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Biomedical subjects

P Russo

Publications and source records attributed to P Russo.

At least 19 recordsLinked to original sources

Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study on rabbit aorta.

Effects of cocaine on vascular endothelium relaxing properties and the related mechanism were investigated in vitro in rabbit aorta. Several vasorelaxing agents with different mechanisms, i.e. acetylcholine, substance P, calcium ionophore A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprusside, were employed. Cocaine effects on the vascular response to relaxing agents in cumulative (acetylcholine, substance P, or A23187) or single dose (2,5-di-tert-butyl-hydroquinone) were performed in endothelium-intact aortic rings precontracted with phenylephrine. Relaxing activity of cumulative doses of sodium nitroprusside was evaluated in endothelium-denuded aortic rings, in the presence of cocaine. Cocaine significantly reduced endothelium-dependent relaxations induced by acetylcholine, or substance P. By contrast A23187 endothelium-mediated relaxation as well as endothelium-independent relaxation by sodium nitroprusside were unaffected by cocaine. Furthermore, cocaine significantly increased endothelium-dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic Ca2+-ATPase pump inhibitor, in the aortic rings. These findings indicate that cocaine reduces nitric oxide release from vascular endothelium apparently through the inhibiting action of Ca2+-ATPase pump.

Acetylcholine↗

RACK1 interacts with E1A and rescues E1A-induced yeast growth inhibition and mammalian cell apoptosis.

The adenoviral E1A proteins are able to promote proliferation and transformation, inhibit differentiation, induce apoptosis, and suppress tumor growth. The extreme N terminus and conserved region one of E1A, which are indispensable for transcriptional regulation and for binding to p300/CBP, TBP, and pCAF, play essential roles in these abilities. These observations strongly suggest an intrinsic link between E1A-mediated transcriptional regulation and other effects. In this report, we show that E1A inhibits the normal growth of Saccharomyces cerevisiae HF7c, and this inhibition also depends on the domains required for transcriptional regulation. We demonstrate that E1A associates with histone acetyltransferase activity and represses the transactivation activity of transcription factor in S. cerevisiae, suggesting that E1A may suppress the expression of genes required for normal growth. Based on yeast growth rescue, we present a genetic screening strategy that identified RACK1 as an E1A antagonizing factor. Expression of human RACK1 efficiently relieves E1A-mediated growth inhibition in HF7c and protects human tumor cells from E1A-induced apoptosis. Finally, we show that RACK1 decreases E1A-associated histone acetyltransferase activity in yeast and mammalian cells, and physically interacts with E1A. Our data demonstrate that RACK1 is a repressor of E1A, possibly by antagonizing the effects of E1A on host gene transcription.

Adenovirus E1A Proteins↗

Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance.

PURPOSE: To determine the relative risk (RR) of upper-tract tumors (UTT) after bladder cancer, stratified by bladder tumor characteristics, demographic factors, and follow-up duration, in order to develop an improved risk-based surveillance strategy. PATIENTS AND METHODS: The 1973 to 1996 Surveillance, Epidemiology, and End Results (SEER) database was used to determine the observed and expected number of UTT after bladder cancer. The RR with 95% confidence intervals (CI) were calculated, stratifying by race, sex, stage, grade, histology, and follow-up duration. The tumor characteristics and clinical outcome were compared in patients with UTT after bladder cancer and those with de novo UTT. RESULTS: A total of 94,591 patients had a first diagnosis of bladder cancer, of whom 91,245 had follow-up (median, 4.1 years), with no antecedent or synchronous UTT. UTT developed subsequently in 657 of 91,245 (0.7%), with 12.80 expected cases (RR = 51.3; 95% CI, 47.5 to 55.4). The respective RRs for UTT for white men and women were 64.2 (95% CI, 55.1 to 74.3) and 75.4 (95% CI, 57.7 to 96.9) at less than 2 years, 44.3 (95% CI, 36.7 to 53.0) and 40.5 (95% CI, 27.9 to 56.8) at 2 to 5 years, 50.8 (95% CI, 42.2 to 60.7) and 42.1 (95% CI, 28.8 to 59.4) at 5 to 10 years, and 43.2 (95% CI, 32.6 to 56.1) and 22.2 (95% CI, 10.1 to 42.2) at >or= 10 years. Similar RRs were seen among different strata of race, stage, grade, and histology. Patients with UTT after bladder cancer had lower stage and improved disease-specific survival compared with those with de novo UTT. CONCLUSION: The incidence of UTT is stable on long-term follow-up, with no significant risk factors identified. These findings suggest that upper-tract surveillance remain rigorous on extended follow-up of bladder cancer patients.

