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Biomedical subjects

A Leone

Publications and source records attributed to A Leone.

At least 109 records · Page 6Linked to original sources
PubMed1992

Postinfarction cardiac rupture in the nineties: do we know determinating factors?

Postinfarction cardiac rupture (PCR) up to the present accounts for approximately 20 percent of autopsy infarcted cases, ranking only behind arrhythmias and cardiac failure in the frequency of AMI complications. We re-examined our observations of a previous anatomo-clinical study of 96 patients who underwent autopsy after death from AMI. Sixteen patients had rupture of the free wall of the left ventricle at the site of infarction. All the patients with rupture showed the following statistically significant characteristics (p less than 0.01) if compared to those without rupture: cardiac hypertrophy (heart weight 390 to 1020 gm; mean: 627.5 +/- 201 gm; left ventricular wall thickness 18 mm to 29 mm; mean: 25.17 +/- 3.6 mm), sudden death (6 cases) without premonitory symptoms or with symptoms of less than an hour's duration or reappearance of chest pain not improved by opiates before late death, that occurred 240 to 660 minutes from chest pain, recorded electrocardiograms showing sinus rhythm with unchanged ST-segment (12 cases), atrioventricular block (2 cases) and junctional rhythm (2 cases). Hypertension pre-existing to the infarction was seen in 6 cases with rupture versus 9 cases without rupture (p less than 0.01). Blood pressure, heart weight and wall thickness of the left ventricle are the most increased parameters in the patients with PCR. Preventive measures against these factors can reduce PCR.

Aged↗
PubMed1991

Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma.

A prospective study analysed the prognostic value of nm23-H1 allelic deletions in colorectal cancer. Of 21 patients with no evidence of distant metastases at initial operation, 11 showed nm23-H1 allelic deletions (including 1 homozygous deletion); 10 had no nm23-H1 deletions. After median follow-up of 25 months, distant metastases had developed in 8 of 11 (73%) patients with nm23-H1 deletions but in only 2 of 10 (20%) without nm23-H1 deletions (p less than 0.03). Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.

Aged↗
PubMed1991

A nuclear factor binds to the metal regulatory elements of the mouse gene encoding metallothionein-I.

The ability of vertebrate metallothionein (MT) genes to be induced by heavy metals is controlled by metal regulatory elements (MREs) present in the promoter in multiple, non-identical copies. The binding specificity of the mouse L-cell nuclear factor(s) that interact with the element MREd of the mouse MT-I gene was analyzed by in vitro footprinting, protein blotting, and UV cross-linking assays. In vitro footprinting analyses revealed that synthetic oligodeoxynucleotides (oligomers) corresponding to the metal regulatory elements MREa, MREb, MREc, MREd and MREe of the mouse MT-I gene, as well as the MRE4 of the human MT-IIA gene and the MREa of the trout MT-B gene, all competed for the nuclear protein species binding to the MREd region of the mouse MT-I gene, the MREe oligomer being the weakest competitor. In addition, protein blotting experiments revealed that a nuclear protein of 108 kDa, termed metal element protein-1 (MEP-1), which specifically binds with high affinity to mouse MREd, binds with different affinities to the other mouse MRE elements, mimicking their relative transcriptional strength in vivo: MREd greater than or equal to MREa = MREc greater than MREb greater than MREe greater than MREf. Similarly, human MRE4 and trout MREa bind to MEP-1. A protein similar in size to MEP-1 was also detected in HeLa-cell nuclear extracts. In UV cross-linking experiments the major protein species, complexed with mouse MREd oligomers, migrated on a denaturating gel with an apparent Mr of 115,000 and was detected using each of the mouse MRE oligomers tested. These results show that a mouse nuclear factor can bind to multiple MREs in mouse, trout, and human MT genes.

Animals↗
PubMed1991

Somatic allelic deletion of nm23 in human cancer.

Tumor progression to the metastatic phenotype is accompanied in certain cell types by reduced expression of the nm23 gene. We have localized human nm23-H1 to chromosome 17 by somatic cell hybrid analysis. Regional localization in the CEPH database and in situ hybridization is reported. Somatic allelic deletion of nm23-H1 was observed in human breast, renal, colorectal, and lung carcinoma DNA samples, as compared to DNA from matched normal tissues. A homozygous deletion of nm23-H1 was observed in a lymph node metastasis of a colorectal carcinoma, indicating that nm23-H1 can be recessively inactivated. The data identify nm23-H1 as a novel, independent locus for allelic deletion in human cancer, a characteristic shared with previously described suppressor genes.

