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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 379 records · Page 21Linked to original sources
PubMed1994

Cross-resistance to cisplatin in cells resistant to photofrin-mediated photodynamic therapy.

This study shows that a Photofrin-induced photodynamic therapy-resistant variant (RIF-8A) of a radiation-induced fibrosarcoma-1 cell line (RIF-1) is cross-resistant to cis-diamminedichloroplatinum(II) (cisplatin). This is the first study to show cross-resistance to cisplatin in photodynamic therapy-resistant variants in vitro. Resistance does not appear to be the result of elevated glutathione levels since neither the resistant variant (RIF-8A) nor the parental line (RIF-1) varied in total glutathione levels. However, cisplatin-DNA adduct levels differed significantly between the two cell types. Immediately following a 1-h exposure to cisplatin (50 microM), RIF-1 cells contained 44.6 +/- 2.0 (SEM) pg platinum/micrograms DNA while RIF-8A cells contained 24.8 +/- 6.3 pg platinum/micrograms DNA. In addition, the resistant variant had decreased plasma and mitochondrial membrane potentials. The plasma and mitochondrial membranes of the resistant variant accumulated 3- and 3.6-fold less rhodamine 123, respectively. The difference in rhodamine 123 accumulation could not be attributed to elevated P-glycoprotein expression because both the parental line and the variant contained similar amounts of P-glycoprotein. In conclusion, alterations in the plasma and/or mitochondrial membrane potentials may provide cells with a survival advantage when challenged with either photodynamic therapy or cisplatin in vitro. This appears to be a novel mechanism of resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Measurement of health status in children with juvenile rheumatoid arthritis.

OBJECTIVE: To develop and validate a self- or parent-administered instrument for measuring functional status in children with juvenile rheumatoid arthritis (JRA). METHODS: We adapted the Stanford Health Assessment Questionnaire (HAQ) for use in children ages 1-19 years, by adding several new questions, such that for each functional area, there was at least 1 question relevant to children of all ages. The face validity of the instrument was evaluated by a group of 20 health professionals and parents of 22 healthy children. The questionnaire was then administered to parents of 72 JRA patients (mean age 9.1 years, onset type systemic in 16, polyarticular in 21, pauciarticular in 35). RESULTS: The instrument showed excellent internal reliability (Cronbach's alpha = 0.94), with a mean inter-item correlation of 0.6. The convergent validity was demonstrated by strong correlations of the Disability Index (average of scores on all functional areas) with Steinbrocker functional class (Kendall's tau b = 0.77, P < 0.0001), number of involved joints (Kendall's tau b = 0.67, P < 0.0001), and morning stiffness (Kendall's tau b = 0.54, P < 0.0001). Spearman's correlation coefficient between Disability Index scores from questionnaires administered to parents and those from questionnaires administered to older children (> 8 years) was 0.84 (n = 29; P < 0.001), showing that parents can accurately report for their children. The test-retest reliability, studied at a 2-week interval, revealed virtually identical Disability Index scores measured on the 2 occasions (0.96 versus 0.96; P > 0.9 by paired t-test; Spearman's correlation coefficient = 0.8, P < 0.002). CONCLUSION: The Childhood HAQ, which takes less than 10 minutes to complete, is a valid, reliable, and sensitive instrument for measuring functional status in children with JRA.

Arthritis, Juvenile↗
PubMed1994

Splenic arterial hemorrhage in pancreatitis: report of three cases.

Gastrointestinal hemorrhage is a rare complication of pancreatitis and can involve any of the peripancreatic vessels. The three cases reported herein illustrate the involvement of the splenic artery in diverse forms of pancreatitis: chronic pancreatitis, a pancreatic pseudocyst, and necrotizing pancreatitis. Bleeding was controlled in all cases by a bipolar ligation of the bleeding vessel at surgery.

Adult↗
PubMed1994

Patient education and health promotion can be effective in Parkinson's disease: a randomized controlled trial. PROPATH Advisory Board.

