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Biomedical subjects

N K Gupta

Publications and source records attributed to N K Gupta.

At least 19 recordsLinked to original sources
PubMed2006

The role of mast cells and eosinophils in chronic gastritis.

The role of mast cells and eosinophils in influencing the pathology of chronic gastritis remains unclear. We attempted to study the relationship between endoscopy and the mast cell and eosinophil infiltrate. We also studied the role of gene polymorphisms, Helicobacter pylori density and the CagA antibody status in influencing the mast cell and eosinophil infiltrate. One hundred and twenty consecutive patients were studied. Endoscopic evaluation was done and 3 antral biopsies were taken from each patient and were assessed for eosinophilic and mast cell infiltration, H. pylori density and the density of the other inflammatory cells as per the revised Sydney system. Cytokine gene polymorphisms (IL-1beta, IL-1RA and TNF-alpha) were done on the DNA extracted from the peripheral blood by PCR-RFLP. ELISA was done on the patients' serum for the anti-CagA antibody titres. Nodularity is strongly associated with the presence and density of eosinophils on biopsy (P < 0.05). Eosinophil density is strongly associated with the density of H. pylori, neutrophils, lymphocytes, plasma cells, atrophy, ulceration, foveolitis and lymphoid follicles. The mast cell density is not associated with any of the other histopathological variables. Gene polymorphisms and the CagA antibody titres have no relationship to the mast cell and eosinophil density. Eighty-one patients showed positive anti-CagA antibody titres but there was no association with the eosinophilic or the mast cell infiltrate. It is likely that eosinophilic infiltration is influenced by the H. pylori density but the CagA protein has no role to play in influencing the grade of the eosinophilic infiltrate in the Indian context. Cytokine gene proinflammatory polymorphisms have no role to play in influencing the eosinophilic or the mast cell response. It is likely that other mediators are involved in the inflammatory cell responses.

Adolescent↗
PubMed2001

Concomitant methotrexate and radiotherapy in advanced head and neck cancer: 15-year follow-up of a randomized clinical trial.

Long-term follow-up for patients who receive chemoradiation for head and neck cancer is lacking from most studies reported in the literature. This report gives a 15-year review of the use of concomitant methotrexate and radiation in advanced head and neck cancer. Although there has not been any significant benefit in overall survival, the primary control rate is higher in patients who received methotrexate in addition to radiotherapy. However, in those with oropharyngeal cancer, both primary control and survival were significantly improved when chemotherapy was used. The other most significant benefit from chemoradiation is the much lower rate of salvage operations for primary recurrence. The addition of methotrexate failed to show any effect on the development of metastatic neck nodes. The rate of block dissection of the neck was similar in both arms of the study and is comparable with the historical data collected at this institute. There has not been any significant increase in serious late morbidity. The timing of the methotrexate with radiotherapy has a significant influence on primary control and survival in head and neck cancer.

Antimetabolites, Antineoplastic↗
PubMed2001

Bilateral ectopia lentis as a presenting feature of medulloepithelioma.

Ectopia lentis may be a feature of numerous systemic and ocular disorders. Kivela and Tarkkanen described an 8-year-old girl with medulloepithelioma who presented with ectopia lentis and a mass behind the temporal iris. Shields reported 2 children with medulloepithelioma who had ectopia lentis associated with neovascular glaucoma. To date, there has been no report of a child with ectopia lentis as the only presentation of an intraocular tumor. We present 2 children with malignant medulloepitheliomas who presented in this fashion.

Child, Preschool↗
PubMed2000

331 cases of clinically node-negative supraglottic carcinoma of the larynx: a study of a modest size fixed field radiotherapy approach.

