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Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 181 records · Page 10Linked to original sources
PubMed1994

Isolation of new genes in distal Xq28: transcriptional map and identification of a human homologue of the ARD1 N-acetyl transferase of Saccharomyces cerevisiae.

In this paper, we describe the physical and transcriptional organization of a region of 140 kb in Xq28, 5' to the L1CAM gene. By isolation and mapping of CpG islands to the physical map of the region, isolation of cDNAs, determination of partial nucleotide sequences and study of the pattern of expression and of the orientation of the transcripts identified we have established a transcriptional map of this region. In this map, previously identified genes (L1CAM, V2R, HCF1 and RnBP) have been positioned as well as 3 new genes. All genes in the region are rather small, ranging in size from 2 to 30 kb, and very close to one another. With the exception of the V2R gene, they are housekeeping, have a CpG island at their 5' end and the same orientation of transcription. This kind of organization is consistent with the one previously described for the more distal portion of Xq28, between the Color Vision (CV) and the G6PD genes and indicates that genes with housekeeping and tissue specific pattern of expression are interspersed in the genome but they are probably found in different 'transcriptional domains'. Among the new genes, TE2 demonstrated 40% identity with the protein N-acetyl transferase ARD1 of S. cerevisiae: TE2 may be the human homologue of the S. cerevisiae gene.

Acetyltransferases↗
PubMed1994

A comparison of antioxidant status and free radical peroxidation of plasma lipoproteins in healthy young persons from Naples and Bristol.

Ischaemic heart disease mortality is much lower in Southern Italy than in the U.K. and this is not entirely explained by differences in classical risk factors. Differences in antioxidant intake, affecting free radical peroxidation of plasma lipoproteins, may be relevant. Therefore, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons eating typical regional diets from Naples (22) and Bristol (26). The Naples group consumed more fresh tomatoes, more fat as monounsaturates (from olive oil) and had higher plasma levels of the lipid antioxidants vitamin E (mean (SD; 95% CI) 29.1 (4.5; 26.8 to 31.3) vs 25.1 (3.86; 23.4 to 26.8) mumol.l-1, P = 0.005) and beta-carotene (4.74 (1.2; 4.14 to 5.34) vs 2.85 (0.8; 2.5 to 3.2) mumol.l-1, P < 0.001). Intakes of vitamin C, total uncooked fruit and vegetables, plasma vitamin A, serum selenium and copper levels were similar. All indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (median (interquartile range; non-parametric 95% CI)) 29 (21.5-39.9; 24 to 36.7) vs 41.5 (37-48.5; 38 to 44.5) mumol.l-1, P < 0.001; diene conjugation index 1.38 (1.02-1.55; 1.06 to 1.49) x 10(-2) vs 1.57 (1.43-1.74; 1.44 to 1.71) x 10(-2), P = 0.019; lipid peroxides (geometric mean (95% CI) 1.24 (1.12 to 1.37) vs 4.58 (3.84 to 5.46) mumol.l-1, P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A 'novel' infectious bronchitis strain infecting broiler chickens in Italy.

An outbreak of severe respiratory disease in flocks of broiler chickens was associated with the isolation of a 'novel' strain of infectious bronchitis virus (IBV). The isolate, designated 624/I, was isolated from 9 of the 11 flocks sampled. The results of cross neutralisation and haemagglutination-inhibition tests showed isolate 624/I to be antigenically distinct from several European and American strains. In a serological survey carried out on affected flocks, specific antibodies to IBV strain 624/I and turkey rhinotracheitis (TRT) virus were detected.

Animals↗
PubMed1994

Vaccine-induced neutralizing antibodies directed in part to the simian immunodeficiency virus (SIV) V2 domain were unable to protect rhesus monkeys from SIV experimental challenge.