We performed a randomized controlled trial to evaluate the effectiveness of a patient education and health promotion program in the treatment of Parkinson's disease. The health promotion program (PROPATH) was designed to improve health confidence, provide information and support, improve physical function through exercise, and work with the physician to optimize medical treatment and compliance. The intervention was delivered by mail, with disease assessment questionnaires completed by patient or caregiver at 0, 2, 4, and 6 months, with computer-generated reports and individualized recommendation letters returned to patients and reports to physicians. Two hundred ninety patients completed the 6-month trial, 140 patients in the intervention group and 150 in a control group of patients who received only questionnaires. The intervention group had significantly increased exercise, decreased "time off" and percentage of time off, reduced side effects, and decreased summary Parkinson's scores by approximately 10% (P > 0.05). Twelve of 13 variables showed differences favoring the intervention group. The rate of progression of summary scores became essentially flat during the program for the intervention group and continued to rise sharply for controls (P > 0.01). Levodopa dose rose for controls and slightly decreased for the intervention group. Doctor visits, hospital days, and sick days were reduced in the intervention group. The quality-of-life assessment demonstrated improvement in patient global, self-efficacy scores, and spouse or caregiver assessments. We conclude that a low-cost patient education program provides a useful adjunct to medical therapy of Parkinson's disease, may reduce costs, and can improve intermediate term outcomes.

Activities of Daily Living↗
PubMed1994

Diminished brain synaptic plasma membrane Ca(2+)-ATPase activity in rats with streptozocin-induced diabetes: association with reduced anesthetic requirements.

Recent evidence suggests that chronic hyperglycemia may inhibit plasma membrane Ca(2+)-ATPase (PMCA) in cells from several tissues. Inhalational anesthetics (IA) can inhibit brain synaptic PMCA activity. We proposed that diabetic rats may manifest chronic inhibition of brain synaptic PMCA and thus provide a model for testing the hypothesis that synaptic PMCA plays a key role in IA pharmacodynamics. Ca2+ pumping activity of PMCA was measured in cerebral synaptic plasma membrane (SPM) vesicles prepared from rats with streptozocin (STZ)-induced diabetes and from control, normoglycemic rats. Dose requirements for halothane and xenon were estimated in treated and untreated rats. Brain PMCA activity in hyperglycemic rats was depressed by about 8.4%, compared to controls. In vitro glycation also caused a significant decrease in PMCA pumping activity. Halothane requirement for STZ-hyperglycemic rats was dramatically reduced to about 65% of control. Xenon requirement was also significantly reduced, to 88% of control. Correlation of IA dose with percent glycated hemoglobin for each rat revealed a strong association between reduced requirements for halothane or xenon and increased protein glycation. These results indicate that inhibition of brain synaptic PMCA in chronically hyperglycemic rats is associated with a significant reduction in IA requirement.

Anesthetics, Inhalation↗
PubMed1994

Renal endothelin mechanism in altered thyroid states.

Endothelin (ET) mechanisms were studied in hyper- and hypo-thyroid states in rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the kidneys using radioimmunoassay. Systemic hemodynamics and renal blood circulation was measured using a radioactive microsphere technique. A significant increase in systolic and diastolic blood pressure, heart rate and cardiac output was observed in hyperthyroid rats as compared to eu- and hypo-thyroid rats. Total peripheral resistance was found to be similar in eu-, hyper- and hypo-thyroid rats. The endogenous concentration of ET-1 in the kidneys was significantly lower in hyper- as compared to eu- and hypo-thyroid rats. The blood flow to the kidneys was significantly increased in hyper- as compared to eu- and hypo-thyroid rats. Infusion of ET-1 (100 ng/kg/min i.v. for 45 min) produced a significant decrease in blood flow to the kidneys of eu-, hyper- and hypo-thyroid rats. The decrease in blood flow was similar in eu-, hyper- and hypo-thyroid rats, indicating that the response of renal blood vessels to exogenous ET-1 is not altered during thyroid dysfunction. Since endogenous ET-1 is involved in the regulation of vascular tone, it may be concluded that in hyper-thyroid rats decrease in concentration of the renal ET-1 could be contributing to an increase in blood flow to the kidney.

Animals↗
PubMed1994

Relation between platinum-DNA adducts and complete remission in adult acute nonlymphocytic leukemia.

