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Biomedical subjects

A Leone

Publications and source records attributed to A Leone.

At least 91 records · Page 5Linked to original sources
PubMed1993

Cardiovascular damage from smoking: a fact or belief?

A large series of epidemiological, clinical and pathological studies relate cigarette smoking to the development of cardiac damage. Both active and passive smoking seen to act negatively on the heart causing atherosclerotic coronary alterations, focal myocardial lesions and arrhythmias. Acute exposure to passive smoking impairs cardiac performance in healthy people and subjects who survived a first acute myocardial infarction. Several variables, which are due to type of smoking, subject and environment, may interfere with experimental results. When we standardize these variables, cardiac damage caused by cigarette smoking is an undoubted fact.

Cardiovascular Diseases↗
PubMed1993

Anti-CEA immunoscintigraphy might be more useful than computed tomography in the preoperative thoracic evaluation of lung cancer. A comparison between planar immunoscintigraphy, single photon emission computed tomography (SPECT), and computed tomography.

While a clinical, plain radiographic, and bronchoscopic assessment yields most of the essential information needed in lung cancer, computed tomography (CT) of the thorax provides diagnostic information previously unobtainable, potentially capable of reducing the number of explorative thoracotomies. In a few recent studies, immunoscintigraphy with anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies (MA) has shown remarkable staging potential. To compare the diagnostic accuracy of the two techniques, we photoscanned with indium-111 (111In)-labeled-F(ab')2 fragments of the murine anti-CEA MA FO23C5 45 patients, who were pathologically assessed for possible loco-regional extension of lung cancer. Both planar and single photo emission computed tomography (SPECT) images were obtained. Additionally, CT of the thorax (contiguous CT slices, 10 mm thick, from the lung apices to the upper abdomen), and other routine tests of preoperative evaluation were obtained. On the basis of 37 (N1, T3, and T4), 38 (N2), and 12 (N3) pathologically documented sites, an accuracy of 65, 76, 92, 78, and 86 percent (SPECT images), and 62, 68, 42, 78, and 84 percent (CT images) was calculated (figures are relevant to N1, N2, N3, T3, and T4 disease, respectively). Thus, both techniques shared a significant margin of error in almost all the categories of evaluation; however, immunoscintigraphy showed equivalent, and, in the lymph node assessment, superior results to CT. A marginal improvement of diagnostic accuracy was recorded combining the three techniques in one case (SPECT plus planar immunoscintigraphic images), while there was no benefit in any possible integration of CT and immunoscintigraphic images. In patients with peripheral nonsquamous cell cancers, the accuracy of anti-CEA immunoscintigraphy was of 90 percent or higher. Variations in the modality of performing immunoscintigraphy, such as changes in the dose of antibody fragments to be injected, in the percentage of radiolabeling, or in the time of imaging, affected the quality of immunoscintigraphic series, and the consequent interpretation of findings. At the present time, there are very few reliable tests capable of selecting patients to proceed directly to thoracotomy or to receive some intermediate surgical test, such as a prior mediastinoscopy. Traditionally, CT has been this type of "filter-test." If current findings will be confirmed in future studies, anti-CEA immunoscintigraphy might replace CT in the evaluation of particular subgroups of patients, such as patients with peripheral nonsquamous cell bronchogenic carcinoma.

Adult↗
PubMed1993

Low dose lidocaine combined with magnesium sulfate in warning ventricular arrhythmias.

This study was designed to assess if low dose lidocaine (L) (0.8 mg/min at a constant rate infusion following a 100 mg bolus) combined with magnesium sulfate (M) (2.5 mg/min) controlled warning ventricular arrhythmias (a total of 119,806 ectopic beats and 146 runs of sustained ventricular tachycardia) in 7 (17%) out of 41 patients undergoing ambulatory monitoring. L alone was administered during the first 48 hours, then L+M for 48 hours, followed by L alone for a further 48 hours. Every 12 hours L serum levels were measured. Serum levels of L alone ranged from 0.33 to 2.06 mg/l (mean: 1.28 +/- 0.7 mg/l) during the first 48 hours and from 0.30 to 2.96 mg/l (mean: 1.24 +/- 1.02 during the last 48 hours). When the subjects received L+M, L serum levels were 0.69 to 3.28 mg/l (mean: 1.60 +/- 0.9 with p less than 0.05, statistically significant). Ambulatory monitoring also displayed a 70% reduction in warning ventricular arrhythmias during L+M treatment. L+M are more effective in the control of warning ventricular arrhythmias and we can also administer a lower dose of lidocaine when given in combination.

