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Biomedical subjects

G S Sidhu

Publications and source records attributed to G S Sidhu.

At least 19 recordsLinked to original sources
PubMed2005

Alkaline stress-induced apoptosis in human pulmonary artery endothelial cells.

The effect of alkaline stress, or an increase in extracellular pH (pHext), on cell viability is poorly defined. Human pulmonary artery endothelial cells (HPAEC) were subjected to alkaline stress using different methods of increasing pHext. Viability and mode of cell death following alkaline stress were determined by assessing nuclear morphology, ultrastructural features, and caspase-3 activity. Incubation of monolayers in media set to different pHext values (7.4-8.4) for 24-h induced morphological changes suggesting apoptosis (35-45% apoptotic cells) following severe alkaline stress. The magnitude of apoptosis was related to the severity of alkaline stress. These findings were confirmed with an assessment of ultrastructural changes and caspase-3 activation. While there was no difference in the intracellular calcium level ([Ca(2+)](i)) in monolayers set to pHext 7.4 versus 8.4 following the first hour of alkaline stress, blockade of calcium uptake with the chelator, EGTA, potentiated the magnitude of apoptosis under these conditions. Potentiation of apoptosis was reduced by calcium supplementation of the media. Finally, alkaline stress was associated with an increase in intracellular pH. This is the first report of apoptosis following alkaline stress in endothelial cells in the absence of other cell death stimuli.

Apoptosis↗
PubMed2002

Migratory pulmonary infiltrates in a patient with rheumatoid arthritis.

The case history is described of an elderly man with rheumatoid arthritis receiving treatment with sulfasalazine and the cyclooxygenase-2 inhibitor celecoxib who presented with severe shortness of breath, cough, and decreased exercise tolerance. The chest radiograph showed unilateral alveolo-interstitial infiltrates and a biopsy specimen of the lung parenchyma showed changes consistent with acute eosinophilic pneumonia. Antibiotic treatment was unsuccessful, but treatment with steroids and discontinuation of sulfasalazine and celecoxib resulted in a marked clinical improvement confirmed by arterial blood gas analysis. The condition may have developed as an adverse reaction either to sulfasalazine or to celecoxib, although hypersensitivity to the latter has not previously been reported.

Aged↗
PubMed2001

Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling?

OBJECTIVES: To determine whether repeat biopsy is necessary when the diagnosis of high-grade prostatic intraepithelial neoplasia (HGPIN) is made with a 12-core biopsy. Repeated biopsy has been recommended for individuals with HGPIN noted on sextant prostate biopsy because of the high likelihood of cancer detection. Recently, we have recommended the routine use of 12 cores, rather than 6, to improve cancer detection. METHODS: The charts of all patients undergoing prostate biopsy during a 2-year period at the Manhattan Veterans Administration Medical Center were reviewed. Patients diagnosed with HGPIN on a 12-core biopsy were identified, and those undergoing a repeat 12-core biopsy within 1 year of the initial biopsy were evaluated to determine the rate of cancer detection. RESULTS: A total of 619 men underwent biopsy during the study period. Of 103 men diagnosed with HGPIN, 43 underwent a repeat biopsy within 1 year at the discretion of the managing urologist. The mean age and median prostate-specific antigen level of those undergoing a repeat biopsy was 65.5 years and 5.37 ng/mL, respectively. At the time of the repeat biopsy, 1 patient was found to have cancer (2.3%), 20 had HGPIN (46.5%), 20 had benign pathologic findings (46.5%), and 1 patient (2.3%) had atypical small acinar proliferation. CONCLUSIONS: A repeat biopsy after the diagnosis of HGPIN on 12-core prostate biopsy rarely results in cancer detection. In the absence of other factors increasing the suspicion of cancer, immediate repeat biopsy for HGPIN diagnosed on a 12-core biopsy is unnecessary.

Aged↗
PubMed2001

Synchronous gastric adenocarcinomas in a patient with Meckel's diverticulum.

