Acute respiratory infections with special reference to pneumonia in underfives.
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Cause of Death↗
Biomedical subjects
S Mishra
Publications and source records attributed to S Mishra.
A spin decay assay for tumor necrosis factor cytotoxicity.
Tumor necrosis factor (TNF) is believed to elicit its response primarily by an oxidative process. We present a sensitive biophysical assay system to monitor TNF-induced cell killing by electron paramagnetic resonance (EPR) spectroscopy using the spin label 2,2,6,6-tetramethyl-1-piperidine-n-oxyl (TEMPO). The rate of TEMPO spin decay by the TNF sensitive L929 cells was hypothesized to be an indicator of TNF cytolytic response. The cell-induced rate of loss of TEMPO signal was sensitive to concentration as well as time of incubation with TNF. The TEMPO spin decay first derivative plot correlated well with corresponding TNF cytotoxicity curve as obtained by a standard tetrazolium dye reduction bioassay. While dimethyl sulfoxide (DMSO) (up to 500 mM) and alpha-tocopherol (1 mM) inhibited the TNF induced inhibition of rate of loss of TEMPO decay, superoxide dismutase (SOD) (100 U/ml), catalase (1000 U/ml), and histidine (6 mM) had little effect on the TEMPO decay rate. The loss of TEMPO signal was determined to be at an outer domain of the lipid bilayer as illustrated by its decay and broadening in presence of NiCl2. Thus the reduction of a lipid soluble spin label like TEMPO as monitored by EPR could be a useful reporter to study TNF cytotoxicity in target cells.
Animals↗
Keloid at the venipuncture site.
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Ampicillin↗
Urticaria--an unusual presentation of staphylococcemia.
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Bacteremia↗
Interferon gamma-induced reduction in erbB-2 tyrosyl phosphorylation in human ovarian carcinoma cells.
Interferon, which inhibits growth of ovarian cancer cells in vivo and in vitro, decreases expression of erbB-2 protein in ovarian carcinoma cell lines. We now show that interferon-gamma (IFN-gamma) also decreases constitutive tyrosine phosphorylation of erbB-2 and inhibits erbB-2 kinase activity in an ovarian cancer cell line. SK-OV3 ovarian cancer cells, which over-express erbB-2, were treated with IFN-gamma for 0-72 hr. Immunoblot analysis revealed that IFN decreased the levels of tyrosyl phosphorylated erbB-2 24 hr after IFN treatment. Protein levels of erbB-2 were not changed until 72 hr post-treatment. Tyrosine kinase (TK) activity of immunoprecipitated erbB-2 for an exogenous substrate was decreased in IFN-treated cells. Total cellular protein tyrosine phosphatase (PTPase) activity for the epidermal growth factor receptor was not changed by IFN treatment. Our results suggest that the decreased levels of tyrosyl phosphorylated proteins observed after IFN treatment in SK-OV3 cells may be due to inhibition of erbB-2 kinase activity.
Cell Division↗
Permanent iodine-125 (I-125) boost implants after external radiation therapy in nasopharyngeal cancer.
PURPOSE: Higher doses of external irradiation in patients with nasopharyngeal cancer have resulted in improved control of the primary tumor, but can result in significant late toxicity. Tumor control in locally advanced nasopharyngeal cancer remains suboptimal due to the technical difficulties associated with delivering high doses of radiation to the tumor while shielding the brainstem, spinal cord, optic chiasm, etc. We report the use of I-125 boost implants following moderate dose external radiation therapy in nasopharyngeal cancer, in an attempt at improving the local tumor control without increasing toxicity. METHODS AND MATERIALS: Twenty consecutive patients with nasopharyngeal cancer were treated with external beam irradiation (median dose 60 Gy over 6 weeks) to the primary site and the neck followed by I-125 implant to the primary site. RESULTS: With a median follow-up of 2 years (range 1-5 years) there has been no instance of necrosis or other complications related to the implant. So far, in no patient has the tumor recurred at the primary site, although 6 of the 20 patients (30%) have developed metastases. CONCLUSIONS: These data indicate that elective I-125 implantation could be performed safely after external irradiation in nasopharyngeal cancer, and has yielded an encouraging level of primary tumor control, to date.
