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Biomedical subjects

D Kumar

Publications and source records attributed to D Kumar.

At least 91 records · Page 5Linked to original sources

Detection of EWS-FLI-1 fusion in Ewing's sarcoma/peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue.

The balanced translocation t(11;22)(q24;q12) is specific for the Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in situ hybridization (FISH) to show the translocation; however, most of these have been performed on cell lines or touch preparations and short-term cultures of tumors. Moreover, the existing probes generally have shown only the break in the specific chromosomes rather than the translocation itself. We describe our findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1) and directly show the translocation as juxtaposed red-green signals on der(22) in nuclei extracted from formalin-fixed, paraffm-embedded tissues. After establishing the specificity of the probes (on metaphase spreads and interphase nuclei in two translocation-positive cell lines and normal peripheral blood lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random overlapping signals were present in 2% and 4% of nuclei, whereas the remaining eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in 10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe pair is a specific and sensitive method of detecting t(11;22) on routinely processed tissue and can be useful in the differential diagnosis of ES/PNETs from other small round blue cell tumors when only fixed tissue is available.

Adolescent↗

Vitellins and vitellogenins of Dysdercus koenigii (Heteroptera: Pyrrhocoridae)--identification, purification and temporal pattern.

Two vitellins, VtA and VtB, were purified from the eggs of Dysdercus koenigii by gel filtration and ion exchange chromatography. VtA and VtB have molecular weights of 290 and 260 kDa, respectively. Both Vts are glycolipoproteinaceous in nature. VtA is composed of three polypeptides of M(r) 116, 92 and 62 kDa while VtB contained an additional subunit of M(r) 40 kDa. All subunits except the 116-kDa subunit are glycolipopolypeptides. Polyclonal antibody raised against VtA (anti-VtA antibody) cross-reacted with VtB and also with vitellogenic haemolymph and ovaries and pre-vitellogenic fat bodies, but not with haemolymph from either adult male, fifth instar female, or pre-vitellogenic females demonstrating sex and stage specificity of the Vts. Immunoblots in the presence of anti-VtA revealed two proteins (of 290 and 260 kDa) in both vitellogenic haemolymph and pre-vitellogenic fat bodies that are recognised as D. koenigii Vgs. In newly emerged females, Vgs appeared on day 1 in fat bodies and on day 3 in haemolymph and ovaries. Vg concentration was maximum on day 2 in fat body, day 4 in haemolymph and day 7 in ovary. Although the biochemical and temporal characteristics of these proteins show similarity to some hemipterans, they are strikingly dissimilar with those of a very closely related species.

Animals↗

Carboxylic and dicarboxylic acids extracted from crushed magnesium oxide single crystals.

Carboxylic and dicarboxylic acids (glycolic, oxalic, malonic and succinic) have been extracted with tetrahydrofuran (THF) and H2O from large synthetic MgO crystals, crushed to a medium fine powder. The extracts were characterized by infrared spectroscopy and 1H-NMR. The THF extracts were derivatized with tert-butyldimethylsilyl (t-BDMS) for GC-MS analysis. A single crystal separated from the extract was used for an x-ray structure analysis, giving the monoclinic unit cell, space group P21/c with ao = 5.543 A, bo = 8.845 A, co = 5.086 A, and beta = 91.9 degrees, consistent with beta-succinic acid, HOOC(CH2)COOH. The amount of extracted acids is estimated to be of the order of 0.1 to 0.5 mg g-1 MgO. The MgO crystals from which these organic acids were extracted grew from the 2860 degrees C hot melt, saturated with CO/CO2 and H2O, thereby incorporating small amounts of the gaseous components to form a solid solution (ss) with MgO. Upon cooling, the ss becomes supersaturated, causing solute carbon and other solute species to segregate not only to the surface but also internally, to dislocations and subgrain boundaries. The organic acids extracted from the MgO crystals after crushing appear to derive from these segregated solutes that formed C-C, C-H and C-O bonds along dislocations and other defects in the MgO structure, leading to entities that can generically be described as (HxCyOz)n-. The processes underlying the formation of these precursors are fundamental in nature and expected to be operational in any minerals, preferentially those with dense structures, that crystallized in H2O-CO2-laden environments. This opens the possibility that common magmatic and metamorphic rocks when weathering at the surface of a tectonically active planet like Earth may be an important source of abiogenically formed complex organic compounds.

