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Biomedical subjects

R Bianco

Publications and source records attributed to R Bianco.

At least 55 records · Page 3Linked to original sources

Effect of adaptive pulse train duration on latissimus dorsi blood flow.

Blood flow, intramuscular pressure, and stroke work of the trained latissimus dorsi muscle (LD) were measured during electrical stimulation at contraction rates between 20 and 160/min using pulse trains of 2 to 6 pulses in length. Epimysial electrodes and intramuscular pressure sensors were implanted in the LD of 5 dogs. The muscle remained in situ. After 12 weeks of a progressive training protocol, LD blood flow (BF) was measured using an ultrasonic flow probe and work (SW) was determined from the measured force and shortening. For pulse trains of 2 or 3 pulses, BF increased with rate, and SW was maintained at all rates. For 4 pulses, BF and SW decreased when the contraction rate exceeded 120/min. SW decreased above 100/min and 80/min for 5 and 6 pulses, respectively. An upper rate limit dependent upon the pulse train duration exists above which BF and SW decline. Exceeding these upper rate limits should be avoided in cardiomyoplasty. Excessive stimulation rates could be detrimental to the muscle by creating a metabolic insufficiency or ischemia. The cardiac assistance benefit is compromised as SW declines during high contraction rates of long pulse train duration.

Analysis of Variance↗

Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A.

BACKGROUND: Epidermal growth factor (EGF)-related proteins, such as transforming growth factor-alpha (TGF-alpha), control cancer cell growth through hormonal pathways (i.e., autocrine [hormone acts on cell that produces it] and paracrine [hormone acts on nearby cells] pathways). Overexpression of TGF-alpha and/or its receptor (EGFR) has been detected in human cancers. The blockade of EGFR activation by the use of anti-EGFR monoclonal antibodies (MAbs) has been proposed as a potential anticancer therapy. The type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is generally overexpressed in human cancer cells and is involved in neoplastic transformation. Inhibition of PKAI by selective cAMP analogues, such as 8-chloro-cAMP (8-CI-cAMP), induces growth inhibition in various human cancer cell lines. PURPOSE: On the basis of our previous observations of a cooperative anti-proliferative effect of anti-EGFR Mab 528 and 8-Cl-cAMP in human cancer cell lines in vitro, we evaluated the anticancer activity in vivo of the combination of an anti-EGFR MAb (MAb C225) and 8-Cl-cAMP. METHODS: Athymic mice were injected subcutaneously with 10(7) human colon carcinoma GEO cells. After 7 days, when established tumor xenografts of 0.30-0.35 cm3 were detectable, 10-15 mice per group were treated intraperitoneally twice weekly with different doses of 8-Cl-cAMP and/or MAb C225. Cancer cell expression of various growth factors was evaluated by immunohistochemical analysis in tumors obtained from control and treated mice. Data were evaluated for statistical significance using the Student's t test and the Mantel-Cox logrank test. All P values represent two-sided tests of statistical significance. RESULTS: A 5-week treatment with low doses of 8-Cl-cAMP (0.5 mg/dose) and MAb C225 (0.25 mg/dose) blocked GEO tumor growth (compared with that in control mice; P < .00001) and suppressed cancer cell production of autocrine growth factors, such as TGF-alpha, amphiregulin, and CRIPTO, and of angiogenic (promotes new blood vessel formation) factors, such as vascular endothelial growth factor and basic fibroblast growth factor, with no signs of toxicity. Control and 8-Cl-cAMP (0.5 mg/dose)-treated mice died within 9-10 weeks after tumor cell injection. In MAb C225 (0.25 mg/dose)-treated mice, GEO tumors resumed a growth rate comparable to that in control animals within 3 weeks following the end of treatment and the mice died between 11 and 20 weeks after tumor cell injection. GEO tumor growth was significantly delayed in the MAb C225 plus 8-Cl-cAMP treatment group (P < .00001) and was accompanied by a prolonged survival of mice (P < .00001) as compared with the control group. CONCLUSIONS: Long-term treatment with a combination of agents that selectively inhibit two intracellular signal-transduction enzymes, such as the PKAI serine-threonine kinase and the EGFR tyrosine kinase, has anticancer activity in vivo, reflected by suppression of tumor proliferation and angiogenesis, with no signs of toxicity. IMPLICATIONS: Since these inhibitors of intracellular mitogenic (growth-stimulating) signaling have a different mechanism(s) of action and do not antagonize the effects of cytotoxic therapy, a combination of anti-EGFR MAb C225 and 8-Cl-cAMP should be investigated as a nontoxic, long-term treatment for cancer patients following chemotherapy.

