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Biomedical subjects

J Nigro

Publications and source records attributed to J Nigro.

9 recordsLinked to original sources
PubMed2004

Fenofibrate modifies human vascular smooth muscle proteoglycans and reduces lipoprotein binding.

AIMS/HYPOTHESIS: Vascular disease in type 2 diabetes is associated with an up-regulation of atherogenic growth factors, which stimulate matrix synthesis including proteoglycans. We have examined the direct actions of fenofibrate on human vascular smooth muscle cells (VSMCs) and have specifically investigated proteoglycan synthesis and binding to LDL. METHODS: Proteoglycans synthesised by human VSMCs treated with fenofibrate (30 micromol/l) were assessed for binding to human LDL using a gel mobility shift assay, metabolically labelled with [(35)S]-sulphate and quantitated by cetylpyridinium chloride. They were then assessed for electrophoretic mobility by SDS-PAGE, for size by gel filtration, for sulphation pattern by fluorophore-assisted carbohydrate electrophoresis, and for glycosaminoglycan (GAG) composition by enzyme digestion. RESULTS: Proteoglycans synthesised in the presence of fenofibrate showed an increase in the half-maximum saturation concentration of LDL from 36.8+/-12.4 microg/ml to 77.7+/-17 microg/ml under basal conditions, from 24.9+/-4.6 microg/ml to 39.1+/-6.1 microg/ml in the presence of TGF-beta1, and from 9.5+/-4.4 microg/ml to 31.1+/-3.4 microg/ml in the presence of platelet-derived growth factor/insulin. Fenofibrate treatment in the presence of TGF-beta1 inhibited the incorporation of [(35)S]-sulphate into secreted and cell-associated proteoglycans synthesised by human VSMCs by 59.2% (p<0.01) and 39.8% (p<0.01) respectively. The changes in sulphate incorporation following treatment with fenofibrate were associated with a concentration-related increase in the electrophoretic mobility due to a reduction in GAG length. There was no change in the sulphation pattern; however, there was an alteration in the disaccharide composition of the GAGs. CONCLUSIONS/INTERPRETATION: Fenofibrate modifies the structure of vascular proteoglycans by reducing the length of the GAG chains and GAG composition, resulting in reduced binding to human LDL, a mechanism which may lead to a reduction of atherosclerosis and cardiovascular disease in people with diabetes treated with fenofibrate.

Cells, Cultured↗
PubMed2004

Regulation of glycosaminoglycan structure and atherogenesis.

Cardiovascular disease is the major cause of premature death in modern society, and its impact is increasing due to rising rates of obesity and type 2 diabetes. Clinical studies based on targeting metabolic abnormalities and biomarkers demonstrate significant benefits, but always an element of disease remains which is resistant to treatment. Recent evidence has strongly implicated an early interaction of atherogenic lipoproteins with vascular matrix proteoglycans as the initiating step in atherogenesis. Expert commentary has pointed to the need for vascular directed therapies to provide reductions in the residual disease component. We propose that the regulation of synthesis and thus structure of glycosaminoglycans on proteoglycans provides a potential pathway to this reduction. We review existing evidence that the vascular synthesis of glycosaminoglycan chains can be regulated in a manner which reduces lipoprotein binding and the potential application of this strategy to attenuation of the current cardiovascular disease pandemic.

Animals↗
PubMed2001

Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients.

Glioblastoma multiforme (GBM) carries a dismal prognosis. However, a range of survival times exists, and parameters that define prognostic groups may help to optimize treatment. To identify such prognostic groups, we analyzed tumor tissue from 110 cases of newly diagnosed GBM from two clinical protocols. Similar to other studies, we found no association of epidermal growth factor receptor (EGFR) overexpression (as assessed by immunohistochemistry), p53 immunopositivity, or p53 mutation with survival in the entire sample. However, EGFR overexpression showed trends toward worse prognosis in patients younger than the median age, but better prognosis in patients older than the median age. This interaction of EGFR with age group was statistically significant and led us to focus our further analyses on the younger patients. In this group, a statistically significant association of EGFR overexpression with worse survival was identified in the p53-negative but not p53-positive tumors. We found a similar result after screening these cases for mutations in p53: EGFR overexpression was negatively associated with survival only in the p53 wild-type cases. To confirm this unexpected result, this finding was reproduced in a validation sample of an additional 42 tumors from younger patients on the same two clinical protocols. This complex relationship between EGFR and p53 in younger patients remained in a multivariate analysis that incorporated additional prognostic variables. The results suggest that analysis of prognostic markers in GBM is complex, and maximal information may require analysis of subgroups based on age and the status of specific markers such as p53. In addition, they suggest a specific group of patients on which to focus promising therapies targeting EGFR.

Adult↗
PubMed2000

Measurement of DNA copy number at microsatellite loci using quantitative PCR analysis.