Meckel's diverticulum, which is the most common congenital anomaly of the gastrointestinal tract, occurs when the vitelline duct persists past the 7th week of gestation. Although complications may occur in 8% to 22% of patients with Meckel's diverticula, adenocarcinoma is very uncommon. We describe a patient with early gastric cancer who was incidentally found to have a superficial adenocarcinoma arising from ectopic gastric mucosa within a Meckel's diverticulum. To the best of our knowledge, synchronous gastric adenocarcinoma in a patient with Meckel's diverticulum has not been previously reported.

Adenocarcinoma↗
PubMed2000

A study of energy and effective atomic number dependence of the exposure build-up factors in biological samples.

A theoretical method is presented to determine the gamma-radiation build-up factors in various biological materials. The gamma energy range is 0.015-15.0 MeV, with penetration depths up to 40 mean free paths considered. The dependence of the exposure build-up factor on incident photon energy and the effective atomic number (Zeff) has also been assessed. In a practical analysis of dose burden to gamma-irradiated biological materials, the sophistication of Monte Carlo computer techniques would be applied, with associated detailed modelling. However, a feature of the theoretical method presented is its ability to make the consequences of the physics of the scattering process in biological materials more transparent. In addition, it can be quickly employed to give a first-pass dose estimate prior to a more detailed computer study.

Models, Biological↗
PubMed1999

Picroliv -- a natural product protects cells and regulates the gene expression during hypoxia/reoxygenation.

Cellular adaptation to hypoxia involves regulation of specific genes such as vascular endothelial growth factor (VEGF), erythropoietin (EPO) and hypoxia inducible factor (HIF)-1 . In this study, we have evaluated the protective effect of picroliv (a purified iridoid glycoside fraction from roots of Picrorhiza kurrooa with hepatoprotective, anti-inflammatory and antioxidant properties) against hypoxic injury by examining lactate dehydrogenase (LDH) release in Hep 3B and Glioma cells. The expression of hypoxia regulated genes, VEGF and HIF-1 was studied in human umbilical vein endothelial cells (HUVEC), Hep 3B and Glioma cells. Picroliv reduced the cellular damage caused by hypoxia as revealed by a significant reduction in LDH release compared to untreated control. The expression of VEGF and HIF-1 subunits (HIF-1alpha and HIF-1beta) was enhanced by treatment with picroliv during normoxia and hypoxia in HUVEC and Hep 3B cells and on reoxygenation the expression of these genes was significantly reduced as revealed by mRNA analysis using RT-PCR. Simultaneous treatment with picroliv during hypoxia inhibited VEGF and HIF-1 expression in Glioma cells whereas the expression was not reduced by picroliv treatment during reoxygenation as evidenced by both RT-PCR and Northern hybridization. VEGF expression as revealed by immunofluorescence studies correlates well with the regulations observed in the mRNA expression. We have also examined the kinase activity of tyrosine phosphorylated proteins and protein kinase C (PKC) in Glioma cells treated with picroliv during hypoxia/reoxygenation. A selective inhibition of protein tyrosine kinase activity leading to tyrosine dephosphorylation of several proteins including 80 kd protein, and a reduction in PKC was seen in cells treated with picroliv and hypoxia. These findings suggest that picroliv may act as a protective agent against hypoxia/reoxygenation induced injuries, and the underlying mechanism may involve a novel signal transduction pathway.

Base Sequence↗
PubMed1999

Thymosin beta4 accelerates wound healing.

Angiogenesis is an essential step in the repair process that occurs after injury. In this study, we investigated whether the angiogenic thymic peptide thymosin beta4 (Tbeta4) enhanced wound healing in a rat full thickness wound model. Addition of Tbeta4 topically or intraperitoneally increased reepithelialization by 42% over saline controls at 4 d and by as much as 61% at 7 d post-wounding. Treated wounds also contracted at least 11% more than controls by day 7. Increased collagen deposition and angiogenesis were observed in the treated wounds. We also found that Tbeta4 stimulated keratinocyte migration in the Boyden chamber assay. After 4-5 h, migration was stimulated 2-3-fold over migration with medium alone when as little as 10 pg of Tbeta4 was added to the assay. These results suggest that Tbeta4 is a potent wound healing factor with multiple activities that may be useful in the clinic.