Aged↗
PubMed1993

Histopathologic coronary patterns in people with acute myocardial infarction and PTCA.

We studied coronary artery specimens histologically in 96 patients who died from acute myocardial infarction(AMI), to assess those who could benefit from in-hospital percutaneous transluminal coronary angioplasty (PTCA). For the left anterior descending artery, old stenoses within 1 cm from its origin in 80 cases (83.3%), coronary narrowing over 90% and occlusive thrombi in 40 observations (41.6%) were seen. Left main artery showed proximal stenoses with an occlusive thrombus in 4 cases (41.6%). Left circumflex artery had stenoses within 1 cm from its origin in 32 cases (33.3%), with an occlusive thrombus 6 times (6.25%) and coronary narrowing 75%. Right coronary artery showed stenoses in the proximal and midportion respectively in 20 (20.8%) and 36 cases (37.5%), with 26 occlusive thrombi (27%) and coronary narrowing 85%. Four cases (4.16%) had minimal coronary changes. The patients who had one, two and three vessel disease were 32 (33.3%), 32 (33.3%) and 28 times (29.16%) respectively. Only one-third of patients could benefit from PTCA.

Adult↗
PubMed1993

Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas.

Reduced expression of nm23 RNAs/proteins has been associated previously with high tumor metastatic potential. In contrast, we report that regional (state III) and metastatic (stage IV) childhood neuroblastomas exhibit elevated nm23 RNA levels as compared with localized tumors. Elevated neuroblastoma nm23 RNA levels were associated with significant reductions in patient survival in the overall (n = 75) and N-myc non-amplified (n = 61) portion of the cohort. Amplification of the chromosomal nm23-H1 gene was observed in 6/18 stage III and IV tumors; amplification of nm23-H2 was not demonstrated. Genomic amplification of nm23-H1 was associated with increased tumor nm23 RNA expression and reduced patient survival. Single-strand conformational polymorphism (SSCP) analysis was performed on seven neuroblastomas. Minor subpopulations of cDNAs exhibiting altered mobility were apparent in both nm23-H1 and nm23-H2 translated regions of stage III and IV tumors, suggestive of mutations. Confirmation of the SSCP data was provided by direct sequencing of nm23-H2 in a stage IV tumor, revealing a leucine to valine mutation at position 48. The data indicate that molecular alterations to nm23 other than its reduced expression can be associated with tumor aggressiveness, and provide the first evidence for nm23 mutation in a human cancer.

Amino Acid Sequence↗
PubMed1993

Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.

We report the phenotypic effects of transfection of human nm23-H1 cDNA into the human MDA-MB-435 breast carcinoma cell line. Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines. Reductions in tumor metastatic potential in vivo were accompanied by decreased colonization in soft agar and an altered colonization response to transforming growth factor beta in vitro. Total nucleoside diphosphate kinase activity, an enzymatic activity possessed by the Nm23 family, was not directly correlated with Nm23-H1 expression levels or suppression of metastatic potential in all cases examined. The data establish that nm23-H1 has functional suppressive effects on the tumor metastatic potential of a human breast carcinoma cell line, and suggest that it may regulate signal responsiveness in the colonization response.

Animals↗
PubMed1992

Post-translational processing of an O-glycosylated protein, the human CD8 glycoprotein, during the intracellular transport to the plasma membrane.

