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Biomedical subjects

L Pastore

Publications and source records attributed to L Pastore.

At least 37 records · Page 2Linked to original sources
PubMed1998

Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose production in control and diabetic rats. A re-examination in the presence of euglycaemia.

Several studies have suggested that, in non-insulin-dependent diabetes mellitus, augmented gluconeogenesis is responsible for increased endogenous glucose production (EGP) and in the end determines fasting hyperglycaemia. However, human and animal studies have been conducted by comparing euglycaemic control subjects to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis comparing control and diabetic rats in the fasting state (with diabetic animals in hyperglycaemia), re-examining them in the presence of identical euglycaemia (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during a hyperinsulinaemic clamp. All rats were infused with [3-3H]-glucose and [U-14C]-lactate; the ratio between 14C-uridine-diphosphoglucose (reflecting 14C-glucose 6-phosphate) and 2 14C-phosphoenolpyruvate specific activities (both purified by high performance liquid chromatography from liver) measured hepatic gluconeogenesis. In diabetic animals, although overall EGP ( approximately 19.5 mg x kg[-1] x min[-1]) remained unaffected by experimental euglycaemia, the contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg x kg(-1) min(-1), hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1 mg x kg(-1) x min[-1]); both were responsible for the augmented EGP (control rats, EGP: 12.7 mg x kg(-1) x min(-1); gluconeogenesis: 5.9 mg x kg(-1) x min(-1); glycogenolysis: 6.7 mg x kg[-1] x min[-1]). Finally, during insulin clamp, gluconeogenesis and glycogenolysis were similarly decreased, and both contributed to the hepatic insulin-resistance of diabetic animals. We conclude that, in this model of non-insulin-dependent diabetes, augmented gluconeogenesis is not primarily responsible for fasting hyperglycaemia and hepatic insulin resistance. Finally, failure to accurately match the experimental conditions in which diabetic and control humans or animals are compared affects gluconeogenesis, overestimating its role in determining hyperglycaemia.

Animals↗
PubMed1997

Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder characterized by hypoplastic or absent clavicles, large fontanelles, dental anomalies and delayed skeletal development. The phenotype is suggestive of a generalized defect in ossification and is one of the most common skeletal dysplasias not associated with disproportionate stature. To date, no genetic determinants of ossification have been identified. CCD has been mapped to chromosome 6p21, where CBFA1, a gene encoding OSF2/CBFA1, a transcriptional activator of osteoblast differentiation, has been localized. Here, we describe two de novo missense mutations, Met175Arg and Ser191Asn, in the OSF2/CBFA1 gene in two patients with CCD. These two mutations result in substitution of highly conserved amino acids in the DNA-binding domain. DNA-binding studies with the mutant polypeptides show that these amino acid substitutions abolish the DNA-binding ability of OSF2/CBFA1 to its known target sequence. Concurrent studies show that heterozygous nonsense mutations in OSF2/CBFA1 also result in CCD, while mice homozygous for the osf2/cbfa1 mull allele exhibit a more severe lethal phenotype. Thus, these results together suggest that CCD is produced by haploinsufficiency of OSF2/CBFA1 and provide direct genetic evidence that the phenotype is secondary to an alteration of osteoblast differentiation.

Amino Acid Sequence↗
PubMed1997

[Evaluation of quality of life in oncology. Rationale and objectives of the first phase of the Quality of Life in Oncology project].

Although the subjective nature of quality of life perception is generally accepted, less attention has been paid to the procedure of selecting domains to be explored with questionnaires. In most cases domains are selected by panel of experts. It is not known whether these domains are relevant for the patients. Moreover, questionnaires developed in 'foreign' countries may not be culturally sound or relevant for patients living in different cultural background. In order to explore what really contributes to quality of life of Italian patients, a survey was conducted with the aim of identifying any dimension of quality of life, positively or negatively impacted on from the illness and therapies. A sample of two hundred and eighty eight cancer patients with previously specified characteristics (primary tumor, stage of disease and place of residence) were identified. After consenting to partecipate to the study, a staff member (a physician, a nurse or a psychologist) asked the patient to complete an open-ended questionnaire in the out-patient clinic or at home. This questionnaire, partially derived from a study by Padilla et al. made up of 5 questions: 'What does the term quality of life mean to you?', 'What contributes to a good quality of life?', 'What contributes to a poor or bad quality of life?', 'Which either physical or psychological symptom interferes with your quality of life?', 'State any positive or negative change in your quality of life, due to illness or treatments'. The first question was asked to explore the meaning of quality of life for the patient; the second and third question were asked to determine the contents of quality of life not health related; the fourth question and the diary provided information about quality of life contents related to his own experience of disease. Two hundred and forty eight questionnaires (86.1%) were obtained from 7 Cancer Centres participating to the study (Genova, Milano, Roma, Perugia, Napoli, Cagliari, Palermo). All the questionnaires were transcribed and subsequently broken down in phrases on a form that allowed coding. Three raters (a research nurse, an oncologist and a clinical psychologist) made the content analysis using as conceptual framework the list of domains identified by the Italian Society of Psycho-Oncology. The present study shows the possibility to define the content domain of quality of life attributes for cancer patients, using patients as experts.

