Biomedical subjects

P Russo

Publications and source records attributed to P Russo.

At least 199 records · Page 11Linked to original sources

PubMed1995

Insulin receptor tyrosine-kinase activity is altered in both muscle and adipose tissue from non-obese normoglycaemic insulin-resistant subjects.

We performed i.v. insulin tolerance test in 30 non-obese (BMI < 30 male and < 28 female) non-diabetic (by oral glucose tolerance test) subjects and subdivided them into three groups of 10 subjects each, according to their insulin sensitivity (K(itt) values). Then we compared the tyrosine-kinase activity of immunopurified insulin receptors (using 32P-ATP and poly-glu-tyr (4:1) from both muscle and adipose tissue in 7 of the most insulin-sensitive and 7 of the most insulin-resistant subjects. No difference was observed between the two groups in the basal (no insulin) receptor tyrosine-kinase activity from both tissues. In contrast, tyrosine-kinase activity response to insulin was significantly higher (p < 0.05 by 2-way ANOVA test) in receptors from both tissues of insulin-sensitive subjects. In addition, a decreased tyrosine-kinase sensitivity to insulin was observed in muscle, but not adipose, tissue of insulin-resistant subjects (insulin ED50 being 0.87 +/- 0.05 nmol/l vs 2.03 +/- 0.07, p < 0.05 in insulin-sensitive and -resistant subjects). Insulin ED50 of muscle receptor tyrosine-kinase significantly (p = 0.001) correlated to both K(itt) values (r = -0.79) and plasma insulin values at 120 min during OGTT (r = + 0.80). Insulin receptor content, as assessed by radioimmunoassay, was similar in both muscle (7.9 +/- 1.3 and 9.2 +/- 1.9 ng/mg protein) and adipose tissue (8.2 +/- 1.3 and 7.5 +/- 1.4) of insulin-sensitive and -resistant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1995

Characterization and response to interleukin 1 and tumor necrosis factor of immortalized murine biliary epithelial cells.

BACKGROUND & AIMS: Biliary epithelial cells are the target of numerous immune-mediated liver diseases, yet their role in pathogenesis remains unclear because of difficulties in obtaining pure preparations. The aim of this study was to establish pure clones of immortalized murine intrahepatic biliary epithelial cells. METHODS: The transgenic mouse harboring the SV40 thermosensitive immortalizing mutant gene TsA58 under the control of the major histocompatibility complex class I promoter was used to establish conditionally immortalized intrahepatic bile duct cells by countercurrent centrifugal elutriation and clonal dilution. RESULTS: Immortalized clones of cells expressing cytokeratin 19, which organized themselves into ductlike structures, were obtained. On electron-microscopic sections, cells were well differentiated and polarized. Cells proliferate in response to epidermal growth factor, interleukin 1 alpha, and tumor necrosis factor alpha. Using the reverse-transcriptase polymerase chain reaction technique, these cells were found to contain messenger RNA, which encodes for the interleukin 1 and tumor necrosis factor receptors. CONCLUSIONS: The availability of unlimited numbers of pure bile duct cells that behave in an identical fashion to biliary epithelial cells from "normal" mice will allow for more rigorous studies of the behavior and function of this epithelium.

Animals↗

PubMed1995

Isolated congenital esophageal stenosis.

The incidence of congenital esophageal stenosis (CES) is approximately 1 in 25,000 to 50,000 live births. There is associated esophageal atresia in one third of cases; the remainder are classified as isolated CES. Histologically, the anomaly may include tracheobronchial remnants, a membranous diaphragm, or diffuse fibrosis of the muscularis and submucosa. The authors report their experience with three patients who had isolated CES. The patients were free of symptoms for the first 6 months of life. All had difficulty with feeding from 6 to 12 months of age, which corresponded with the introduction of solids. Most solid feedings were regurgitated. Evaluation consisted of cine-esophagogram, pH monitoring, manometry, and endoscopy, with biopsies to exclude the diagnosis of gastroesophageal reflux. All patients underwent hydrostatic dilatation, but the benefit was only transient. The patients were referred for surgical correction when symptoms recurred. Limited resection of the esophageal stenosis with primary anastomosis was performed on all three patients via a left thoracotomy. The stenoses were located in the distal third of esophagus, near the junction with the middle third. Pathological examination showed tracheobronchial remnants in one patient and fibrotic muscle in the other two. The average age at the time of surgery was 19 months. The hospital stay averaged 8 days. The contrast study 1 week postthoracotomy showed esophageal patency in all patients, with no leakage. All were discharged from the hospital, tolerating solid food. CES should be sought for in patients who present with dysphagia to solid food that begins after the first 6 months of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

PubMed1995

Presence of tumor necrosis factor alpha and interleukin-6 in renal mesangial cells of lupus nephritis patients.

Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) antigenic sites were shown within the resident glomerular mesangial cells of lupus nephritis patients applying the colloidal gold immunocytochemical approach at the electron microscopic level. Using specific polyclonal antibodies against human recombinant (hr) TNF alpha and hrIL-6 in conjunction with the protein A-gold complex, TNF alpha and IL-6 were shown in the mesangial cells, being particularly associated with the membranes of the rough endoplasmic reticulum. In addition, IL-6 also was present in glomerular immune deposits and occasionally in glomerular epithelial cells. In normal renal tissue the TNF alpha and IL-6 immunoreactivities were undetectable. The specific presence of TNF alpha and IL-6 in pathological specimens was shown by several control experiments. Thus, our results offered morphological support that TNF alpha and IL-6 might play a role in human lupus nephritis. The data showed their synthesis by the mesangial cells and their possible participation in the progression to chronicity of the renal injury on secretion.

Glomerular Mesangium↗

PubMed1995

Interferon-alpha or beta potentiate platinum analogous in human glioblastoma cell lines.

The effect of interferon-alpha or beta on platinum analogues [cisplatin (CDDP) and carboplatin] cytotoxicity was studied in four glioblastoma cell lines (U373MG, T98G, A172 and U118Mg). All cell lines were strongly resistant to the cytotoxic effect of CDDP or carboplatin. Although both interferons were not cytotoxic in all cell lines, they were able to significantly increase the cell platinum-sensitivity. Specifically interferon-alpha increased the magnitude of CDDP-induced DNA interstrand crosslinks. Our findings suggest that interferons are able to induce a very strong potentiation of platinum analogues cytotoxicity in drug-resistant human glioma cell lines.

Antineoplastic Agents↗

PubMed1995

Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation.

OBJECTIVE: To define the role of salvage prostatectomy in patients who have locally recurrent prostate cancer following pelvic lymph node dissection and 125I implantation. PATIENTS AND METHODS: Over 1000 patients underwent 125I implantation for localized prostate cancer at the Memorial Sloan Kettering Cancer Center between 1970 and 1986. Salvage radical prostatectomy was performed in a highly selected group of 10 patients with locally recurrent disease. RESULTS: Three of the 10 patients had organ-confined residual prostate cancer following salvage radical prostatectomy. The remaining seven patients had extra-prostatic disease including four patients with positive surgical margins. Two patients with organ-confined disease and one with extracapsular tumour had no evidence of locally recurrent or metastatic disease and continue to have undetectable prostate-specific antigen (PSA) levels at 50, 44, and 31 months following salvage radical prostatectomy. After a mean follow-up of 30 months, the remaining seven patients had a rising PSA level consistent with locally persistent and/or metastatic disease (median 5 ng/mL; range 1.0-144). This PSA elevation occurred within 20 months of salvage radical prostatectomy (median 6 months). Two of these patients developed clinically evident bone metastases. CONCLUSION: Salvage radical prostatectomy, although technically feasible in highly selected patients, should not be widely advocated as an effective treatment option for patients with locally recurrent prostate cancer after 125I implantation.

Aged↗

PubMed1995

The caprine arthritis encephalitis virus tat gene is dispensable for efficient viral replication in vitro and in vivo.

Caprine arthritis encephalitis virus (CAEV) is a lentivirus closely related to visna virus and more distantly to other lentiviruses, such as human immunodeficiency virus. The genomes of visna virus and CAEV contain a tat gene encoding a protein able to weakly transactivate its own long terminal repeat, suggesting that transactivation may be a dispensable function for viral replication. Three different tat gene mutants of an infectious molecular clone of CAEV were used to study their replication after transfection or infection of primary goat synovial membrane cells and of blood-derived mononuclear cells or macrophages. Our results showed no difference between replication of the wild type and either the complete tat deletion mutant or the tat stop point mutant, whereas slower growth kinetics and lower levels of expression of the partial tat deletion mutant that of the wild type were obtained in these cells. Quantitative PCR and reverse transcription-PCR analyses of the different steps of a single replicative cycle revealed an identical pattern of retrotranscription, transcription, and viral production, whereas time course analysis demonstrated that the intracellular level of viral genomic RNA was affected by the partial tat deletion at later time points. We then compared the infectious properties of the wild-type and tat mutant viruses in vivo by direct inoculation of proviral DNAs into the joints of goats. All the animals seroconverted between 27 and 70 days postinoculation. Moreover, we were able to isolate tat mutant CAEV from blood-derived macrophages that was still able to infect synovial membrane cells in vitro. This study clearly demonstrates that the tat gene of CAEV is dispensable for viral replication in vitro and in vivo.