8-Bromo Cyclic Adenosine Monophosphate↗

[Pneumocystis carinii lung infections in AIDS patients: a study with high-resolution computed tomography (HRCT)].

In 1993, a hundred and fifty AIDS patients were submitted to high-resolution CT (HRCT). In 102 patients, bronchoalveolar lavage and/or transbronchial biopsy findings suggested the diagnosis of Pneumocystis carinii pneumonia--a pure Pneumocystis carinii infection in 75 patients and associated with other pathogenic agents in 27. We report the most common HRCT patterns, such as ground-glass opacities, cysts, interstitial changes and nodules. Ground-glass opacities were demonstrated in 57.8% of cases, cysts in 44.1%, interstitial involvement in 52.9% and nodules in 28.4%. HRCT permitted lung disease to be demonstrated in 55% of our patients, suffering from impaired breathing, with negative chest films. Respiratory function tests and gallium scintigraphy show their low specificity in the diagnosis of Pneumocystis carinii infection because, although depicting diffuse interstitial involvement, they fail to detect the pathogenic agent. As for hemogasanalysis, in the presence of hypoxia, this technique can suggest the diagnosis of Pneumocystis carinii infection, while the pathogenic agent can be isolated with bronchoalveolar lavage, which demonstrates the simultaneous decrease in CD4 and increase in CD8 lymphocytes, respectively. To conclude, HRCT does detect the basic changes occurring in Pneumocystis carinii pneumonia, thus contributing to the diagnosis of this condition.

AIDS-Related Opportunistic Infections↗

[High-resolution computerized tomography in diffuse forms of bronchiolo-alveolar carcinoma].

Bronchioloalveolar carcinoma (BAC) is a relatively uncommon tumor of the lung accounting for 1 to 9% of all pulmonary neoplasms. Its radiologic appearance is characterized by solitary nodular opacity or diffuse air-space consolidation. The aim of this work is to report the different patterns of this neoplasm, particularly in the diffuse form, and to demonstrate the sensitivity and specificity of HRCT in its early identification. We examined 11 patients affected with multifocal bronchioloalveolar carcinoma to identify HRCT signs which could lead to improved diagnostic criteria. These signs are represented by ground-glass opacity (8/11) and alveolar consolidation (6/11), with a plurilobular, segmentary or lobar distribution. The lesions were bilateral in 8/11 cases and abnormal mediastinal lymph nodes were found in 5/11 cases. Air bronchogram was seen in all cases of ground-glass opacity and in 5/11 cases of air-space consolidation. In conclusion, in our experience, HRCT is a useful tool in the study of BAC, which has a long and slow evolution and is underestimated at chest radiograph in its early stage. Moreover, HRCT can help distinguish this condition from other lung diseases characterized by diffuse air-space consolidations, whose clinical history is useless to make an unquestionable diagnosis.

Adenocarcinoma, Bronchiolo-Alveolar↗

Differential sensitivity to non-major histocompatibility complex-restricted recombinant interleukin 2-activated lymphocyte killing of human mammary epithelial MCF-10A cells overexpressing oncogenes or protein kinase A subunits.