This report describes the development and validation of quantitative microsatellite analysis (QuMA) for rapid measurement of relative DNA sequence copy number. In QuMA, the copy number of a test locus relative to a pooled reference is assessed using quantitative, real-time PCR amplification of loci carrying simple sequence repeats. Use of simple sequence repeats is advantageous because of the large numbers that are mapped precisely. In addition, all markers are informative because QuMA does not require that they be polymorphic. The utility of QuMA is demonstrated in assessment of the extent of deletions of chromosome 2 in leukemias arising in radiation-sensitive inbred SJL mice and in analysis of the association of increased copy number of the putative oncogene ZNF217 with reduced survival duration in ovarian cancer patients.

Animals↗
PubMed2000

Infestations in the pediatric patient.

This article specifically focuses on arthropods that act as ectoparasites to the human host. A cutaneous eruption caused by the larvae of roundworms is briefly discussed.

Child↗
PubMed2000

Endoscopic valvuloplasty for GERD.

BACKGROUND: The transoral, endoscopic route has been suggested as a possible approach for the correction of severe gastroesophageal reflux. Such a procedure would involve no mobilization of the cardia or other structures. The optimal placement, number, and configuration of sutures remains undefined. METHODS: With the use of a previously developed endoscopic sewing machine, this study was undertaken in baboons with two suture arrangements immediately below the lower esophageal sphincter. A linear arrangement (group I) and a circular arrangement (group II) were compared. During the 6 months after the procedure, the animals were evaluated using manometry, fluoroscopic barium swallow, upper gastrointestinal endoscopy, and a pressure volume test. RESULTS: A significant increase in lower esophageal sphincter length was demonstrated only in group II (p = 0. 010). A significant increase in lower esophageal sphincter pressure was demonstrated only in group I animals (p = 0.008). The abdominal length increased in group I (p = 0.004) and group II (p = 0.004). The yield pressure and yield volume did not differ significantly from those measured previously in control animals. No evidence of reflux, stricture formation, esophagitis, or other pathology was noted. CONCLUSIONS: Some manometric parameters associated with gastroesophageal reflux are altered by the endoscopic placement of sutures below the gastroesophageal junction, with no associated serious complications.

Animals↗
PubMed1998

Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis (DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient?

BACKGROUND: Deep venous thrombosis (DVT) in severely injured patients is a life-threatening complication. Effective and safe thromboprophylaxis is highly desirable to prevent DVT. Low-dose heparin (LDH) and sequential compression device (SCDs) are the most frequently used methods. Inappropriate use of these methods because of the nature or site of critical injuries (eg, brain lesion, solid visceral or retroperitoneal hematoma, extremity fractures) may lead to failure of DVT prophylaxis. STUDY DESIGN: A prospective study was performed to evaluate the efficacy of a policy of aggressive use of LDH and SCDs in patients who are at very high risk for DVT. From January 1996 to August 1997, 200 critically injured patients were followed by weekly Doppler examinations to detect DVT at the proximal lower extremities. Only 3 patients did not receive any thromboprophylaxis. SCDs were applied in 97.5% and LDH was administered to 46% of the patients; 45% had both. RESULTS: DVT was found in 26 patients (13%). The majority (58%) developed DVT within the first 2 weeks, but new cases were found as late as 12 weeks after admission. The incidence of DVT was the same among patients who had SCDs only or a combination of LDH and SCDs. Mechanism of injury, type and number of operations, site of injury, Injury Severity Score, and the incidence of femoral lines were not different between patients with and without DVT. Differences were found in the severity of injury to the chest and the extremities and the need for high-level respiratory support. Patients with DVT had prolonged ICU and hospital stays (on average, 34 and 49 days, respectively) and a high mortality rate (31%). CONCLUSIONS: The incidence of DVT remains high among severely injured patients despite aggressive thromboprophylaxis. A combination of LDH and an SCD showed no advantage over SCD alone in decreasing DVT rates. Risk factors in this group of patients who are already at very high risk are hard to detect; Doppler examinations are justified for surveillance in all critically injured patients. Current methods of thromboprophylaxis seem to offer limited efficacy, and the search for more effective methods should continue.

Adult↗
PubMed1986

Efficient singlet oxygen inactivation of firefly luciferase.

Firefly luciferase is inactivated by singlet oxygen at near diffusion controlled rates, 1.9 X 10(9) M-1 s-1, based on direct comparison with the oxidation of L-histidine. The inactivation kinetics are multiphasic. Inactivation is inhibitable by NaN3. Surface-separated-sensitizer (SSS) system in which singlet oxygen is produced above an air gap separating the reaction solution from the Rose Bengal sensitizer, ensuring only Type II reactions, was compared with a Sensitox II system in which the polymer bound Rose Bengal is contained in the reaction solution and both Type I and Type II reactions can occur. A slight stabilization is afforded by MgSO4.

Histidine↗