Animals↗
PubMed1999

Arnebin-1 accelerates normal and hydrocortisone-induced impaired wound healing.

Wound healing involves inflammation, cell proliferation, matrix deposition, and tissue remodeling. Interaction of different cells, extracellular matrix proteins, and their receptors are mediated by cytokines and growth factors during wound healing. In this study, we have evaluated the effect of arnebin-1, a natural product isolated from Arnebia nobilis, on normal and impaired wound healing in cutaneous punch wound model. Arnebin-1 was applied topically daily on wounds of hydrocortisone-treated or untreated animals. Arnebin-1 significantly accelerated healing of wounds with or without hydrocortisone treatment as revealed by a reduction in the wound width and gap length compared with controls. Arnebin-1 treatment promoted the cell proliferation, migration, and vessel formation to form a thick granulation tissue and re-epithelialization of the wounds. An increase in the synthesis of collagen, fibronectin and transforming growth factor-beta1 was seen in arnebin-1-treated wounds compared with the untreated control. As transforming growth factor-beta1 is known to enhance wound healing, and associated with the wound healing defect in hydrocortisone-treated wounds, the enhanced expression of transforming growth factor-beta1 at both translational and transcriptional level by arnebin-1 may be responsible for the enhancement of wound healing during normal and impaired wound repair. These studies suggest that arnebin-1 could be developed as a potent therapeutic agent for wound healing in steroid-impaired wounds.

Animals↗
PubMed1999

Role of vacuolar H(+)-ATPase in interferon-induced inhibition of viral glycoprotein transport.

We have shown previously that interferon-beta (IFN-beta) induces the alkalinization of trans-Golgi network (TGN) and inhibits the transport of G protein of vesicular stomatitis virus (VSV) in L(B) cells and gD protein of herpes simplex virus (HSV-1) in LMtk- cells transfected with gD cDNA. The vacuolar H(+)-ATPase (V-ATPase) is responsible for maintaining pH in TGN, and V-ATPase-mediated acidification is required for normal transport of proteins. To examine whether alkalinization caused by IFN is mediated through V-ATPase, the activity of V-ATPase was determined in IFN-treated cells by coupling ATP hydrolysis to NADH oxidation. Bafilomycin (Baf) was used as positive control, as it specifically inhibits V-ATPase. The activity of V-ATPase was reduced in IFN-treated or Baf-treated cells compared with untreated cells. Doses of IFN-beta or Baf that neither alter pHi nor inhibit the transport of viral glycoproteins concomitantly inhibited the transport of G and gD proteins in TGN, as demonstrated by indirect immunofluorescence studies, and raised the pH of TGN as demonstrated by a decrease in the uptake of DAMP. Further, the effect of Baf on IFN-induced antiviral activity against VSV was examined to correlate the biologic significance of these findings. Data showed that Baf significantly enhances (5-50-fold) the IFN-induced antiviral activity as demonstrated by viral titers from supernatants. These findings suggest that the inhibition of transport of G and gD proteins by IFN-beta, may be related to the inhibition of V-ATPase-mediated acidification of TGN.

Animals↗
PubMed1999

Acceleration of viral replication and up-regulation of cytokine levels by antimalarials: implications in malaria-endemic areas.

