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Biomedical subjects

A Pizzuti

Publications and source records attributed to A Pizzuti.

At least 55 records · Page 3Linked to original sources
PubMed1999

A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.

The genes responsible for insulin resistance are poorly defined. Plasma cell differentiation antigen (PC-1) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance. We describe here a novel polymorphism in exon 4 of the PC-1 gene (K121Q) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese (BMI <30 kg/m2) nondiabetic (by oral glucose tolerance test [OGTT]) Caucasians from Sicily. Compared with 80 KK subjects, Q allele carriers (n = 41, 39 KQ and 2 QQ) showed higher glucose and insulin levels during OGTT (P < 0.001 by two-way analysis of variance) and insulin resistance by euglycemic clamp (M value = 5.25 +/- 1.38 [n = 24] vs. 6.30 +/- 1.39 mg x kg(-1) x min(-1) [n = 49], P = 0.005). Q carriers had higher risk of being hyperinsulinemic and insulin resistant (odds ratio [CI]: 2.99 [1.28-7.0], P < 0.001). Insulin receptor autophosphorylation was reduced (P < 0.01) in cultured skin fibroblasts from KQ versus KK subjects. Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects (33 +/- 16.1 vs. 17.5 +/- 15 ng/mg protein, P = 0.3). These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype, and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance, a condition that predisposes to type 2 diabetes and coronary artery disease.

Adult↗
PubMed1998

Immunomagnetic isolation of human developing motor neurons.

Human motor neuron (MN) isolation provides a critical tool to study neurophysiological properties and the effects of molecules of clinical relevance on isolated neurons. We developed an immunomagnetic separation technique based on specific MN antigen recognition for nerve growth factor receptor (p75-NGFR). We cultured an average of 250,000 cells from the anterior horns of a single cord (four specimens at postconception Weeks 6.0, 7.2, 8.0, and 8.3). At day 7 in vitro (DIV), choline acetyltransferase (ChAT) and/or p75-NGFR-expressing cells (MNs) represented 72 +/- 2% of the total growing cells. MNs survived for at least 4 weeks in biochemically defined medium. The immunomagnetic separation method has been demonstrated to be effective, reproducible, and quantitative for separation of MNs.

Cells, Cultured↗
PubMed1998

Structure and expression of the human ubiquitin fusion-degradation gene (UFD1L).

We report the genomic organization, RNA and protein expression patterns of the gene encoding for the human homolog of the yeast ubiquitin fusion-degradation protein-1 (UFD1L). This enzyme is involved in a ubiquitin-dependent proteolytic pathway (UFD), firstly described in yeast. The human UFD1L gene is organized into 12 exons ranging in size from 33 to 161 bp. Sequence analysis of the 5'-flanking region of the gene revealed a high GC content, multiple CCAAT-binding motifs, CREB, CFT, and AP-2 sites. RNA transcripts were detected in all tissues and cell lines examined, including thymus, thymocytes, T- and B-cells, fibroblasts, chorionic villi, and amniocytes. In Western blot, the UFD1L antibody demonstrated the presence of multiple protein isoforms in all the tested tissues. Expression profile and promoter characteristics suggest UFD1L is a housekeeping gene with implications in the pathogenesis of DiGeorge/velo-cardio-facial syndrome, due to 22q11.2 deletions.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Human NRD convertase: a highly conserved metalloendopeptidase expressed at specific sites during development and in adult tissues.

We report the cloning of the human homologue of the rat metalloprotease N-arginine dibasic convertase (NRD convertase). This endopeptidase is responsible for the processing, at the Arg-Lys dibasic site on the N-terminal side of the arginine residue, of propeptides and proproteins. Comparisons of the human and rat full-length cDNAs show similarity and identity of 94 and 91%, respectively. In humans NRD convertase is predominantly expressed in heart, skeletal muscle, and testis. We have also studied the expression of this gene in mouse at various developmental stages and found that the neural tissue is the almost exclusive site of expression in early development (between E 10.5 and E 16.5). To gain information about the possibility that defects in this gene are linked to inherited neuromuscular disorders, we determined the chromosomal location of the human NRD convertase gene by FISH analysis, showing that the gene resides at 1p32.2.

