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Biomedical subjects

N Gupta

Publications and source records attributed to N Gupta.

At least 217 records · Page 12Linked to original sources

Identification of a novel hydroxyproline-rich glycoprotein as the major allergen in Parthenium pollen.

BACKGROUND: The airborne pollen of the Compositae weed, Parthenium hysterophorus, is a major cause of allergic rhinitis in the Indian subcontinent and in certain parts of the southern United States and western Australia. Earlier studies have identified a 31 kd protein as the major allergen in Parthenium pollen. OBJECTIVE: This study was undertaken to carry out the purification, immunochemical characterization, sequencing, and epitope analysis of this major allergen, designated as Par h I. METHODS: The IgE-binding activity of the allergen was evaluated by immunoblot and inhibition ELISAs. Pronase digestion, periodate oxidation, and chemical deglycosylation were performed to determine the role of peptide and carbohydrate components of the allergen in IgE binding. RESULTS: The data provide evidence for the involvement of carbohydrate moieties on Par h 1 in its IgE-binding ability. The N-terminal 91 amino acid sequence of Par h 1 shows 81% identity with a protein from sunflower anther, and the hydroxyproline-rich region of Par h 1 is 30% to 40% identical to similar stretches in extensins, a class of hydroxyproline-rich cell wall glycoproteins from different plant species. IgE antibodies in the sera of individuals allergic to Parthenium cross-reacted with a 50 kd hydroxyproline-arabinose-rich extensin precursor from potato tuber, and this binding was periodate-sensitive. CONCLUSIONS: It appears that a group of soluble plant glycoproteins, which are related to the ubiquitous extensins, have certain carbohydrate-containing IgE-binding epitopes that may contribute to allergenic cross-reactivity among specific pollens and foods.

Allergens↗

Membrane characterization of amastigote-like forms of Leishmania donovani.

During in vitro transformation, Leishmania donovani promastigotes converted into amastigote-like forms and underwent several changes in membrane parameters. They exhibited significantly increased microviscosity comparable to true amastigotes. Activities of several functionally important membrane bound enzymes were also altered, thereby indicating a change in their orientation. Peanut agglutinin was found to be specific for agglutination of stationary phase promastigotes whereas wheat-germ agglutinin was specific for the amastigote-like forms as well as for pure amastigotes, implying the presence of specific glycoconjugates on the parasite surface.

Animals↗

Permanent blindness after cyclosporine neurotoxicity in a kidney-pancreas transplant recipient.

Blindness is an extremely rare complication of cyclosporine neurotoxicity. In all 10 cases in the literature, this form of blindness is completely reversible with the reduction or withdrawal of cyclosporine. We describe the first case of sudden, complete, and permanent blindness within 36 h after administration of intravenous cyclosporine in a kidney-pancreas transplant recipient.

Adult↗

A Sleepy, Hungry Teenager.

A 16-year-old male was admitted for repeated episodes of hypersomnia, hyperphagia, and abnormal behavior, the first of which was preceded by alcohol and marijuana use. He was started on lithium therapy and lethargy and hyperphagia gradually improved, although he remained oppositional and irritable. After careful evaluation, his symptoms were concluded to meet Critchley's criteria for the diagnosis of Klein-Levin syndrome, which was supported by his response to prophylactic use of lithium.

Journal Article↗

A statistical approach for analyzing clonogenic survival data.

The assay of colony-forming efficiency is a mainstay in the measurement of cell response in vitro to many physical and chemical agents. Currently, data on colony-forming efficiency can be calculated in a variety of ways. Authors rarely describe in detail the methods used to determine the extent of biological variation within experiments. The use of standard methods of data analysis and presentation would improve interpretation of data and facilitate comparison between laboratories. Here we propose such a method. Binomial and Poisson probability theory were used to increase the accuracy of the estimate of the surviving fraction and to create an objective criterion for determining whether data obtained from serial dilutions of cell numbers used in the assay of colony-forming efficiency should be excluded or included for further analysis. The variability inherent in the calculation of surviving fraction was determined by using Fieller's theorem, a special statistical application for assessing ratios of estimates, to determine the 95% confidence interval. All calculations were done on a simple and commercially available spreadsheet program.

Cell Line↗

Remission with carbimazole therapy & assessment of T4 suppression test as an index of relapse in patients with Graves' disease in India.