PURPOSE: For node-negative supraglottic carcinoma of the larynx, radiotherapy with surgery in reserve commonly provides very good results in terms of both local control and survival, while preserving function. However uncertainty exists over the treatment of the node-negative neck. Elective whole neck radiotherapy, while effective, may be associated with significant morbidity. The purpose of this study was to examine our practice of treating a modest size, fixed field to a high biologically effective dose and compare it with the patterns of recurrence from other centers that use different dose/volume approaches. METHODS AND MATERIALS: Over a 10-year period 331 patients with node-negative supraglottic carcinoma of the larynx were treated with radiotherapy at the Christie Hospital Manchester. Patients were treated with doses of 50-55 Gy in 16 fractions over 3 weeks. Data were collected retrospectively for local and regional control, survival, and morbidity. RESULTS: Overall local control, after surgical salvage in 17 cases, was 79% (T1-92%, T2-81%, T3-67%, T4-73%). Overall regional lymph node control, after surgical salvage in 13 cases, was 84% (T1-91%, T2-88%, T3-81%, T4-72%). Five-year crude survival was 50%, but after correcting for intercurrent deaths was 70% (T1-83%, T2-78%, T3-53%, T4-61%). Serious morbidity requiring surgery was seen in 7 cases (2.1%) and was related to prescribed dose (50 Gy-0%, 52.5 Gy-1. 3%, 55 Gy-3.4%). DISCUSSION: Our results confirm that treating a modest size, fixed field to a high biologically effective dose is highly effective. It enables preservation of the larynx in most cases, with acceptable regional control and no loss of survival compared to whole neck radiotherapy regimes.

Adult↗
PubMed2000

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Adolescent↗
PubMed1999

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.

Administration, Oral↗
PubMed1999

Self-expanding oesophageal metal stents for the palliation of dysphagia due to extrinsic compression.

The role of self-expanding metallic stents is well established in the palliation of oesophageal stenosis and dysphagia due to primary oesophageal malignancy. However, their role in palliation of dysphagia due to external compressive mediastinal malignancies is not well established. The purpose of this study was to assess the efficacy of self-expanding metallic stents in the palliation of dysphagia due to extrinsic oesophageal compression by mediastinal malignancy. Between January 1995 and January 1998, 21 patients with oesophageal compression due to malignant mediastinal tumours underwent oesophageal stent placement for palliation of dysphagia. Complete data were available in 17 patients (10 men and 7 women). The mean age was 63.5 years (range 46-89 years). A total of 19 stents were placed successfully. The dysphagia grade prior to and after oesophageal stent placement was assessed and the complications documented. Of the 17 patients, 16 reported an improvement in dysphagia. The mean dysphagia score improved from 3.1 prior to treatment to 1.3 after treatment. In 1 patient the stent slipped during placement and another stent was placed satisfactorily. Early complications (within 48 h) in the form of mild to moderate retrosternal chest pain occurred in 5 patients. This was treated symptomatically. Late complications (after 48 h) in the form of bolus impaction occurred in 2 patients. This was successfully treated with oesophagoscopy and removal of bolus. In 2 patients the stent was overgrown by tumour and in one of these an additional stent was placed. In 1 patient incomplete closure of a tracheo-oesophageal fistula was observed. There was no procedure- or stent-related mortality. The mean survival time of this group was 2. 1 months. Self-expanding metallic stents can be safely and effectively used in the palliation of dysphagia due to external mediastinal malignancies.

Aged↗
PubMed1999

Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing.

Although many pharmacological studies indicate that bulbospinal noradrenergic projections contribute to antinociception, lesions of the major brainstem noradrenergic cell groups have provided conflicting evidence. Here we used a new immunotoxin, anti-dopamine beta-hydroxylase-saporin, to re-examine the contribution of noradrenergic pathways to nociception and to morphine analgesia. We treated rats intrathecally by lumbar puncture with the immunotoxin and examined dopamine beta-hydroxylase (DbetaH) immunoreactivity seven and 14 days after treatment. There was no change in DbetaH staining at 7 days; however, 14 days after treatment we demonstrated significant destruction of noradrenergic neurons in the locus coeruleus and in the A5 and A7 cell groups. There was a concomitant loss of noradrenergic axons in the dorsal and ventral horns of the lumbosacral and cervical cord. Consistent with the lack of anatomical changes, we found no difference in nociceptive responses in the hot-plate, tail-flick or formalin tests one week post-toxin. On day 14 we examined the behavioral response to injection of formalin into the hindpaw and found that responses during the second phase of pain behavior were significantly reduced. There was no change during the first phase. Formalin-evoked fos expression in the spinal cord was also reduced. We also evaluated morphine analgesia in the formalin test and found that toxin-treated animals exhibited enhanced morphine analgesia. These results establish the utility of using this immunotoxin to selectively destroy subpopulations of noradrenergic cell groups and provide evidence that acute and persistent nociception are differentially regulated by descending noradrenergic pathways.

