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Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 433 records · Page 24Linked to original sources
PubMed2000

Interaction of a mitogen-activated protein kinase signaling module with the neuronal protein JIP3.

The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPKs) is activated in response to the treatment of cells with inflammatory cytokines and by exposure to environmental stress. JNK activation is mediated by a protein kinase cascade composed of a MAPK kinase and a MAPK kinase kinase. Here we describe the molecular cloning of a putative molecular scaffold protein, JIP3, that binds the protein kinase components of a JNK signaling module and facilitates JNK activation in cultured cells. JIP3 is expressed in the brain and at lower levels in the heart and other tissues. Immunofluorescence analysis demonstrated that JIP3 was present in the cytoplasm and accumulated in the growth cones of developing neurites. JIP3 is a member of a novel class of putative MAPK scaffold proteins that may regulate signal transduction by the JNK pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

p53 mutants have selective dominant-negative effects on apoptosis but not growth arrest in human cancer cell lines.

A bidirectional expression vector that allowed equal transcription of cloned wild-type and mutant p53 cDNAs from the same vector was developed. The vector was transfected into CaLu 6 lung carcinoma cells or Saos-2 osteosarcoma cells. All p53 mutants examined were recessive to wild-type p53 transactivation of p21(WAF1/CIP1) but dominant-negative for transactivation of Bax. An examination of effects on growth arrest and apoptotic pathways indicated that all mutants were recessive to wild type for growth arrest but only three of seven mutants were dominant negative for induction of apoptosis.

Apoptosis↗
PubMed2000

Multiple, genital lobular capillary haemangioma (pyogenic granuloma) in a young woman: a diagnostic puzzle.

A 21 year old woman presented with multiple lobulated lesions on the labia majora. The surface of most of the lesions was ulcerated revealing a glistening surface. All lesions were excised. The histopathology revealed features suggestive of lobular capillary haemangioma (pyogenic granuloma). Pyogenic granuloma is considered as a reactive hyperproliferative vascular response to trauma or other stimuli. A literature search revealed reports of a few cases of lobular capillary haemangioma of the glans penis but not on the female genitalia. This case is presented to help physicians become aware that lobular capillary haemangiomas (pyogenic granuloma) may occur at this site.

Adult↗
PubMed2000

Dorsal perforation of prepuce: a common end point of severe ulcerative genital diseases?

Severe ulcerative genital diseases can cause destruction of the prepuce, glans, or sometimes of the whole penis (phagedena). We observed a characteristic pattern of partial destruction of the prepuce as a result of a wide variety of ulcerative genital diseases. Five patients, two with severe genital herpes, one with hidradenitis suppurativa, and two with donovanosis presented with perforation on the dorsal surface of the prepuce. In four of them, the glans protruded through the defect and in one, the defect was not large enough to allow protrusion of the glans. In two patients, the preputial sac was obliterated. The relatively decreased blood supply of the prepuce is the probable explanation for perforation at this selective site.

Adult↗
PubMed2000

Transplanted reporter cells help in defining onset of hepatocyte proliferation during the life of F344 rats.

Transplanted hepatocytes integrate in the liver parenchyma and exhibit gene expression patterns that are similar to adjacent host hepatocytes. To determine the fate of genetically marked hepatocytes in the context of hepatocellular proliferation throughout the rodent life span, we transplanted Fischer 344 (F344) rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. The proliferative activity in transplanted hepatocytes was studied in animals ranging in age from a few days to 2 yr. Transplanted hepatocytes proliferated during liver development between 1 and 6 wk of age, each dividing an estimated two to five times. DNA synthesis in occasional cells was demonstrated by localizing bromodeoxyuridine incorporation. There was no evidence for transplanted cell proliferation between 6 wk and 1 yr of age. Subsequently, transplanted cells proliferated again, with increased sizes of transplanted cell clusters at 18 and 24 mo of age. The proliferative activity of transplanted cells was greater in rats entering senescence compared with during postnatal liver development. In old rats, some liver lobules were composed entirely of transplanted cells. We conclude that hepatocyte proliferation in the livers of very young and old F344 rats is regulated in a temporally determined, biphasic manner. The findings will be relevant to mechanisms concerning liver development, senescence, and oncogenesis, as well as to cell and gene therapy.

Age Factors↗
PubMed2000

Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver.