Animals↗

PubMed1995

Renovascular hypertension in children: curability predicted with negative intrarenal Doppler US results.

PURPOSE: To assess whether intrarenal Doppler ultrasound (US) enables prediction of the outcome of renovascular hypertension in a pediatric population. MATERIALS AND METHODS: A prospective study of 29 children with renin-mediated hypertension was performed. In these patients, intrarenal Doppler US was performed before angiography. Doppler US and angiographic findings were compared with patient outcome with respect to treatment required and blood pressure (BP) status after therapy. Cure was defined as a normal BP without medication. RESULTS: Intrarenal Doppler US was positive in 15 patients (52%), group 1, and negative in 14 patients (48%), group 2. In 10 patients (67%) in group 1, the severity of the vascular lesion precluded permanent cure. Cure was achieved in all patients in group 2, except for patients with neurofibromatosis. Thus, there was a statistically significant association (P < .05) between cure and a negative Doppler US result. CONCLUSION: In children with renovascular hypertension, a negative Doppler US result enables the prediction that a cure is more likely to be achieved with endovascular therapy or surgery.

Angioplasty, Balloon↗

PubMed1995

Nitric oxide and beta-adrenergic mechanisms modify contractile responses to norepinephrine in ovine fetal and newborn cerebral arteries.

Ovine fetal cerebral arteries exhibit an enhanced contractile response to norepinephrine (NE) compared with newborns and adults. It is possible that beta-adrenergic receptors and/or nitric oxide (NO), a putative endothelium-dependent relaxing factor, differentially modulate cerebrovascular responsiveness to NE as a function of development. The present study evaluated the effect of the beta-adrenoceptor antagonist, propranolol, and the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (LNAME), on the contractile response of isolated middle cerebral artery (MCA) and basilar artery (BA) to NE during fetal development. MCAs isolated from four preterm fetal lambs (105 d of gestation), seven near-term fetal lambs (125-130 d of gestation), and eight newborn lambs (2-7 d of age) were evaluated using organ baths. BAs isolated from the near-term fetal and newborn lambs were also evaluated. Contractile reactivity of MCAs to NE decreased significantly during fetal maturation as manifested by a marked decrease in Fmax (maximal relative contractile force generated) and an increase in EC50 (Fmax = 100 +/- 7, 41 +/- 7, and 28 +/- 8% of KCl contraction; EC50 = 0.14 +/- 0.03, 1.09 +/- 0.36, and 1.07 +/- 0.22 microM for preterm fetus, near-term fetus, and newborn lamb MCAs, respectively, p < or = 0.05). Propranolol treatment (10(-5) M) increased Fmax (2-fold) only for newborn lamb MCAs. Pretreatment with LNAME (10(-4) M) markedly enhanced the contractile response to NE (7-fold decrease in EC50 and 2-fold increase in Fmax, p < 0.05) for near-term fetus MCAs, whereas preterm fetus and newborn lamb MCAs were unaffected by the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1995

Elective coronary angioplasty with and without surgical standby: clinical and angiographic criteria for the selection of patients.

BACKGROUND: The cardiac catheterization laboratory (CCL) of our hospital is the only facility for invasive cardiology in a large district. No cardiac surgery is carried out in our hospital at present, the nearest facility being approximately 50 miles away. METHODS: Over a period of 2 years we recommended percutaneous transluminal coronary angioplasty (PTCA) with surgical standby for 164 cases, who were referred to CCLs with on-site surgical standby, and PTCA without surgical standby for 232 cases, 199 of whom underwent PTCA in our CCL. Criteria used in the selection of patients for PTCA without surgical standby were the following: (a) either limited extent or severely impaired function of the ventricular segment in jeopardy; (b) normal or near-normal function of the uninvolved myocardial segments; (c) absence of lesions of the left main or left anterior descending coronary arteries when the target stenosis was in the left coronary artery; (d) non-applicability and high risk-benefit ratio of emergency surgical revascularization in the individual patient. Clinical and angiographic characteristics of patients assigned to PTCA with and without surgical standby are compared. RESULTS: An initial success was achieved in 186 cases (93%) in our CCL. In 12 cases (6%), PTCA was not successful, and in two cases (1%) it was complicated by myocardial infarction. None of the patients died, or had to undergo further coronary interventions within 1 month. Coronary stents were implanted in 24 cases. CONCLUSION: For many PTCA candidates, emergency coronary surgery is not an option in case of occlusive complications. Our data suggest that PTCA can be performed with minor complications in these patients in the absence of surgical standby, provided strict criteria are used in the selection of cases.

