Search PubMed⌕ Search

Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 199 records · Page 11Linked to original sources
PubMed2000

Instability at dinucleotide and trinucleotide repeats in breast cancer.

We analyzed 7 mono-, 6 di- and 2 trinucleotide repeat loci in a well characterized series of 69 breast cancer cases, treated in the period 1985-1986 and followed for 12 years. Tumor-associated allele contractions or expansions were observed only at di- and trinucleotide repeats, and were detected in 14/69 cases (20%), of which 7 (10%) showed instability at 2 or more loci (10%). No alterations were detected at mononucleotide repeats known to be unstable in gastrointestinal tumors with the microsatellite mutator phenotype. Disease-free survival at 5 years, overall survival at 12 years of follow-up, tumor stage, estrogen/progesteron receptor status, and expression of the Ki-67 proliferation marker were independent of microsatellite status.

Adult↗
PubMed2000

Prognostic significance of DNA ploidy, S-phase fraction, and tissue levels of aspartic, cysteine, and serine proteases in operable gastric carcinoma.

A consecutive series of 63 untreated patients undergoing surgical resection for stage I-IV gastric adenocarcinomas (GCs) has been prospectively studied. Our purpose was to analyze the predictive relevance of DNA ploidy, S-phase fraction (SPF), and tissue levels of lysosomal proteinases cathepsin D (CD), cathepsin B (CB), cathepsin L (CL), and urokinase-type plasminogen activator (uPA) and that of the intracellular cysteine proteinase inhibitor stefin A on clinical outcome. All of the patients taking part in this study were followed up for a median of 73 months. DNA aneuploidy was present in 71% of the cases (45/63), whereas 9% of these (4/45) showed multiclonality. Both DNA ploidy and SPF were associated with tumor-node-metastasis (TNM) stage and node status, whereas only DNA ploidy was related to depth of invasion. CB, CL, uPA, but not CD, levels were significantly higher in GC as compared to paired normal mucosa, whereas stefin A levels were lower in tumor tissues. CB levels were significantly associated with TNM stage, nodal status, histological grade, and DNA ploidy. At univariate analysis, only node involvement, advanced TNM stage, DNA aneuploidy, and high SPF proved to be significantly related to quicker relapse and to shorter overall survival, whereas depth of invasion was related only to survival. With multivariate analysis, only high SPF (>15.2%) was related to risk of relapse (RR = 8.50), whereas high SPF and DNA aneuploidy were independently related to risk of death (RR = 1.88 and 2.09, respectively). Our preliminary prospective study has identified SPF and DNA ploidy as important biological indicators for predicting the outcome of patients with GC.

Adenocarcinoma↗
PubMed2000

In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring.

An expert working group on the in vivo micronucleus assay, formed as part of the International Workshop on Genotoxicity Test Procedures (IWGTP), discussed protocols for the conduct of established and proposed micronucleus assays at a meeting held March 25-26, 1999 in Washington, DC, in conjunction with the annual meeting of the Environmental Mutagen Society. The working group reached consensus on a number issues, including: (1) protocols using repeated dosing in mice and rats; (2) integration of the (rodent erythrocyte) micronucleus assay into general toxicology studies; (3) the possible omission of concurrently-treated positive control animals from the assay; (4) automation of micronucleus scoring by flow cytometry or image analysis; (5) criteria for regulatory acceptance; (6) detection of aneuploidy induction in the micronucleus assay; and (7) micronucleus assays in tissues (germ cells, other organs, neonatal tissue) other than bone marrow. This report summarizes the discussions and recommendations of this working group. In the classic rodent erythrocyte assay, treatment schedules using repeated dosing of mice or rats, and integration of assays using such schedules into short-term toxicology studies, were considered acceptable as long as certain study criteria were met. When the micronucleus assay is integrated into ongoing toxicology studies, relatively short-term repeated-dose studies should be used preferentially because there is not yet sufficient data to demonstrate that conservative dose selection in longer term studies (longer than 1 month) does not reduce the sensitivity of the assay. Additional validation data are needed to resolve this point. In studies with mice, either bone marrow or blood was considered acceptable as the tissue for assessing micronucleus induction, provided that the absence of spleen function has been verified in the animal strains used. In studies with rats, the principal endpoint should be the frequency of micronucleated immature erythrocytes in bone marrow, although scoring of peripheral blood samples gives important supplementary data about the time course of micronucleus induction. When dose concentration and stability are verified appropriately, concurrent treatment with a positive control agent is not necessary. Control of staining and scoring procedures can be obtained by including appropriate reference samples that have been obtained from a separate experiment. For studies in rats or mice, treatment/sampling regimens should include treatment at intervals of no more than 24 hr (unless the test article has a half-life of more than 24 hr) with sampling of bone marrow or blood, respectively, within 24 or 40 hr after the last treatment. The use of a DNA specific stain is recommended for the identification of micronuclei, especially for studies in the rat. In the case of a negative assay result with a non-toxic test article, it is desirable that systemic exposure to the test article is demonstrated. The group concluded that successful application of automated scoring by both flow cytometry and image analysis had been achieved, and defined criteria that should be met if automated scoring is employed. It was not felt appropriate to attempt to define specific recommended protocols for automated scoring at the present time. Other issues reviewed and discussed by the working group included micronucleus assays that have been developed in a number of tissues other than bone marrow. The group felt that these assays were useful research tools that could also be used to elucidate mechanisms in certain regulatory situations, but that these assays had not yet been standardized and validated for routine regulatory application.