Adult↗
PubMed1997

mRNA distribution in adult human brain of GRIN2B, a N-methyl-D-aspartate (NMDA) receptor subunit.

The expression of the N-methyl-D-aspartate (NMDA) receptor subunit NR2B/epsilon2 (GRIN2B) in the human adult brain was assayed by in situ hybridisation, by using a specific cRNA probe. The full length GRIN2B cDNA was cloned and sequenced. It showed a 90% nucleotide conservation when compared to the rodent homologue. GRIN2B gene is expressed at high levels in the fronto-parieto-temporal cortex and hippocampus pyramidal cells and, at a lower extent, in the basal ganglia (amygdala and striatum). The cerebellar granule cells does not show any mRNA expression. The non-ubiquitous anatomical distribution of the GRIN2B mRNA in the central nervous system suggests that the gene could be involved in specific functions pertaining to the expressing cell groups.

Adult↗
PubMed1997

SMT3A, a human homologue of the S. cerevisiae SMT3 gene, maps to chromosome 21qter and defines a novel gene family.

cDNA selection was used to isolate coding sequences from cosmids mapping to the gene-rich telomeric region of human chromosome 21q. A novel cDNA, termed SMT3A, was isolated and mapped between the loci PFKL and D21S171, about 2.2 Mb proximal to the telomere. The predicted protein of 103 amino acids appears to be a homologue of the Saccharomyces cerevisiae SMT3 protein, whose gene was previously isolated as a suppressor of mutations in the MIF2 gene. The yeast MIF2 gene encodes an essential centromeric protein and shows homology to mammalian CENP-C, an integral component of active kinetochores. SMT3A was found to be highly homologous to two other recently isolated human genes, suggesting the presence of a new gene family. Homologous sequences were also found in protozoa, metazoa, and plants. Moreover, all predicted proteins show significant homology to ubiquitin. The proposed role of yeast SMT3 as centromeric protein and the strong evolutionary conservation of the SMT3A gene suggest an involvement of the encoded protein in the function and/or structure of the eukaryotic kinetochore.

Amino Acid Sequence↗
PubMed1997

Expression study of survival motor neuron gene in human fetal tissues.

In order to investigate the spinal muscular atrophy (SMA) disease processes, the expression of the survival motor neuron gene (SMN) has been analyzed in human fetal tissues using RT-PCR and in situ hybridization. These studies allowed the detection of SMN RNA in all the examined tissues, with no significant variation between different developmental stages. In particular, SMN mRNA was detected in spinal cord (dorsal and ventral portions), skeletal muscle, lung, heart, kidney, liver, and spleen. Moreover, RT-PCR studies demonstrated that the expression pattern of SMN isoforms was similar to that observed in adult tissues. The present data confirm a housekeeping role for the SMN protein and may have implications on the search for early therapeutic strategies.

Cyclic AMP Response Element-Binding Protein↗
PubMed1997

Hepatitis G virus infection in hemodialysis patients.

The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.

Adult↗
PubMed1997

UFD1L, a developmentally expressed ubiquitination gene, is deleted in CATCH 22 syndrome.