Cell transplantation into hepatic sinusoids, which is necessary for liver repopulation, could cause hepatic ischemia. To examine the effects of cell transplantation on host hepatocytes, we transplanted Fisher 344 rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. Within 24 h of cell transplantation, areas of ischemic necrosis, along with transient disruption of gap junctions, appeared in the liver. Moreover, host hepatocytes expressed gamma-glutamyl transpeptidase (GGT) extensively, which was observed even 2 years after cell transplantation. GGT expression was not associated with alpha-fetoprotein activation, which is present in progenitor cells. Increased GGT expression was apparent after transplantation of nonparenchymal cells and latex beads but not after injection of saline, fragmented hepatocytes, hepatocyte growth factor, or turpentine. Some host hepatocytes exhibited apoptosis, as well as DNA synthesis, between 24 and 48 h after cell transplantation. Changes in gap junctions, GGT expression, DNA synthesis, and apoptosis after cell transplantation were prevented by vasodilators. The findings indicated the onset of ischemic liver injury after cell transplantation. These hepatic perturbations must be considered when transplanted cells are utilized as reporters for biological studies.

Animals↗
PubMed2000

A survey of GP views in intra-uterine contraception.

AIMS: To investigate knowledge and attitudes towards intra-uterine contraception. DESIGN: Anonymous postal survey of 441 GPs (153 female and 288 male GPs) from the FHSA register in Stockport and Manchester. SETTING: General practices in Stockport and Manchester. Main outcome measure. Response to a series of questions concerning attitudes and knowledge of intra-uterine contraception. RESULTS: One hundred and forty-two responses were received, giving a 35% response rate. Thirty-four percent of responding GPs did not fit intra-uterine devices (IUDs), with only 10% fitting more than 30 a year. There was a significant trend against IUD fitting by male GPs and GPs aged <40 years. Younger GPs with <10 years experience were significantly more aware of the reliability of intra-uterine contraception, but perceived IUD fitting as inconvenient for both the patient and the doctor. Female GPs had better knowledge and more positive attitudes to IUDs than male GPs. CONCLUSION: GPs may have difficulties in maintaining expertise. Primary care groups may opt to concentrate fittings in a few expert practices, or refer women to centrally based family planning clinics for IUD fitting.

Adult↗
PubMed2000

New grading system to predict resectability of anterior clinoid meningiomas.

Sixty patients with anterior clinoid meningiomas (mean age 48 years) were surgically treated. There was a slight female predominance. Headache and visual impairment were the commonest clinical symptoms at presentation. The patients were classified on the basis of extent of the visual impairment, size of the tumor, and the tumor relationship with the internal carotid artery. A grading system was designed using the total scores in these classifications on the scale of 2-10. The classifications and the grading system were assessed for planning of the operative strategy, anticipating the extent of resectability, possible difficulties in dissecting the carotid artery and optic nerve during the operation, and prognosis. Total resection was achieved in 42 cases (scores 4-8), subtotal resection in 17 cases (scores 7-10), and only partial resection in one case (score 10). Vision improved in 14 cases. Three patients died following surgery. Mean follow up was 26 months. There was one recurrence. Fifty-four patients are leading independent and active lives.

Adolescent↗
PubMed2000

Pneumococcal pneumonia in patients requiring hospitalization: effects of bacteremia and HIV seropositivity on radiographic appearance.

OBJECTIVE: Our purpose was to establish the incidence of lobar versus bronchopneumonia patterns in patients hospitalized for pneumococcal pneumonia and to determine whether bacteremia or HIV status affects the radiographic appearance. MATERIALS AND METHODS: Eighty-one patients with community-acquired pneumococcal pneumonia and positive findings on admission chest radiographs were selected from a group of 105 patients with positive findings for Streptococcus pneumoniae from sputum or blood cultures. Patients less than 16 years old and those with nosocomial pneumonia, aspiration pneumonia, or coexistent lung disease were excluded. The dominant pattern was classified as lobar or lobular bronchopneumonia by two radiologists who were unaware of results from blood cultures and HIV testing. RESULTS: Forty-three females and 38 males, with a mean age of 48 years (age range, 16-92 years), required admission for pneumococcal pneumonia. Fifty-nine (73%) of the 81 patients were bacteremic and 20 (25%) of the 81 patients were HIV-positive, including 14 patients (17%) who were both bacteremic and HIV-positive. Among all the patients, focal lobar consolidation was the most common pattern, observed in 48%. Multifocal lobar consolidation was the next most frequent pattern, occurring in 33%. Multifocal and focal bronchopneumonia patterns were seen in 16% and 2% of the patients, respectively. Overall, multifocal consolidation occurred in 49%. The dominant radiographic pattern and incidence of multicentric disease were not affected by HIV seropositivity (p = 0. 61) or bacteremia (p = 0.17). CONCLUSION: Lobar consolidation, involving single or multiple lobes, is the most common radiographic pattern of community-acquired pneumococcal pneumonia in patients requiring hospitalization. The pattern of consolidation is not influenced by bacteremia or HIV status.