Animals↗
PubMed2000

Collection of fetal stem cells and newborn effects.

The aim of this work was to test fetal stem cells (FSC) number modification in relation to clamping time and newborn effect. The results show that a fast sample, between 20 and 40 seconds, from umbilical cord after fetus birth and before placental detachment assured a greater quantity of blood useful for the transplants; and that it was necessary to enrich the collected blood in CD34+ cells with specific clonogenic culture, as this is otherwise a small number for a donation to an adult. In the "new donors" the effects of the unconscious donation always depend on the clamping time, which should be the shortest possible to avoid blood overload, which is very dangerous in the presence of heart malformation.

Antigens, CD34↗
PubMed2000

A large 6q deletion is a common cytogenetic alteration in fibroadenomas, pre-malignant lesions, and carcinomas of the breast.

To assess whether early breast lesions are the precursors of invasive carcinomas, three classes of breast lesions, namely benign tumors (including fibroadenomas), putative premalignant lesions (including cases of atypical hyperplasia), and invasive carcinomas, were compared at the cytogenetic and molecular cytogenetic levels. Genetic relatedness was clearly demonstrated by the sharing of several anomalies, among which 6q deletions outnumbered all of the other alterations detected. Indeed, deletions of the long arm of chromosome 6, most likely occurring in epithelial cells, were present in 83.9% of benign breast tumors, 64% of putative premalignant lesions, and 77.4% of analyzable carcinomas. Furthermore, the interval between 6q24 and qter appeared to be the common region of deletion in all three classes of breast lesions, whereas the minimal common region of deletion was 6q27-qter. Interestingly, the latter region was reported previously to be deleted in benign ovarian tumors and recently found to harbor a gene (SEN6) that is important for SV40-mediated immortalization of human cells.

Adolescent↗
PubMed2000

Induction of interleukin-1beta and interleukin-6 gene expression in hypoperfused skeletal muscle of patients with peripheral arterial disease.

BACKGROUND: A growing amount of data supports the role of inflammation in the pathophysiology of atherosclerotic diseases but the cellular source of cytokines has not been clearly identified. Cytokines could be produced by inflammatory cells, activated endothelial and smooth muscle cells, and by the tissue exposed to recurrent ischemia. Accordingly, we evaluated whether hypoperfusion induces gene expression of interleukin (IL)-1beta and IL-6 in the skeletal muscle of patients with peripheral arterial disease and critical limb ischemia. METHODS: Skeletal muscle biopsies were obtained, during a femoral-distal bypass, from normoperfused (control) and hypoperfused skeletal muscles in 8 patients. Gene expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction, using glyceraldehyde-phosphate-deydrogenase mRNA levels as a normalization factor. RESULTS: In the hypoperfused biopsies, the level of IL-1beta gene expression was significantly higher in all but 2 patients (mean upregulation > 8.8 fold, p = 0.043), and the level of IL-6 gene expression was significantly higher in all but 1 patient (mean upregulation > 23.7 fold, p = 0.031). CONCLUSIONS: We report that IL-1beta and IL-6 gene expression is markedly upregulated in hypoperfused skeletal muscle of patients with critical lower limb ischemia. To our knowledge this is the first report of a local activation of the inflammatory cascade at the level of hypoperfused skeletal muscle. This activation, which could worsen symptoms and tissue viability and be involved in the pathophysiology of reperfusion injury, might be considered as a therapeutic target. It remains to be investigated whether our results may also apply to coronary artery disease.

Aged↗
PubMed2000

Intravenous versus oral initial load of propafenone for conversion of recent-onset atrial fibrillation in the emergency room: a randomized trial.