Adolescent↗
Absorbable mesh in placement of temporary implants.
PURPOSE: To evaluate absorbable mesh for the suturing of afterloading catheters in patients with tumors involving the chest wall. METHODS AND MATERIALS: Patients underwent thoracotomy and resection of tumor; a layer of absorbable mesh was then sutured to the tumor bed. Nylon flexiguide afterloading catheters were sutured into the mesh at about 1.5 cm distance from each other. A second layer of mesh was then sutured on top of the catheters. The chest wall was closed. Orthogonal radiographs and CT scans of the area of implants were done to verify catheter position in each patient on day 1 and on the last day of implant. Computer dosimetry by digitization of dummy sources was performed on each set of radiographs. The same seed for both sets of films was chosen as the origin of digitization. All seed coordinates were compared directly to offset for any rotation of the patient during the two sets of films. The distances were calculated from all seed positions to the origin, then tabulated and compared. RESULTS: The distances agreed within a few millimeters (7-8 mm). The differences may be attributed to the patient's breathing and to the localization uncertainty. The resulting dose alteration was negligible. CONCLUSION: This technique appears to provide adequate anchorage of catheters with resulting constant seed position and dose distribution in areas of scant tissues or in surgical beds of considerable size.
Aged↗
Palladium 103 plaque radiotherapy for uveal melanoma. Clinical experience.
PURPOSE: To evaluate the effect of palladium 103(103Pd) ophthalmic plaque brachytherapy on patients with uveal melanoma. BACKGROUND: Radioactive 103Pd seeds have become available for plaque brachytherapy, and computer-aided simulations have compared the intraocular dose distribution of 103Pd versus iodine 125 (125I) plaques in patients with uveal melanoma. The use of the lower-energy radionuclide 103Pd increased the radiation to the tumors and decreases irradiation of most normal ocular structures. METHODS: The authors have begun a phase 1 clinical trial evaluating the effect of 103Pd ophthalmic plaque radiotherapy on intraocular tumors. Uveal melanoma was diagnosed, and the patients were found to be negative for metastatic disease. All patients were given one 103Pd radioactive plaque treatment, and six patients also were given adjuvant microwave hyperthermia. RESULTS: Palladium 103 ophthalmic plaque radiotherapy was used to treat 23 patients with uveal melanoma. Patients were followed for up to 27 months (mean, 13.5 months). One eye was enucleated for progressive tumor enlargement (4 months after treatment). One patient died (of metastatic melanoma). Eight patients have lost greater than two lines of visual acuity, one has gained more than two lines. Fifteen patients (65%) were within two lines or had better than their preoperative visual acuity. Relating to the effect of treatment on visual acuity, 15 (65%) tumors were located equal to or less than 2 mm from the fovea. CONCLUSION: Palladium 103 ophthalmic plaque radiotherapy was noted to control the growth of uveal melanomas. Compared with other forms of plaque radiotherapy at this follow-up interval, the authors have noted no new complications, no difference in local control, and/or changes in tumor response to treatment. More long-term follow-up will be required to demonstrate differences between 125I and 103Pd ophthalmic plaque brachytherapy.
Brachytherapy↗
Persistent diarrhoea: an unusual presentation of typhoid fever.
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Child, Preschool↗
Ca2+ influx induced by photodynamic action in human cerebral glioma (U-87 MG) cells: possible involvement of a calcium channel.
