Irritable bowel syndrome.
Explore the source record for details and available documents.
Colonic Diseases, Functional↗
Biomedical subjects
D Kumar
Publications and source records attributed to D Kumar.
Recombinant Mycobacterium aurum expressing Escherichia coli beta-galactosidase in high throughput screening of antituberculosis drugs.
Mycobacterium aurum is considered a surrogate of M. tuberculosis and recently has been proposed as test organism in high throughput screening of antituberculosis drugs (3). In this investigation, we suggest use of a recombinant M. aurum expressing E. coli lacZ gene, in which beta-galactosidase production is the reporter system as recently reported by us (6). The assay is based on production of beta-galactosidase in presence of drugs during growth. Enzyme production was inhibited within 4 h by frontline antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, ofloxacin, and sparfloxacin at their MICs. The assay could be performed conveniently in 96-well microtiter plate format.
Antitubercular Agents↗
Radiotherapy for rectal cancer.
Explore the source record for details and available documents.
Humans↗
beta-Galactosidase reporter system in mycobacteria and its application in rapid antimycobacterial drug screening.
Pathogenic mycobacteria are generally slow growing organisms and it takes several weeks to evaluate inhibitors of growth. Therefore, for rapid screening of the inhibitors of mycobacterial growth, a beta-galactosidase reporter system has been described which utilises a recombinant Mycobacterium smegmatis mc(2)155 expressing E. coli lacZ gene as the test organism. The assay is based on production of beta-galactosidase in presence of drugs during growth. A correlation between beta-galactosidase production and colony forming ability of mycobacteria was obtained. beta-galactosidase production was inhibited within 6 h by front line standard antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, pyrazinamide and ofloxacin at their reported MICs. The assay was performed on mycobacterial cells permeabilized with chloroform and sodium dodecyl sulfate.
Anti-Bacterial Agents↗
Familial aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal digits in an inbred Pakistani Muslim family: a possible new autosomal recessive disorder with overlapping manifestations of the syndromes of Fuhrmann, Al-Awadi, and Raas-Rothschild.
We describe four affected children belonging to a large, highly inbred Muslim family originating from the North West Frontier Province of Pakistan. All children have a similar pattern of skeletal abnormalities, including aplasia/hypoplasia of the ulnae, hypoplasia of the pelvis, aplasia/hypoplasia of the femora, fibular aplasia, and variable digital abnormalities and absent/dysplastic nails. The phenotype overlaps with the syndromes of Fuhrmann, Al-Awadi, and Raas-Rothschild. The present and previously reported families probably share the same geographic and racial origin, indicating a common genetic basis of the reported skeletal abnormalities in these limb-pelvis aplasia and hypoplasia syndromes. A possibility of a new autosomal recessive syndrome in the present family cannot be excluded. Further delineation and molecular studies are required to clarify the genetic cause and phenotypic variation in Fuhrmann, Al-Awadi, and Raas-Rothschild syndromes.
Abnormalities, Multiple↗
Treatment of rectal cancer.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Parenteral gene therapy with p53 inhibits human breast tumors in vivo through a bystander mechanism without evidence of toxicity.
Mutations of the p53 tumor suppressor gene are the most frequently observed genetic lesion in human cancer. Previously, we found that multiple intravenous injections of a liposome:p53 complex inhibited the growth of a malignant human breast cancer cell line that was implanted into nude mice. In the present study, we evaluated the toxicity of the liposome:p53 complex and the mechanism of this in vivo treatment in reducing tumor growth. Intravenously delivered liposome:p53 complex at dosages sufficient to inhibit human breast cancer in nude mice showed no evidence of toxicity. Clinical chemistries, complete blood counts, and histopathologic examination of various organs from the p53-treated groups did not demonstrate any difference from the control groups. To elucidate the mechanism by which the liposome:p53 complex inhibits cancer, the transfection efficiency of a liposome:chloramphenicol acetyltransferase (CAT) complex into the tumor was determined. Interestingly, less than 5% of the tumor was transfected with a liposome:CAT complex. A mechanism that could account for p53 reduction of tumor size and a low transfection efficiency is inhibition of angiogenesis. After one treatment, we found that the liposome:p53 complex reduced the number of blood vessels in the p53-treated group by approximately 60% compared to the control group (p < 0.001). The close correlation between the antitumor effect of p53 and the reduction of blood vessel density in the tumor suggests that p53 effects are mediated, at least in part, by an antiangiogenesis mechanism.