The potential of the simian immunodeficiency virus (SIV) variable 2 (V2) domain as an effective region to boost SIV-neutralizing antibodies and to protect against live SIV challenge was tested in rhesus macaques. In this study, two rhesus macaques were primed with vaccinia virus recombinants expressing the surface glycoprotein gp140 of SIVmac and were given booster injections with the SIVmac V2 domain presented by a highly immunogenic carrier, the hepatitis B surface antigen (HBsAg). The two vaccinated macaques exhibited SIV-neutralizing antibodies after primer injections that were enhanced by the V2/HBsAg injections. Part of these SIV-neutralizing antibodies were directed specifically to the V2 region, as shown by neutralization-blocking experiments. However, despite having consistent SIV-neutralizing antibody titers, animals were not protected against homologous challenge with BK28, the molecular clone of SIVmac251. No SIV envelope-specific cellular cytotoxic response was detected throughout the immunization protocol, suggesting that neutralizing antibodies directed to SIV envelope gp140 and especially to the V2 domain were unable on their own to protect against SIV challenge. Furthermore, the vaccinees seemed to have higher viral loads than control animals after challenge, raising the question of whether neutralizing antibodies induced by vaccination and directed to the SIV envelope selected viral escape mutants, as shown previously in SIV-infected macaques. This mechanism is certainly worthy of intensive investigation and raises some concern for SIV envelope-targeted immunization.

Amino Acid Sequence↗
PubMed1994

Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke.

We evaluated 106 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. A positive family history for ischemic complications of atherosclerosis was more common in subjects with a history of stroke than in those without; moreover, plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (TPA) were higher in patients with documented previous events. A strong positive significant correlation was found between TPA and PAI-1 levels, and an interaction between age and TPA was observed when the sample was stratified according to ages being above or below 70 years. When the patient population was analyzed according to the number of ischemic events, it was found that 62 of the 106 subjects with a history of stroke had experienced more than one ischemic event. Under these conditions, the levels of TPA and PAI-1 still correlated with the occurrence of previous ischemic episodes. As in the whole patient sample, TPA was the strongest discriminator. We conclude that in subjects attending a metabolic ward, TPA and PAI-1 levels consistently help identify subjects with a history of cerebral ischemic episodes and that TPA is the strongest discriminator.

Adult↗
PubMed1994

Early changes of the arterial carotid wall in uncomplicated primary hypertensive patients. Study by ultrasound high-resolution B-mode imaging.

Arterial hypertension is frequently responsible for arteriosclerotic damage in the carotid region. Nevertheless, there is as yet no general agreement that hypertension is correlated with lesions detected by noninvasive means in the carotid arteries. We studied, by noninvasive echotomographic technique, 70 uncomplicated primary hypertensive individuals without clinically evident end-organ complications and 30 normotensive matched control subjects to detect early lesions of carotid arteries. The presence of other cardiovascular risk factors was assessed, and heart structure and function were studied by echocardiography. Although hypertensive individuals were comparable to control subjects for other risk factors, they showed a marked increase in the thickness of the intimal-medial complex of the carotid wall (0.71 +/- 0.4 versus 0.56 +/- 0.2 mm, P < .001 in the right carotid and 0.83 +/- 0.3 versus 0.58 +/- 0.2, P < .003 in the left), in left ventricular mass (203 +/- 52 versus 176 +/- 37 g, P < .05), and in the prevalence of definite plaques of the carotid wall, both monolaterally and bilaterally (P < .003 by chi 2 test). Among the different factors contributing to the increase in thickness of the carotid artery wall, standing blood pressure, serum triglycerides, and age were found to be the best predictors (they accounted for about 16% of the variability, P < .005). These results indicate that carotid arteries of hypertensive individuals undergo degenerative changes, just as shown for hypercholesterolemic and diabetic patients in other studies. This supports the use of B-mode ultrasound imaging to detect early involvement of the carotid region before the appearance of any end-organ damage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex.