Antimalarial drugs are widely used in malaria endemic areas, both for chemoprophylaxis and also empirically to treat patients presenting with fever. Previously, we have reported that chloroquine enhances the severity of Semliki forest virus (SFV) and encephalomyocarditis virus infection. The studies presented herein show that a broad spectrum of antimalarial drugs augmented the replication of SFV in mice, concomitant with greater tissue damage and up-regulation of mRNA levels of various inflammatory cytokine genes, including interleukin-1 receptor antagonist (IL-1Ra), II-1alpha, IL-1beta, IL-6, IL-12p40, and interferon-gamma inducing factor. Furthermore, chloroquine enhances IL-1Ra production in RAW cells in vitro. Since IL-1Ra is known to be up-regulated in a number of viral infections, we propose that a further enhancement of its expression by antimalarials may be responsible for the increased severity of viral infection in our studies. Thus, the widespread use of antimalarials in malaria-endemic areas may predispose the population to viral infections. Further studies are in progress to delineate mechanism(s) involved in cytokine up-regulation and acceleration of viral replication.

Alphavirus Infections↗
PubMed1998

Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound healing.

In wound healing, lymphoid cells release soluble factors that attract fibroblasts and macrophages, initiating repair, endothelial cell migration, angiogenesis, and matrix production. We analyzed the effect of thymosin alpha1 (Talpha1) on endothelial cell migration, angiogenesis, and wound healing. Talpha1, a 28 amino acid peptide initially isolated from the thymus, enhanced the morphologic differentiation of endothelial cells and was a potent chemoattractant for endothelial cells and monocytes in vitro. In vivo, Talpha1 stimulated angiogenesis in a subcutaneous model. When given either topically or i.p., it accelerated wound healing in a punch model, demonstrating that Talpha1 promotes angiogenesis and wound healing.

Adjuvants, Immunologic↗
PubMed1998

Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin.

Angiogenesis is a crucial step in the growth and metastasis of cancers. Curcumin inhibits tumor initiation and growth. We analyzed the effect of curcumin on endothelial cell migration, attachment, and tube formation on Matrigel. Curcumin had no effect on endothelial cell migration or attachment to either plastic or Matrigel. Curcumin treatment resulted in a dose-dependent inhibition of tube formation when the cells were treated before plating or at the time of plating on Matrigel. Curcumin treatment also caused the preformed tubes to break down. Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice. The role of metalloproteinases has been shown to be important in angiogenesis; therefore, zymography was performed to determine whether curcumin affected protease activity. Zymographs of curcumin-treated culture supernatants showed a decrease in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases. Western and Northern analysis showed a dose-dependent decrease in the protein expression and transcript of 72 kDa, indicating that curcumin may be exerting its inhibitory effect at both the transcriptional and posttranscriptional level. These findings suggest that curcumin acts as an angiogenesis inhibitor by modulating protease activity during endothelial morphogenesis. Curcumin could be developed as an antiangiogenic drug.

Animals↗
PubMed1997

Role of psychiatric disorders in self-inflicted periodontal injury: a case report.

Self-inflicted or factitious injuries (FI) are not uncommon in psychiatric patients. In general, this kind of behavior is linked to secondary gain. However, the role of underlying psychiatric illness should not be overlooked. Usually, the diagnosis of factitious injury can be confirmed by a careful medical-dental history, clinical appearance of the lesion, laboratory investigations, and response to established treatment protocol. A case is presented in which repetitive injurious behavior resulted in rapid periodontal attachment loss. The lesion responded well to conservative periodontal treatment. The role of underlying psychiatric morbidity leading to repetitive self-injurious behavior is discussed.

Adolescent↗
PubMed1996

Curcumin inhibits the proliferation and cell cycle progression of human umbilical vein endothelial cell.

We have studied the effect of curcumin (diferuloylmethane), a major component of the food flavor turmeric, on the proliferation and cell cycle progression of human umbilical vein endothelial cells (HUVEC). Curcumin inhibited the DNA synthesis of HUVEC as revealed by [3H]thymidine incorporation in a dose-dependent manner without significantly affecting the viability of the cells. The growth of HUVEC stimulated with fibroblast growth factor (FGF) and endothelial growth supplement (ECGS) was also inhibited by curcumin. Addition of curcumin to HUVEC resulted in an accumulation of > 46% of the cells in early S-phase, as determined by the FACS analysis. Pulse labeling studies with [3H]thymidine demonstrated that curcumin affected cells that were actively undergoing DNA synthesis. The de-novo synthesis of thymidine depends on thymidine kinase (TK) enzyme. Curcumin caused a significant loss of TK activity, which may be one of the possible mechanism(s) for the inhibition of DNA synthesis activity of HUVEC by curcumin. These studies have revealed a unique mode of action of curcumin whereby it effectively blocked the cell cycle progression during S-phase by inhibiting the activity of TK enzyme. The migration, proliferation and differentiation of HUVEC leads to angiogenesis, which facilitates the tumor initiation and promotion. Since curcumin inhibited the proliferation of HUVEC, it could turn out to be a very useful compound for the development of novel anti-cancer therapy.