Animals↗
Coronary artery bypass graft surgery in Ontario and New York State: which rate is right? Steering Committee of the Cardiac Care Network of Ontario.
BACKGROUND: Previous studies have shown that the rate of coronary artery bypass graft (CABG) surgery is much higher in New York State than in Ontario. OBJECTIVE: To compare the service context and clinical characteristics of patients having CABG surgery in New York and Ontario. DESIGN: Retrospective analysis of data from cardiac surgery registries in New York and Ontario. PATIENTS: All 16,690 patients in New York and 5517 patients in Ontario who had isolated CABG surgery in 1993. MEASUREMENTS: Clinical characteristics of patients having CABG surgery and rates of CABG surgery by coronary anatomy. RESULTS: The overall age-adjusted rate of isolated CABG surgery was 1.79 times (95% CI, 1.74 to 1.85) greater in New York than in Ontario. Patients who had CABG surgery in New York were more likely to be elderly and female and to have recently had myocardial infarction (P < 0.001), whereas patients who had CABG surgery in Ontario were more likely to have had left ventricular dysfunction and severe coronary artery disease (two-vessel disease with proximal left anterior descending disease, three-vessel disease, or left main disease) (P < 0.001). The relative rate of CABG surgery for left main disease was 2.53 times (CI, 2.35 to 2.73) greater in New York than in Ontario but was 8.97 times (CI, 8.01 to 10.06) greater for patients with limited coronary artery disease (one-vessel or two-vessel disease without proximal left anterior descending disease). CONCLUSIONS: The higher rates of CABG surgery in New York are associated with higher rates of CABG surgery among the elderly, women, and patients who recently had myocardial infarction. Potential underservicing in Ontario is suggested by a lower rate of CABG surgery for left main disease; however, the higher rate of CABG surgery in New York is also associated with a strikingly higher rate of surgery in patients with limited coronary disease. Such trade-offs highlight the difficulty of defining an optimal rate of CABG surgery.
Adult↗
Cardiorespiratory and neuromuscular effects of O-ethyl S--2-(diisopropylamino) ethyl- methylphosphonothioate (VX) in rats.
Explore the source record for details and available documents.
Adrenalectomy↗
Elevated cytosolic calcium and impaired proliferation of B lymphocytes in type II diabetes mellitus.
Patients with diabetes mellitus have increased susceptibility to infection attributable, at least in part, to defective function of polymorphonuclear leukocytes (PMNLs) and B cells. Certain data suggest that cytosolic calcium ([Ca2+]i) is elevated in various cells in diabetes, and high [Ca2+]i adversely affects cell function. Indeed, the [Ca2+]i of PMNLs of diabetic patients is elevated, and phagocytosis of the PMNLs is impaired. The current study examines whether the [Ca2+]i of B cells is also elevated in diabetes and whether this derangement impairs B cell function. We studied 32 patients with non-insulin-dependent diabetes mellitus (NIDDM) and eight normal subjects. All patients had hyperglycemia (11.6 +/- 0.80 mmol/L) and elevated HbA1c (13.2% +/- 0.99%). The basal levels of [Ca2+]i of the B cells (113 +/- 3.3 nmol/L) were significantly (P < 0.01) higher than the values in normal subjects (85 +/- 1.7 nmol/L). There was a direct and significant correlation (r = 0.88; P < 0.01) between the [Ca2+]i of B cells and the blood levels of glucose. Proliferation of B cells in response to Staphylococcus aureus Cowan I (SAC) was significantly impaired in these patients (7.3 +/- 0.48 x 10(3) cpm v 12.5 +/- 0.61 x 10(3) cpm in normal subjects). Normalization of blood glucose with the hypoglycemic agents, glyburide, was associated with the return of both [Ca2+]i of B cells and their proliferation in response to SAC to normal. The results show that hyperglycemia in type II diabetes mellitus is associated with a significant increase in [Ca2+]i of B cells and with a decrease in their proliferation in response to mitogen. These derangements are reversed after the correction of the hyperglycemia. The data of the current study and those previously reported in PMNLs provide for a new pathogenetic process underlying the dysfunction of these cells in diabetes mellitus.