The CATCH 22 acronym outlines the main clinical features of 22q11.2 deletions (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia), usually found in DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. Hemizygosity of this region may also be the cause of over 100 different clinical signs. The CATCH 22 locus maps within a 1.5 Mb region, which encompasses several genes. However, no single defect in 22q11.2 hemizygous patients can be ascribed to any gene so far isolated from the critical region of deletion. We have identified a gene in the CATCH 22 critical region, whose functional features and tissue-specific expression suggest a distinct role in embryogenesis. This gene, UFD1L, encodes the human homolog of the yeast ubiquitin fusion degradation 1 protein (UFD1p), involved in the degradation of ubiquitin fusion proteins. Cloning and characterization of the murine homolog (Ufd1l) showed it to be expressed during embryogenesis in the eyes and in the linear ear primordia. These data suggest that the proteolytic pathway that recognizes ubiquitin fusion proteins for degradation is conserved in vertebrates and that the UFD1L gene hemizygosity is the cause of some of the CATCH 22-associated developmental defects.

Adaptor Proteins, Vesicular Transport↗
PubMed1997

[Pseudoaneurysm of the left ventricle after mitral valve replacement. Diagnosis 6 years after the intervention].

We present a case of left ventricular pseudoaneurysm diagnosed by chance 6 years after a second surgical intervention on the mitral valve (replacement with a St. Jude prosthesis). A combination of cross sectional and color-Doppler studies led to the correct diagnosis. A transesophageal echocardiographic investigation did not provide further information, while the diagnosis was confirmed by computed tomography with contrast agent. A retrospective analysis of previous examinations revealed that the pseudoaneurysm developed shortly after the mitral valve replacement, remaining stable over the years. The patient was clinically asymptomatic, the size of the pseudoaneurysm did not increase during a 2 years followup, and we decided to follow a conservative treatment.

Aged↗
PubMed1997

[Anticoagulation and electrical cardioversion of chronic atrial fibrillation: proposal for an abbreviated protocol].

BACKGROUND: Several weeks of prophylactic anticoagulation are routinely prescribed before and after electrical cardioversion of atrial fibrillation. Recent studies have supported the use of transesophageal echocardiography to guide early cardioversion: patients in whom no thrombus is observed are treated with heparin followed by one month of warfarin therapy after the procedure. This kind of treatment requires hospital admission during heparin infusion, because of the need for monitoring partial thromboplastin time. AIM OF THE STUDY: To evaluate if a short at-home treatment (three days) with warfarin is sufficient to reach a good level of anticoagulation, in order to permit safe electrical cardioversion in day-hospital for patients who show no thrombi on transesophageal echocardiography. METHODS: One hundred twenty-four patients with atrial fibrillation, who were candidates for cardioversion, were treated with warfarin: 10 mg the first and second day, 5 mg the third day in group A patients (n = 79); 15 mg the first day, 10 mg the second and third day in group B patients (n = 45). On the fourth day, INR value was measured and if it was < 2, warfarin therapy was prolonged until patients reached a good level of anticoagulation. Transesophageal echocardiography was performed when the INR was > or = 2, and patients were cardioverted with DC shock if there were no thrombi. The patients were discharged on the same day of the procedure, and warfarin therapy was continued for 4 weeks there-after. If a thrombus was detected, patients repeated transesophageal echocardiography after 6 weeks of warfarin therapy, and were cardioverted if the thrombus disappeared. Otherwise, cardioversion was deferred and they received prolonged warfarin treatment. If there was poor visualization of the left atrial appendage, patients received conventional warfarin therapy for 3 weeks before and 4 weeks after electrical cardioversion. RESULTS: Mean INR value after three days of warfarin treatment was 2.41 in group A patients and 3.02 in group B patients. Twenty-one patients from group A and 3 patients from group B required anticoagulant therapy for a mean of 3.3 and 5.1 days, respectively, before reaching a good level of anticoagulation (INR value > or = 2). Eight patients reverted spontaneously to sinus rhythm before transesophageal echocardiography. Eighteen thrombi (15.5%) were identified on the transesophageal echocardiography, all of which were in the left atrial appendage. In 11 cases, thrombus disappeared after 6 weeks of warfarin therapy. In 7 patients (6%), the atrial appendage was not sufficiently visualized. Electrical cardioversion was performed on 109 patients and was successful in 88 (80.7%). None of them experienced a clinical thromboembolic event. CONCLUSIONS: In the majority of patients in atrial fibrillation, a short at-home warfarin treatment is sufficient to reach a good level of anticoagulation in order to permit safe electrical cardioversion in a day-hospital situation. Larger initial doses can achieve even better results. This treatment algorithm minimizes the anticoagulation period, hospital stay, overall duration of atrial fibrillation and the time required for the mechanical function of the left atrium to return.