The pharmacological characteristics and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of the human adrenal cortex using radioligand binding and autoradiographic techniques. [3H]SCH 23390 was used as a ligand of D1-like receptors, whereas [3H]spiroperidol was used to label D2-like receptors. No specific [3H]SCH 23390 binding was detectable in sections of the human adrenal cortex. On the other hand, [3H]spiroperidol was bound to sections of the adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time, temperature and concentration dependent, belonging in the range of concentrations of the radioligand used for a single class of high-affinity sites. The dissociation constant (Kd) averaged 2.7 nmol/l, whereas the maximum density of binding sites (Bmax) was 160 nmol/mg tissue. Experiments on the pharmacological specificity of [3H]spiroperidol binding to sections of the human adrenal cortex revealed that clozapine was the most powerful displacer of [3H]spiroperidol from sections of the human adrenal cortex. This suggests the presence in the human adrenal cortex of dopamine receptors of the D4 subtype. Light microscope autoradiography showed the highest density of specific [3H]spiroperidol binding sites in the zona glomerulosa and to a lesser extent in the zona reticularis. Only sparse [3H]spiroperidol binding sites were localized in the zona fasciculata. The possible functional consequences of this localization of dopamine D2-like receptor sites in the human adrenal cortex are discussed.

Adrenal Cortex↗
PubMed1994

Immunogenicity of hybrid hepatitis B surface antigen particles.

Hepatitis B surface antigen (HBsAg) produced by recombinant DNA technology is now widely and safely used worldwide for hepatitis B vaccination. We used the HBsAg particle as a carrier molecule for presentation of selected human immunodeficiency virus type 1 (HIV-1) determinants to the immune system. Immunization studies carried out in primates showed that the particles elicit HIV specific virus neutralizing antibodies as well as T cell proliferative responses to both pathogens. As an experimental approach to active immunotherapy for hepatitis B virus (HBV) chronic carriers, we evaluated the efficiency of such hybrid antigen to overcome B cell tolerance in HBV transgenic mice.

AIDS Vaccines↗
PubMed1994

Urapidil in hypercholesterolemic hypertensive patients.

The association of arterial hypertension and hyperlipidemia strikingly enhances prevalence, incidence and mortality of cardiovascular disease. In the light of recent evidence that some antihypertensive drugs with alpha-1 blocking properties reduce blood pressure (BP) and total cholesterol (chol), increasing chol content in the non-atherogenic high density lipoproteins (HDL-chol), the effects of urapidil, a peripheral alpha-1 adrenoceptor antagonist, with a central action component on BP and plasma lipids were evaluated in 49 mild, hypertensive patients with mild to moderately severe hypercholesterolemia (serum chol 220-320 mg/dl) for a 6 month period in a double-blind randomized study versus placebo. Five out of the 49 patients (3 on urapidil, 2 on placebo) discontinued treatment due to adverse side effects. Five patients on placebo did not meet protocol requirement of serum triglycerides < 350 mg/dl (3.95 mmol/L) and were only included in the BP efficacy assessment. The groups of urapidil and placebo were comparable for age (50 +/- 10 vs 49 +/- 7 years), body weight (72 +/- 9 vs 73 +/- 10 kg), sex (18M, 8F vs 14M, 9F) and mean arterial pressure (119.4 +/- 4 vs 119.7 +/- 4 mmHg). The actively treated group significantly decrease BP values from 159/99 +/- 13/2 to 152/90 +/- 23/8 mmHg, whilst no change was observed in the placebo group. Between group analysis showed a significant difference at the end of treatment (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1994

Serum uric acid and hypertension: the Olivetti heart study.

The association between serum uric acid and hypertension was evaluated in a sample of male workers in southern Italy enrolled in the Olivetti Heart Study, an ongoing longitudinal epidemiological investigation on risk factors for coronary heart disease carried out at the Olivetti factory in the suburban area of Naples. Participants were screened at baseline (1975) and at five year (1980) and 12 year (1987) follow-up examinations. The present report focuses on 619 male workers for whom information on coronary heart disease risk factors was available both at baseline and 12 year follow-up examination. At baseline, after excluding hypertensive participants (systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP), > or = 90 mmHg and/or on antihypertensive therapy; n = 72), serum uric acid was positively and significantly related to age, SBP, DBP, body mass index (BMI), serum total cholesterol (CHOL) and serum triglycerides (TG) in 547 normotensive participants. At 12 year follow-up examination, hypertension was defined by SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or being on antihypertensive therapy. Multiple logistic regression analysis showed an independent positive association between serum uric acid levels and development of hypertension (RR = 1.23, 95% CI = 1.07-1.39; p = 0.011) after adjustment for age, BMI, CHOL and TG. Furthermore, according to more severe degrees of hypertension (SBP > or = 160 mmHg and/or DBP > or = 95 mmHg and/or being on antihypertensive therapy), the relative risk to develop hypertension was still significant (RR = 1.19; CI = 1.01-1.38; p = 0.051).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hypertension, calcium metabolism, and nephrolithiasis.