Adult↗

PubMed1995

Concomitant myocardial infarction in identical twins with similar coronary lesions.

Two 42-year-old male twins were referred to our hospital for coronary angiography within 3 months. Despite some gross similarities in the aspect of the coronary tree, the coronary dominance pattern was not the same in these twins, but coronary lesions involved almost the same sites. Genetically determined local factors, such as the rheologic profile in some sections of the coronary tree, or the susceptibility to lipid deposition in some spots, may be important in the development of atheromatous lesions in special sites.

Adult↗

PubMed1995

[The use of activated clotting time (ACT) to optimize heparinization during coronary angioplasty. The nursing personnel of the Hemodynamics Laboratory].

BACKGROUND: Suboptimal anticoagulation during coronary angioplasty is reported to be a major risk factor for occlusive complications. AIM: To define an appropriate timing for activated clotting time (ACT) tests in order to optimize anticoagulation with heparin during coronary angioplasty. METHODS: In 50 consecutive procedures of elective angioplasty ACT was measured at baseline, at 30, 60 and 120 min after heparin 10,000 U iv. In a subgroup of 25 patients (SG1) no additional heparin was given until the ACT test at 60 min. In a second subgroup of 25 patients (SG2) heparin 5,000 U was administered 30-45 min after the initial bolus if the ACT at 30 min was < 300 sec. ACT values were analyzed, and the correlation with the biological variables of patients was tested. RESULTS: In 20 patients out of 50 (40%) ACT values at 30 min were < 275 min. Heparin response was correlated with the body surface area but nor with age, neither with baseline ACT. Values at 60 min showed an adequate anticoagulation in only 6 patients (24%) in SG1 vs 21 (84%) in SG2. There were not complications. CONCLUSIONS: ACT testing 30 min after heparin 10,000 U during coronary angioplasty identifies most patients requiring early supplemental heparin. This yields an adequate anticoagulation at 60 min in most patients.

Adult↗

PubMed1995

[Emergency angioplasty in high-risk acute infarct].

BACKGROUND: Primary coronary angioplasty in acute myocardial infarction yields superior results in terms of effective vessel patency, recurrent ischemia and acute morbidity, as compared to intravenous thrombolysis. Despite obvious logistic and economic limitations, this early invasive approach could be strictly indicated in selected groups of patients. AIM: A prospective study to test the immediate and short-term results of an early invasive strategy with angioplasty in patients with high-risk acute myocardial infarction. METHODS: Forty-one consecutive patients with high-risk acute myocardial infarction were submitted to coronary angiography and angioplasty of the involved vessel within 12 hours of onset of symptoms. Twenty-eight had anterior myocardial infarction and 6 were in cardiogenic shock. RESULTS: Primary success was achieved in 38 patients (93%): 30 of these were discharged without complications or further revascularization procedures, and none has symptoms or re-infarction at one-month follow-up. CONCLUSIONS: Immediate invasive treatment with angioplasty in high-risk acute myocardial infarction seems to achieve good results, due to both effective infarct vessel recanalization, and early identification of candidates to urgent complete surgical revascularization.

Adult↗

PubMed1995

A new technique for measurements on long bones: development of a new instrument and techniques comparison.

In this paper we present a new instrument for measurements on long bones. The instrument is based on the use of a digital coordinatometer-goniometer connected to an optical collimator: such device allows angles as well as lengths to be measured. With regard to observing procedures, an innovative method for bone axis location by points has been applied. It is also possible to locate an axis using a symmetry and tangency criterion. As for torsion angles, the proposed technique is absolutely new; it utilizes a reference plane, which the bone must be leaned against, and the symmetry conditions that are generated by rotating the bone around an axis orthogonal to this plane. In order to verify the precision of the new instrument (digital osteogoniometer), several tests were performed. For this purpose we have studied the results of measurements carried out with the new instrument as well as with traditional apparatuses by four different observers on a sample of 10 skeletons (humerus, radius, ulna, femur, tibia of left side). The analysis of intrapersonal and interpersonal differences points out that the new osteogoniometer is more precise in angular measurements than traditional instruments. Moreover the time requested for carrying out measurements prooved to be shorter, above all with regard to torsion angles measurements.