Carboxylic Acids↗

Involvement of signal transduction pathways in Salmonella typhimurium porin activated gut macrophages.

Many membrane proteins are implicated in the regulation of cell functions by triggering specific signaling pathways. Porins are known potential modulators of cell proliferation and differentiation. We explored the possible involvement of this protein in signal transduction pathways in mouse gut macrophages. In the present work we have shown that porins can trigger signal transduction in mouse macrophages infected with S. typhimurium. Activation of macrophages by porins results in an increase in inositol trisphosphate and intracellular Ca2+ mobilization. There is a translocation of protein kinase C to the membrane which is accompanied by nitric oxide release within the macrophages. This effect is the outcome of the expression of nitric oxide synthase, which is dependent on Protein kinase C. Further, we observed that there is an increased binding of the porins on macrophages infected with S. typhimurium which results in activation of macrophages and triggering of specific signaling pathways. These results indicate that porins induce the production of nitric oxide via a protein kinase C dependent pathway. Nitric oxide plays a fundamental role in macrophage effector function where it has both communication and defensive function.

Animals↗

Fecal incontinence.

Explore the source record for details and available documents.

Fecal Incontinence↗

Preoperative staging of rectal carcinoma.

BACKGROUND: The development of treatment modalities for rectal cancer, including local excision, total mesorectal excision and preoperative radiotherapy, has increased the importance of accurate preoperative staging to allow the optimum treatment to be selected. METHODS: A literature review was undertaken of methods of preoperative staging of rectal carcinoma and the evidence for each was evaluated critically. RESULTS: Clinical assessment of rectal carcinoma may give an indication of fixity but is not accurate for staging. Endoanal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), radioimmunoscintigraphy and positron emission tomography have all been used for staging. The extent of tumour spread through the bowel wall (T stage) is most accurately assessed by endoanal ultrasonography, although this technique is poor at assessing tumour extension into adjacent organs for which both CT and MRI are more accurate. No method accurately determines lymph node involvement, but endoanal ultrasonography is the best available. Liver metastases may be assessed by abdominal ultrasonography, CT, MRI and CT portography (with increasing sensitivity and cost in that order). CONCLUSION: Endoanal ultrasonography is the most effective method of local tumour staging, with the addition of either CT or MRI if adjacent organ involvement is suspected. Abdominal ultrasonography or CT is recommended for routine preoperative assessment of the liver.

Humans↗

Low rates of Helicobacter pylori reinfection in children.

BACKGROUND & AIMS: Reinfection after treatment for Helicobacter pylori is uncommon in adults. It is more likely to occur in children because they acquire primary infection. The aim of this study was to determine whether children are likely to become reinfected with H. pylori and if there are any risk factors for reinfection. METHODS: A prospective study of children who had documented evidence of successful treatment for H. pylori infection was performed. Sixty children were eligible for inclusion; results for 52 are presented. Children, parents, and siblings underwent [(13)C]urea breath tests. Details of family size and socioeconomic status were documented. Cox logistic regression analysis was used to determine the risk factors for reinfection. RESULTS: The duration of follow-up was 103.8 patient-years (mean +/- SD, 24 +/-14.0 months). Forty-six (88.5%) of the index children remained clear of infection, and 6 (11.5%) children were reinfected. The mean age of those who became reinfected was 5.8 +/- 5.6 years compared with 12.3 +/- 3.0 years for those who remained clear of infection (P = 0.00001). Only 2 of 46 (4.3%) children older than 5 years of age were reinfected, although 80.8% had 1 infected parent and 65% of siblings were infected. Reinfection rate was 2.0% per person per year in children older than 5 years. Living with infected parents and siblings and low socioeconomic status were not risk factors for reinfection. In logistic regression analysis, age was the only risk factor for reinfection. CONCLUSIONS: Reinfection with H. pylori occurs rarely in children older than 5 years of age regardless of socioeconomic group or number of infected family members. These findings also indicate that it is not necessary to treat all family members to achieve long-term eradication of H. pylori.

