Toxicokinetic study of rat intestinal brush border membrane enzymes following in vitro exposure to lead and vanadium.
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Biomedical subjects
Publications and source records attributed to K Gupta.
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Anti-nutritional factors of developing seeds and pod walls of fenugreek were evaluated which affect their nutritional value. Sucrose, raffinose and stachyose decreased with maturity of seeds in all the cultivars. Total, non-reducing sugars increased and reducing sugars decreased at maturity in all the cultivars. The reducing sugars decreased with maturity of pod walls. The flatus producing sugars were maximum in PEB pod walls. Saponin content increased towards maturity of seeds but decreased at maturity of seeds and decreased at maturity in pod walls of all cultivars. Phytate increased with seed maturity up to 95 days after anthesis, while phytate decreased in pod walls of all the cultivars with maturity. Total phenol, catechol and flavonol decreased with advancement of pod wall development. Total phenol decreased except HM 46 a maturity of seeds.
The EGF receptor (EGFR) upon activation signals increased cell movement. However, the domains within the receptor, and the pathway which trigger movement are undefined. We expressed EGFR mutants at physiologic levels in receptor-devoid NR6 cells to investigate this biologic response. The receptors possessed kinase activity and underwent autophosphorylation as predicted by primary amino acid sequence. EGF-induced cell motility was assessed in vitro by excess migration into an acellular area and colony scatter in the presence of saturating concentrations of EGF. Wild-type (WT)-EGFR signaled increased motility. However, replacing the conserved lysine721 with methionine resulted in a kinase-inactive receptor which did not elicit movement. Removal of the entire terminus by truncation (c'973) also abrogated ligand-induced motility. Thus, we concentrated on the carboxy-terminal domains. EGF-induced movement was seen with a less-truncated mutant (c'1000) that contained a single autophosphorylated tyrosine (tyrosine992). Other mutants, c'991 and c'1000F992, in which this tyrosine was removed did not signal motility. Fusion mutants which presented other autophosphorylated tyrosine domains also exhibited EGF-induced movement. These findings suggested that the presence of both an autophosphorylated tyrosine signaling domain and the kinase activity are necessary for this biologic response. All kinase-positive mutants signaled cell proliferation but only those that contained autophosphorylatable tyrosines induced movement. The motility responses mediated by these EGFR were identical in the presence or absence of mitomycin-C, at a dose (0.5 micrograms/ml) which completely inhibited cell proliferation. On the other side, D-actinomycin (50 ng/ml) blocked EGF-induced motility but did not affect thymidine incorporation. Thus, EGF-induced mitogenesis and cell motility are mediated through different pathways.
We recently have demonstrated that EGF receptor (EGFR)-induced cell motility requires receptor kinase activity and autophosphorylation (P. Chen, K. Gupta, and A. Wells. 1994. J. Cell Biol. 124:547-555). This suggests that the immediate downstream effector molecule contains a src homology-2 domain. Phospholipase C gamma (PLC gamma) is among the candidate transducers of this signal because of its potential roles in modulating cytoskeletal dynamics. We utilized signaling-restricted EGFR mutants expressed in receptor devoid NR6 cells to determine if PLC activation is necessary for EGFR-mediated cell movement. Exposure to EGF (25 nM) augmented PLC activity in all five EGFR mutant cell lines which also responded by increased cell movement. Basal phosphoinositide turnover was not affected by EGF in the lines which do not present the enhanced motility response. The correlation between EGFR-mediated cell motility and PLC activity suggested, but did not prove, a causal link. A specific inhibitor of PLC, U73122 (1 microM) diminished both the EGF-induced motility and PLC responses, while its inactive analogue U73343 had no effect on these responses. Both the PLC and motility responses were decreased by expression of a dominant-negative PLC gamma-1 fragment in EGF-responsive infectant lines. Lastly, anti-sense oligonucleotides (20 microM) to PLC gamma-1 reduced both responses in NR6 cells expressing wild-type EGFR. These findings strongly support PLC gamma as the immediate post receptor effector in this motogenic pathway. We have demonstrated previously that EGFR-mediated cell motility and mitogenic signaling pathways are separable. The point of divergence is undefined. All kinase-active EGFR mutants induced the mitogenic response while only those which are autophosphorylated induced PLC activity. U73122 did not affect EGF-induced thymidine incorporation in these motility-responsive infectant cell lines. In addition, the dominant-negative PLC gamma-1 fragment did not diminish EGF-induced thymidine incorporation. All kinase active EGFR stimulated mitogen-activated protein (MAP) kinase activity, regardless of whether the receptors induced cell movement; this EGF-induced MAP kinase activity was not affected by U73122 at concentrations that depressed the motility response. Thus, the signaling pathways which lead to motility and cell proliferation diverge at the immediate post-receptor stage, and we suggest that this is accomplished by differential activation of effector molecules.