Alleles↗
PubMed1991

Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells.

Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential. To investigate the functional effects of nm23 expression, we have transfected a constitutive murine nm23-1 expression construct into highly metastatic K-1735 TK murine melanoma cells. TK clones expressing the exogenous nm23-1 construct exhibited a reduced incidence of primary tumor formation, significant reductions in tumor metastatic potential independent of tumor cell growth, and altered responses to the cytokine transforming growth factor beta 1 in soft agar colonization assays, compared with control-transfected TK clones. In contrast, nm23-1-transfected TK clones exhibited no significant differences in intrinsic tumor cell growth, i.e., primary tumor size in vivo, anchorage-dependent growth rate in vitro, and anchorage-independent colony formation in soft agar in vitro. The data demonstrate a suppressive effect of nm23 on several aspects of the cancer process, including tumor metastasis.

Amino Acid Sequence↗
PubMed1991

Identification of a second human nm23 gene, nm23-H2.

Reduced RNA and/or protein levels corresponding to the murine nm23-1 and human nm23-H1 complementary DNA clones have been correlated with high tumor metastatic potential in several rodent model systems and human breast carcinomas. We report the identification of a second human nm23 gene, designated nm23-H2. The pNM23-H2S complementary DNA clone predicted a Mr 17,000 protein 88% identical to nm23-H1. nm23-H2 also shared a significant homology with nucleoside diphosphate kinases and a Drosophila developmental gene. Southern blots containing BglII-restricted genomic DNA, which exhibited an allelic restriction fragment length polymorphism for nm23-H1, contained nonallelic bands upon rehybridization to the nm23-H2 probe. Thus, nm23-H1 and nm23-H2 are distinct genes. Northern blot hybridization of nm23-H1- and nm23-H2-specific probes to breast tumors and cell lines indicated that nm23-H1 expression was reduced in high metastatic potential tumor cells to a greater extent than nm23-H2. The data indicate the existence of a family of independently regulated nm23 genes.

Amino Acid Sequence↗
PubMed1991

Indoor passive smoking: its effect on cardiac performance.

We studied 19 nonsmoker male volunteers, 9 healthy (mean age 30.5 +/- 8.5), and 10 with previous myocardial infarction (mean age 53.8 +/- 5.3), who underwent exercise stress testing twice: in a smoke-free environment and in a smoking environment (carbon monoxide concentration 30-35 ppm). We measured peak exercise power, time to recovery of pre-exercise heart rate, expired concentration of carbon monoxide and plasma carbon monoxide. Obtained data were compared by using t-test. P less than 0.05 was statistically significant. Mean data observed in healthy people were as follows. Peak exercise power 220 +/- 30 watts in a smoking environment versus 220 +/- 30 in a smoke-free environment (P greater than 0.05). Time to recovery of pre-exercise heart rate 19 +/- 4 minutes in a smoking environment versus 8.5 +/- 4 in a smoke-free environment (P less than 0.01). Expired concentration of carbon monoxide before exercise 2.3 +/- 2.01 ppm versus 8.5 +/- 1.6 (P less than 0.01) after exercise in a smoking environment, and 2.3 +/- 2 ppm before exercise versus 2.1 +/- 1.9 after exercise in a smoke-free environment (P less than 0.05). Plasma carbon monoxide before exercise 1.4 +/- 0.2% versus 1.7 +/- 0.4 after exercise in a smoking environment (P greater than 0.05), and 1.2 +/- 0.4% before exercise versus 1.2 +/- 0.4 in a smoke-free environment (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Hemodynamic response to molsidomine in patients with ischemic cardiomyopathy tolerant to isosorbide dinitrate.

Unlike nitrates, molsidomine is able to relax vascular smooth muscle without depending on the availability of sulfhydryl groups. To assess the clinical relevance of this property, the hemodynamic effects of a 24-h i.v. infusion of molsidomine were studied in 14 patients with ischemic cardiomyopathy rendered tolerant to i.v. isosorbide dinitrate. In order to determine the role of neurohormonal activation, six of these patients were studied in the presence of an angiotensin-converting enzyme (ACE) inhibitor (enalapril, 5 mg, b.i.d.) (group 2). Six patients out of eight in group 1 (without ACE inhibition) and all patients in group 2 responded to molsidomine with a marked reduction of pulmonary artery wedge pressure (PAWP) (49% +/- 5 and 50% +/- 4 versus baseline value, respectively). However, the reduction of PAWP in group 1 was no longer significant at 12 h, and at 24 h the loss of the peak effect reached 67% +/- 7. On the contrary, PAWP remained persistently reduced in group 2 (loss of peak effect, 20% +/- 3 at 24 h, p less than 0.005). In addition, a significant decrease in hematocrit and increase in epinephrine occurred in group 1 but not in group 2. These results suggest that both the absence of dependence on sulfhydryl groups and the blockade of neurohormonal reactions are needed to avoid nitrate tolerance.