Acute Disease↗
PubMed1999

Submandibular gland carcinoma; an audit of local control and survival following adjuvant radiotherapy.

Carcinoma of the submandibular gland is a rare diagnosis, accounting for less than 2% of cases of salivary gland tumours. We have examined the treatment and outcome of a total of 30 patients treated with radiotherapy at the Christie Hospital, Manchester between 1980 and 1993. In most cases this followed radical surgery, though 12 patients were referred following either incomplete excision or biopsy only. Adenoid-cystic histology accounted for 19 cases (63%). Standard radiotherapy was delivered using a beam directed technique to treat the whole submandibular compartment. Doses prescribed were most commonly from 50 to 55 Gy in 16 fractions over three weeks. Cancer specific survival was 79% and 57% at 5 and 10 yr respectively, the continued fall at 10 yr reflected late recurrence seen in patients with adenoid-cystic histology. Local control was 85% and 73%, respectively. Nine of twelve patients with incomplete excision or biopsy only had local control with radiotherapy. Six patients developed lung metastases, all of whom had adenoid-cystic histology. Radiotherapy was well-tolerated acutely, and only one patient experienced osteoradionecrosis requiring surgical intervention. The incidence of adenoid-cystic carcinoma is higher in the submandibular than the parotid gland. This typically results in late recurrence, and a high incidence of lung metastases and this was confirmed in our study. However, overall survival was very similar to that of parotid carcinoma.

Adult↗
PubMed1998

Expression and activity of p67 are induced during heat shock.

p67, a cellular glycoprotein, protects eIF2 alpha from phosphorylation by inhibitory kinases such as PKR and HCR. p67 promoter contains heat shock element (HSE). To investigate whether this HSE of p67 has any role during heat-shock, rat tumor hepatoma cells were transiently transfected with CAT reporters linked to p67 promoter with HSE and without HSE. Heat shock induced CAT activity when p67 promoter contained HSE and this induction was not observed when HSE was deleted from the p67 promoter. In response to heat-shock, the endogenous p67 mRNA was also induced to more than 36-fold, and much of it translated into protein which was modified by GlcNAc moieties. The time of induced glycosyl modification at the later stages of the heat-shock correlates with the reduced level of eIF2 alpha phosphorylation. During later stages of the heat shock of animal cells, there is a preferential translation of a small class of messages encoding heat shock proteins. Our results suggest that the expression and activity of p67 are induced at the later stages of the heat-shock, and may be involved in the preferential translation of the heat-shock messages.

Aminopeptidases↗
PubMed1997

Viral infection. I. Regulation of protein synthesis during vaccinia viral infection of animal cells.

Regulation of vaccinia viral infection was studied using three animal cell lines: KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (African green monkey kidney). KRC-7 is highly enriched in p67, a glycoprotein which protects eIF-2 alpha-subunit from phosphorylation by eIF-2 kinases. We report: (i) At 5 pfu per cell of the virus, KRC-7 is resistant to the virus. Other cells are sensitive. At 25 pfu per cell of the virus, KRC-7 is also sensitive to the virus. After productive viral infection, the cell extracts showed strong p67-DG activity and actively deglycosylated exogenous p67. After p67-deglycosylation, the cell extracts also phosphorylated eIF-2. (ii) The rate of synthesis of a major host protein (approximately 45 kDa) in infected L929 cells measured after 2 h of viral infection declined more than 50%. The rate declined thereafter. The rate of synthesis of host proteins in viral-resistant KRC-7 cells (infected with 5 pfu per cell of the virus) remained unchanged. The mechanism of resistance of KRC7 cells to vacinia virus at 5 pfu per cell of the virus was investigated. The p67 level in these cells was varied by growing the cells under different physiological conditions such as serum starvation and expression of p67-sense and p67-antisense DNA. At low p67 level in the cells, p67-DG is activated. This deglycosylates p67 and inactivates p67. This accompanies eIF-2 phosphorylation and shutoff of host protein synthesis. At high p67 level in the cells, activation of p67-DG is prevented. This prevents shut-off of host protein synthesis and viral growth.