BACKGROUND: Non-valvular paroxysmal atrial fibrillation is a common clinical condition associated with a high risk of thromboembolism and hemodynamic problems which increase with the duration of arrhythmia. Therefore, even if arrhythmia ceases spontaneously within 24 hours in about half of the patients, a higher early conversion rate is desirable. Propafenone either by intravenous or oral load has been shown effective in conversion to sinus rhythm. METHODS: We consecutively randomized all emergency patients with non-valvular atrial fibrillation lasting no more than 48 hours to either intravenous or oral initial load of propafenone. They all received further oral doses if still on atrial fibrillation after the initial load. Exclusion criteria were: mean ventricular rate < 65 b/min, age > 75 years, recent acute myocardial infarction, overt heart failure, conduction defects, ventricular preexcitation, thyroid dysfunction, renal or hepatic insufficiency, pregnancy, current treatment with propafenone or other antiarrhythmic drugs, and intolerance to propafenone. Primary and secondary end-points were the conversion to sinus rhythm within 12 and 48 hours of randomization respectively. RESULTS: Ninety-seven patients were randomized to intravenous (n = 49) or oral (n = 48) treatment. Overall, sinus rhythm restoration occurred in 83.3% of patients within 12 hours and in 98.9% at 24 hours. Recovery rate resulted significantly greater for intravenous treatment at 1 and 3 hours (p < 0.001 and p = 0.001, respectively). At 6, 12 and 24 hours no significant difference between the two groups was observed (p = 0.77, p = 0.81 and p = 0.99, respectively). No patient needed treatment suspension. CONCLUSIONS: In patients with recent-onset non-valvular atrial fibrillation treated with propafenone within 48 hours, conversion to sinus rhythm occurred in more than 80% within 12 hours. Even if intravenous initial load appears to be slightly more rapid, the oral way is easier to administer and cheaper. The choice may depend on the specific organization of the single emergency room.

Administration, Oral↗
PubMed2000

Back to work more quickly after an inguinal hernia repair.

Tension-free hernia repair plus recovery expectancy statements return personnel to work more quickly. On the day of primary inguinal hernia repair, patients were given statements about their likelihood of returning from convalescent leave after 7 days and performing nonstrenuous work. Similar statements were given to them by telephone at 72 hours postoperatively and at a 1-week follow-up appointments. Seventy-four percent of the 73 patients returned to nonstrenuous work within 7 days, and 90% returned to strenuous work within 30 days. In this small sample, 385 work days were saved from the Navy's recommended 14 days of convalescent leave. By combining recovery expectancy statements with an effective surgical procedure, it is possible to avoid prolonged convalescence, thereby enhancing military readiness.

Absenteeism↗
PubMed2000

[Treatment of residual acoustic neurinomas].

Generally the main objective of acoustic neurinoma (AN) surgery is to totally remove the tumor associated with minimum morbidity. Nevertheless, in some cases residual tumor fragments are intentionally or accidentally left in place. These residues can lead to new growth. The present study provides a retrospective analysis of 14 cases of residual AN have undergone surgery at the Otology Group in Piacenza from 1987 to 1999. All these patients had previously undergone at least one retrosigmoidal exeresis although only one had been performed at the Otology Group. All patients except 1 were affected by anacusia at the time of surgery. The list of post-operative deficits included 2 hemipareses, 3 irreversible facial paralysis with consequent corneal opacity in 2 cases, 1 dysmetria and 1 paralysis of the abducent nerve. The patients had also undergone the following additional treatments: 1 emergency revision to drain a cerebellar hematoma, 3 ventricle-peritoneal derivations, 1 double application of stereotactic radiotherapy and 2 surgical procedures for facial plasty. Ten cases underwent the revision surgery at the Otologic Group using a translabyrinthine approach and 4 using a transcochlear approach. Tumor removal was deemed complete in all cases. The sole post-operative complications were a subcutaneous hematoma at the point where abdominal fat was removed and a temporary paralysis of the abducent nerve. Post-operative hospitalization was an average of 6.9 days. Analysis of the results showed that AN must be operated at selected centers in order to reduce the post-operative neurological deficit and the percentage of residual tumor. It also indicated that the retrosigmoid approach has a higher risk of accidentally leaving tumor residues than the other approaches. Finally, in the presence of a residual AN, the translabyrinthine approach offers the greatest advantages.

Adult↗
PubMed2000

At term pregnancies in transfusion-dependent beta-thalassemic women.