Adolescent↗
PubMed1997

CTG repeat number in the nonaffected allele of myotonic dystrophy patients is not critical for disease expression.

To investigate whether unusual allele segregation might explain the dominant negative effect of the expanded allele for myotonic dystrophy on myotonin protein kinase mRNA metabolism, which is suggested to cause the disease, we determined the number of CTG repeats at the DM locus in the nonaffected alleles of 64 DM (dystrophia myotonia) patients. The relative distribution was then compared with the distributions obtained from alleles of the normal parents and normal siblings of DM patients. Comparison was also made with the allele distribution of normal subjects from the same geographic area. It appears that the CTG repeat number of the nonaffected allele in DM patients is not critical for the expression of the disease.

Alleles↗
PubMed1996

A quantitative polymerase chain reaction (PCR) assay completely discriminates between Duchenne and Becker muscular dystrophy deletion carriers and normal females.

Duchenne/Becker muscular dystrophy (DMD/BMD) is a severe X-linked myopathy. In 65% of the patients, the mutations responsible for the disease are macrodeletions in the dystrophin-encoding gene that can be identified with multiplex polymerase chain reaction (PCR) technology. We developed a method for quantitative PCR analysis of deletion carriers involving the use of phosphorimager-based scanning of radioactive-labelled PCR products. We calculated the ratios between the areas of two peaks, one corresponding to the deleted segments to be analysed and the other taken as a reference. In carriers, these ratios (R value) were always about half those obtained in normal females. The final diagnostic result, the diagnostic index (DI), is the ratio of the R values between the propositus and a normal subject. We also assessed the variability of each step of the procedure and the overall variability of the DI value, thus obtaining cut-off values that completely discriminated BMD/DMD deletion carriers from normal females. We were also able to classify, as either 'carrier' or 'normal', several females whose status was not identified with linkage analysis.

DNA Primers↗
PubMed1996

Allele frequency distributions at several variable number of tandem repeat (VNTR) and short tandem repeat (STR) loci in a restricted Caucasian population from south Italy and their evaluation for paternity and forensic use.

Allele frequencies at six VNTR loci, 11 STR loci, and at the HLA-DQA1 locus were evaluated in a well-defined population from Campania (South Italy). The allele frequencies of three VNTR loci, 11 STR loci, and the HLA-DQA1 locus were compared with data obtained from a general Caucasian reference population in the USA. The aim of this study was to determine the power of each single locus and group of loci for forensic and paternity testing purposes. Significant differences between the allele frequencies of the two populations were found in two VNTR loci, four STR loci and in the HLA-DQA1 locus. The two populations were in Hardy-Weinberg equilibrium for the STR loci, but as expected, not for some VNTR loci. It was also found that: (i) the discriminatory power of two STR systems (nine and 11 loci, respectively) is similar in the two populations analysed; and (ii) that the allele frequencies for the STR systems of a large reference population can always be applied to subjects of a small subpopulation. In conclusion, for forensic purposes and for paternity testing, most of the 11 STR loci examined can be analysed using allele frequencies from a general Caucasian reference population without typing subpopulations, whereas the VNTR loci must be subtyped.

Adult↗
PubMed1995

Direct detection of proviral gag segment of human immunodeficiency virus in peripheral blood lymphocytes by colorimetric PCR assay as a clinical laboratory tool applied to different at-risk populations.

We used a colorimetric polymerase chain reaction (PCR)-based assay in kit form to detect directly human immunodeficiency virus type 1 (HIV-1) proviral gag sequences in peripheral blood cells from 68 healthy blood donors, 51 subjects at risk for HIV infection, 122 patients with HIV-1 infection, 11 patients with indeterminate Western blot (immunoblot) results, 4 blood donors HIV-1 positive by enzyme immunoassay, and 13 children born to HIV-1-seropositive mothers. The results obtained in the blood donors and HIV-1-infected patients demonstrated the high degree of diagnostic specificity and sensitivity of the PCR method. HIV-1 infection was excluded in 10 of the 11 patients with indeterminate Western blot results and in all four enzyme immunoassay-positive blood donors. A diagnosis of HIV infection was ruled out by negative PCR results in 5 of 13 children from seropositive mothers, which excluded vertical transmission of the infection in these cases; these children were younger than 3 months and had positive serological results. Two at-risk patients with negative serological results had positive PCR results. All results were confirmed by conventional PCR. In conclusion, colorimetric PCR, which is commercially available in kit form, is an easy and reliable technique that can be used to detect proviral HIV-1 genomes in blood cells, and despite the limitations owing to HIV genome variability, it is useful in the clinical setting for the diagnosis of HIV infection in selected categories of patients.

Blotting, Western↗
PubMed1993

Loop electrosurgical excision procedures for cervical dysplasia: experience in a community hospital.