The purpose of this study was to determine the relationship between platinum-DNA adducts in leukemic cells and the success of remission induction therapy in adult patients with acute nonlymphocytic leukemia (ANLL). Freshly isolated cells from pre-treatment bone marrow aspirates of 14 patients were incubated with cisplatin in vitro and the amount of platinum bound to DNA was determined using a competitive ELISA procedure and an antibody directed against platinum-modified DNA. Platinum-DNA adduct levels discriminated well between complete remission (CR) and remission failure (RF) patients, treated with mitoxantrone, cytosine arabinoside +/- carboplatin.

Adolescent↗
PubMed1994

Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9 A resolution.

The Clara cell phospholipid-binding protein, previously referred to as CC10, is a homodimeric protein of M(r) 15,800. It is secreted into the bronchioalveolar lining layer in mammalian lung. A combination of X-ray crystallography and chemical analysis was used to determine that phosphatidylcholine and phosphatidylinositol are bound to the protein as isolated from human lung lavage. We now report the crystal structure of the protein-phospholipid complex at 1.9 A resolution. The phospholipid is bound inside the protein's large hydrophobic cavity. A model is proposed for the manner in which a channel may open to provide access to the cavity, allowing the binding or potential release of phospholipid.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Nature of cholinesterase in the rat retina.

The occurrence of cholinesterases has been demonstrated in retinas of several mammalian species. Histochemical staining techniques indicate that the acetylcholinesterases (AChE) are present in amacrine cells and their neighboring bipolar cells. However, the nature of retinal cholinesterases and their interactions with specific cholinesterase inhibitors are not known. Therefore, we have studied the inhibition of the rat retinal cholinesterase activity by BW284C51, a selective inhibitor of AChE, and iso-OMPA, a selective inhibitor of butyrylcholinesterase (BChE). Retinas from Zivic-Miller rats were solubilized by sonication in phosphate buffer (0.134 M, pH 7.2) at 4 degrees C for 20 min. The cholinesterase activity in the sonicate was determined by a radiometric method using 14C-acetylcholine (ACh) as substrate (10(-2) M). Excess 14C-ACh was adsorbed by Amberlite CG-120 cation exchange resin. 14C-acetate formed and retained in the aqueous medium was determined by liquid scintillation counting. This study gave the following results: (a) Rat retinal sonicate gave total cholinesterase activity of 3.76 mumol of ACh hydrolyzed/mg protein/15 min; (b) This activity was inhibited by BW284C51 (IC50, 0.115 microM). Iso-OMPA (IC50, 500 microM) did not cause significant inhibition at 0.115 microM. These observations suggest that the rat retinal cholinesterase is predominantly AChE.

Animals↗
PubMed1994

Severe depression of gut absorptive capacity in patients following trauma or sepsis.

Although clinical studies suggest enteral, as opposed to parenteral, feeding lowers morbidity and mortality rates following severe trauma and after sepsis, it is unknown whether gut absorptive capacity (GAC) is indeed maintained under such conditions. To study this, GAC was determined in patients with blunt trauma (n = 8) and with sepsis (n = 11) by the 1-hour D-xylose absorption test. Excluded were patients with ileus, nasogastric output of more than 600 mL/24 hours, or residual gastric content of more than 25 mL after the D-xylose test. Trauma patients (ISS 8-14) and patients with intra-abdominal sepsis had an initial D-xylose test within 24 to 48 hours of admission, at 72 to 96 hours, and then weekly until D-xylose absorption had returned to normal. D-xylose (25 g in 200 mL water) was given via nasogastric tube to patients and orally to healthy volunteers (controls: n = 8). Results show that GAC was depressed at 24 to 96 hours in both groups but returned to normal by 1 to 3 weeks after trauma or resolution of sepsis. Thus (1) gut absorptive capacity was severely depressed early after trauma and after the onset of sepsis; and (2) the 1-hour D-xylose absorption test provided a simple, quantitative assessment of GAC in critically ill patients. Hence, therapeutic agents that restore gut absorptive capacity may be useful for further reducing morbidity and mortality rates following trauma or the onset of sepsis.

Adult↗