Antineoplastic Agents↗
PubMed1996

Enhanced biosynthesis of extracellular matrix proteins and TGF-beta 1 by polyinosinic-polycytidylic acid during cutaneous wound healing in vivo.

In our previous study, we have shown that polyinosinic-polycytidylic acid (poly I:C), a double-stranded RNA, and a potent inducer of interferon, enhanced the wound healing in rats and mice. Increased levels of laminin and collagen, and greater influx of dermal fibroblasts were observed in poly I:C-treated wounds as compared to untreated wounds (Bhartiya et al., 1992, J. Cell. Physiol., 150:312-319). In this study, we have explored the mechanism of enhanced wound healing by poly I:C in rats. Poly I:C (1 mg/kg) in phosphate buffered saline was injected intraperitoneally 18 h prior to wound healing, and the animals were sacrificed on day 3 postwounding. Immunofluorescence studies showed increased expression of adhesion molecules that includes ICAM-1 (intercellular adhesion molecule-1;CD54) and VCAM-1 (vascular cell adhesion molecule; CD 106) in poly I:C-treated wounds as compared to untreated control. Poly I:C treatment resulted in an increase in the mRNA levels of collagen type 1 (alpha), collagen III, laminin B1, and transforming growth factor-beta 1(TGF-beta 1) in wounds compared to untreated wounds as demonstrated by in situ hybridization and PCR analysis. These studies suggests that poly I:C upregulates the biosynthesis of adhesion molecules, extracellular matrix proteins (ECM), and TGF-beta 1 in the wound bed. Adhesion molecules and ECM play a major role in wound healing, and TGF-beta 1 has been known to be a potent wound healer. Therefore, the increased expression of these molecules may play a role in the enhanced healing by poly I:C observed in rats.

Animals↗
PubMed1996

Brefeldin A inhibits the antiviral action of interferon against encephalomyocarditis virus.

Brefeldin A (BFA), a unique fungal metabolite of a 13-membered lactone ring, exhibits various biological actions, including antitumor, antifungal and antiviral activities. In the present study, mouse LB cells were treated with various concentrations of interferon (IFN) and/or BFA overnight and infected with encephalomyocarditis virus (EMCV) after removal of IFN and BFA. Doses of BFA which neither inhibit the metabolism of the cell nor the infectivity of EMCV, decreased the IFN-induced antiviral activity against EMCV as demonstrated by virus titer from supernatants. Since 2-5A synthetase and double-stranded RNA (dsRNA)-dependent protein kinase (PKR) have been suggested to be involved in the antiviral action of IFN against EMCV, their activities were investigated in LB cells after BFA treatment. Northern blot analysis and in situ hybridization showed a decrease (2-3-fold) in the mRNA of 2'-5' oligoadenylate (2-5A) synthetase after BFA treatment. BFA also inhibited the activity of 2-5A synthetase, 2-5A dependent RNase and phosphorylation of PKR in cellular extracts, indicating that BFA may be exerting its inhibitory effect both at the transcriptional and post-transcriptional levels. This study reports a new biological action of BFA, demonstrating that BFA antagonized the antiviral action of IFN by inhibiting IFN-induced enzymatic pathways. These studies also suggest that both 2-5A and PKR are important in the antiviral activity of IFN against EMCV.

2',5'-Oligoadenylate Synthetase↗