Aged↗
PubMed1991

Are we able to prevent death due to postinfarction cardiac rupture by early diagnosis and surgical treatment?

Death from postinfarction cardiac rupture (PCR) may occur in two ways. There are patients who die suddenly without symptoms or with symptoms of less than an hour's duration (sudden cardiac death), whereas other patients die several hours after the onset of the rupture. Ninety-six patients who died from AMI and underwent autopsy have been studied. Sixteen patients displayed a rupture of the free wall of the left ventricle at the site of infarction, cardiac hypertrophy and severe coronary alterations. Six of these patients were included among patients who died suddenly. The other 10 showed signs before death that occurred from 240 to 660 min after their appearance. Signs of impending rupture were appearance or increase of chest pain that was not improved by opiates, preterminal sinus rhythm with an unchanged ST-segment and echocardiographic infarct expansion or pericardial effusion. We propose that the emergence of these signs during AMI suggests an impending rupture. Early surgical intervention is essential to save those patients who survive several hours after the initial signs of PCR.

Aged↗
PubMed1991

Life-threatening arrhythmias after intravenous lidocaine alone or with magnesium in myocardial infarction complicated by ventricular fibrillation.

To compare the effects of Lidocaine (LID) alone or with Magnesium Sulfate (M) on life-threatening ventricular arrhythmias which followed cardioverted prolonged ventricular fibrillation (VF) during an acute myocardial infarction (AMI), we studied 34 (24.63%) out of 138 patients aged from 52 to 83 years (mean: 66.92 + 8.82) with an anterior AMI, who had cardioverted prolonged VF. Twenty patients (58.8%)--Group A--received LID 2 mg/min at constant-rate infusion through a subclavian catheter following a bolus of LID 100 mg, whereas 14 patients (14.2%)--Group B--received LID at the same dose + M 2.5 mg/min. All the patients had continuous monitoring and LID serum level was measured daily by means of immunofluorescent method (TDX Abbot; range 1.5-5 micrograms/ml). Group A had the following mean serum levels of LID; 250 + 0.9; 1.52; 245 +/- 0.9; 3.20 + 1.1. Group B showed: 2.65 + 1.2; 2.80 + 1.8; 3.10 + 1.2; 3.25 + 1.1. Continuous monitoring displayed the following arrhythmias respectively for Group A and Group B: VT 37 times vs 16(P less than 0.05, significant), transiently cardioverted VF during therapy 17 times vs 6(p less than 0.01, significant), 8 deaths from VF vs 6 - 3 from VF and 3 from asystole - (p = NS). LID + M treatment seemed to be more effective than LID alone to reduce life-threatening arrhythmias following cardioverted prolonged VF of AMI but not the deaths. In addition, M would raise moderately LID serum level and this fact, not yet well known, needs further investigation.

Aged↗
PubMed1991

Tumor metastasis and nm23: current concepts.

Reduced expression and/or somatic allelic deletion of nm23 is associated with high metastatic potential in several types of rodent tumors and human breast and colorectal carcinomas. Transfection of murine nm23-1 cDNA into highly metastatic murine K-1735 TK melanoma cells results in a reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered responsiveness to the cytokine, transforming growth factor beta. Here we discuss emerging concepts concerning nm23, such as its varied pattern of alteration/expression in tumor metastasis, its effect on tumorigenesis, and its possible biochemical functions.

Animals↗
PubMed1991

Detection of suspected primary lung cancer by scintigraphy with indium-111-anti-carcinoembryonic antigen monoclonal antibodies (type F023C5)

Immunoscintigraphy with 111In-labeled anti-CEA-Mab (F023C5i) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was centrally located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies.

Carcinoembryonic Antigen↗
PubMed1990

Anchorage-dependent surface distribution and partition during freeze-fracture of viral transmembrane glycoproteins.