OBJECTIVE: The study was undertaken to evaluate the use of the loop electrosurgical excision procedure as an outpatient hospital or surgicenter procedure. STUDY DESIGN: The records of 358 patients treated for cervical intraepithelial neoplasia at a large community hospital over a 1-year period were reviewed. RESULTS: The specimens obtained by loop electrosurgical excision procedure and laser cone excision were comparable in size but smaller than those by means of cold-knife conization. Seventy-two percent of loop electrosurgical excision procedure specimens consisted of two to eight tissue fragments (mean 3.4). In addition, 48% of the loop electrosurgical excision procedure specimens and 38% of laser cones had moderate or severe thermal artifacts. Fragmentation and cautery damage precluded orientation of tissue and evaluation of margins in 19% of the cases. CONCLUSIONS: The advent of the loop electrosurgical excision procedure has shifted the management of cervical intraepithelial neoplasia from the office to the outpatient surgery centers. This negates and, in fact, reverses the advantage of loop electrosurgical excision procedure over other methods in regard to cost and convenience through evaluating and treating a patient with cervical intraepithelial neoplasia in one office visit. Loop electrosurgical excision procedures provide specimens that are inferior compared with cold-knife cones; therefore the role of loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia outside the office appears limited.

Adolescent↗
PubMed1991

Effects of psychotropic drugs on somatosensory evoked potentials in cerebral ischemia.

Several authors have demonstrated a correlation between short latency somatosensory evoked potentials (short latency SEPs) and cerebral blood flow (CBF). It is also known that ischemia may modify the amplitude of the cortical SEP while its latency is less sensitive to CBF fluctuations. Phychotropic drugs--Oxiracetam, SAMe, Naloxone, L-acetylcarnitine and GM1--affect some parameters of the early components of cortical SEPs, chiefly the amplitude, which makes SEP recording a useful method for monitoring pharmacological activity in acute stroke.

Brain Ischemia↗
PubMed1982

Pulmonary fat embolization in the immunocompromised patient: its relationship to steroid medication.

Three immunosuppressed patients developed respiratory distress while receiving steroids. The main pulmonary findings were fat embolization with secondary hemorrhagic alveolitis. The pulmonary changes were similar to those found in patients who had traumatic fat embolization. Pulmonary distress in immunosuppressed patients may develop for a variety of reasons; fat embolization should be included in the differential diagnosis when these patients are receiving steroids.

Adolescent↗
PubMedDate not supplied

Squamous cell carcinoma of the lower lip: FAS/FASL expression, lymphocyte subtypes and outcome.

Squamous cell carcinoma (SCC) of the lip is a relatively common malignancy of the head and neck region. Tumour thickness, grading and perineural invasion are significant prognostic indicators. However, there is still the need of new reliable biological markers able to predict the prognosis of the single cases with an unfavourable biological behaviour unpredictable by the classic clinical-pathological parameters. 32 cases of (SCC) of the lower lip were analysed for their clincopathologic features, and immunohistochemical expression of Fas/FasL in neoplastic cells and in inflammatory infiltrate. Moreover the density and phenotype of tumour-infiltrating lymphocytes (TIL) were analysed. The results were related with the follow-up of the patients ranging from 2 to 6 years. The cases with over-expression of Fas/FasL in neoplastic cells and Fas+ in T cells preferentially showed a more aggressive clinical behaviour (P<0.01). Moreover we found an alteration of the normal expression of CD4 and CD8 lymphocyte types in ten cases. This data suggest that the Fas/FasL pathway is involved in the close relation between neoplastic cells and T cells and so in the biological behaviour of these tumours.

Adult↗
PubMedDate not supplied

Stromal osseous metaplasia in metastatic adenocarcinoma of the gallbladder.

A case of stromal osseous metaplasia in the abdominal scar metastasis of a gallbladder adenocarcinoma is described. The occurrence of stromal osseous metaplasia in carcinomas probably does not affect prognosis; however, it must be recognized to avoid a misdiagnosis of carcinosarcoma.

Adenocarcinoma↗
PubMedDate not supplied

Detection of hepatitis C virus-RNA in saliva from chronically HCV-infected patients.

The possibility of the non-parenteral Hepatitis C Virus (HCV) transmission is supported by the demonstration that the actual virus is present in several body fluids, including saliva. From a review of the literature many investigators have found the presence of HCV-RNA in saliva, however, widely contrasting results emerge, with detection rates ranging from 0-100%. To further examine HCV salivary shedding, saliva samples were collected from 46 chronically HCV-infected patients and tested for HCV-RNA and occult blood. Quantification and genotyping of serum HCV-RNA were also carried out for each patient. HCV-RNA was detected in 39.13% of the saliva samples. The viral salivary shedding was significantly related to viraemia levels, serum viral genotype and the presence of salivary occult blood. Our findings indicate that the HCV salivary shedding occurs in about one third of HCV infected patients, but seem to suggest that it is unlikely when the serum viral genotype is 3a. Moreover, blood leakage into the oral cavity is possibly the main source of the salivary HCV-RNA. Although the occurrence of the viral salivary shedding does not necessarily mean that HCV transmission occurs by saliva, our results suggest the need for further investigations into the biological factors possibly involved in HCV mucosal transmission related to both the source and the exposed subjects.

Adult↗