This study determined the relapse rate following the use of antithyroid drugs (ATD) in patients with Graves' disease and assessed T4 suppression test as a follow up index for predicting relapse after carbimazole treatment in 21 patients who had taken 9-12 months of ATD treatment continuously with good compliance. T4 suppression test was done before stopping ATD treatment. During one year of follow up after stopping ATD therapy, 12 (57%) patients relapsed and 9 (43%) remained in remission. Six of the 12 relapses occurred in the first 3 months of stopping ATD therapy. The response following the use of carbimazole therapy was comparable to that reported from iodine sufficient western countries and may be because of the salt iodination programme in our country. T4 suppression test was normal in 14 (66%) and abnormal in 7 (34%) patients. All the patients with abnormal T4 suppression test relapsed after stopping ATD. The overall accuracy of the T4 suppression test (76%) also favourably compared with reported values of other useful but less readily available markers such as thyrotropin releasing hormone (TRH) stimulation test and thyroid receptor antibodies. Thus, in our experience antithyroid drugs were able to induce long term remission in 43 per cent patients with Graves' disease and abnormal T4 suppression test can be used as a reliable parameter for predicting relapse.

Adult↗

Hypocholesterolemia is not associated with neurotoxicity in renal transplant patients.

Cyclosporine-associated neurotoxicity has been reported in recipients of solid organ and bone marrow transplantation. Neurotoxicity during cyclosporine therapy has been suggested to be associated with low levels of serum total cholesterol (TC). We report seven hypocholesterolemic (TC < 150 mg/dl) renal transplant recipients who remained asymptomatic during cyclosporine therapy. Three of these patients were hypocholesterolemic at the time of transplantation and received intravenous cyclosporine as induction therapy. The other four patients became hypocholesterolemic > or = 9 months after renal-transplantation. None of these patients developed neurologic signs or symptoms during cyclosporine therapy. Our short and long-term observations in renal transplant recipients suggest that perhaps factors other than low cholesterol levels may be responsible for cyclosporine-associated neurotoxicity.

Administration, Oral↗

Pancreaticocystostomy revision for obstructive pancreatitis and pancreatic fistula after segmental pancreatic transplantation.

Combined kidney-pancreas transplantation is an effective surgical therapy for end-stage renal failure secondary to type I diabetes mellitus. However, obstructive pancreatitis and pancreaticocutaneous fistula remain significant postoperative complications unique to extraperitoneal segmental pancreatic transplantation. We present our experience with 13 patients (7 with obstructive pancreatitis and 6 with pancreaticocutaneous fistulae) after segmental extraperitoneal pancreatic transplantation, who subsequently underwent intraperitoneal reconstruction of the pancreaticocystostomy. This reconstruction was successful in 11 of 13 (85%) patients with minimal morbidity and no mortality. This intraperitoneal approach to reconstruction of the pancreaticocystostomy after segmental extraperitoneal pancreatic transplantation is a safe and effective means of graft salvage and this technique has not been described in the literature.

Adult↗

ATGAM associated coagulopathy in renal transplant patients: a report of two unusual cases.

Polyclonal antibodies, used for both induction and rejection therapy in renal transplant recipients, are associated with such side effects as chills and fever. We describe two patients who developed a coagulopathy during antithymocyte globulin (ATGAM) therapy, a previously unknown complication. The laboratory tests revealed prolonged prothrombin and partial thromboplastin times and thrombocytopenia. Discontinuation of ATGAM therapy resulted in correction of these abnormalities.

Adult↗

Cytogenetic damage and the radiation-induced G1-phase checkpoint.