The biosynthesis of human CD8 glycoprotein in transfected rat epithelial cells produces an unglycosylated precursor, an intermediate species only initially O-glycosylated, and a doublet mature form carrying neutral and sialylated O-linked oligosaccharides with the core-2 structure (Pascale, M. C., Malagolini, N., Serafini-Cessi, F., Migliaccio, G., Leone, A., and Bonatti, S. (1992) J. Biol. Chem. 267, 9940-9947). In this study the most relevant post-translational events: dimerization, addition of the first O-linked GalNAc, fulfillment of O-linked chains, as well as expression of involved glycosyltransferases, have been examined and correlated with the localization and transit rate of CD8 through the exocytic pathway. The glycosyltransferase activities measured in rat epithelial cells transfected with human CD8 DNA are entirely consistent with the primary structure assigned to CD8 oligosaccharides. The half-time of appearance of the initially O-glycosylated precursor and mature form was estimated to be 4 and 14 min, respectively, and the half-time for delivery of mature CD8 to the cell surface was found to be about 30 min, indicating a very fast routing. Pulse experiments with [35S]cysteine at 37 degrees C followed by chase-periods at low temperatures showed that folding/dimerization occurs before routing to the Golgi apparatus, whereas the addiction of O-linked GalNAc appears to take place later, very likely in cis-Golgi cisternae. Treatment of cells with monensin accumulated the intermediate CD8 form carrying non-elongated O-linked GalNAc, whereas brefeldin A treatment produced a sialylated glycoprotein species with a mobility faster than the mature CD8. These results indicate that the two drugs affect assembly of O-linked chains at different time of their processing.

Animals↗
PubMed1992

Imaging lung cancer by scintigraphy with Indium 111-labeled F(ab')2 fragments of the anticarcinoembryonic antigen monoclonal antibody FO23C5.

BACKGROUND: Anticarcinoembryonic (CEA) monoclonal antibodies are able to react specifically with the antigen and have the potential for the detection of CEA-bearing tumors. METHODS: The authors photoscanned with indium 111 (111In)-labeled F(ab')2 fragments of the murine CEA monoclonal antibody FO23C5 63 patients with a newly diagnosed and pathologically documented bronchogenic carcinoma. Planar dual views of the thorax, abdomen, and brain were acquired between the 24th and 144th hour after the radiotracer injection. Patients had a complete pretreatment workup, which included a routine multiorgan computed tomography (CT) scan, and the determination of the serum and tissue CEA concentration. All patients were followed up clinically and radiologically. Nineteen needle aspirations and biopsies, 23 surgical explorations, and 4 mediastinoscopic studies yielded 121 pathologically documented sites of reference. RESULTS: Fifty-seven of 63 scans were positive for the primary tumor (sensitivity, 0.90). The uptake of the radiotracer correlated significantly with the intensity of tissue CEA expression (Spearman R [Rs], 0.25; P less than 0.05), but not with the serum CEA level or with the histotype. Overall, the sensitivity of the anti-CEA immunoscintigraphy (IS) for the N1, N2, N3, T3, T4, and M1 disease (1987 International Union Against Cancer [UICC] staging classification) was 0.67, 0.64, 0.62, 0.31, 0.29, and 0.86, respectively. Corresponding values of specificity were 0.67, 0.81, 0.90, 1, 1, and 0.93; accuracy values were 0.67, 0.71, 0.85, 0.71, 0.76, and 0.92. The authors limited the analysis to all of the pathologically documented sites and obtained slightly superior values but no meaningful differences. The stage derived from IS readings was correct in 33 patients. The same figure was obtained after an initial clinical workup, which included physical examination, laboratory routine tests, chest radiographs, bronchoscopy, and any diagnostic procedure indicated by those tests. CONCLUSIONS: Anti-CEA FO23C5-F(ab')2 fragments are not yet "magic bullets" for perfect diagnoses; however, their staging potential seems to be remarkable. Technical improvements, single-photo emission CT, and the use of such fragments in combination with other imaging techniques might enable researchers to further improve the current results.

Adult↗
PubMed1992

Biosynthesis and oligosaccharide structure of human CD8 glycoprotein expressed in a rat epithelial cell line.