The plasma membrane has been implicated as a critical target of photodynamic action on cells. We have observed that the photosensitization of human cerebral glioma (U-87 MG) cells by hematoporphyrin derivative (HpD) causes a large increase in intracellular calcium [Ca2+]i. This increase in [Ca2+]i was solely due to the influx of extracellular Ca2+ through the plasma membrane and showed a dependence on HpD concentration, light dose and concentration of calcium in the extracellular medium. The magnitude of the Ca2+ influx decreased with increasing postirradiation time, which suggests that the cell membrane partially recovers from the photodynamic injury. The photoinduced Ca2+ influx was inhibited by the Ca2+ channel blocker diltiazem and the reducing agent dithioerythritol. These findings are discussed in terms of possible activation of a Ca2+ channel as a result of photosensitization.
Biological Transport↗
How do mothers recognize and treat pneumonia at home?
Two hundred mothers of children under five years of age having lower respiratory tract infection were interviewed with the help of pretested unstructured questionnaire to know the danger signs perceived by her in a child suffering from pneumonia and the home remedies used by them before seeking medical help. 'Pasli Chalna' and refusal to feed were the most common symptoms perceived as dangerous. 'Pasli Chalna' correlated with retractions in 91.9% and fast breathing in 8.1% cases. Honey (25%) and Ginger (27%) were the most common home remedies used for relief of cough. Self advised medications were used by 24% mothers and majority (58.4%) gained this knowledge from mass media.
Child, Preschool↗
Role of adrenal in establishment and development of conceptus in unilaterally ovariectomized mated rats.
The model of unilateral ovariectomy induced ovarian compensatory hypertrophy in mated bilaterally adrenalectomized rats was used to assess the role of adrenal in conceptus development. Replacement dose of dehydroepiandrosterone (DHA) or corticosterone (Comp. B) from day 2-14 post coitum was given with or without ip injections of estrogen (E, on day 2) and progesterone (P, on day 3 or 3-9). Replacement of adrenal hormones failed to support ipsilateral uterine horn (IP) pregnancy. But injections of E2 and P support IH pregnancy in variable percentages (about 38-75%) of rats depending on the type of adrenal steroids and single or multiple doses of P. Contralateral horn (CH) pregnancy developed under any of these conditions. Adrenalectomy induced reduction of fetal weight and pregnancy index (No. of fetus divided by No. of implantation sites), were not significantly improved by adrenal hormone replacement, except pregnancy index of those animals which received Comp. B and P. Adrenalectomy inhibited compensatory increase of contralateral corpus luteum (CL) volume and ovarian delta 5(3)beta-hydroxy steroid dehydrogenase (delta 5(3)beta-HSD) activity. Replacement of DHA or Comp. B induced these compensatory changes. Comp. B and P appears to be a better combination in establishment of IH pregnancy, pregnancy index maintenance and stimulation of ovarian compensatory changes. Results suggest that adrenocorticoids were not obligatory for conceptus development but were important for efficient action of ovarian steroids in establishment and maintenance of pregnancy. Relationship between nutrition or pituitary gonadotropins and adrenal steroids, having relevance to conceptus development has been discussed.
Adrenal Glands↗
Modulation of the cytotoxic activity of tumor necrosis factor by protein tyrosine kinase and protein tyrosine phosphatase inhibitors.
The mechanism by which tumor necrosis factor (TNF) inhibits cell growth is not known. The importance of tyrosine phosphorylation in mediating the cytotoxicity of TNF has been suggested from previous studies. In this report, we investigated the effects of both tyrosine kinase (TK) and protein tyrosine phosphatase (PTP) inhibitors on the cytotoxic effects of TNF. TNF-induced changes in cellular PTPase activity were also examined. Incubation of tumor cells with genistein or tyrphostin, known TK inhibitors, protected against TNF cytotoxicity in a dose-dependent manner. Protection by TK inhibitors was observed at early time points after the start of TNF incubation. Preincubation of tumor cells with sodium orthovanadate, a known PTPase inhibitor, also protected against TNF cytotoxicity only at early time points after addition of TNF. Activation of total cellular PTPase activity by TNF was observed at early times of TNF incubation only in TNF-sensitive cell lines. Immunoblot analysis revealed that TNF enhanced tyrosyl phosphorylation of the epidermal growth factor receptor (EGFR) only in TNF-sensitive cell lines. No other substrates were tyr-phosphorylated after addition of TNF. The results suggest that both cellular PTKs and PTPases play a significant role in orchestrating the early events in the cytotoxic response of TNF. The nature and types of PTKs and PTPases involved in this process need further investigation.