Adolescent↗

Phosphorylation in coronary artery cold-induced contraction in the newborn lamb.

Myocardial dysfunction after hypothermic protection has been linked to various mechanisms. Coronary vasospasm in particular may be responsible for ischemic injury during reperfusion. Herein we hypothesized that coronary arteries (CA) sustain a cold-induced contraction during hypothermia mediated by a protein tyrosine kinase (PTK)-/protein tyrosine phosphatase (PTP)-dependent pathway. Isolated newborn lamb CA rings were studied in a tissue bath for isometric contraction during 2-h profound (17 degrees C) or ultra-profound (7 degrees C) hypothermia. In parallel, protein tyrosine phosphorylation was evaluated by use of the Western blot technique. Na-orthovanadate (SOV) and genestein (GEN) were used separately and in combination to evaluate the effect of PTK/PTP activation on CA contraction and tyrosine phosphorylation during cooling (17 or 7 degrees C) vs 37 degrees C. Cooling from 37 to 7 degrees C induced transient contraction at approximately 17 degrees C (29% KCl response), which was more prominent during rewarming to 37 degrees C (36% KCl). Cooling to 17 degrees C resulted in sustained contraction (7-10% KCl), which was reversible upon rewarming. Cold-induced contraction was significantly enhanced by SOV (7- to 10-fold at 17 degrees C; 2-fold at 7 degrees C) and abolished by GEN. Concurrently, tyrosine phosphorylation of 33-, 45-, and 104-kDa proteins increased during cooling (35-100% at 17 degrees C; 46-66% at 7 degrees C). Tyrosine phosphorylation was similarly enhanced by SOV (1.7- to 2.3-fold at 17 degrees C; 2.9- to 3.9-fold at 7 degrees C) and abolished by GEN in the presence or absence of SOV. These results support a prominent role for the PTK/PTP signal transduction pathway in the coronary artery cold-induced contraction. This information provides one possible biomolecular mechanism linked to ischemia/reperfusion pathophysiology of CA in neonatal hearts exposed to hypothermic myocardial protection.

Animals↗

Altered renal sodium handling and hypertension in men carrying the glucagon receptor gene (Gly40Ser) variant.

A higher prevalence of hypertension has been associated with the G-->A/GT (Gly40Ser) polymorphism of the glucagon receptor gene (GCGR) in two population studies. As the mutated receptor is less responsive to glucagon, it has been speculated that the increased susceptibility to hypertension is due to deprivation of the recognized natriuretic effect of the hormone. To test this hypothesis we determined the frequency of the polymorphic variant and evaluated the segmental renal sodium handling by the clearances of uric acid and of exogenous lithium in the Olivetti Heart Study participants (n=971). The polymorphic variant was present only in heterozygous form in 37 individuals (3.8%). After controlling for age and body mass index, the carriers of the variant were twice more likely to be hypertensive and almost three times more likely to be on antihypertensive treatment at the time of examination. Compared to participants carrying the wild type, those carrying the Gly40Ser allele had higher serum uric acid and lower fractional excretion of uric acid and exogenous lithium, independently of age, body mass, and current pharmacological treatment. We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.

Adult↗

Renal mass within a horseshoe kidney: preoperative evaluation with three-dimensional helical computed tomography.

Tumors arising within a horseshoe kidney are uncommon and may be difficult to characterize. We report a case of transitional cell carcinoma in a horseshoe kidney. Although several conventional imaging techniques were used to define the mass, each provided limited information. Recent advances in computer technology permit radiologic imaging to provide detailed examination of the horseshoe kidney with a single study. We describe the use of three-dimensional multislice helical computed tomography as the preferred modality to clarify the suspected neoplasm, vasculature, and collecting system of a horseshoe kidney. High-quality anatomic characterization will certainly enhance the opportunity for nephron-sparing surgery within this population.

Carcinoma, Papillary↗

Primary genitourinary melanoma.

OBJECTIVES: To describe the presentation, management, and clinical outcome of patients with genitourinary melanoma. METHODS: We identified 14 patients with genitourinary melanoma treated at Memorial Sloan-Kettering Cancer Center, New York and Tripler Army Medical Center, Honolulu, Hawaii. The presentation, surgical treatment, disease progression, and outcome of these patients were reviewed. Survival was analyzed, using the Kaplan-Meier product limit method. RESULTS: The presentation and management of patients with genitourinary melanoma were varied. Overall, the prognosis was poor, with a median survival of 43 months, and only 3 patients were alive, without disease, at last follow-up. Our findings confirm a poor prognosis in patients with this rare disease. CONCLUSIONS: Genitourinary melanoma is a rare form of the disease with an unfavorable clinical outcome. Less than one third of patients survive long term, although patients with scrotal melanomas may have a better prognosis.

