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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 433 records · Page 24Linked to original sources
PubMed1995

Comparative effects of 1,25-dihydroxyvitamin D3 and EB 1089 on mouse renal and intestinal 25-hydroxyvitamin D3-24-hydroxylase.

EB 1089 is a vitamin D analog that is less potent than 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in its calcemic action but more potent in its antiproliferative action. We characterized the interaction of 1,25(OH)2D3 and EB 1089 with renal 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway, and compared the effects of 1,25(OH)2D3 and EB 1089 on induction of 24-hydroxylase mRNA in mouse kidney and intestine. 1,25(OH)2D3 and EB 1089 were competitive inhibitors of 24-hydroxylase activity. However, the Ki for 1,25(OH)2D3 (5.2 +/- 2.5 nM) was significantly lower than that for EB 1089 (286 +/- 59 nM). In the kidney, the time course and extent of 24-hydroxylase mRNA induction, relative to 18S rRNA, was similar for 1,25(OH)2D3 and EB 1089 with a peak response at approximately equal to 6 h that was sustained for at least 16 h. In the intestine, however, induction of 24-hydroxylase mRNA, relative to 18S rRNA, was approximately 50% lower for EB 1089 than for 1,25(OH)2D3 at 3 h (p < 0.05) and 6 h (p < 0.05) while at 16 h 24-hydroxylase mRNA was no longer detectable. Moreover, while both 1,25(OH)2D3 and EB 10898 elicited a similar dose-dependent induction of 24-hydroxylase mRNA in the kidney (EC50 = 0.4 +/- 0.13 and 0.3 +/- 0.08 ng/g for EB 1089 and 1,25(OH)2D3, respectively), the EC50 for EB 1089 (6.6 +/- 1.7 ng/g) was significantly higher than that for 1,25(OH)2D3 (0.9 +/- 0.32 ng/g) in the intestine (p < 0.01). EB 1089 was also less effective than 1,25(OH)2D3 in the induction of intestinal but not renal calbindin-D9k mRNA. To determine the mechanism for tissue-specific differences in potency, we determined the binding affinity of 1,25(OH)2D3 and EB 1089 for the vitamin D receptor. In the kidney, Kd values for 1,25(OH)2D3 (0.40 +/- 0.95 nM) and EB 1089 (0.48 +/- 0.04 nM) were not different. However, in the intestine, the Kd for EB 1089 (1.43 +/- 0.19 nM) was significantly higher than that for 1,25(OH)2D3 (0.85 +/- 0.06 nM; p < 0.05). Our results demonstrate that: (i) EB 1089 has a 50-fold lower affinity than 1,25(OH)2D3 for renal 24-hydroxylase, suggesting that it is more resistant to catabolism by the C-24 oxidation pathway; and (ii) EB 1089 and 1,25(OH)2D3 exhibit tissue-specific differences in vitamin D receptor-mediated responses in vivo that may be ascribed, at least in part, to differences in binding affinities for the vitamin D receptor.

Analysis of Variance↗
PubMed1995

Ah receptor involvement in mediation of pyruvate carboxylase levels and activity in mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The arylhydrocarbon receptor (AhR) plays a central role in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity in animals. The investigations described here provide evidence that support a role for the AhR in TCDD-mediated pyruvate carboxylase (PC) level/activity reductions in mice. Pyruvate carboxylase plays a pivotal role in gluconeogenesis and in supplying carbon units for the citric acid cycle. Delivered ip in a corn oil carrier, TCDD suppresses PC activity/amount at doses as low as 1 microgram/kg in responsive C57BL/6J(Ahb/b) mice. Corn oil alone injected ip into mice at 4 mL/kg appears to be an inducer that increases the amount and activity of PC. However, TCDD suppresses this induction. In the Ahb/b mouse, PC levels and activity are reduced to 10% of control values at a dose of 75 micrograms/kg. A time-course experiment shows that the PC reductions are apparent within 16 hours post-TCDD exposure. Here we report investigations on the PC/TCDD response using a congenic C57BL/6J(Ahd/d) mouse strain having an AhR with a low affinity for TCDD. If the PC/TCDD response is AhR mediated, the congenic mouse strain (Ahd/d) would require much higher doses of TCDD to suppress PC. In the Ahd/d mice, we observe that an approximately 60-fold increase in TCDD dose is necessary to produce a PC/TCDD effect. We also find that in Ahd/d mice, corn oil does not induce an increase in PC activity/amounts, as reported for Ahb/b mice.