It is proposed that genomic integrity is preserved after DNA damage in a variety of ways. X irradiation induces a p53-dependent G1-phase cell cycle checkpoint which putatively allows time for repair of DNA damage. The p53 protein is also involved in the initiation of apoptosis after radiation-induced DNA damage, presumably leading to the elimination of lethally damaged cells from the irradiated population. To test the hypothesis that repair occurs in the additional time provided by the activation of the G1-phase checkpoint, we investigated whether the presence of a G1-phase arrest modified the frequency and type of chromosomal rearrangements at the first mitosis after irradiation. Isogenic cell lines derived from the same human glioma cell line, but differing in p53 status, were used. Purified G1-phase cells, isolated by centrifugal elutriation and X-irradiated, were studied. The wild-type p53 cell line demonstrated a dose-dependent arrest during G1 phase, as determined by flow cytometry. These cells remained in G1-phase as long as 48 h after irradiation. Cells expressing a dominant-negative p53 mutation accumulated to a much lesser extent in G1 phase after irradiation. Cells lacking the G1-phase checkpoint showed increased survival at all radiation doses. There were no significant differences in the type or frequency of total chromosomal aberrations in mitotic cells from either cell line after 1,2,4 or 6 Gy X rays, as measured by conventional cytogenetic analysis. There was an increase, however, in the number of reciprocal translocations in mitotic cells with mutant p53 (lacking a G1-phase checkpoint), as measured by fluorescence in situ hybridization with a chromosome 4-specific DNA library, but only after 6 Gy. The results suggest that the presence of a well-defined p53-dependent G1-phase arrest does not reduce chromosomal aberrations caused by low doses of ionizing radiation markedly, but may reduce the overall degree of survival by triggering other G1-phase events.

Apoptosis↗

Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions.

PURPOSE: To investigate the importance to outcome of treatment for squamous cell carcinomas of the tonsillar fossa, of dose per fraction, overall treatment duration, and total dose. METHODS AND MATERIALS: A collaborative retrospective study was undertaken in nine centers that used widely different dose-fractionation patterns for external beam radiation therapy. RESULTS: There were 676 eligible cases treated only with photon beams during the years 1976-1985. The probability of local control (of the tonsillar fossa primary) was influenced by both T-stage and N-stage. Significant treatment parameters were total dose and overall treatment duration, but not dose per fraction. Over the range of about 40 to 90% and for a constant overall treatment duration, local tumor control probability increased by nearly 2% for each 1 Gy increase in total dose. For a constant total dose there was a decrease in the probability of local control associated with prolongation of overall treatment duration, presumed to result from accelerated regrowth of surviving tumor clonogens during the course of treatment. If it is assumed that accelerated regrowth occurred at a constant rate and began within 9 days of the start of treatment, an average of 0.53 Gy extra dose per day's extension of treatment would be required to maintain a constant probability of local control. Correspondingly, the probability of local control from a constant dose would be lowered by an average of at least 1% for each day's extension of treatment duration. However, the data are slightly more consistent with an average delay of as long as 30 days before onset of accelerated repopulation, with a consequent increase to an average of 0.73 Gy per day for the value of the compensatory dose. The alpha/beta ratio for this tumor is high enough that the effect of fraction size on the probability of local control can be ignored; a precise estimate is not possible because the best value for beta was close to zero. After accounting for the significant variables studied (treatment time, T-stage, N-stage), the dose-response curves for tumor control were still shallow, suggesting that there are additional causes for heterogeneity of responses among these tumors. CONCLUSIONS: Total dose is important to treatment outcome: After accounting for other treatment variables, there is about a 2% per Gy increase in probability of tumor control over the ranges of control commonly achieved. Overall treatment duration is important. There is at least a 1% per day decrease in tumor control probability if delivery of a constant total dose is prolonged, requiring a compensatory increase in dose by 0.5-0.7 Gy per day to achieve a constant rate of tumor control. Fraction size is not, of itself, an important factor in the response of primary carcinoma of the tonsil. If a tumor has demonstrated a capacity for metastatic spread to lymph nodes, a higher total dose should be considered to achieve control rates at the primary site equivalent to those in node negative patients. Even after accounting for variables such as tumor stage, total dose, and overall treatment duration, there is sufficient heterogeneity in other undocumented determinants of tumor control to cause the tumor control probability curve to be a shallow function of dose.

Analysis of Variance↗

Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: patterns of fractionation study of radiobiology.

PURPOSE: To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for carcinoma of the tonsil. METHODS AND MATERIALS: A retrospective analysis was made of the results in 676 patients treated with a spectrum of fractionation regimens in nine centers during the years 1976-1985. Only severe (Grades 3-4) late complications were analyzed. RESULTS: With more than 5 years follow-up, it was found that total dose was a factor for all three types of complications, but that in other respects, the radiobiology of late-(> 3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Dose per fraction was a significant factor for bone and muscle (estimated alpha/beta values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0-3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high alpha/beta ratio, inverse relationship with overall treatment duration, and faster development of mucosal complications suggests that they may develop as a consequence of earlier mucosal injury. As anticipated, adequate retrospective analysis of acute complications could not be made even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalization during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. CONCLUSION: The radiobiological characteristics of bone and muscle were those characteristic of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.