The mouse Unp gene is related to TRE17, a human oncogene, but is not its mouse homolog. Unp is a ubiquitously expressed gene producing two related mRNAs. The protein product of Unp is localized in the nucleus. Expression of Unp from a highly active promoter results in tumorigenic transformation of NIH3T3 cells injected into athymic mice. Unp therefore encodes a novel nuclear oncoprotein.
The sensitivity, specificity, and accuracy of computed tomography (CT)-myelography, magnetic resonance imaging (MRI), and myelography in making the diagnosis of herniated nucleus pulposus (HNP) and spinal stenosis were compared in a retrospective study involving 59 surgical procedures in 57 patients who had all three tests performed preoperatively. One hundred nineteen levels were surgically explored for evidence of HNP and spinal stenosis. The results of each test were correlated with what was found at each surgical level explored. Overall, myelo-CT was the most accurate test for diagnosing HNP (76.4%) as well as the most sensitive (77.8%), whereas myelography was the most specific (89.2%). In making the diagnosis of spinal stenosis, myelo-CT and MRI were equally accurate (85.3%) and sensitive (87.2%), whereas myelography was the most specific (88.9%). In a special subset of patients who had revision surgery, the accuracy rate in diagnosing spinal stenosis or HNP was highest with MRI (84.9%), as was the sensitivity (69.2%) and specificity (95%). According to the results obtained from this series of patients, myelo-CT seems to be the most sensitive and accurate test in diagnosing HNP and spinal stenosis, whereas myelography is the most specific, although no statistical significance was noted in this study. However, because MRI did compare favorably with myelo-CT in most instances, particularly in revision surgery; it may be the procedure of choice due to its noninvasiveness and relative lack of side effects.
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To detect the prevalence of hypertension in an asymptomatic rural community from Central India, we screened 4045 subjects (2247 men and 1798 women) aged 20 and beyond. The prevalence of hypertension was 34.12 per thousand population, being higher in women (40.60 per thousand) than in men (28.92 per thousand). Level of physical activity, economic status, smoking and body mass index showed real association with hypertension.
We have cloned cDNAs from a novel gene designated Unp. Unp cDNAs contain a large open reading frame that would encode a protein of 89 kDa. The predicted protein contains a putative nuclear localization signal, as well as consensus sequences for binding to the retinoblastoma gene product. The latter elements are contained within a region having strong similarity to the human tre oncogene. We have localized the Unp gene to mouse chromosome 9 in a region of homology with human chromosome 3p. This region has been implicated in a number of human malignancies.
Needle aspiration was performed on a breast mass in a 91-year-old woman. The cytologic features in the aspirate were a diffuse, prominent, intracytoplasmic vacuolization and secretion in malignant cells and occasional signet ring-like forms. This was confirmed in a subsequent cell block which was made from the aspirate. Immunocytochemical studies showed a positivity for mucin by alcian blue stain in the vacuolated cells which was periodic acid-Schiff positive and resistant to diastase digestion. Oil-red-O staining was negative and on Colloidal iron stain the tumour cells were positive. Immunopositivity to carcinoembryonic antigen, cytokeratin, and epithelial membrane antigen was found in the malignant cells, while on electron microscopy the tumour cells contained a significant amount of intracytoplasmic secretory material. Secretory carcinoma of the breast is a rare tumour and can be diagnosed and differentiated from other breast carcinomas in view of its characteristic cytologic features.
