Cardiorespiratory and neuromuscular effects of O-ethyl S--2-(diisopropylamino) ethyl- methylphosphonothioate (VX) in rats.
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Adrenalectomy↗
Biomedical subjects
D Kumar
Publications and source records attributed to D Kumar.
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↗
Congenital renal tubular dysplasia and skull ossification defects similar to teratogenic effects of angiotensin converting enzyme (ACE) inhibitors.
An apparently autosomal recessive syndrome of congenital renal tubular dysplasia and skull ossification defects is described in five infants from two separate, consanguineous, Pakistani Muslim kindreds. The clinical, pathological, and radiological features are similar to the phenotype associated with fetal exposure to angiotensin converting enzyme (ACE) inhibitors: intrauterine growth retardation, skull ossification defects, and fetal/ neonatal anuric renal failure associated with renal tubular dysplasia. There was no fetal exposure to ACE inhibitors in the affected infants. Phenotypic similarities between these familial cases and those associated with ACE inhibition suggest an abnormality of the "renin-angiotensin-aldosterone" system (RAS). It is postulated that the molecular pathology in this uncommon autosomal recessive proximal renal tubular dysgenesis could be related to mutations of the gene systems governing the RAS.
Abnormalities, Drug-Induced↗
Tuberculosis in England and Wales in 1993: results of a national survey. Public Health Laboratory Service/British Thoracic Society/Department of Health Collaborative Group.
BACKGROUND: A national survey of tuberculosis notifications in England and Wales was carried out in 1993 to determine the notification rate of tuberculosis and the trends in the occurrence of disease by ethnic group in comparison with the findings of similar surveys in 1978/79, 1983, and 1988. The prevalence of HIV infection in adults notified with tuberculosis in the survey period was also estimated. METHODS: Clinical, bacteriological, and sociodemographic information was obtained on all newly notified cases of tuberculosis in England and Wales during the six months from 2 January to 2 July 1993. The prevalence of HIV infection in 16-54 year old patients with tuberculosis notified throughout 1993 was assessed using "unlinked anonymous" testing supplemented by matching of the register of patients with tuberculosis with that of patients with AIDS reported to the PHLS AIDS centre. Annual notification rates were calculated using population estimates from the 1993 Labour Force Survey. RESULTS: A total of 2706 newly notified patients was eligible for inclusion in the survey of whom 2458 were previously untreated the comparable figures for 1988 were 2408 and 2163. The number of patients of white ethnic origin decreased from 1142 (53%) in 1988 to 1088 (44%) in 1993 whereas those of patients of Indian, Pakistani, or Bangladeshi (Indian subcontinent (ISC)) ethnic origin increased from 843 (39%) in 1988 to 1014 (41%) and those of "other" (non-white, non-ISC) ethnic origins increased from 178 (8%) to 356 (14%). The largest increase was seen in the black African ethnic group from 37 in 1988 to 171 in 1993. Forty nine per cent of patients had been born abroad and the highest rates were seen in those who had recently arrived in this country. The overall annual notification rate for previously untreated tuberculosis in England and Wales increased between 1988 and 1993 from 8.4 to 9.2 per 100,000 population. The rate declined in the white, Indian, and black Caribbean ethnic groups and increased in all other groups. In the white group the rate of decline has slowed since the last survey: in several age groups the rates were higher in 1993 than 1988 but the numbers in these groups were small. Thirty six (4.1%) of the 882 previously untreated respiratory cases were resistant to isoniazid and three (0.3%) to isoniazid and rifampicin. Sixty two (2.3%) adults aged 16-54 years were estimated to be HIV-infected. Evidence of under-reporting of HIV positive tuberculosis patients was found. CONCLUSIONS: The number of cases and annual notification rate for previously untreated tuberculosis increased between 1988 and 1993. Although the decline in rates in the white population has continued, the rate of decline has slowed. The high rates in the ISC ethnic group population have continued to decline since 1988 whereas rates in the black African group have increased. An increased proportion of cases were found among people born abroad, particularly those recently arrived in this country. In previously untreated cases the level of drug resistance remains low and multi-drug resistance is rare. A small proportion of adults with tuberculosis were infected with HIV but there may be selective undernotification of tuberculosis in these patients.
Adolescent↗
Diabetic RBC-induced oxidant stress leads to transendothelial migration of monocyte-like HL-60 cells.
Red blood cells (RBC) from patients with diabetes mellitus exhibit an increased propensity to adhere to cultured human umbilical vein endothelial cells (HUVEC) as a result of interaction of advanced glycation end products with their counter receptors, contributing to the pathogenesis of vascular complications. We determined whether the interaction of diabetic RBC with HUVEC induced cellular oxidant stress that would culminate in adherence and diapedesis of monocytes, these being initiating events in endothelial injury and atherogenesis. We show that the adherence of diabetic RBC (2% hematocrit), but not normal RBC, to HUVEC results in a fourfold increase in the production of lipid peroxides. Furthermore, diabetic RBC-induced oxidant stress causes a sixfold increase in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosphorylation and doubles transendothelial migration of monocyte-like HL-60 cells; both are blocked by antioxidants and protein kinase C (PKC) inhibitors. Our results show that the adherence of diabetic RBC to endothelial cells initiates a cascade of cellular events resulting in PKC activation, causing PECAM-1 phosphorylation and concomitant transendothelial migration of monocytes. The increased diapedesis of monocytes, brought about by the interaction of diabetic RBC across vascular endothelium, may play an important role in accelerated atherosclerosis and cardiovascular disease in diabetics.