Adolescent↗

Transcutaneous electrostimulation: emerging treatment for diabetic neuropathic pain.

Three independent studies utilizing transcutaneous electrical nerve stimulation to relieve diabetic peripheral neuropathic pain were reviewed. The proprietary equipment, an H-wave machine, administered all electrotherapy. The first two studies assessed the efficacy of electrotherapy alone and electrotherapy with amitriptyline. The treated electrotherapy group reported an overall greater reduction of symptoms, 52% with 2-3 weeks of active treatment. Amitriptyline alone produced a 26% reduction of pain after 4 weeks. The addition of active electrotherapy to amitriptyline produced a 66% reduction of pain. The final study looked at patients who have utilized electrotherapy for over one year. A reported 44% improvement of symptoms was attained with continuous electrotherapy treatment. The data also suggested that a maintenance treatment protocol for long-term pain relief would have to be developed.

Amitriptyline↗

Differential diagnosis between monomorphic clear cell adenocarcinoma of salivary glands and renal (clear) cell carcinoma.

Clear cell adenocarcinoma of salivary glands (CCASG) is a relatively rare tumor, composed entirely of clear cells of putative ductal origin. It bears striking morphologic similarities to renal cell carcinoma (RCC) of clear cell type on hematoxylin and eosin stains. Differentiation between CCASG and metastatic RCC to the salivary glands has been considered problematic or even impossible on morphologic grounds. We examined three cases of CCASG and 12 cases of RCC (6 primary and 6 metastatic) by hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. Two distinctive immunohistochemical and ultrastructural patterns emerged from this analysis. CCASG showed positivity for high molecular weight cytokeratin and carcinoembryonic antigen and ultrastructurally showed prominent squamoid differentiation, glycogen pools, and absence of lipid. In contrast, RCC was characterized by positivity for vimentin and complete absence of staining for high molecular weight cytokeratin and carcinoembryonic antigen. On ultrastructural studies, RCC lacked any squamoid differentiation, and the tumor cells contained abundant cytoplasmic lipid in addition to glycogen. Thus, based on the consistent differences on the immunohistochemical staining patterns and their characteristic subcellular morphology, CCASG and RCC can be distinguished on pathologic evaluation. The different direction of differentiation of the cells in CCASG and RCC (i.e., ductal in the former and renal tubular and mesodermal in the latter) results in their distinctive immunophenotypical and ultrastructural features.

Adenocarcinoma, Clear Cell↗

Access to coronary artery bypass surgery by race/ethnicity and gender among patients who are appropriate for surgery.

OBJECTIVE: The study sought to determine if there were race/ethnicity or gender differences in access to coronary artery bypass graft (CABG) surgery among patients who have been designated as appropriate and as necessary for that surgery according to the RAND methodology. METHODS: RAND appropriateness and necessity criteria were used to identify a race/gender stratified sample of postangiography patients who would benefit from coronary artery bypass graft surgery. These patients were tracked for 3 months to determine if they had undergone coronary artery bypass graft surgery in New York State. Subjects were a total of 1,261 postangiography patients in eight New York hospitals in 1994 to 1996. Measures included percentages of patients for whom coronary artery bypass graft surgery was appropriate and necessary undergoing surgery by race/ethnicity and gender, as well as multivariate odds ratios for race/ethnicity and gender. RESULTS: After controlling for age, payer, number of vessels diseased, and presence of left main disease, African-American and Hispanic patients were found to be significantly less likely to undergo coronary artery bypass graft surgery than white non-Hispanic patients (respective odds ratios 0.64 and 0.60). When "necessity" was used as a criterion instead of "appropriateness," significant differences in access for African-American patients remained. The gatekeeper physician recommended surgery only 10% of the time that patients did not undergo "appropriate" coronary artery bypass graft surgery, and this percentage did not vary significantly by race/ethnicity or gender of the patient. CONCLUSIONS: Even after controlling for appropriateness and necessity for coronary artery bypass graft surgery in a prospective study, African-American patients had significant access problems in obtaining coronary artery bypass graft surgery. These problems appeared not to be related to patient refusals.