Adult↗
Immunomodulatory effects of NIM-76, a volatile fraction from Neem oil.
The immunomodulatory properties of NIM-76 have been described in this paper. Pre-treatment of rats with a single i.p. injection of NIM-76 resulted in an increase in polymorphonuclear (PMN) leukocytes with a concomitant decrease in lymphocyte counts. The immunomodulatory activity of NIM-76 was found to be concentration-dependent. At 120 mg/kg body weight, there was an enhanced macrophage activity and lymphocyte proliferation response, while the humoral component of immunity was unaffected. At higher concentrations of NIM-76 (300 mg/kg body weight), there was a stimulation of mitogen-induced lymphocyte proliferation, while macrophage activity remained unaffected. However, a fall in primary and secondary antibody titres was observed. The study indicates that NIM-76 acts through cell-mediated mechanisms by activating macrophages and lymphocytes.
Adjuvants, Immunologic↗
Cloning and characterisation of a gene encoding an antiviral protein from Clerodendrum aculeatum L.
The Clerodendrum aculeatum-systemic resistance inducing (CA-SRI) protein, a 34 kDa basic protein, plays a key role in inducing strong systemic resistance in susceptible plants against various plant viruses [22]. We have cloned the cDNA encoding the CA-SRI from C. aculeatum leaves using antibodies raised against the purified protein and degenerate oligonucleotide probes derived from microsequencing of the CA-SRI protein. The full-length cDNA consisted of 1218 nucleotides with an open reading frame of 906 bp. The deduced amino acid sequence of CA-SRI protein showed varying homology (ranging from 11 to 54%) to the ribosome inactivating proteins (RIPs) from other plant species. CA-SRI inhibited in vitro protein synthesis both in rabbit reticulocyte lysate and wheat germ lysate but not in Escherichia coli in vitro translation system. The CA-SRI open reading frame was expressed in an E. coli expression vector and the purified recombinant protein inhibited protein synthesis in rabbit reticulocyte lysate. Southern blot analysis indicated that the CA-SRI gene may be present in low copy number.
Amino Acid Sequence↗
Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.
Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis.
Adolescent↗
Adriamycin cardiomyopathy: pathophysiology and prevention.
Current knowledge about adriamycin cardiomyopathy indicates that the major cause of this condition is increased oxidative stress although the drug's antitumor action in patients may involve other mechanisms. Controversies about the different antioxidants in preventing cardiomyopathy likely stem from the fact that antioxidants must be effective in both the lipid and water phases, and the dose must be optimal, in order to be protective. Probucol, an antioxidant and promoter of endogenous antioxidants, is one such agent. Conducting clinical trials with an optimal dose of probucol is the next step and should make this great anticancer drug safer and more efficient in the fight against the cancer.
Animals↗
Primary low-grade B-cell lymphoma of the dura: a mucosa associated lymphoid tissue-type lymphoma.
The clinicopathologic findings in five patients with primary low-grade B-cell lymphoma of the intracranial dura are described. All patients were women, 40-62 years of age, who presented with focal neurologic symptoms. Radiologic studies showed a well-localized dural mass in each case, raising a preoperative diagnosis of meningioma. Cytologically these were composed of a diffuse infiltrate of small lymphocytes with plasmacytoid differentiation, with a variable admixture of centrocytelike cells. Lambda light chain restriction was found in three cases, and kappa light chain in one. VJ polymerase chain reaction for immunoglobulin heavy-chain rearrangement was positive in three of four cases, including one case in which immunostaining results were equivocal. Staging procedures did not show involvement at any other site. Therapy consisted of radiation (n = 3), chemotherapy (n = 1), or both (n = 1), with excellent response. There was no evidence of recurrence or subsequent dissemination at follow-up of up to 63 months. Low-grade B-cell lymphomas arising in the intracranial dura are rare but appear to be similar to other low-grade B-cell lymphomas arising in extranodal sites in terms of clinical presentation as stage 1E disease, indolent behavior, and favorable response to treatment, suggesting that they may be part of the mucosa associated lymphoid tissue (MALT) lymphoma spectrum. They appear to arise at dural sites where meningothelial cells are concentrated.