The health background management and outcome of five pregnancies in women affected by Cooley Disease are described and the preconceptual guidance and care are considered. The patients were selected from a group of 103 thalassemic women divided into three subgroups according to their first and successive menstruation characteristics. Only one woman needed induction of ovulation. A precise and detailed pre-pregnancy assessment was done before each conception. All the women were in labour at 38 weeks' gestation, and five healthy babies were born at term, weighing between 2,600 and 3,200 g. The improvement in current treatments will result in a continuous increase in pregnancies in thalassemic women, making pregnancy a real eventuality for them. Furthermore, we are studying the possibility of collecting foetus umbilical cord blood after delivery, with the aim of obtaining complete marrow reconstitution in an attempt at heterologous transplantation to the mother.

Adolescent↗
PubMed1999

Central pulmonary artery lesions in chronic obstructive pulmonary disease: A transesophageal echocardiography study.

BACKGROUND: In patients with acute pulmonary embolism, transesophageal echocardiography (TEE) often reveals presumably thrombotic lesions within the central pulmonary arteries (CPAs). These CPA lesions, when found in patients with primary pulmonary hypertension, have been attributed to in situ thrombosis or atherosclerosis. We hypothesized that similar CPA lesions may also develop in patients with chronic obstructive pulmonary disease (COPD) in the absence of pulmonary embolism. METHODS AND RESULTS: We examined by TEE 25 patients with COPD and 27 control patients with left heart disease. None of the patients had previous pulmonary embolism or ileofemoral and popliteal vein thrombosis. By use of TEE, CPA lesions were found in 12 COPD patients (48%) and 2 control patients (7.4%) (P<0.01). When CPA lesions were subdivided into types 1 (protruding and mobile) and 2 (wall-adherent), type 1 lesions proved to be uncommon, being found within the pulmonary trunk in 12% and 3.7% of COPD and control patients, respectively (P=NS). Conversely, type 2 lesions, which were always localized in the right pulmonary artery, were frequent in COPD patients (36%) and rare in control patients (3.7%) (P<0.01). When available, helical CT and MR angiography confirmed TEE findings, supporting an atherosclerotic origin of type 2 lesions, which were different from typical thrombotic lesions. FEV(1)/FVC ratio, RV/TLC ratio, PaO(2), hematocrit value, and pulmonary artery systolic pressure were not significantly different in COPD patients with and without CPA lesions. At TEE, however, COPD patients with CPA lesions showed a larger size of the main and right pulmonary arteries. CONCLUSIONS: TEE often reveals CPA lesions in stable patients with COPD even in the absence of significant pulmonary hypertension and not in close relation with the severity of pulmonary dysfunction.

Aged↗
PubMed1999

Inhibition of cytoplasmic antigen, glucose- 6-phosphate dehydrogenase, by VH-CH1, an intracellular Fd fragment antibody derived from a semisynthetic Fd fragment phage display library.

A library of Fd fragment antibody binding proteins was created by random mutation of 15 nucleotides within the CDRIII region of the immunoglobulin heavy chain gene and displayed as Fd coat protein fusion constructs of M13 phage. The library was screened for those VHbinding sites that bound glucose-6-phosphate dehydrogenase (G6PD). One isolate (DH27bp) inhibited G6PD activity by 85 %. The DH27bpgene was re-engineered, placed in a eukaryotic expression vector having an isopropyl-beta-delta-thiogalactopyranoside (IPTG) inducible promoter, and transfected and then expressed in Chinese hamster V79 cells. G6PD activity was completely inhibited. Removal of IPTG reverted the cell to full G6PD activity. The intracellular dynamics of the G6PD/DH27bpcomplex showed that when the proteasomes of cells expressing DH27bpwere inhibited (N -acetyl-Leu-Leu-norleucinal or lactacystin) G6PD activity increased. Metabolic labelling of newly synthesized IPTG-induced proteins during/absence of proteasomal inhibitors showed that both G6PD and DH27bpare signaled for degradation when the intracellular complex is formed. Furthermore, semi-quantitative RT/PCR demonstrated that G6PD mRNA is upregulated over the time course of G6PD inactivation by DH27bpFd binding protein. These effects were not observed in those cells expressing a non-mutated Fd (UMHC) or in IPTG-treated non-transduced V79 cells. Our results demonstrate that an Fd-based intracellular binding protein can find and disable the function of a specific intracellular target and once the Fd expression is repressed the activity of intracellular targeted protein can revert to normal.

Acetylcysteine↗
PubMed1999

cDNA cloning and characterization of PD1: a novel human testicular protein with different expressions in various testiculopathies.