The sensitivity of human tumor cells to activated lymphocytes is considered to play an essential role in the antitumor activity of recombinant interleukin-2 (rIL-2)-based immunotherapy. We have investigated the effects of several genes involved in the regulation of cell growth and transformation on the sensitivity of human mammary epithelial MCF-10A cells to non-MHC-restricted, rIL-2-activated lymphocytes. Therefore, the lysability of MCF-10A cells overexpressing activated oncogenes (Ha-ras, erbB-2, and a mutated p53), growth factors [transforming growth factor alpha (TGFalpha)], or cAMP-dependent protein kinase A subunits (RIalpha, RIIbeta, and Calpha) was evaluated comparatively at different effector:target ratios by a 51Cr release assay. Parental MCF-10A, MCF-10A p53-mutated, and MCF-10A RIIbeta cells showed an intermediate sensitivity. Lysability was increased significantly in MCF-10A Ha-ras, MCF-10A TGFalpha, and MCF-10A RIalpha cells, reduced in MCF-10A Calpha cells, and completely abrogated in MCF-10A erbB-2 cells. These differences could not be explained by simple changes in the cell surface expression of MHC class I and intercellular adhesion molecule-1 proteins or by secretion of TGFbeta. Treatment with TAb 250, a mouse anti-p185(erbB-2) monoclonal antibody, or down-regulation of p185(erbB-2) expression resulted in circumvention of MCF-10A erbB-2 cell resistance. We conclude that molecular changes at the single-gene level resulting in alterations of intracellular signaling and/or cell transformation modulate sensitivity of human mammary epithelial cells to non-MHC-restricted, rIL-2-induced cytotoxicity, regardless of MHC class I and/or intercellular adhesion molecule-1 expression or TGFbeta secretion. Furthermore, anti-p185(erbB-2) monoclonal antibodies may be useful as adjuncts to rIL-2 treatment in patients with erbB-2-overexpressing tumors.

Animals↗

Repair of tetralogy of Fallot in the first six months of life: transatrial versus transventricular approach.

BACKGROUND: This report describes our experience with primary correction of tetralogy of Fallot in infants. METHODS: Fifty-one consecutive infants younger than 6 months underwent primary correction of tetralogy of Fallot between January 1978 and October 1994. Mean age at repair was 4.2 months. Four were neonates. Correction was accomplished through a right ventriculotomy in the first consecutive 22 patients (43%; group A); since 1991, a combined transatrial-transpulmonary approach was used in 29 consecutive patients (57%; group B). A transannular patch was necessary in 33 infants (65%) 16 of group A (73%) and 17 of group B (59%). RESULTS: There was one early death from possible left anterior descending coronary artery distortion in group A and no deaths in group B. Two patients required early reoperation for systemic-to-pulmonary artery collateral ligation (postoperative day 6) and permanent pacemaker implantation (postoperative day 30). There were no late deaths. All 50 survivors are currently asymptomatic and in New York Heart Association class I. Three patients required late reoperations 36 months, 30 months, and 13 months after repair for (1) subaortic stenosis and dysfunctioning dysplastic mitral valve, (2) residual pulmonary artery branch stenosis, and (3) residual right ventricular outflow obstruction. Four patients underwent balloon dilation and stent insertion (1 patient) for peripheral pulmonary artery stenosis 1.5 year to 12 years (mean, 5 years) after initial repair. Actuarial freedom from need for reintervention at 4 years was 78.4% in group A and 85.7% in group B. Two-dimensional and Doppler echocardiographic follow-up studies showed a residual mild to moderate pulmonary artery branch stenosis in 4 patients in group A, and a recurrent subaortic stenosis in 1 patient in group A. Right ventricular peak systolic pressure was less than 40 mm hg in all but 3 asymptomatic patients who had a residual pulmonary artery branch stenosis. Right ventricular end-systolic and end-diastolic volumes showed larger volumes and reduced ejection fraction in group A compared with group B. CONCLUSIONS: This limited experience with repair of tetralogy of Fallot in patients less than 6 months of age demonstrates that the transatrial-transventricular approach is possible in neonates and young infants with a very low mortality and morbidity and also a low incidence of residual lesions. Follow-up echocardiographic data suggest that right ventricular function is better preserved in those patients who underwent the transatrial-transpulmonary repair.

Cardiac Surgical Procedures↗

Characterization of a satellite DNA from Antilocapra americana.

The nucleotide sequence of a cloned satellite DNA from Antilocapra americana (American pronghorn antelope) is presented. The 1477-bp satellite is composed of degenerate 31-bp sub-repeats which are very similar in sequence to those of the major satellite DNAs from cattle and sheep. The sub-repeat sequence is more degenerate and variable in pronghorn than it is in cattle or sheep. The sequence is organized in the pronghorn genome in multicopy tandem arrays.

Animals↗

Mid-term results of heart transplantation in diabetic patients.