Adult↗
Assessment of coronary artery bypass graft surgery performance in New York. Is there a bias against taking high-risk patients?
OBJECTIVES: The purpose of this study was to determine whether performing coronary artery bypass surgery on high-risk patients adversely affects the risk-adjusted mortality rates for patients of surgeons and hospitals in New York State compared with the impact of performing surgery on more routine patients. METHODS: Risk-adjusted mortality-rates were calculated for 31 hospitals and 87 surgeons for high-risk (a predicted mortality rate of at least 7.5%) and low-risk patients during the time period 1990 to 1992. RESULTS: The risk-adjusted mortality for all high-risk patients was lower (2.94%) than the risk-adjusted mortality for other patients (3.02%). Fifteen of the 31 hospitals had a lower risk-adjusted mortality for all patients than they did for low-risk patients only, and no differences in either direction were statistically significant. Forty-one of 87 surgeons (47%) had risk-adjusted mortality for all patients that was at least as low as the risk-adjusted mortality for low-risk patients. In general, hospitals and surgeons with the lowest risk-adjusted mortality for all cases also had the lowest risk-adjusted mortality for high-risk cases. CONCLUSIONS: The authors conclude that there is no systematic bias against operating on high-risk coronary artery bypass graft patients in the risk-adjusted performance system in New York.
Bias↗
A new multiple malformation syndrome of Müllerian dysgenesis and conductive hearing loss with facial hypoplasia, bilateral forearm deformity, brachydactyly, spinal stenosis and scoliosis.
Multiple congenital malformations in a young girl with bilateral conductive hearing loss are described. Facial dysmorphic features include prominent supraorbital ridges, facial hypoplasia, facial asymmetry, downward-slanting palpebral fissures, high prominent nasal bridge with bifid nasal tip and a small lower jaw, and hypoplastic ear lobules with bilaterally narrow and oblique external auditory canals. Recognisable skeletal abnormalities include hypoplastic facial bones, hypoplastic clavicles, narrow and anteriorly sloping shoulders, bowing of both forearm bones, brachydactyly due to short metacarpals and hypoplastic terminal phalanges, thoracolumbar kyphoscoliosis, narrow transverse measurements of most vertebrae with prominent coccyx, spinal canal narrowing, hypoplasia of lower ilia, medially bowed femora, tibiae and fibulae and brachysyndactyly of the second, third and fourth toes bilaterally. Gynaecological evaluation revealed abnormalities of the Mullerian duct structures: urogenital sinus, a vestigial uterus, a posteriorly placed small but patent vagina and a septum at the vaginal introitus. The pattern of MCA probably refers to a new syndrome within the "community of syndromes" involving anomalies of the Mullerian duct structures, limbs, spine and external ears.
Abnormalities, Multiple↗
Standardisation of polymerase chain reaction for the detection of Salmonella typhi in typhoid fever.
To improve the diagnosis of Salmonella typhi infection, a polymerase chain reaction (PCR) assay was developed for the amplification of the dH flagellin gene of S typhi. Primers were designed from dH flagellin gene sequence which will give an amplification product of 486 base pairs. In tests to study the specificity of the assay, no amplification was seen in non-salmonella strains or salmonella strains with flagellar gene other than "d". Sensitivity tests determined that 28 pg of S typhi target DNA or 3 x 10(2) target bacteria could be detected by the PCR assay. Subsequently, the PCR technique was used for detection of S typhi in blood or clot cultures from 84 patients clinically suspected of having typhoid fever, and from 20 healthy control subjects. Twenty five of 84 samples from clinically suspected cases were positive by PCR; four of which were culture negative. No amplification was seen in samples from patients who were culture positive for organisms other than S typhi or from controls. The time taken for each sample for PCR analysis was less than 48 hours compared with three to five days for blood or clot culture. PCR appeared to be a promising diagnostic test for typhoid fever.
DNA, Bacterial↗