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A randomised study of the efficacy, duration of action and side-effects of two analgesic regimens following lower abdominal surgery is described. Patients received extradural pentazocine 30 mg or extradural buprenorphine 0.3 mg to provide postoperative analgesia. Interval for the next analgesia was significantly greater after extradural buprenorphine (18.96 hours) than after extradural pentazocine (8.39 hours) (p less than 0.001). No serious side-effects were reported.
Twenty patients with thoracic stomach were subjected to hepatobiliary scintigraphy for the diagnosis of duodenogastric reflux. The results of the radionuclide studies were correlated with those of endoscopy and biochemical estimation of total intragastric bile acid. Hepatobiliary scintigraphy was found to be more sensitive (91.6%) and accurate (95%) than endoscopy (25% and 55% respectively) and biochemical estimation of total intragastric bile acid content (66.6% and 80% respectively). Being noninvasive and physiological, radionuclide study appears suitable for routine clinical use in the diagnosis of duodeno-gastric reflux.
Sex and sexuality in old age have been traditionally viewed as immoral, inappropriate, and even sinful. It is only in recent years that the sexual function of aging men and women has been recognized as an integral part of the total well-being of elderly individuals. Continuing sexual wellbeing in senescence can, of course, be one of the few remaining pleasures of life for the older person.
Eleven females and five males with fall/winter seasonal affective disorder were randomly assigned to 7-day treatment regimens from 8 p.m. to 10 p.m. using identical light at 2000 or 300 lux. A modified Hamilton Rating Scale for Depression and a Beck Depression Inventory were administered before treatment, after treatment # 7, and 2 weeks after phototherapy was terminated. Analysis of variance with repeated measures revealed a significant interaction between sex of the patient, intensity of the lights, and day of rating for scores on both the modified Hamilton Rating Scale for Depression and the Beck Depression Inventory. For both measures, the interaction occurred because all groups showed a decrease in depression ratings during the phototherapy exposure period, but only females at the higher intensity continued to have low depression scores 2 weeks after light treatment had stopped. These data indicate that bright light at both high (2000 lux) and low (300 lux) intensities is able to reduce depression in patients with seasonal affective disorder. The data also indicate that both sex of the patient and intensity of the light may interact to determine the latency to relapse.
Vascularity of the thyroid gland was measured in twenty thyrotoxic patients (including Graves and multinodular goitres) and eight normal subjects by a new objective parameter--'Thyroid Vascularity Index' (TVI). The TVI was calculated by comparing the areas under the normalized thyroid and carotid artery curves up to the time of peak of the arterial curve caused by the first passage of a radioactive bolus. Compared to normal thyroid, all the toxic goitres had increased TVI (p less than 0.001); it being maximum in Graves disease (p less than 0.05). TVI in Graves disease was not affected by carbimazole therapy but decreased dramatically in eight out of ten patients (p less than 0.01) two weeks after Lugol's iodine was added. There was a sustained fall in TVI in all the ten patients (p less than 0.001) with chronic iodine therapy up to six weeks without any hormonal escape. TVI in multinodular goitres showed no significance change with carbimazole or iodine therapy.
A block to elongation of transcription has been shown to occur within the first exon of the human and murine c-myc genes. The extent of this block was found to vary with the physiological state of cells, indicating that modulation of the transcriptional block can serve to control the expression of this gene. To determine which sequences are required in cis for the transcriptional block, we generated a series of constructs containing various portions of murine c-myc 5'-flanking and exon 1 sequences. We established populations of HeLa and CV-1 cells stably transfected with these constructs. The transcription start sites were determined by S1 nuclease mapping analysis, and the extent of transcriptional block was measured by nuclear run-on transcription assays. Our results demonstrate that at least two cis-acting elements are necessary for the transcriptional block. A 3' element was found to be located in the region where transcription stopped and showed features reminiscent of some termination sites found in procaryotes. A 5' element was positioned between the P1 and P2 (C. Asselin, A. Nepveu, and K. B. Marcu, Oncogene 4:549-558, 1989). Removal of the more 3' binding site abolished the transcriptional block.