Aged↗

Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.

BACKGROUND: Previous health economic studies have demonstrated the cost-effectiveness of simvastatin in the treatment of coronary heart disease (CHD) based on clinical results of the Scandinavian Simvastatin Survival Study. A prior analysis evaluated the "cost of getting to goal," but ignored all costs after titration. However, when evaluating the cost-effectiveness of long-term therapies, it is important to consider the maintenance costs as well. OBJECTIVE: The purpose of this study was to evaluate the maintenance costs of treatment with simvastatin versus that of treatment with another more recently available statin, atorvastatin, in a European context. METHODS: We assessed the long-term maintenance cost of simvastatin versus atorvastatin in terms of the cost of reducing low-density lipoprotein cholesterol (LDL-C) levels to the recommended goals based on a previously published clinical trial in patients with CHD. The analysis focused on the patients in the original clinical trial who were randomized to treatment with simvastatin or atorvastatin. Patients began therapy with 10 mg of simvastatin or atorvastatin; the dose of study drug was titrated every 12 weeks up to 40 mg simvastatin or 80 mg atorvastatin, with the addition of up to 8 g/d of cholestyramine until a modified European Atherosclerosis Society LDL-C goal (<2.84 mmol/L) was reached. As there was no significant difference between the 2 groups in resource utilization for adverse events, only drug costs were included. The calculated average annual maintenance cost was based on the distribution of the final daily dosing regimens and the public drug prices for each regimen. Individual country analyses were conducted using each local currency. RESULTS: There was no significant difference between groups in the percentage of patients reaching their LDL-C goal over the study period (80% for simvastatin-treated pa- tients vs 89% for atorvastatin-treated patients, P = 0.135). However, the cost of maintaining a similar percentage of patients at their appropriate LDL-C levels was significantly lower in the simvastatin group compared with the atorvastatin group in 13 of the 17 countries assessed. In the remaining 4 countries, there was a cost advantage for simvastatin, but it did not reach statistical significance. CONCLUSIONS: Across Europe there was a significant reduction in the cost of maintaining patients at their appropriate LDL-C levels with simvastatin versus atorvastatin. The results of this analysis, along with the proven clinical benefits of simvastatin, support the use of this drug as the treatment of choice in the secondary prevention of CHD.

Anticholesteremic Agents↗

Gly40Ser polymorphism of the glucagon receptor gene is associated with central adiposity in men.

OBJECTIVE: To study the association between the Gly40Ser polymorphism of the glucagon receptor gene (GCG-R) and central adiposity. RESEARCH METHODS AND PROCEDURES: Data from 985 working men (The Olivetti Heart Study) examined in 1994 were used in a cross-sectional design. A complete anthropometry was performed; body mass index and waist circumference were taken as measures of total and central adiposity, respectively. The GCG-R Gly40Ser polymorphism was characterized. Biochemical variables linked to energy metabolism were measured. RESULTS: The GCG-R Gly40Ser variant was present in 37 individuals only in heterozygous form and was significantly associated with anthropometric indices of central adiposity, accounting for age and body mass (odds ratio for waist circumference > 94 cm; 95% confidence interval: 3.14, 1.26 to 7.81), whereas no difference between the two groups was found with regard to biochemical indices of insulin resistance or plasma leptin levels. DISCUSSION: The Gly40Ser polymorphism of the GCG-R gene is associated with central adiposity independently from total body mass in men.

Adipose Tissue↗

Differential effects of short and long duration insulinotropic agents on meal-related glucose excursions.

AIM: Abnormal beta-cell function, characterized as the inability of the beta-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. METHODS: Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. RESULTS: There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (Delta AUC(-15 to 3 min) = 0.5 +/- 0.01, 1.6 +/- 0.4, 3.6 +/- 0.0, 1.2 +/- 0.1 and 1.73 +/- 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (Delta AUC(0--30 min) = 39 +/- 6, 8 +/- 7, 5 +/- 7, - 1 +/- 8 and - 3 +/- 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. CONCLUSION: These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion.

Animals↗

Expression of neuropeptides in normal and abnormal appendices.