BACKGROUND: Diabetes mellitus (DM) has been considered a relative contraindication to heart transplantation (HTx) because of possible increased infection rates and worsening DM with prednisone immunosuppression. The introduction of cyclosporine has allowed us to reduce the dosage of oral steroids and to accept DM patients (pts) for HTx. We reviewed the mid-term outcome of our DM pts who had undergone HTx. MATERIALS AND METHODS: Out of 257 HTx recipients, 19 males and 3 females, aged 53 +/- 8 years, were diabetic. Prior to HTx, DM was controlled with insulin in 5, with oral hypoglycemic agents in 7 and with diet in the remaining patients. Immunosuppression consisted of cyclosporine and azathioprine; low-dose prednisone was added in 10 patients because of repeated rejections. RESULTS: All patients survived HTx and were followed 2 to 75 (mean 38 +/- 21) months. There were 4 late deaths, with actuarial survival of 84% at 5 years. DM was more difficult to control after HTx (12 patients requiring insulin vs 5 pre-HTx), but comparison of diabetic vs non diabetic patients following HTx showed no significant difference in frequency of rejection or infection during the 1st year (2.6 +/- 1.6 vs 2.1 +/- 1.5; 0.5 +/- 0.4 vs 0.4 +/- 0.3 episode/patient respectively) and in 5-year actuarial survival (84% vs 77%). Renal function is preserved in all DM patients, hypertension has developed in 11/18 (61%); annual post-HTx cardiac catheterisation has shown normal graft function and coronary arteries in all but 2 patients. CONCLUSIONS: Mid-term results indicate that HTx can be safely performed in diabetic patients; a longer follow-up is required to determine whether DM is no longer a contraindication to HTx.

Actuarial Analysis↗

[Atypical radiological images in Pneumocystis carinii infection in HIV-positive patients].

To assess the prevalence of atypical PCP patterns in AIDS patients, the chest films of 300 patients with clinical and laboratory diagnosis of PCP were reviewed. We considered as atypical patterns the finding of an asymmetric lesion, the involvement of apical regions, pleural effusion, hilar and/or mediastinal lymphadenopathy, parenchymal nodules and pneumatoceles. In some patients more than one of these patterns was found. Atypical patterns were observed in 32% of cases and consisted of: unilateral involvement in 11% of cases, apical involvement in 6%, pleural effusion in 9%, hilar and/or mediastinal lymph nodes in 4%, parenchymal nodules in 6% and finally pneumatocele in 12% of cases.

AIDS-Related Complex↗

[Niemann-Pick disease type C in monozygotic twins].

The Authors describe two monochorionic twins affected by Niemann-Pick disease type C with a clinical picture beginning in the neonatal age and with a progressive mental deterioration, loss of speech and spasticity started at 30 months. The importance of cultured skin fibroblasts is emphasized. The evidence of a defective intracellular cholesterol esterification is established as an intrinsic feature of Niemann-Pick disease type C.

Cells, Cultured↗

Newborn cardiorenal dynamics: a state of atrial natriuretic peptide unresponsiveness.

The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion were significantly different (P = 0.017). We speculate that ANF unresponsiveness in the 1-day-old lamb is related to physiological transitions during the birth process and that the maturation of the renal response to VE may require maturation of the atrial mechanism which permits ANF secretion.

Aging↗

Measurement of ATP synthesis rates by 31P-NMR spectroscopy in the intact myocardium in vivo.

The ability to measure ATP synthesis rates using 31P-NMR spectroscopy is demonstrated in the normal, ischemic, and postischemic myocardium in vivo. Cardiopulmonary bypass (CBP) was employed to induce 20 min of global myocardial ischemia, and to conduct magnetization transfer measurements during the ischemic episode and following reperfusion and return to normal circulation. For the first few minutes of ischemia, transfer of magnetization from ATP gamma to Pi was extensive and the resultant fractional reduction (delta M/M0) in the Pi resonance intensity reached approximately 100%. Subsequent to reperfusion and stabilization off CPB and on normal circulation, both the fractional reduction and the spin-lattice relaxation time, T1*, of the Pi resonance were determined when ATP gamma spins were saturated. Under these conditions, the unidirectional ATP synthesis rate was 0.41 +/- 0.09 (SEM, N = 4) mumol/s/g wet wt. The data suggest that in the canine myocardium in vivo, glycolytic enzymes mediate a very rapid exchange between Pi and ATP gamma-phosphates during early phases of ischemia; in the postischemic reperfused myocardium, however, the glycolytic contribution to the unidirectional Pi----ATP rate measured by NMR in vivo is relatively small compared to that observed in glucose-perfused, postischemic rat hearts.

Adenosine Triphosphate↗