Animals↗
PubMed1995

Regulation of the transcription factor C/EBP alpha following peritoneal sepsis.

The transcription factors C/EBP alpha and C/EBP beta belong to the leucine-zipper C/EBP (CCAAT/enhancer binding protein) family of DNA-binding proteins. C/EBP alpha and C/EBP beta are expressed in the liver and are implicated in the control of transcriptional events following following sepsis. It is hypothesized that inhibition of C/EBP alpha gene expression following sepsis may lead to some of the phenotypic features we recognize as sepsis syndrome such as decreased visceral protein (albumin) synthesis. In this study we demonstrate that C/EBP alpha mRNA accumulation is transiently inhibited 12 hr following peritoneal insult, consistent with previous data. However, we demonstrate that (1) there is increased binding of hepatic nuclear protein to the C/EBP alpha DNA response element 48 hr following insult, (2) a marked increase in C/EBP alpha protein is observed 48 hr following CLP insult compared with no increase in hepatic C/EBP alpha protein at 12 hr postinsult, (3) the increase in hepatic C/EBP alpha protein at 48 hr following cecal ligation and puncture is not associated with an increase in C/EBP alpha mRNA accumulation, (4) the increase in hepatic C/EBP alpha protein is associated with an increase in C/EBP beta protein, and (5) hepatic albumin mRNA accumulation is decreased at 12 and 48 hr following insult and does not correlate with the C/EBP alpha protein synthesis. We conclude that the possible role of the transcription factor C/EBP alpha with respect to decreased albumin gene expression following sepsis must be reevaluated.

Albumins↗
PubMed1995

A correlative study of in vivo and in vitro labeling index using bromodeoxyuridine in human brain tumors.

The labeling index (LI) of 216 cases of human brain tumors was determined by the immunohistochemical technique with monoclonal antibody to bromodeoxyuridine (BrdU). The proliferative potential of 110 cases was estimated using the intra-operative intravenous infusion of BrdU at a dose of 200 mg/sq m. In another 106 cases, the in vitro technique of incubating freshly resected tumor tissue fragments with 100 microM bromodeoxyuridine was used. The BrdU LI in these tumors was then correlated with the histological types and the data as determined by both the in vivo and in vitro BrdU incorporation were compared. The results indicate that although in vivo and in vitro techniques could possibly provide equivalent data in some histologic types, a clear statistically valid proof however is not apparent from this study.

Adolescent↗
PubMed1995

Expression of alternate forms of brain opioid 'orphan' receptor mRNA in activated human peripheral blood lymphocytes and lymphocytic cell lines.

We screened a PHA (phytohemagglutinin)-activated human lymphocyte cDNA library for clones with homology to the recently cloned brain opioid receptors. A cDNA clone, AT7-5EU, was isolated which encodes the opioid 'orphan' receptor, a molecule with very high homology to the opioid receptor gene family, but which has not been shown to bind opioids or any other known compounds. The protein coding region of AT7-5EU has complete homology with a reported opioid 'orphan' clone isolated from human brain, but the 5' untranslated regions of AT7-5EU and the human brain clones are divergent, suggesting mechanisms for tissue-specific expression of this receptor. Northern analysis of AT7-5EU mRNA demonstrates the expression of this message in human lymphocytic cell lines of both B-and T-cell lineages. Furthermore, analysis of mRNA from human peripheral blood lymphocytes demonstrates that activation of the lymphocytes with PHA results in at least a 10-fold induction of the AT7-5EU message. These results suggest that the opioid 'orphan' receptor may have an important immunological function in addition to its function in the nervous system.

Base Sequence↗
PubMed1995

Percutaneous catheter drainage of amebic liver abscesses with and without intrahepatic biliary communication: a comparative study.

Influence of communication with the intrahepatic biliary system on the clinical picture of amebic liver abscesses in 33 consecutive patients resistant to medical therapy, and their response to percutaneous catheter drainage was evaluated. Abscess-biliary communication was found in 27% of the sample. Patients with abscesses communicating with the biliary tree presented more frequently with jaundice (67% vs. 0%, P < 0.005), with a longer duration of illness (median 20 vs. 12 days, P < 0.001), had larger lesions (median 600 vs. 320 ml, P < 0.001) and required catheter drainage for longer periods (median 17 vs. 6.5 days, P < 0.000001). However the presence of a biliary communication did not materially affect the cure rate with catheter drainage (89% vs 100%, P > or = 0.05). In conclusion, an abscess-biliary communication is not uncommon in refractory amebic liver abscesses, and can be clinically detected by the presence of jaundice. Though a prolonged period of drainage may be necessary in the presence of this complication, catheter drainage can be expected to result in cure.