BACKGROUND/PURPOSE: Increased neuroproliferation in the appendix associated with an increase in substance P (SP), vasoactive intestinal polypeptide (VIP), and growth-associated protein-43 (GAP-43) has been documented in appendices of adults with acute right lower quadrant (RLQ) abdominal pain and absence of gross or histologic signs of appendiceal inflammation. The authors tested whether these findings were present in children with RLQ pain and a normal appendix. METHODS: Immunohistochemistry staining of paraffin-embedded appendices was performed with GAP-43, VIP, and SP. The positive control group included appendices with acute inflammation (group I, n = 5); the negative control group included appendices removed incidentally (group II, n = 5); and the experimental group included appendices from children suspected to have acute appendicitis without histologic signs of inflammation (group III, n = 9). RESULTS: Group I: VIP was strongly expressed in the nerve plexuses. The lamina propria and muscularis showed absent or minimal VIP expression. SP staining was strong in all plexuses and was moderate to strong in the muscularis. SP expression in the epithelium and lamina propria was difficult to quantify secondary to inflammation. Group II: VIP expression was essentially undetectable in the epithelium, lamina propria, and muscularis, and was moderate in the nerve plexuses. Mild SP staining was detected in the nerve plexuses of most specimens, and absent to mild staining was found in the epithelium and muscularis. However, one specimen strongly expressed SP in all layers. Group III: VIP expression was moderate to strong in the lamina propria and muscularis of nearly all specimens, and strong expression was found in all nerve plexuses. All but one specimen strongly expressed SP in plexuses. There was moderate to strong expression of SP in the epithelium, lamina propria, and muscularis in over 50% of specimens. The immunostaining for GAP-43 was very weak and nonspecific and did not help discriminate between the 3 study groups. CONCLUSIONS: Increased neuroproliferation in the lamina propria and muscularis was evident in patients with abdominal pain and normal appendices compared with appendices removed incidentally. The VIP and SP expression in these patients was similar or higher than that observed in patients with acute inflammation on histology.

Adolescent↗

Echocardiography-guided pericardiocentesis with probe-mounted needle: report of 53 cases.

Fifty-three pericardiocentesis procedures were performed on 48 patients from 1993 to 2000 at our coronary care unit. Percutaneous puncture (anterior thoracic in 43 cases, subxiphoid in 10 cases) was performed at the site closest to the exploring probe, where the largest amount of fluid was detected. A needle carrier supported by a bracket with two fixed angulations was mounted on the probe. The needle was advanced through the tissues and inside the pericardial space under continuous visualization. The procedure was successful in 52 of 53 cases. In 1 case of diagnostic pericardiocentesis, the pericardial space was impossible to reach because of the minimal amount of pericardial fluid. In 1 case of acute tamponade after transcatheter ablation of the atrioventricular node, the pericardial puncture caused a pleural-pericardial shunt with consequent drainage of pericardial fluid into the pleural space and symptom resolution. In 1 case, a transient atrioventricular type III block occurred. Emergency surgical drainage was not required in any of the cases. No puncture of cardiac walls ever occurred in this series of patients. No major complications occurred; the incidence of minor sequelae was lower than the incidence reported by other studies on pericardiocentesis without continuous visualization. Our technique appears to be safe and easy to perform even in the presence of minimal amounts of pericardial fluid.

Adolescent↗

Induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor RPR-115135: role of gene mutations.

To investigate the relationship between oncogene activation and induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor, RPR-115135, two isogenic cell lines, human colon cancer line HCT-116, which harbors a K-ras mutation, and spontaneously immortalized human breast epithelial cell line MCF-10A, were utilized. HCT-116 cells were transfected with an empty control pCMV vector (clone CMV-2) or with a dominant negative mutated p53 transgene (clone Mu-p53-2) to disrupt p53 function. In both clones RPR-115135 induced a significant increase in the frequency of micronucleation at concentrations that did not affect cell membrane integrity. RPR-115135 produced a significant increase in the ratio of CREST+ to CREST- micronuclei. MCF-10A cells were stably transfected with either c-Ha-ras or c-erbB-2 or both H-ras + c-erbB-2. No induction of micronuclei was observed. No induction of micronuclei was reported in human lymphocytes and in primary spinal cells obtained from 7-day chick embryos. In conclusion, RPR-115135 acts as an aneugenic agent in a complex manner, dependent upon the complement of mutations in cell regulatory genes in tumour cells and this activity may be independent of ras genotype.

Alkyl and Aryl Transferases↗

Pattern of expression of cyclin T1 in human tissues.