Acetylglucosaminidase↗
PubMed1997

Viral infection. II. Hemin induces overexpression of p67 as it partially prevents appearance of an active p67-deglycosylase in baculovirus-infected insect cells.

The roles of p67-deglycosylase (p67-DG) in the regulation of protein synthesis in baculovirus-infected insect cells were studied. Like vaccinia viral infection, baculovirus infection of insect cells also induced the appearance of a p67-DG. However, p67-DG activity could not be detected because these cells do not contain a detectable level of p67. The baculovirus expression vector system (BEVS), however, promotes significant expression of cloned p67-cDNA. The expression of p67 was significantly enhanced by the addition of hemin to the growth medium. Maximum enhancement was observed at 5 microM hemin. Data suggest that hemin prevents the activation of latent p67-DG inside the cell and does not have any effect on p67 gene transcription. To gain a better understanding of the mechanism of p67-DG activation and hemin stimulation of p67 synthesis, we have now purified p67-DG from baculovirus-infected insect cells. We prepared antibodies against this protein. These antibodies reacted with a 105-kDa protein in cell extracts from the uninfected insect cells (Sf9), KRC-7, and L929 (animal cells). In addition, these antibodies reacted with an additional 60-kDa protein in the cell extracts of baculovirus-infected Sf9 cells and vaccinia virus-infected KRC-7 and L929 cells. Data are also presented to show that the antibodies against p67-DG reacted more efficiently (40%) with the 60-kDa protein in both hemin-deficient reticulocyte lysate and hemin-deficient baculovirus-infected cells. We suggest that hemin prevents the conversion of an inactive p67-DG into an active form possibly by covalent modification such as protein phosphorylation or protein glycosylation. The active form is more efficiently recognized by the p67-DG antibodies since these antibodies were prepared against the active form of p67-DG.

Acetylglucosaminidase↗
PubMed1997

Cloning and characterization of the promoter region of a gene encoding a 67-kDa glycoprotein.

A rat genomic library constructed in lambda-EMBL3 (SP6/T7) vector () was screened using 32P-labeled rat p67 cDNA. A clone containing a segment of 5'-upstream region of p67 genomic DNA was obtained. The DNA (about 1.7 kilobase pairs) was isolated and characterized. Sequence analysis of this DNA fragment showed that the 898 base pairs at the 5'-end of the upstream region was identical to several long interspersed nucleotide sequences. One hundred forty-eight base pairs at the 3'-end contained the beginning of the first exon including the ATG initiator codon. The remaining 652 base pairs in between contained two AT-rich regions and several regulatory sequences. The mRNA initiation site was identified at 89 base pairs upstream from the translation start codon. The DNA fragment was also analyzed by transient transfection. When linked to a firefly luciferase reporter gene, this fragment enhanced transcription in a rat hepatoma cell line (KRC-7). Using a series of deletions in the DNA, the minimum essential promoter region (from -177 to -60) was identified. The promoter activity was also enhanced by treatment with phorbol 13-myristate 12-acetate (PMA). This enhancement required an AP-1 sequence (-298 to -292; 5'-TGACTCA-3') and a similar sequence (-97 to -88; 5'-ATGACATCAT-3'). Deletion of either of these sequences significantly reduced PMA enhancement. Deletion of both of these sequences almost completely eliminated PMA enhancement.

Aminopeptidases↗
PubMed1997

p67 transcription regulates translation in serum-starved and mitogen-activated KRC-7 cells.