Adult↗

PubMed1995

Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer.

Transforming growth factor alpha-Pseudomonas exotoxin-40 (TP40) is a hybrid fusion protein that selectively binds to cancer cells that express the epidermal growth factor receptor. TP40 is then internalized and kills these cells by virtue of its Pseudomonas exotoxin-derived domains. We studied the safety and short-term antitumor activity of intravesical TP40 in 43 patients with refractory superficial bladder cancer. These patients had resected Ta/T1 disease (n = 19), visible Ta or T1 lesions (n = 11), or carcinoma in situ (n = 13). Patients were treated with increasing dose levels of TP40 at 0.15, 0.3, 0.6, 1.2, 2.4, 4.8, or 9.6 mg/week for 6 weeks and evaluated by comparing pretreatment and posttreatment cystoscopic examinations, cytology, and histopathology. All TP40 doses were well tolerated. No evidence of antitumor activity was seen in any of the patients with Ta or T1 lesions. However, 8 of 9 patients with evaluable carcinoma in situ were judged by histopathology of multiple biopsy specimens to exhibit clinical improvement following TP40 therapy. In most of these responsive patients, cystoscopic examination supported the histopathological findings, although cytology of urine and bladder washings persistently demonstrated malignant cells. Therefore, TP40 appears to be a well-tolerated biological agent that may prove to have utility in treating carcinoma in situ of the bladder.

Aged↗

PubMed1995

In vitro synergism between 5-fluorouracil and natural beta interferon in human colon carcinoma cells.

The combination of 5-fluorouracil (FUra) plus IFN-beta was studied in vitro using a human colon carcinoma cell line, HCT-8. Continuous exposure to high concentrations of IFN-beta is cytotoxic to these cells (ED50, 600 +/- 50 IU/ml). A strong synergism (P < 0.002) was observed when a short-term (1-h), high-concentration exposure to fluoropyrimidine (300 or 1000 microM) was followed by IFN-beta given continuously. In fact, the mean ratio between the expected (product of the survival of each agent alone) and the observed clonogenic cell survival rates of the combination was 3.4 (range, 2.4-4.9). Longer exposures to the fluoropyrimidine (24 h, 7 days) produced less than additive effects with IFN-beta, indicating strong schedule dependency for this synergism. The mechanism of interaction was studied at four levels. First, thymidylate synthase (TS) activity, inhibition, and recovery were measured by an in situ assay in cells treated with FUra, IFN-beta, and their combination. When the prolonged infusion of IFN-beta followed a 1-h exposure to FUra, the observed TS inhibition and recovery, at each time point, were very similar to the expected values, indicating that the interactions between these drugs at the level of TS are not the determinant of the synergism. Second, cell cycle analysis was done. During the continuous exposure to IFN-beta, a significant accumulation of HCT-8 cells in S-phase was observed at 24, 48, and 72 h compared to untreated controls (P = 0.003); however, under the same experimental conditions producing synergy in the clonogenic assay, no significant cell cycle perturbations were produced by the combination of FUra followed by IFN-beta compared to those caused by each agent alone. Third, using the alkaline elution test, we also demonstrated that the synergism is not due to enhanced FUra-induced DNA single-strand break frequency in high molecular weight DNA. Finally, nucleic acid incorporation experiments, using tritiated FUra, showed that the cytokine, given continuously (300 IU/ml), enhanced the amount of FUra incorporated into nucleic acids 24 h after a 1-h exposure to 300 and 1000 microM of FUra. The median percentage of enhancement values were 31.6 +/- 11.5%,m for the lower drug concentration and 18. 4 +/- 8.1% for the higher drug concentration tested. These results suggest that the mechanism of this synergism may be related to the ability of IFN-beta to promote the incorporation of intracellular FUra metabolites into nucleic acids and/or to inhibit the cleavage of FUra nucleotides from RNA/DNA.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks.

Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations. The same treatments of resistant (A2780-DX3) cells did not produce chromosomal damage (SCEs, CAs, DSBs) and no cytotoxicity was observed. A plot of cytotoxicity versus SCEs indicated a good correlation between these two parameters for topoisomerase II inhibitors and not for mytomicin C. The plot of DSBs versus SCEs also showed a very good correlation.

Antineoplastic Agents↗

PubMed1994

Autosomal dominant polycystic kidney disease in the fetus.

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early-onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus.

Adult↗