Adult↗
PubMed1995

Complex ruptured amebic liver abscesses: the role of percutaneous catheter drainage.

The failure of medical therapy for amebic liver abscess may be followed by its perforation, a complication associated with high mortality. We assessed the role of percutaneous catheter drainage in management of the sequelae of ruptured amebic abscesses in 13 critically ill patients; 22 intrahepatic lesions, three of which were multiloculated, were drained. Catheters were also placed in 17 extrahepatic collections: pleural space (n = 5), subphrenic (n = 7), perihepatic/subhepatic (n = 3), greater sac of peritoneum (n = 2). No attempt at percutaneous drainage failed. Prompt resolution of clinical features following drainage was a uniform feature. Successful resolution of the abscesses occurred within 20 days in 11 patients. In the remaining two, catheters needed to be retained in situ for 35 and 50 days. The mean hospital stay was 15 days (range 10-20 days). 100% patient survival was achieved, without a single morbid episode. Our results suggest that patients with ruptured amebic abscesses can be effectively and safely managed by percutaneous catheter drainage irrespective of the extent of extrahepatic contamination.

Adolescent↗
PubMed1995

IgA nephropathy: long-term prognosis for pediatric patients.

OBJECTIVE: The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. METHODS: Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. RESULTS: Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. CONCLUSION: With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patient's care is transferred to a physician caring for adults.

Adolescent↗
PubMed1995

Immunobiological studies on experimental visceral leishmaniasis. IV. Kinetics of evolution of disease-promoting versus host-protective cells of monocyte-macrophage lineage and their characterization.

The evolution of cells of the monocyte-macrophage lineage (MML cells) in the spleen of Leishmania donovani (LD) infected BALB/c mice was studied. Spleen cells were fractionated on a discontinuous percoll gradient and adherent cells (AC) were purified from fractionated spleen cells by adherence steps that appeared at the interfaces of 25-35%, 35-40%, 40-45% and 45-50% percoll gradients. The AC were characterized as MML cells on the basis of positive staining for non-specific esterase. Adherent cells that appeared at the interfaces of 25-35% and 40-45% were defined as A and C, respectively, and both of them showed extreme variation in a progressive infection. It was observed that A supported parasite replication whereas C remained refractory when infected with LD in vitro. Furthermore, when A cells and C cells were used as antigen-presenting cells to stimulate mixed population of IFN-gamma producing and IL-4 producing T-cells, it was observed that IL-4 and IFN-gamma were the predominating cytokine in the T-cell supernatant, respectively. Both A and C were found to be increased hand-in-hand up to 5 months of infection and from then on A decreased and C increased in their numerical strength (A-C reciprocity). The evolution of A-C reciprocity coincided with the gradual reduction in the parasitaemia in the spleen suggesting that this may contribute to the acquisition of anti-leishmania immunity.

Animals↗
PubMed1995

Changes in the concentration of endothelin-1 during development of hypertensive rats.

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 +/- 43 pg/g tissue) rats was lower than that of WKY (452 +/- 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 +/- 33 pg/g tissue) rats were higher compared to WKY (439 +/- 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 +/- 33 pg/g tissue) compared to WKY rats (260 +/- 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY rats.

Animals↗
PubMed1995

Phenotypic correction of hypercholesterolemia in apoE-deficient mice by adenovirus-mediated in vivo gene transfer.

To investigate the potential use of apoE in gene therapy of hyperlipidemias, an adenoviral vector was constructed that contained the human apoE3 cDNA under the control of the RSV promoter (Av1RE). Transduction of HepG2 cells resulted in the overexpression of human apoE secreted into the culture medium. Intravenous injection of 5 x 10(11) Av1RE vector particles into apoE-deficient mice resulted in expression of human apoE3 in mouse plasma at levels of 1.2 +/- 0.4 micrograms/L (mean +/- SEM, n = 5) 7 days after injection. Mice injected with the control vector Av1Lacz4 did not express detectable levels of human apoE. Average plasma cholesterol concentrations were reduced approximately eightfold from 737.5 +/- 118 mg/dL (mean +/- SEM, n = 6) to 98.2 +/- 4.4 mg/dL (mean +/- SEM, n = 5) and were unaffected in the control vector group. Expression of human apoE resulted in a shift in the plasma lipoprotein distribution from primarily VLDL and LDL in the control mice to predominantly HDL in the Av1RE-treated group. Western blot analysis of fast protein liquid chromatography-fractionated mouse plasma showed that the human apoE protein was associated with VLDL, LDL, and HDL. Correction of the hyperlipidemic condition found in the apoE-knockout mouse strain by direct in vivo gene transfer establishes the potential of this approach for treatment of hyperlipidemia caused by apoE deficiency or malfunction in human disease.