We have compared in the same cell type the surface distribution and partition in freeze-fractured plasma membranes of Sindbis virus glycoproteins in three different situations: (i) in permanently transformed cells that express the glycoproteins as the only viral product; (ii) in cells in which prebound viruses were forced to fuse with the plasma membrane by low pH treatment; (iii) in virus-infected cells. We report here that the viral proteins expressed on the surface of transfected cells show a uniform and unclustered distribution; conversely, in Sindbis virus-infected cells they appear clustered, regionally distributed, and always associated with budding viruses (i.e., interacting with the nucleocapsid on the cytosolic side of the membrane). Furthermore, the viral proteins expressed on transfected cells or implanted by low pH-mediated fusion partition during freeze-fracture with the exoplasmic faces of the cell plasma membranes, whereas an opposite partition is observed in infected cells. These results strongly suggest that in infected cells the clustering and the partition with the protoplasmic faces of the plasma membrane depend only on the strong "anchorage" of the glycoproteins to the nucleocapsid.

Animals↗
PubMed1990

Human CD8 alpha glycoprotein is expressed at the apical plasma membrane domain in permanently transformed MDCK II clones.

Madin-Darby canine kidney cells (MDCK II) have been cotransfected with plasmids expressing the human CD8 alpha glycoprotein and the bacterial gene which confers resistance to neomycin. Stable transformants have been isolated in the presence of G-418 in the culture medium and screened for CD8 alpha expression by immunofluorescence. The three clones we have characterized showed: 1) high level of synthesis and efficient surface expression of glycosylated, homodimeric CD8 alpha and 2) preferential apical deposition of CD8 alpha in confluent monolayers. This polar distribution has been measured in cells grown on a plastic substratum as well as on nitrocellulose filter by means of EM immunocytochemistry and surface radioimmunoassay. CD8 alpha was 6 to 11-fold enriched on the apical membrane whereas the 58 kDa protein, a basolateral marker in MDCK II cells, resulted about 9-fold enriched on the basolateral membrane of the three clones. We believe these permanently transformed clones could prove to be a useful tool with which to study cell polarity.

Animals↗
PubMed1989

Mapping introns by exon excision.

A direct method for mapping introns has been devised. The technique makes use of a radioactive synthetic RNA transcript of the gene and a complementary, single-stranded DNA copy of mRNA-derived sequences. Upon hybridization of the cDNA to RNA and cleavage with ribonuclease H, only exonic RNA sequences are degraded. The surviving RNA fragments are the introns. Electrophoretic analysis in denaturing agarose gels reveals the number and size of the introns. The order of the introns is determined separately using unlabeled RNA transcripts; surviving RNA fragments are transferred to a solid support and the blot is probed sequentially with a nested set of genomic RNA transcripts of the opposite strand. Using the human prothymosin alpha gene as an example, four introns were identified which from 5' to 3' were 2.6, 0.47, 0.47, and 0.28 kb in size. From mapping and sequencing experiments the sizes are 2.6, 0.465, 0.459, and 0.295 kb, respectively. Similarly, the presence of two 300-bp insertions in a human prothymosin alpha pseudogene was established; the inserts were later identified as 295-bp Alu repetitive elements.

Blotting, Northern↗
PubMed1989

Biosynthesis, membrane translocation, and surface expression of Sindbis virus E1 glycoprotein.

Sindbis virus glycoproteins PE2 (precursor of E2) and E1 are coded in this order by the same monocistronic mRNA, cotranslationally inserted in the endoplasmic reticulum membrane and then transported to the cell surface where the progeny virus is released by budding. In the virion, three E1 plus three E2 molecules form hexameric spike complexes. Previous work (S. Bonatti, G. Migliaccio, G. Blobel, and P. Walter (1984), Eur. J. Biochem. 140, 499-502) revealed a single signal sequence for cotranslational translocation located at the aminoterminus of PE2. We have generated progressive deletions of the coding region upstream of E1 and have engineered the resulting cDNAs in plasmids suitable for in vitro transcription/translation and in vivo expression. The results we obtained with this approach show that (i) internal signal sequence(s) are present upstream of E1, and this protein may be generated and inserted in the endoplasmic reticulum membrane independently of the PE2 signal sequence; and (ii) E1 is efficiently transported to the plasma membrane in the absence of PE2/E2; exit from the endoplasmic reticulum of E1 takes place with almost the same timing in the presence or in the absence of PE2.

Animals↗