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Biomedical subjects

G Bevilacqua

Publications and source records attributed to G Bevilacqua.

At least 19 recordsLinked to original sources
PubMed1992

The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII.

The NM23-Hl gene is a putative tumor suppressor gene that may be important in the metastasic process. Recent genetic and immunological data indicate that the NM23-Hl gene encodes a protein with nucleoside diphosphate (NDP) kinase activity. The mapping of NM23-Hl by panels of rodent-human somatic cell hybrids and in situ hybridization showed that the gene is located in human chromosome band 17q22. A two-allele polymorphism with BglII was demonstrated.

Alleles↗
PubMed1992

Ocular myopathy without ophthalmoplegia can be a form of mitochondrial myopathy.

To characterize muscle pathology in 3 cases affected by ocular myopathy with eyelid ptosis and upper facial weakness, but without ophthalmoplegia, light microscopy and ultrastructural study were performed on levator palpebrae, orbicularis oculi and deltoid muscle biopsies. While levator palpebrae proved uninformative because of the massive fibrous degeneration of muscle, orbicularis oculi biopsies showed histochemical and ultrastructural alterations indicating a mitochondrial involvement, resembling that reported in ocular mitochondrial myopathies (OMM). On the other hand very mild aspecific findings were observed in deltoid. We suggest that these cases with ocular myopathy and without ophthalmoplegia should be considered a partial or initial form of OMM.

Adult↗
PubMed1992

Variability of the expression of muscle mitochondrial damage in ocular mitochondrial myopathy.

In this study we comparatively analysed deltoid histochemistry, biochemistry and mitochondrial DNA (mtDNA) in two groups of ten sporadic ocular mitochondrial myopathies (OMM), respectively with and without ragged red fibres (RRF). (1) All but one RRF--patients presented the mild form of OMM with blepharoptosis but without ophthalmoplegia; (2) the occurrence of cytochrome c oxidase deficient (COX-) fibres was significantly higher in the RRF+ group, but four RRF- cases also showed COX- fibres; (3) no difference was observed in biochemical findings between the groups; (4) two RRF- patients without COX- fibres showed mtDNA heteroplasmy; (5) in two RRF- patients without deltoid mtDNA deletion, biopsy of an eyelid muscle showed significant mitochondrial alterations. These results suggest that the expression of a mitochondrial defect can vary and that the absence of RRF in a skeletal muscle biopsy does not necessarily rule out the diagnosis of OMM, if other data support that.

Adolescent↗
PubMed1991

Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma.

Between January 1988 and June 1990, seven previously untreated patients with histologically confirmed and clinically staged IIIa invasive thymoma (IT) were enrolled in a prospective, single treatment arm study of neoadjuvant chemotherapy (NC) followed by surgery and postoperative radiation therapy (4600 to 6000 cGy). The NC included three cycles of cisplatin (75 mg/m2 on day 1), epirubicin (100 mg/m2 on day 1), and etoposide (120 mg/m2 on days 1, 3, and 5), every 3 weeks. All patients showed a partial response (greater than 50%) and underwent complete (n = 4) or incomplete (gross [n = 1] or microscopic [n = 2] residual tumor) surgical resection. Histologic examination was negative for two completely resected patients. Projected 2-year survival was 80%; all patients but one currently are alive and disease-free. This approach appeared to be feasible and may be a new therapeutic choice in the management of IT, but its use on a regular basis should be reserved until a larger number of patients and longer follow-up are available.

Adult↗
PubMed1990

Cardiac toxicity and antitumor activity of 4'-deoxy-4'-iodo-doxorubicinol.