Alterations in calcium metabolism have been detected in both human and rat primary hypertension at various levels of the biological organization; in particular, an abnormal renal electrolyte handling, leading to chronically enhanced urinary calcium excretion, has been demonstrated. In keeping with this finding, a significant statistical association between high blood pressure and prevalence of nephrolithiasis has been found in three independent population-based surveys. The first was carried out in the early 1960s in Goteborg, Sweden, on 895 50-year-old men, and showed a higher frequency of a positive history of nephrolithiasis with increasing blood pressure. The second and third studies were performed in Italy, one in the town of Gubbio, with screening of a representative sample (n = 3,431; 84%) of the adult population and the other in Pozzuoli, Naples, at the Olivetti factory, where 688 male workers (88% of the total male workforce) were examined. In both studies, the retrospectively evaluated relative risk of nephrolithiasis in hypertensive persons, after controlling for age, was significantly higher than in normotensive persons, with hypertension contributing by 18% to the overall rate of nephrolithiasis. Hypercalciuria is the most common risk factor for nephrolithiasis and, therefore, also a likely pathogenetic link between nephrolithiasis and hypertension. Dietary factors play an important contributory role in the prevention and treatment of these two widespread conditions, and a dietary approach, with particular regard to electrolyte intake, is a powerful tool for the prevention of hypertension-related kidney stone disease.

Calcium↗
PubMed1994

Recent advances in biological and therapeutic aspects of myeloproliferative disorders.

Chronic myeloproliferative disorders are clonal neoplasias that originate from a clonal pluripotent stem cell and may have a more or less pronounced tendency to acute progression. Except for chronic myelogenous leukemia marked by the Ph chromosome, the BCR/ABL rearrangement, or both, the other chronic myeloproliferative disorder subtypes show less specific, although recurrent, karyotypic and molecular abnormalities. We report here more recent advances in cytogenetics, molecular biology, and treatment of the most common chronic myeloproliferative disorders.

Humans↗
PubMed1993

Reduced density of dopamine D2 receptors in the rat tail artery as a function of age.

The present study was designed to investigate the influence of aging on noradrenaline content and the density and pattern of prejunctional dopamine D2 receptors in the tail (ventral caudal) artery of male Sprague-Dawley rats. Tail artery is frequently used as a model for investigating mechanisms of sympathetic vascular control and contains prejunctional dopamine receptor belonging to the D2 subtype. Noradrenaline levels were reduced in rats of 12 months of age in comparison with 3-month-old animals. A further reduction in catecholamine concentration was found in 24-month-old rats. The density of prejunctional D2 receptors, which was measured in frozen sections of the tail artery by using both radioligand binding and autoradiographic techniques, was reduced by about 35% in 12-month rats in comparison with 3-month rats. A decrease by about 55% versus 3-month rats and by about 20% versus 12-month rats was observed in 24-month-old rats. Neither the pharmacological profile nor the anatomical localization of prejunctional D2 receptors was changed in the rat tail artery as a function of age. The parallel decrease in noradrenaline content and in the density of prejunctional dopamine D2 receptor sites in the tail artery of Sprague-Dawley rats of different ages probably accounts for the lack of an age-related change of prejunctional dopamine D2 receptor-linked responses reported in functional studies.

Aging↗
PubMed1993

Differential expression of MAGE-1, -2, and -3 messenger RNA in transformed and normal human cell lines.