Carcinoma, Squamous Cell↗

Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings.

PURPOSE: The purpose of the study was to determine if Positron emission tomography (PET) 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) imaging could detect subclinical local lung cancer recurrence and whether retreatment of such recurrence was feasible and beneficial. METHODS AND MATERIALS: Twenty patients with biopsy proven lung cancer were studied with Positron emission tomography for the purpose of detecting subclinical lung cancer recurrence over a period of 4.25 years. All patients were treated with external radiation as part or all of their therapy. Twenty patients had baseline PET and computed tomography (CT) studies for comparison with later studies. Surviving patients had a total of 40 sequential PET scans and 35 CT scans. The follow-up interval ranged from 5 to 40 months posttreatment. The differential uptake ratio (DUR) was determined for regions of interest of increased FDG uptake. RESULTS: The median DUR value of the 20 baseline PET studies was 5.59. The DUR value of greater than 3 was empirically selected as being positive for tumor detection. On baseline studies, PET had a 100% correlation with the CT findings in regard to detection of the site of primary tumor involvement. Four of 20 patients showed areas of discordance in the mediastinal and hilar areas on initial PET and CT studies. Seven of 17 patients showed discordant posttreatment PET-CT findings. Two false positive PET studies were due to radiation pneumonitis and one to macrophage glycolysis in tumor necrosis. For detection of asymptomatic tumor recurrence, analysis of sequential PET and CT studies, biopsy results, and the patient's clinical course suggested that PET had a sensitivity of 100%, specificity of 89.3%, and accuracy of 92.5%. Computerized Tomography was found to have a sensitivity of 67%, specificity of 85%, and accuracy of 82% for detection of such early-stage recurrence. Five patients went on to have retreatment with external irradiation based upon the PET evidence. Four retreated patients had biopsies that corroborated the positive PET findings, and one patient was retreated on the basis of the qualitative appearance of the posttreatment PET study. Two of the five retreated patients remain alive without evidence of tumor to 34 months following initial therapy. CONCLUSION: Positron emission tomography scanning appears to be effective in detecting and following the progression of recurrent lung cancer. Retreatment of patients with asymptomatic recurrent tumor has resulted in absent or decreased FDG activity. Monitoring of patients with PET may provide prolonged survival in patients who otherwise would fail treatment because of local tumor recurrence.

Adenocarcinoma↗

Recombinant Desulfovibrio vulgaris rubrerythrin. Isolation and characterization of the diiron domain.

The gene encoding Desulfovibrio (D.) vulgaris rubrerythrin (Prickril, B. C., Kurtz, D. M., Jr., LeGall, J., & Voordouw, G. (1991) Biochemistry 30, 1118), a protein of unknown function containing both FeS4 and (mu-oxo)diiron sites, was cloned and overexpressed in Escherichia coli. Upon cell lysis, the overexpressed protein was found in an insoluble form deficient in iron. Iron was incorporated in vitro by dissolving the protein in 3 M guanidinium chloride, adding Fe(II) anaerobically and diluting the denaturant. This recombinant rubrerythrin was found to have properties very similar to those of rubrerythrin isolated from D. vulgaris, except that the recombinant rubrerythrin contained six rather than four (or five) iron atoms per 44 kDa homodimer. Analyses of UV-vis, Mössbauer, and EPR spectra showed that the six iron atoms in recombinant rubrerythrin are organized as two FeS4 and two (mu-oxo/hydroxo)diiron sites. In order to allow examination of the diiron sites in the absence of the FeS4 sites, a truncated gene encoding the N-terminal 152 residues of D. vulgaris rubrerythrin was also cloned and overexpressed as an insoluble protein in E. coli, and iron was incorporated by a procedure analogous to that for recombinant rubrerythrin. This so-called "chopped" rubrerythrin (CRr) was found to consist of an approximately 35 kDa homodimer containing four iron atoms. Spectroscopic characterization indicated that the four iron atoms in CRr are organized as two diiron sites, the majority of which closely resemble the (mu-oxo)diiron(III) sites in E. coli ribonucleotide reductase R2 protein, and a minor fraction of which resemble the mixed-valent diiron(II,III) site in methane monooxygenase hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