The biosynthesis, post-translational modifications, and oligosaccharide structure of human CD8 glycoprotein have been studied in transfected rat epithelial cells. These cells synthesized and expressed on the plasma membrane high amounts of CD8 in a homodimeric form stabilized by a disulfide bridge. Three different CD8 forms were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis after metabolic labeling and immunoprecipitation: a newly synthesized, unglycosylated 27-kDa (CD8u), a palmitylated and initially O-glycosylated 29-kDa (CD8i), and the mature, terminally glycosylated 32-34-kDa doublet (CD8m). CD8i is a transient intermediate form between CD8u and CD8m: characterization of carbohydrate moiety of [3H]glucosamine-labeled CD8i showed that it comprises for the vast majority non-elongated O-linked GalNAc closely spaced on the peptide backbone. Structural analysis of oligosaccharides released by mild alkaline borohydride treatment from the [3H]glucosamine-labeled CD8 34-kDa form showed that the neutral tetrasaccharide Gal beta 1,4GlcNAc beta 1,6(Gal beta 1,3)GalNAcOH, and an homologous monosialylated pentasaccharide, predominate; the disialylated NeuAc2,3Gal beta 1,3(NeuAc alpha 2,6) GalNAcOH tetrasaccharide appeared to be poorly present. In the CD8 32-kDa form the neutral tetrasaccharide was by far the prominent O-linked chain, and no disialyloligosaccharides were identified. These results indicate that the maturation of CD8 glycoprotein in transfected rat epithelial cells results in the formation of branched O-linked oligosaccharides and that a higher degree of sialylation is responsible for the production of the heavier 34-kDa form.

Animals↗
PubMed1992

Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure.

Nitric oxide (NO), synthesised from L-arginine, contributes to the regulation of blood pressure and to host defence. We describe in-vitro and in-vivo evidence that NO synthesis can be inhibited by an endogenous compound, NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA). In man, this inhibitor is found in plasma and more than 10 mg is excreted in urine over 24 h. However, in patients with end-stage chronic renal failure, who have little or no urine output, elimination is blocked and circulating concentrations of the inhibitor rise sufficiently to inhibit NO synthesis. Accumulation of endogenous ADMA, leading to impaired NO synthesis, might contribute to the hypertension and immune dysfunction associated with chronic renal failure.

Adult↗
PubMed1992

The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions.

The six members of the human prothymosin alpha gene family have been cloned and sequenced. One gene (PTMA) contains introns and appears to be the source of all isolated prothymosin alpha cDNAs. The remaining five genes are processed pseudogenes. Four of them have consensus TATA elements upstream of sequences nearly identical to the transcriptional start region of the intron-containing gene. Those four genes also contain open reading frames coding for proteins closely related to prothymosin alpha. In two of the pseudogenes, PTMAP2 and 5, the encoded proteins differ from the product of the parental gene at only two and four locations, respectively. The fifth pseudogene (PTMAP1) encodes a different protein owing to an upstream translational initiation start site and multiple deletions and insertions. Because the potential for expression exists in this system, a search for pseudogenomic transcripts was undertaken using the polymerase chain reaction to amplify reverse transcripts of mRNAs from many human tissues and bulk DNA from several human cDNA libraries. Evidence for pseudogenomic transcripts was not obtained. Therefore, we conclude that the human prothymosin alpha gene family contains only one functional gene.

Amino Acid Sequence↗
PubMed1992

Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis.

Nitric oxide (NO) is a widespread biological mediator with myriad functions. We have demonstrated that methylated arginines capable of inhibiting NO synthesis circulate in the plasma of healthy volunteers and are excreted unchanged in the urine. Up to 10 mg of asymmetric dimethylarginine is excreted in the urine every day, and this compound inhibits NO synthesis in vitro and in vivo, in animals and in humans. This finding raises the possibility that these compounds may act as endogenous regulators of the L-arginine:NO pathway in health and disease.

Amino Acid Oxidoreductases↗
PubMed1992

[Pelvic fractures].

Pelvic fractures, although accounting for only 2-3% of all traumatic skeletal lesions, are extremely important due to the frequent sequelae and complications that can cause the death of the patient. Moreover, their incidence is increasing due to road accidents, sport and work injuries. X-ray examinations, if correctly performed, allow the degree of residual stability of the pelvic ring to be assessed; they allow both the recognition of the mechanisms of injury and the evaluation of bone lesions. The X-ray examination can provide the orthopedist all the necessary information for the correct treatment planning, employing an external setting or, when the lesion is unstable, an open-field setting. The authors, after considering the major types of pelvic ring fractures, classified on the basis of the mechanisms of injury, suggest the best radiologic protocol, in their opinion, for the pelvic fractures whose diagnosis is based on X-ray examinations. In these cases, CT is less useful than in the study of acetabular fractures; it rarely provides additional information and thus remains a supplemental exam to X-rays.

Fractures, Bone↗