The MAGE-1 gene codes for a tumor-specific antigen, MZ2-E, that elicited a cytotoxic T-lymphocyte response in the melanoma patient from whom it was derived. We have developed a simplified method, using polymerase chain reaction amplification of exon 3 followed by restriction enzyme pattern analysis, to distinguish expression of the MAGE-1 gene from MAGE-2 and MAGE-3, other members of this gene family. MAGE-1 mRNA was expressed in 53% of 17 melanoma lines, two of seven Epstein-Barr virus-transformed B-cell lines, and 2 of 5 breast cell lines including a line established form normal breast epithelium. MAGE-1 is not likely to be the common melanoma antigen recognized by the other HLA-A1- or HLA-A2-restricted cytotoxic T-lymphocytes examined in this study, but the fact that it is expressed in about 50% of melanoma cell lines makes it a reasonable target for the immunotherapy of patients bearing HLA-A1.

Antigens, Neoplasm↗
PubMed1993

Induction of anti-hepatitis B surface antigen (HBsAg) antibodies in HBsAg producing transgenic mice: a possible way of circumventing "nonresponse" to HBsAg.

As a model for studying possible mechanisms of nonresponse toward hepatitis B surface antigen (HBsAg) in hepatitis B virus (HBV) carriers, we used transgenic (Tg) mice which constitutively express this antigen in the liver from before birth. The mice secrete large amounts of HBsAg particles into the sera without producing antibodies. Tg and control mice were immunized with either recombinant HBsAg particles of a different subtype, or with recombinant hybrid HBsAg particles carrying a human immunodeficiency virus (HIV) envelope determinant. The presence of determinants to which the mice are tolerant on the injected particles does not hamper the response to the foreign epitope. Moreover, a weak but significant anti-HBs response is clearly detectable in Tg mice immunized with these particles. Antibodies to epitopes carried by the transgenic antigen are made even after injection of homologous antigen, and a concomitant decrease in circulating HBsAg is observed. This immune response does not induce any liver damage. It was demonstrated that in these Tg mice, B cell self-tolerance toward HBsAg can be overcome by immunization. This phenomenon raises the possibility of designing more effective methods of immunotherapy for HBV carriers.

Animals↗
PubMed1993

Abnormal distribution of VLDL subfractions in type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role?

Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf] > 400, B: Sf > 400, B: Sf 175-400, C: Sf 100-175, D: Sf 20-100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbAlc 6.9 +/- 0.5%) (mean +/- SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16 +/- 0.02 vs 0.24 +/- 0.03 mmol/l; p < 0.05). Expressing each VLDL subfraction as percent of the total VLDL lipid concentration, a significant decrease in particles of intermediate size (C) (20.5 +/- 1.6 vs 27.9 +/- 1.5%; p < 0.005) was present, which was compensated by an increase in the smallest ones (D) (50.5 +/- 2.7 vs 37.4 +/- 3.1%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Lowering blood lipids to treat atherosclerosis: vascular tone, plaques, events, and mortality.

Hypercholesterolemia has been associated with an increase in vascular tone, mainly because of an impairment of endothelium-dependent relaxation. This endothelial dysfunction occurs before any definite atherosclerotic lesion is demonstrated. In both animal models and humans the correction of hypercholesterolemia has been associated with hemodynamic improvement. Several controlled trials have demonstrated that long-term treatment with cholesterol-lowering drugs is effective in blocking progression and in some cases in inducing regression of angiographically detected arterial lesions. Arteriographies produce a negative image of the arterial lumen but do not provide sufficient information on vessel wall status. Noninvasive B-mode ultrasound has allowed a direct visualization of the arterial wall in superficial vascular districts, such as the carotid bifurcation. Wall and lesion measures are increasingly used as end points for clinical trials of antiatherosclerotic drugs. In secondary prevention, cholesterol reduction is associated with a lower incidence of coronary heart disease, although the cholesterol reduction should be at least 8-9% to have an impact on total mortality.

Adult↗