p = 0.02) than in group I patients, suggesting a progressive increase in P-gp expression with the advancement of HIV-1 infection. The proportions of CD4+P-gp+ and CD8+P-gp+ T cells did not differ significantly between those who received AZT and those who were not treated with AZT. Contrary to expectation, both CD4+ and CD8+ T cells from patients accumulated significantly more Rh123 as compared to controls. Furthermore, cyclosporin A failed to increase intracellular accumulation of Rh123 in CD4+ and CD8+ T cells from patients. These data suggest a functionally defective P-gp expression in HIV-1 infection that appears to increase with the progression of HIV-1 infection. A study of a large number of patients with HIV-1 infection is needed to determine the effects of opportunistic infection and antiretroviral therapy on the expression of P-gp and to determine whether the expression of P-gp could serve as another surrogate marker for the progression of HIV-1 infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Altered endothelin homeostasis in patients undergoing liver transplantation.

The liver is a major site of synthesis, clearance, and actions of the powerful vasoactive peptide endothelin-1 (ET-1). We investigated the role of the liver in ET-1 homeostasis by comparing circulating and hepatic ET-1 levels and hepatic ET receptors in patients undergoing orthotopic liver transplantation (OLTx) for end-stage liver disease (ESLD) with those in patients undergoing liver resection for focal lesions with otherwise normal hepatic synthetic function. Central venous and radial arterial blood was drawn immediately after induction of anesthesia (point I), 10 minutes before beginning of resection or the anhepatic stage (point II), and 30 minutes after completion of resection or reperfusion of the grafted liver (point III). Portal and hepatic venous blood was drawn at points II and III. Plasma ET-1 levels were higher in ESLD patients than in resection patients. Plasma ET-1 levels rose both during resection and transplantation; the increase in ET-1 was more pronounced during transplantation. In ESLD patients, hepatic venous ET-1 was higher than portal venous ET-1, suggesting reduced clearance and/or enhanced synthesis of the peptide in the cirrhotic liver. Conversely, hepatic venous ET-1 was lower than portal venous ET-1 in resection patients at all time points and at point III in the ESLD patients. Hepatic concentration of ET-1 was greater and the capacity of the liver to catabolize ET-1 was reduced in ESLD patients as compared to the resection patients. Further, hepatic ET receptor density was higher in ESLD than in resection patients. These results suggest that the cirrhotic liver may contribute to elevated plasma ET-1 in ESLD. Considering its potent hemodynamic and metabolic effects in the liver, increased hepatic ET-1 and ET receptors and plasma ET-1 could play a role in the pathophysiology of liver disease and perioperative complications of OLTx.

Adult↗
PubMed1996

Benzoyl peroxide modulates gene expression by epigenetic mechanism in mouse epidermal JB6 cells.

The mechanism by which an oxidant tumor promoter benzoyl peroxide (BP) influences signal transduction, was studied in promotion insensitive (P-), promotion sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. The basal levels of antioxidant enzymes CuZn-superoxide dismutase and catalase were higher in P+ and Tx JB6 cells. BP decreased the activities of these enzymes transiently in P+ and Tx cells, but induced them in P- JB6 cells. BP increased poly ADPR polymerase activity accompanied by a drop in NAD+ levels more significantly in P- JB6 cells, but did not affect PKC activity. It induced c-jun and c-fos gene expression in JB6 variants but to different extents, suggesting that it mediates its effects via genetic- epigenetic mechanism(s).

Animals↗
PubMed1996

Median nerve somatosensory evoked potentials correlation with physical parameters.

Somatosensory evoked potentials (SEPs) following median nerve stimulation of 25 medical students were recorded along with their height, age and upper limb length. Three major positive and negative peaks were recorded. P1 (16 msec), N1 (20 msec), P2 (28 msec), N2 (33 msec), P3 (43 msec), N3 (50 msec). Significant correlation (P value < 0.05) of N1 and P1 with height and limb length was observed. It is therefore suggested that studies involving SEPs must include physical parameters like age, height and limb length. Our future studies will indicate the accurate correction factor for these physical parameters.

Adolescent↗