Bacteremia↗
PubMed2000

Re-Engineering the liver with natural biomaterials.

The extensive regenerative capacity of hepatocytes and the key roles of the liver in metabolic processes have generated interest in the liver as an appropriate target for cell and gene therapy. If cells were considered as natural biomaterials, then liver cell transplantation would fall within the general field of bioengineering. While unmodified hepatocytes engraft in the liver and ectopic sites, biological modifications and optimization of bioengineered systems would facilitate engraftment and survival of transplanted cells, especially in ectopic locations. Acute liver failure, chronic liver disease and metabolic deficiency states are among the conditions that can potentially be treated by cell transplantation. In acute liver failure, cell transplantation into the liver, along with the creation of an extrahepatic reservoir of cells might be required because engraftment and proliferation of transplanted cells in the liver needs time. In other situations, gradual liver repopulation alone might well be effective without additional manipulations.

Animals↗
PubMed2000

Salmonella typhimurium-induced reactivation of latent HIV-1 in promonocytic U1 cells is inhibited by trovafloxacin.

We have previously reported that virulent Salmonella typhimurium induces replication of latent HIV-1 in U1 cells, via activation of tumor necrosis factor-alpha (TNF-alpha) production. In the present study, we show that Trovafloxacin, a new quinolone antibiotic, inhibits S. typhimurium-induced TNF-alpha production and HIV-1 replication. In addition, Trovafloxacin inhibits TNF-alpha-induced reactivation of latent HIV-1 in U1 cells. The concentrations of Trovafloxacin that inhibited HIV-1 replication are comparable to the plasma and tissue levels achieved by therapeutic dosage used in the treatment of bacterial infections. Therefore, Trovafloxacin is a potential candidate for adjunct therapy in HIV-1 infection.

Anti-Infective Agents↗
PubMed2000

Modulation of endothelin-1 expression in pulmonary epithelial cell line (A549) after exposure to RSV.

Respiratory syncytial virus (RSV) is one of the most important respiratory tract pathogens in infants and young children. The airway epithelial cells are the primary target cells for RSV infection. The airway epithelial layer is not only a physical barrier, but also plays a role in a synthesis of a variety of major inflammatory cytokines (IL-6, IL-8, GM-CSF etc.) as previously reported. Endothelin-1 (ET-1) is a potent bronchoconstrictor and vasoconstrictor factor, and involved in pathogenesis of various diseases of the respiratory tract. We hypothesized that RSV may induce the release of ET-1 from the bronchial epithelial cell line. No previous data is available regarding association between RSV infection and ET-1 release. We evaluated the effect of RSV with different concentrations of RSV (MOI 0.1, 1 and 3 pfu/cell) on bronchial epithelial cell line (A549) and measured the production of ET-1 at both protein and mRNA level. A549 cells were treated with different conditions by using LPS, heat-inactivated RSV, RSV or medium alone as control. We observed time-dependent ET-1 release by RSV-infected A549 cells at 4 h, 24 h and maximum at 72 h. ET-1 was expressed in unstimulated A549 cells and was further increased by RSV. RSV with concentration MOI 0.1 (pfu/cell) and LPS appeared to have strongest stimulation on production of ET-1. In addition, ET-1 mRNA was increased significantly by 16 h and decreased to relatively low-level at 24 h. These experiments suggested that airway epithelial cells might play a role in the local airway smooth muscle tone through the production of endothelin-1 during RSV infection.

Bronchi↗
PubMed2000

Differential transcriptional regulation of silencer of death domains in cord blood and peripheral blood lymphocytes.

We have shown that neonatal lymphocytes are deficient in TNF-induced apoptosis. Recently, a 60 kDa protein termed silencer of death domains (SODD) has been shown to prevent spontaneous apoptosis. The binding of SODD to DD of the TNFR-I maintains DD in monomeric form and prevents their aggregation which is required for the apoptotic signal. We examined the expression of SODD mRNA during TNF-induced apoptosis. Although in non-stimulated cord blood lymphocytes the constitutive expression of SODD mRNA was lower than that of non-stimulated peripheral blood lymphocytes, following anti-CD3 stimulation SODD mRNA was significantly increased in cord blood lymphocytes at 12 and 24 h, returning to the baseline at 48 h. In contrast, a modest decrease in SODD transcript was observed in peripheral blood lymphocytes. Furthermore, TNF downregulated SODD mRNA expression in peripheral blood lymphocytes, whereas it had no significant effect on SODD transcripts in cord blood lymphocytes. Therefore, differential regulation of SODD may be one of the mechanisms responsible for decreased TNF-induced apoptosis in neonatal lymphocytes.

Adaptor Proteins, Signal Transducing↗