Adenoviridae↗
PubMed1995

In vitro and in vivo antimicrobial action of fluphenazine.

The antipsychotic drug fluphenazine was obtained in a dry powder form and was screened with respect to 482 strains of bacteria, which included 170 Gram-positive and 326 Gram-negative strains. Nutrient agar plates containing increasing concentrations of fluphenazine (0-200 micrograms/ml) were used for the determination of the minimum inhibitory concentration (MIC) which was demonstrated by inoculating a loopful of an overnight peptone water culture of the organism on nutrient agar plates and determining the MIC against a control. Fluphenazine was detected to possess pronounced action against both Gram-positive and Gram-negative bacteria at 20-100 micrograms/ml. In the in vivo studies it was seen that when fluphenazine was used at a concentration of 1.5 micrograms/g and 3 micrograms/g mouse body weight both the levels offered significant protection to Swiss strain of white mice when challenged with 50 minimum lethal dose (MLD) of a virulent strain of Salmonella typhimurium 74. The in vivo data with fluphenazine were highly significant (p < 0.001) according to the chi-square test.

Animals↗
PubMed1995

L-rhamnose inhibits proliferation of murine splenocytes by the lipopolysaccharide and polysaccharide moiety of Shigella dysenteriae type 1 lipopolysaccharide.

The induction of proliferation of murine splenocytes by lipopolysaccharide (LPS) of Shigella dysenteriae type 1 and its polysaccharide (PS) and lipid A fractions was investigated. The LPS-induced proliferation reached a maximum at a concentration of 30 ng/ml. The PS and lipid A induced proliferation of murine splenocytes at similar concentrations. Preincubation of murine splenocytes with varying concentrations of L-rhamnose blocked LPS- and PS-induced proliferation in a dose-dependent manner. The lipid A-induced stimulation, on the contrary, was not affected by preincubation of the cells with L-rhamnose. These data suggest that activation of splenocytes by LPS and PS is mechanistically different from that induced by lipid A and is presumably involved in the specific recognition of carbohydrate structures on LPS and PS.

Animals↗
PubMed1995

Risk factors and angiographic profile of coronary artery disease in young.

A total of 124 patients of ischaemic heart disease under 40 years of age (96 with myocardial infarction and 28 with angina) were studied for risk factors of coronary artery disease. Electrocardiogram, treadmill test, lipid profile and coronary arteriography were done in all cases. Smoking (56.4%) and hyperlipidaemia (30.6%) emerged as the major risk factors. Further stratification of lipid profile revealed that predictive value of hypercholesterolaemia could be enhanced by considering the different ratios of lipoproteins and indices of atherogenicity. Coronary arteriography revealed a preponderance of single vessel disease (48.4%)-left anterior descending being most commonly involved (71.8%). Increase in low density lipoprotein fraction was related to multivessel involvement.

Adult↗
PubMed1995

Cardiovascular effects of centrally administered endothelin-1 in rats.

The effect of centrally administered endothelin-1 (ET-1) or IRL 1620 (5, 15, and 45 ng) on systemic hemodynamics was studied in anesthetized rats using a radioactive microsphere technique. Administration of saline (5 microliters, i.c.v.) did not product any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR). However, the highest dose (45 ng) produced a transient rise followed by a sustained fall in BP. The CO and SV decreased significantly, whereas HR and TPR were not affected. Pretreatment with BQ-123 (10 micrograms, i.c.v.) 15 min before administration of ET-1, completely antagonized the systemic hemodynamic effects of ET-1. Centrally administered IRL 1620, a specific ETB receptor agonist, did not produce any effect on BP, HR, CO, SV, and TPR in rats. It is concluded that ETA but not ETB receptors are involved in the central cardiovascular actions of ET.

Amino Acid Sequence↗