Antioxidants↗
Wheelchairs as a sign of functional abdominal pain.
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Abdominal Pain↗
Geographic variation in the utilization and choice of procedures for treating coronary artery disease in New York State. Ischaemic Heart Disease Patient Outcomes Research Team (PORT).
OBJECTIVES: To examine geographical variations in rates of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in New York State, and to examine variations in the choice between these two procedures. METHODS: A retrospective analysis of data from the New York registries for CABG and angioplasty was conducted. Rates were compared for 12 different regions of the state to assess geographic variations. To assess variations in the choice of procedure, frequencies of each procedure by region were compared with expected frequencies obtained by a logistic regression model that related procedure performance to various patient risk factors. RESULTS: There was more than a three-fold variation in age/sex adjusted CABG rates and more than a two-fold variation in age/sex adjusted angioplasty rates among regions. The regional percentages of patients undergoing CABG rather than PTCA ranged from 49% to 70%, and most of the disparity was not related to patient risk factors. Instead, the disparity was largely a result of differences in racial composition and the hospitalization rate for myocardial infarctions. CONCLUSIONS: There is considerable regional variation in New York in the tendency to use aggressive cardiac procedures and in the choice of which procedure to use, and these differences are mostly unrelated to patient need.
Age Distribution↗
Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation.
OBJECTIVE: To evaluate the efficacy of transcutaneous electrotherapy for chronic painful peripheral neuropathy in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-one patients with symptoms and signs of peripheral neuropathy were randomized to the electrotherapy or sham treatment (control) group. The electrostimulation was given by a portable unit (H-Wave machine) than generated a biphasic, exponentially decaying waveform (pulse width 4 ms, 25-35 V, > or = 2 Hz). Patients treated each of their lower extremities for 30 min daily for 4 weeks at home. Nine patients from the sham-treatment group participated for a second period, during which all of them received the active electrotherapy. Patient's degree of pain and discomfort was graded on a scale of 0 to 5. RESULTS: In the sham-treated group (n = 13), the neuropathic symptoms improved in five (38%) patients, and the pain score declined from 2.92 +/- 0.13 to 2.38 +/- 0.26 (P < 0.04), suggesting a procedure-related placebo effect. In the electrotherapy group (n = 18), symptomatic improvement was seen in 15 (83%) cases, 3 of which were completely asymptomatic; the pain score declined from 3.17 +/- 0.12 to 1.44 +/- 0.25 (P < 0.01) and the posttreatment pain scores were considerably lower (P < 0.03), indicating a substantial treatment effect over and above any placebo influence. Patients in the electrotherapy group reported greater reduction in symptoms (52 +/- 7% vs. 27 +/- 10% in control subjects, P < 0.05) on an analog scale. Moreover, the electrotherapy decreased pain scores (from 3.0 +/- 0.62 to 1.56 +/- 0.32, P < 0.02) in nine patients who had received sham treatment earlier. CONCLUSIONS: A form of transcutaneous electrotherapy ameliorated the pain and discomfort associated with peripheral neuropathy. This novel modality offers a potential non-pharmacological treatment option.
Adult↗
Lispro analog for treatment of generalized allergy to human insulin.
OBJECTIVE: To evaluate the clinical usefulness of the human insulin analog lispro in a patient with generalized allergy to human insulin. RESEARCH DESIGN AND METHODS: A 34-year-old obese female patient developed systemic allergic reactions to human insulin but tolerated insulin lispro. Sequential analyses of the anti-insulin IgE and IgG immunoglobulins were performed. RESULTS: On intradermal test, the lispro insulin produced a 50% less intense wheal-flare response, compared with human insulin, which was presumed to be due to lispro's molecular form. The intradermal reactivity to both human and lispro insulins decreased with time and disappeared by week 25. 125I-labeled lispro and human insulin binding antibody titers of both the IgE and IgG immunoglobulins were high initially, but decreased progressively, becoming very low by the end of 1 year. In in vitro immunoassay, the lispro and human insulins show a complete cross-reactivity. CONCLUSIONS: Lispro may be useful for the management of allergy to human insulin. This analog of human insulin appears to have a reduced immunogenic potency.
Adult↗
Calcium modulatory properties of O,O-diphenyl O-N-cyclooctyl phosphoramidate [corrected] isolated from Ptychodiscus brevis in rat atria and smooth muscle.
Calcium modulatory activity of a marine toxin has been studied employing in vitro preparations. The toxin induced contracture in rat diaphragm was not modified by denervation, d-tubocurarine and tetrodotoxin (TTX). In contrast, varying concentrations of calcium, EGTA and ryanodine inhibited the contracture significantly. The toxin produced a series of repeating contractions in vas deferens. Experiments with TTX, adrenoceptor blockers and other agents exclude a release of neuromediators or direct stimulation of post synaptic receptors to account for the rhythmic effect in vas deferens. The dependence of rhythmicity on external Ca2+ concentration and inhibiting effect of Mn2+, ryanodine and nifedipine indicate a direct activation of voltage-sensitive calcium channel. The toxin also evoked a similar pattern of response in paced atria mediated through Ca2+ influx.
Animals↗