The acute and chronic cardiotoxicity as well as the cytotoxicity of 4'-deoxy-4'-iodo-doxorubicinol (I-DXRol), the major metabolite of the doxorubicin (DXR) derivative 4'-deoxy-4'-iodo-DXR (I-DXR), were compared with those of I-DXR and DXR. In the acute study, anesthetized rats received i.v. DXR (10 mg/kg), I-DXR (4 mg/kg), or I-DXRol (4 mg/kg) and were monitored for ECG (S alpha T segment and T wave), systolic (SBP) and diastolic (DBP) blood pressure, the first derivative of the systemic arterial pressure (SA dP/dtmax), and heart rate. Treatments induced a significant widening of the S alpha T segment, but I-DXRol was significantly less toxic than I-DXR or DXR. As compared with control values, DXR induced a marked increase in SBP and DBP and a decrease in SA dP/dtmax, whereas I-DXR and I-DXRol induced modest changes in hemodynamic parameters. In the chronic study, 3 mg/kg DXR given to rats by i.v. bolus once a week for 3 weeks resulted in severe chronic cardiotoxicity that lasted 6 weeks and was characterized by S alpha T-segment widening, T-wave flattening, and severe cardiac histological damage. Doses of 1.2 mg/kg I-DXR and 1.2 and 2.4 mg/kg I-DXRol, given i.v. once a week for 3 weeks, and 3.6 mg/kg I-DXRol given as a single dose were associated with a significant T-wave voltage reduction; I-DXR and 2.4 mg/kg I-DXRol induced significant histological alterations of cardiac tissue as compared with control values, whereas modest alterations of heart tissue were observed after injections of 1.2 and 3.6 mg/kg I-DXRol in three doses and in a single dose, respectively. The cytotoxicity of the three anthracyclines against one glioblastoma cell line and two human small-cell lung cancer lines was similar. Results indicate that the acute cardiotoxicity of I-DXRol is lower than that of I-DXR and DXR, whereas the chronic heart damage is similar to that induced by I-DXR and significantly lower compared than that caused by DXR. Moreover, the cytotoxicity of the metabolite appears to be similar to that of I-DXR and DXR. The lack of additional cardiac toxicity due to I-DXRol further supports the lower overall cardiac toxicity of I-DXR, which retains a cytotoxic activity similar to that of the parent drug.

Animals↗
PubMed1990

Phase II study of high-dose epirubicin in untreated patients with small-cell lung cancer.

Eighteen previously untreated patients with histologically confirmed small-cell lung cancer were treated with high-dose epirubicin (course 1, 100 mg/m2; courses 2-6, 140 mg/m2, day 1), every 3 weeks. Overall response rate was 33% (95% confidence limits, 14-52%), including two complete and four partial responses. The response rates for limited (n = 11) and extensive (n = 7) disease patients were 45% and 14%, respectively. With a median follow-up of 18 months, estimated 2-year survival of all patients was 29% and the median duration of response 18.5 months. The dose-limiting toxicity was myelosuppression, with a median granulocyte nadir of 1,150/mm3; 39% of patients had neutropenic fever. Nausea/vomiting, alopecia, and stomatitis were the most common nonhematological toxicities, usually mild to moderate. Acute cardiac toxicity was unusual and no episodes of congestive heart failure were observed. Cumulative doses of 800 mg/m2 were associated with moderate cardiotoxicity (grade 2), as assessed by endomyocardial biopsy and electron microscopy analysis. These results indicate that epirubicin, at the present doses and schedule, is an active single agent in patients with small-cell lung cancer, with acceptable general and moderate cardiac toxicity.

Aged↗
PubMed1989

Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential.

Expression of a recently identified murine gene, nm23, has been previously proposed to be inversely correlated to tumor metastatic potential in rodent model systems. The present study was designed to investigate whether nm23 RNA was detectable in human tumor tissue, and if it was differentially expressed. nm23 RNA levels in 27 human primary infiltrating ductal breast carcinomas were determined by using Northern blots or in situ hybridization. These data were compared to traditional histopathological indicators of metastatic potential, including the number of involved (tumor bearing) lymph nodes, grade of differentiation, and hormone receptor status. A striking consistency was observed in all tumors from patients with involved lymph nodes. Using Northern blot or in situ hybridizations, all of these tumors expressed low levels of nm23 RNA. Quantitative in situ hybridization on tumors from patients with 0 involved lymph nodes identified two groups: (a) approximately 75% contained high nm23 RNA levels, and (b) 25% contained significantly (alpha = 0.05) lower nm23 RNA levels. Low nm23 RNA levels in the 0 involved lymph node tumors were accompanied by two additional histopathological indicators of high metastatic potential, low nuclear and cytoplasmic estrogen receptor content, and poorly differentiated histological grade. In contrast, none of the high nm23 RNA level tumors were both receptor negative and poorly differentiated. We conclude that nm23 RNA levels are differentially expressed in human breast tumors, and that low nm23 RNA levels are associated with histopathological indication of high metastatic potential. Short term (median follow-up of 16 months) clinical course data were consistent with nm23 RNA levels, in that 2 of 11 low nm23 RNA content patients (including one from the 0 involved lymph node group) developed metastases, while none of the high nm23 RNA patients have experienced recurrent disease.

Biomarkers, Tumor↗
PubMed1989

Role of hepatic histologic findings in the prognosis and treatment of bleeding esophageal varices.

In the period from 1976 to 1986, we performed 329 hepatic needle biopsies using a posterior extraperitoneal approach in patients with bleeding esophageal varices. The histologic findings subdivided according to a four-stage classification were correlated significantly with immediate survival. Specifically, 21 of 23 stage IV patients with severe degenerative and necrotic parenchymal lesions died after immediate emergency surgery, whereas 26 of 48 stage IV patients who did not undergo emergency surgery survived. Stage IV patients appeared unable to withstand major surgery. According to our data, histologic stage and Child's class are independent parameters, especially in emergency situations, since they quantify different aspects of functional liver failure. Therapeutic implications are presented based on cumulative analysis of histologic stages and Child's classes.