A novel human cDNA sequence has been isolated from human testis cDNA library. This sequence, named PD1, reveals an open reading frame encoding a protein of 520 amino acids. A partial sequence similarity has been found with the RBM gene involved in the regulation of human spermatogenesis. Northern blot analysis for PD1 mRNA from several human tissues demonstrated two distinct transcripts of 2.7 (more abundant) and 4.0 kb and revealed that PD1 is expressed in testis and to a lesser extent also in spleen, thymus, and prostate. Immunohistochemical analysis of human testis showed that this protein is detected in the cytoplasm of Sertoli cells. Antibodies against a rhPD1 fragment were used for Western blot analysis, which confirmed the presence of a 60-kDa molecule in crude extract of human testicular cells obtained from fine-needle aspiration and showed different patterns in various testiculopathies, suggesting a role for such gene in human spermatogenesis.

Amino Acid Sequence↗
PubMed1999

Survival of patients with hereditary colorectal cancer: comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer.

Conflicting data exist on the prognosis of hereditary colorectal cancer. HNPCC patients, in particular, are often reported to have a better survival. We examined 2,340 colorectal-cancer patients treated in our Institution: 144 HNPCC patients (Amsterdam Criteria), 161 FAP patients and 2,035 patients with sporadic cancer. Data on hereditary-cancer patients treated between 1980 and 1995 was collected in a registry. The 2,035 sporadic colorectal-cancer patients (controls) included all new cases treated in the Department of Gastrointestinal-Tract Surgery during the same period. Observed survival was estimated using the Kaplan-Meier method. Cumulative survival probability was estimated at 5 years within each group and stratified by various clinical and pathological variables. The age distribution at diagnosis of sporadic patients was significantly higher than that of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001). In the HNPCC group, 40% had a right cancer location, vs. 14% in the FAP group and 13% in the sporadic-cancer group. In the sporadic group, 51% were early-stage cancers (Dukes A or B) vs. 48.4% and 52.1% in the FAP and HNPCC groups respectively. In the HNPCC, FAP and sporadic-cancer groups, the 5-year cumulative survival rate was 56.9%, 54.4% and 50.6% respectively. Survival analysis by the Cox proportional-hazards method revealed no substantial survival advantage for HNPCC and FAP patients compared with the sporadic group, after adjustment for age, gender, stage and tumor location. The hazard ratio for HNPCC was 1.01 (95% CI 0.72-1.39) and 1.27 (95% CI 0.95-1.7) for FAP patients compared with the sporadic-colorectal-cancer group.

Adenomatous Polyposis Coli↗
PubMed1999

Plasma levels of antioxidant vitamins and cholesterol in a large population sample in central-northern Italy.

BACKGROUND: In a population-based multicenter case-control study of diet, life-style, and gastric cancer a large series of adults, aged 30-75 years (mean 58.9 years), were randomly sampled from the general population in 3 areas of Central-Northern Italy. AIM OF THE STUDY: To evaluate the relationship between plasma levels of antioxidant vitamins and cholesterol, and sociodemographic characteristics, life-style factors, and dietary intake of selected nutrients in a sample of the Italian population. METHODS: A fasting blood sample was available for 945 subjects (553 men, 392 women). The plasma concentrations of ascorbic acid, carotene, retinol, alpha-tocopherol, and cholesterol were determined by a centralized laboratory. All participants answered to a detailed questionnaire collecting information on sociodemographic and anthropometric characteristics, smoking, alcohol drinking, and dietary habits. Covariance analysis models, with post hoc Dunnett tests, including terms for age, sex, study center, and period of blood drawing, were used for selected multiple-way comparisons of mean values of plasma nutrients. RESULTS: Mean plasma values of retinol were higher among men while women had higher levels of plasma carotene, ascorbic acid, alpha-tocopherol, and cholesterol. Plasma carotene levels showed an inverse association with body mass index, alcohol consumption, and smoking and a positive association with social class. Carotene concentrations were higher in plasma samples obtained in spring/summer, while ascorbic acid levels were higher in autumn/winter. Partial correlation co-efficients between plasma vitamin levels showed a strong correlation between carotene and ascorbic acid (0.69 in men; 0.74 in women), between carotene and alpha-tocopherol (0.44; 0.37), and between alpha-tocopherol and ascorbic acid (0.45; 0.41). Plasma alpha-tocopherol and retinol correlated with plasma cholesterol. On the other hand, plasma carotene and ascorbic acid were correlated with their estimated dietary intakes, while the intakes of other nutrients, as expected, correlated rather poorly with the respective plasma concentrations. CONCLUSIONS: Socio-economic factors, life-style, and specific nutrient intake, in addition to gender, are related to nutrient plasma levels in Italian adults and may provide specific suggestions for the prevention of chronic diseases.

Adult↗