Catechols↗
A microtiter enzyme-linked immunosorbent assay for protein tyrosine phosphatase.
We report the development of an enzyme-linked immunosorbent assay (ELISA) for protein tyrosine phosphatases (PTPases). PTPase activity, was monitored by quantitating the disappearance of O-phospho-L-tyrosine (P-Tyr) in an ELISA system using antigen capture followed by double antibody labelling. PTPase activity of agarose conjugated PTP-1B was demonstrated using the ELISA system. PTPase activity was sensitive to both PTB-1B concentrations and time of incubation. 1 mU of PTPase activity was defined as that amount of enzyme producing a rate of loss of 0.01 absorbance units/minute with a specific activity of 150 pmol P-Tyr/min per micrograms protein based on the unit of PTPase activity from the conventional assay system. The PTP-1B activity was shown by the ELISA system to be completely inhibitable by Poly (Glu,Tyr)4:1 at 100 micrograms/ml. We used the ELISA system to detect PTPase activity in lysates of cultured cells. The PTPase activity of cell lysates of MDA-MB 468 breast carcinoma cells as obtained by the ELISA were compared with those obtained by a standard 32P(i) release assay using radio-labelled Raytide as PTPase substrate. The decrease in P-Tyr concentration was dependent on the time of incubation with the lysate and on lysate concentration and compared well with the release of 32P(i) in the radioactive assay system. Orthovanadate as well as heat denaturation inhibited the PTPase activity of the cell lysates in both the assay systems. The assay presented here is a simple immunological system capable of measuring activity of purified PTPases as well as PTPase levels in cell and tissue extracts.
Enzyme-Linked Immunosorbent Assay↗
Role of intracellular Ca2+ in the epidermal growth factor induced inhibition of protein tyrosine phosphatase activity in a breast cancer cell line.
Increased protein tyrosyl phosphorylation in response to growth factors has been assumed to be solely due to activation of protein tyrosine kinases (PTKs). We report that total cellular protein tyrosine phosphatase (PTPase) activity declined in MDA-MB 468 breast carcinoma cells exposed to epidermal growth factor (EGF). The PTPase activity decreased with concentration as well as with time of EGF incubation. As EGF induces increases in intracellular Ca2+ concentrations and such changes may result in depression of PTPase activity, we treated cells with the calcium ionophore A 23187. Increases in calcium induced by the ionophore resulted in activation of cellular PTPases as indicated by increased dephosphorylation of tyrosine phosphorylated EGFR by cellular lysates. Thus, both the extracellular ligand EGF and the intracellular messenger Ca2+ were shown to modulate cellular PTPase activity in MDA-MB 468 breast carcinoma cells. However, EGF-induced decreases in PTPase activity cannot be attributed to EGF-induced increases in intracellular Ca2+ levels.
Breast Neoplasms↗
O-phospho-L-tyrosine inhibits cellular growth by activating protein tyrosine phosphatases.
O-Phospho-L-tyrosine (P-Tyr), a substrate for a wide range of protein tyrosine phosphatases, inhibited growth of human renal and breast carcinoma cells. Growth was blocked in the S phase of the cell cycle. A decrease in the amount of cyclin proteins A and B was also observed. P-Tyr incubation led to activation of cellular protein tyrosine phosphatases resulting in the inhibition of tyrosine phosphorylation of epidermal growth factor receptor as well as of p34cdc2. P-Tyr synergistically sensitized the renal carcinoma ACHN cells to killing by the chemotherapeutic agents doxorubicin and etoposide. These growth inhibitory properties of P-Tyr in vitro suggest its possible use as an anticancer agent.
Breast Neoplasms↗