Black or African American↗

Inter-observer reproducibility of quantitative radionuclide colonic transit imaging.

The colonic transit of an indium-111 enteric coated capsule was imaged with a gamma camera over a period of 3 days. The geometric centre of activity in the colon was calculated from regions drawn over four segments of the colon, plus a fifth segment as the estimated passed stool activity. Fifteen healthy subjects were scanned and the results analysed. The images were analysed by two observers to assess reproducibility of the geometric centre quantitative index (correlation, r = 0.985). In conclusion, although it can be difficult to identify the anatomical segments of the colon from the gamma camera images, by following a protocol with clear guidelines for ROI placement, good inter-observer reproducibility can be obtained.

Adult↗

Primary repair of obstetric anal sphincter rupture using the overlap technique.

OBJECTIVE: To evaluate the feasibility of a new technique of primary overlap anal sphincter repair instead of end-to-end repair. SETTING: A teaching hospital and a district general hospital. METHODS: Between June 1995 and November 1996, two obstetricians repaired 32 anal sphincters ruptured during vaginal delivery. A ruptured internal sphincter was repaired separately and the torn ends of the external sphincter were overlapped and sutured with 3/0 polydioxanone sulphate sutures (Ethicon, Edinburgh, UK). MAIN OUTCOME MEASURES: Bowel function, clinical assessment, anal endosonography and manometry performed at a mean of 140 days after delivery. RESULTS: Eight percent of the women experienced incontinence of flatus. Fifteen percent had persistent sonographic external sphincter defects, and 44% had internal sphincter defects. The maximum mean resting pressure was 58 mmHg (range 37-135) and the mean maximum incremental squeeze pressure 54 mmHg (range 8-104). None had defaecatory difficulty and no complications were encountered with the new technique of repair. CONCLUSIONS: Reservations regarding the feasibility of the overlap technique of primary repair are unfounded, as both subjective and objective outcomes are favourable compared with other studies using end-to-end approximation. A multicentre randomised study of the overlap vs end-to-end repair technique is now planned.

Adolescent↗

Rhabdomyolysis complicating unrecognized hypophosphatemia in an alcoholic patient.

Rhabdomyolysis occurring as a complication of hypophosphatemia has been infrequently described. A 58-year-old male with a history of daily alcohol consumption presented with two generalized tonic clonic seizures secondary to hypovolemic hyponatremia. He was volume-resuscitated, and antiepileptic medication was administered. After three days of hospitalization, the patient developed severe rhabdomyolysis despite the absence of further seizure activity. Serum phosphate levels were depressed. He was treated with intravenous mannitol, alkaline diuresis, and intravenous and oral phosphate supplementation. He recovered uneventfully. Hypophosphatemia can potentially lead to multisystem organ dysfunction including severe rhabdomyolysis. It is, therefore, important to maintain a low threshold for measuring serum phosphate levels in patients admitted to hospital.

Alcoholism↗

Cellular immune response to retinal S-antigen and interphotoreceptor retinoid-binding protein fragments in Eales' disease patients.

The role of retinal antigens in Eales' disease was studied in 24 patients and an equal number of healthy controls. Lymphocyte proliferative responses were tested in vitro against native S-antigen, its uveitopathogenic peptides (peptide M and peptide G), yeast histone H3 peptide and uveitopathogenic fragment of interphotoreceptor retinoid-binding protein (IRBP; R16) to establish their role in the pathogenesis of Eales' disease. Out of 24 Eales' disease patients, 6 showed significant proliferative response against S-antigen, its uveitogenic fragments or IRBP. None among the controls showed any response to any retinal antigen used in this study. There was no statistically significant difference in the response to purified protein derivative between patients and controls. These results suggest that retinal antigens may play a role in the etiopathogenesis of Eales' disease. An extraneous agent that could result in exposure of normally sequestered uveitopathogenic antigens of the immune system, leading to an exuberant immune response in the eye may initiate the disease.

Adolescent↗