Adult↗
PubMed1997

[Natriuretic peptides and the heart. Critical review and application].

This paper deals with a literature survey on natriuretic peptides (NP) and their clinical use in prognostic stratification and therapy of arterial hypertension and cardiac failure. After a brief historical introduction, the phylogenesis of NP is analyzed and the reasons of their preservation in the evolution are emphasized. The biochemistry of the NP is then treated, and the structure, synthesis, mechanism of cellular action and systems of regulation are analyzed. Subsequently, the authors have analyzed the physiology of the NP as well as their hemodynamic and biohumoral effects and actions on the central nervous system. A literature review on the significance of NP in arterial hypertension, on their usefulness as indicators of damage and on their therapeutic practice is then made. In particular, the possible future applications in the prevention of atherosclerotic damage are analyzed. The significance of NP and of their metabolites in heart failure and the prognostic implication of these peptides particularly in ischemic heart failure are then discussed. The most important papers on this topic are described. Finally the studies on the use of NP in the therapy of heart failure are analyzed and a guide on research of this topic is defined.

Atrial Natriuretic Factor↗
PubMed1996

Prediction of myotonic dystrophy clinical severity based on the number of intragenic [CTG]n trinucleotide repeats.

We carried out a genotype-phenotype correlation study, based on clinical findings in 465 patients with myotonic dystrophy (DM), in order to assess [CTG] repeat number as a predictive test of disease severity. Our analysis showed that the DM subtypes defined by strict clinical criteria fall into three different classes with a log-normal distribution. This distribution is useful in predicting the probability of specific DM phenotypes based on triplet [CTG] number. This study demonstrates that measurement of triplet expansions in patients' lymphocyte DNA is highly valuable and accurate for prognostic assessment.

Disease Progression↗
PubMed1996

Deletion analysis of the simple tandem repeat loci physically linked to the spinal muscular atrophy locus.

Multicopy dinucleotide repeats have been characterized in the spinal muscular atrophy (SMA) region on chromosome 5q13, which reveal deletions in some SMA patients. 119 Italian and Spanish SMA families have been analysed using the C272 and C212 markers. Seventy percent of these families were informative. We found 9.4% de novo deletions in SMA I and 1.5% in SMA II families. A single inherited deletion segregating in a Spanish pedigree was detected in three affected brothers. A SMA II patient showed deletion only of C272. The data presented in this study are relevant to the molecular diagnosis of SMA families in Italy and Spain and provide additional insights toward the understanding of the molecular pathology of SMA.

Alleles↗
PubMed1996

cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene.

The Drosophila dishevelled gene (dsh) encodes a secreted glycoprotein, which regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3. DVL-1 and DVL-3 putative protein products show 64% amino acid identity. The DVL-1 product is 50% identical to dsh and 92% to a murine dsh homologue (Dvl-1). Both human DVL genes are widely expressed in fetal and adult tissues, including brain, lung, kidney, skeletal muscle and heart. DVL-1 locus maps to chromosome 1p36 and DVL-3 to chromosome 3q27. DVL-1 locus on chromosome 1 corresponds to the murine syntenic region where Dvl-1 is located. DVL-1 and DVL-3 are members of a human dsh-like gene family, which is probably involved in human development. Although the precise role of these genes in embryogenesis is only conjectural at present, the structural and evolutionary characteristics suggest that mutations at their loci may be involved in neural and heart developmental defects.

Adaptor Proteins, Signal Transducing↗