The regulation of protein synthesis was studied in KRC-7 cells (rat hepatoma) grown in complete medium, during serum starvation, and mitogen activation. Upon serum starvation, the cells lost almost completely p67 mRNA, p67 protein, and protein synthesis activity. After phorbol 12-myristate 13-acetate addition, the same serum-starved cells regained p67 mRNA, p67 protein, and protein synthesis activity. Also, the extracts from the serum-starved cells phosphorylated the eukaryotic initiation factor-2 (eIF-2) alpha-subunit. This eIF-2 alpha-subunit phosphorylation was not observed when the extracts from either the cells grown in complete medium or mitogen-activated cells were used (Gupta, S., Wu, S., Chatterjee, N., Ilan, J., Ilan, J., Osterman, J. C., and Gupta, N. K. (1995) Gene Expr. 5, 113-122). We now report the following. 1) The eIF-2 kinase activity was the same in the cells grown in complete medium, after serum starvation, and subsequent mitogen stimulation. However, the eIF-2 kinase in the cells grown in complete medium and also after mitogen activation of the serum-starved cells cannot phosphorylate eIF-2 alpha-subunit as these cells contain p67. After removal of endogenous p67 by p67 antibodies, the extracts from all these cells similarly phosphorylated exogenously added eIF-2. 2) None of the cell extracts showed p67 deglycosylase activity. 3) The p67 mRNA was synthesized in serum-starved cells by expression of a p67 cDNA. The appearance of p67 mRNA in the serum-starved cells was accompanied by the appearance of p67 protein. Also, the rates of protein synthesis in the serum-starved cells were restored nearly to the level observed in the confluent cells. The expression of p67 cDNA also significantly increased protein synthesis rates in the cells grown in complete medium and in mitogen-activated cells. These results show that the loss of protein synthesis activity in serum-starved cells was due to loss of p67 mRNA. The expressed p67 mRNA was stable in serum-starved cells. These results, therefore, suggest that the loss of p67 mRNA in serum-starved cells is due to loss of p67 transcription. The p67 transcription regulates translation.

Aminopeptidases↗
PubMed1997

Intracavitary radiotherapy boosting for nasopharynx cancer.

Intracavitary radiotherapy is conceptually an attractive method of boosting dose to nasopharynx cancer whilst sparing sensitive normal tissues. A high dose rate (HDR) microselectron can be used to deliver a brachytherapy boost conveniently, safely, comfortably and effectively. Following external radiotherapy a single outpatient treatment has been given to patients using the remote afterloading system of sources placed in modified paediatric endotracheal tubes. This has been associated with good primary control and no evidence of serious morbidity in eight patients. The main limitation of this method is restriction of its utilization to small volume primary disease.

Brachytherapy↗
PubMed1996

A eukaryotic translation initiation factor 2-associated 67 kDa glycoprotein partially reverses protein synthesis inhibition by activated double-stranded RNA-dependent protein kinase in intact cells.

A eukaryotic translation initiation factor 2 (eIF-2)-associated 67 kDa glycoprotein (p67) protects the eIF-2 alpha-subunit from inhibitory phosphorylation by eIF-2 kinases, and this promotes protein synthesis in the presence of active eIF-2 alpha kinases in vitro [Ray, M. K., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 539-543]. We have now examined the effect of overexpression of this cellular eIF-2 kinase inhibitor in an in vivo system using transiently transfected COS-l cells. In this system, coexpression of genes that inhibit PKR activity restores translation of plasmid-derived mRNA. We now report the following. (1) Transient transfection of COS-1 cells with a p67 expression vector increased p67 synthesis by 20-fold over endogenous levels in the isolated subpopulation of transfected cells. (2) Cotransfection of p67 cDNA increased translation of plasmid-derived mRNAs. (3) Overexpression of p67 reduced phosphorylation of coexpressed eIF-2 alpha. (4) p67 synthesis was inhibited by cotransfection with an eIF-2 alpha mutant S51D, a mutant that mimics phosphorylated eIF-2 alpha, indicating that p67 cannot bypass translational inhibition mediated by phosphorylation of the eIF-2 alpha-subunit. These results show that the cellular protein p67 can reverse PKR-mediated translational inhibition in intact cells.

Aminopeptidases↗
PubMed1996

First-rib exostosis bursa.

We describe a case of exostosis bursa of the first left rib. Clinical features, investigations, and surgical management are described in detail.

Adult↗