Cyclin T1 was recently identified, together with cdk9 (previously named PITALRE), as part of the TAK multiprotein complex, a co-factor targeted by the human immunodeficiency virus Type 1 (HIV-1) protein named Tat, suggesting a role for this complex in transcription elongation. Although studies on mRNA and protein expression have shown that cyclin T1 is ubiquitous in adult human tissues, no data have yet been reported regarding the expression of this protein in different cell lineages. Using a polyclonal antiserum raised against cyclin T1, we investigated the pattern of expression of this protein in adult human tissues by immunohistochemistry. Cyclin T1 was expressed ubiquitously, although different levels of expression were found in various organs. Some specialized tissues, such as blood, lymphoid tissues, and cells of connective tissue origin, showed high cyclin T1 expression. These specific expression patterns are only partially justified by some well-known specialized functions of cyclin T1 in certain cell types, such as its involvement in peripheral blood lymphocytes and monocyte differentiation. The high expression level found in other tissues suggests new possible roles for cyclin T1 in cell types other than those of lymphoid tissue.

Adult↗

Cyclin T2a gene maps on human chromosome 2q21.

Cyclin T2a was recently identified as one of the regulatory subunits of the cdk-cyclin complex P-TEFb, the most studied positive factor in the regulation of transcription elongation. By fluorescent in situ hybridization (FISH), the gene codifying for cyclin T2a has been mapped on human chromosome 2q21. This locus also has been linked to different forms of myopathy. By use of a new specific antiserum raised against cyclin T2a, the immunohistochemical pattern of expression of cyclin T2a in human tissues has been examined and compared to that of cyclin T1, described in the previous report. The observation that immunohistochemical expression of cyclin T2a was high in skeletal muscle cells, whereas it was undetectable in two cases of centronuclear myopathy, together with its chromosomal location, suggests an involvement of the cdk9-cyclin T2a complex in this disease.

Antibody Specificity↗

Dermatan sulfate versus unfractionated heparin for the prevention of venous thromboembolism in patients undergoing surgery for cancer. A cost-effectiveness analysis.

BACKGROUND: In a recent clinical trial, dermatan sulfate was found to be more effective than unfractionated heparin (UFH), but equally well tolerated, for the prevention of deep vein thrombosis (DVT) after major surgery for cancer. OBJECTIVE: To perform a cost-effectiveness analysis of dermatan sulfate versus UFH in this clinical setting. DESIGN AND SETTING: This was a retrospective economic analysis using data from a randomised clinical trial, and was performed from the hospital perspective. METHODS: Clinical event rates were extrapolated from the observed venographic DVT rates, using appropriate assumptions from the scientific literature. The economic effects of switching DVT prophylaxis from UFH to dermatan sulfate and the potential lives saved were assessed by a predictive decision model. RESULTS: The per patient cost, including the burden of residual thromboembolic events and major bleeding complications, was estimated to be 154 euros (EUR) for dermatan sulfate and EUR185 for UFH (1998 values). With reference to a potential target population of 60,000 patients/year undergoing surgery for cancer in Italy, the total prophylaxis-associated cost was EUR9,258,000 for dermatan sulfate and EUR11,096,000 for UFH, whereas the potential deaths from prophylaxis failure were 204 and 392, respectively. This represented a saving of EUR1,838,000 and 188 potential lives per year with the dermatan sulfate option. The final costs and effects were mainly sensitive to variations in the rates of DVT and pulmonary embolism, and to the possible need for 1 extra day of hospitalisation because of the earlier preoperative initiation of dermatan sulfate prophylaxis. CONCLUSION: Dermatan sulfate is more cost effective than UFH for the prevention of postoperative venous thromboembolism in patients with cancer. If the hospital stay needs to be prolonged, then the dermatan sulfate option may involve a small additional cost (EUR47) per potential life saved.

Adult↗

Interaction between cognitive style and school environment: consequences on self-evaluated anxiety and depression.

This study investigated the effect of the interaction between cognitive style (CS) and school environment on self-perceived anxiety and depression. Two groups of 280 students each--one attending Fine Arts school and the other one Humanities school--were evaluated. CS was assessed by Preference Test, a paper-and-pencil test providing a measure of the extent to which individuals rely on the cognitive processes of each hemisphere. Anxiety and depression were assessed by a visual-analogue scale. Right-CS was associated to higher depressive tendencies than left-CS, and a similar but not significant pattern was observed for anxiety. A significant interaction between CS and school environment was found, i.e., the more the CS was in consonance with the environment cognitive demands, the less depressive tendencies were present, and vice versa.

Adolescent↗