Biopsy, Needle↗
PubMed1989

Ultrastructural features of the intestinal absorption of mouse mammary tumor virus in newborn BALB/cfRIII mice.

The retrovirus mouse mammary tumor virus is present in mouse strains with a high incidence of mammary tumors as a causative agent. It is produced mainly in the mammary glands of sexually mature females and is milk-transmitted to newborns. The fate of the mouse mammary tumor virus is almost unknown. Where it enters, how it is distributed, and where it remains latent, remain unresolved problems. This study tries to answer the first of these questions. Viruses are for the most part digested in the stomach. Very few well-preserved B particles, i.e., the infective particles, are allowed to enter through a process of endocytosis, mainly in the newborn-type epithelial cells. These are epithelial cells with a very rich absorptive apparatus, characteristic of newborn rodents. The adult-type absorptive cells and the M cells of the Peyer's patches might be partly involved.

Animals↗
PubMed1989

Antenatal prevention of respiratory distress syndrome; a multicentre survey.

Obstetric and neonatal data were collected on 934 preterm deliveries in 11 Italian centres in 1980, 1985 and 1986. Therapeutic regimens for prevention of respiratory distress syndrome (RDS) were applied in 42% of the cases in 1980, 32% in 1985 and 42% in 1986. Prevention was made in most cases with corticosteroids, although their use fell progressively from 94% in 1980 to 74% in 1986. A combination of two substances was used in a percentage of cases varying from 5 to 10% in all three years. In 903 non-malformed infants, the overall incidence of RDS was not significantly different in cases in which pharmacological prevention was attempted compared with cases without prevention. The only factors significantly affecting the incidence of RDS were gestational age, birth weight and Apgar score.

Data Collection↗
PubMed1989

Management of preterm infants receiving surfactant supplementation.

The use of exogenous surfactant in the clinical management of severe neonatal respiratory distress syndrome (RDS) has raised some potential new problems related to the rapid variations in oxygenation and pulmonary compliance occurring after this treatment. We advise a strict monitoring of arterial oxygen tension (Pao2), preferably by a non-invasive technique and rapid resetting of the ventilator as indicated by changes in pulmonary compliance and lung aeration after surfactant administration. The goal should be to minimize the risks of air leakage, left-to-right shunt, and overloading of the pulmonary circulation. Rapid diagnosis and treatment of patent ductus arteriosus and appropriate fluid intake are also essential for a favourable outcome in newborn infants with severe RDS treated with surfactant.

Blood Gas Monitoring, Transcutaneous↗
PubMed1988

Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis.

NM23, a novel gene associated with low tumor metastatic potential, has been investigated in an experimental system in which metastasis is inhibited by the transfection of viral and cellular oncogenes. The experimental system utilizes transfection of the Adenovirus 2 Ela gene to inhibit metastasis: rat embryo fibroblasts (REF) transfected with c-Ha-ras were highly metastatic, while REF cotransfected with ras and Ela were virtually nonmetastatic. NM23 RNA levels were higher in three independently ras + Ela-cotransfected, low metastatic REF lines than in three independently ras-transfected, highly metastatic REF line. Differences in hybridizable NM23 RNA levels between the two groups of transfected cell lines ranged from 2- to 8-fold. In situ hybridization demonstrated that the relatively high NM23 RNA levels in low metastatic ras + Ela-cotransfected REF cells were not due to overexpression of the NM23 gene by a subpopulation of cells. Thus, the metastasis-inhibitory effect of the exogenously added Ela gene has been associated with increased activation of the cellular NM23 gene. This associated is particularly significant in light of the very few changes observed in translatable steady-state RNA levels between ras- and ras + Ela-transfected REF lines. The data identify NM23 as a candidate for a gene that suppresses the malignant state.

Adenoviridae↗
PubMed1988

Evidence for a novel gene associated with low tumor metastatic potential.

We describe a gene, NM23, that is associated with the tumor metastatic process. NM23 RNA levels were highest in cells and tumors of relatively low metastatic potential in two experimental systems: (1) murine K-1735 melanoma cell lines, in which the gene was identified, and (2) N-nitroso-N-methylurea-induced rat mammary carcinomas. NM23 RNA levels did not correlate with cell sensitivity to host immunological responses and may, therefore, be associated with intrinsic aggressiveness. The predicted carboxy-terminal protein sequence encoded by the pNM23 cDNA clone is novel compared with Genebank animal, bacterial, and viral sequences.

Amino Acid Sequence↗