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Biomedical subjects

G Pagano

Publications and source records attributed to G Pagano.

At least 91 records · Page 5Linked to original sources
PubMed1999

[A case of appendiceal mucocele associated with adenocarcinoma of the left colon].

The Authors report an unusual case of appendiceal mucocele associated with a large bowel carcinoma occasionally observed in the course of examinations for the first pathology. Due to the rareness of the association of the two affections, the clinical problems and pathogenetic theories are reviewed, also analysing the histological differences of the various mucoceles which need a different surgical approach. They conclude stating that the preoperative diagnosis of appendiceal mucocele, is easier today than in the past, thanks to the routine use of ultrasonography and tomography through which it is possible to reveal concomitant pathologies often clinically silent.

Adenocarcinoma↗
PubMed1999

[New aspects in the evaluation of risk factors for fetal development].

Much knowledge concerning the effects of xenobiotics on prenatal development derive from experimental studies, which are generally performed on laboratory animals according to standardized protocols. Conventional in vivo studies should be integrated by other models within a scientifically-based risk assessment strategy. The paper reviews a few in vitro and/or in vivo approaches: identification of critical effects through the characterization of the pathogenesis as well as the use of dose-response relationships; alternative models to identify reproductive risks from single substances and/or mixtures present in the environment; interactions between in vitro and in vivo studies in the risk assessment of solvents: embryonic metabolism in teratogenicity; interactions between experimental and epidemiological studies to understand the pathogenesis of embryolethality; risk assessment of the effects of prenatal exposure to ionizing radiations.

Animals↗
PubMed1999

Oxidative stress in cancer prone genetic diseases: a review.

A number of congenital conditions include oxidative stress as a phenotypic hallmark, in spite of very distinct genotypic assets. These disorders include some rare chromosomal instability syndromes and two frequent congenital conditions, Down's syndrome and cystic fibrosis. All of these disorders generate severe biomedical and social handicaps in their progression, resulting in neurological symptoms or malformations, early ageing and cancer proneness. The onset of oxidative stress has been related to excess formation or defective detoxification of reactive oxygen species. Investigations conducted so far have focussed on individual disorders and have utilised a range of different methodologies, so leading to a number of unanswered questions regarding the role(s) for oxidative stress in these disorders. Comparative studies are required, based on homogeneous methods, to provide insights into the pathogenesis of each individual condition, which may open up new avenues for studying ageing and cancer.

Chromosome Aberrations↗
PubMed1999

[The Italian Fanconi Anemia Registry].

The Italian Registry of Fanconi's Anaemia (RIAF) was established in 1994 at the Cytogenetics Department of the Elena d'Aosta Hospital in Naples. Its aim is to collect data regarding Italian Fanconi's anaemia (FA) patients and their relatives. Since FA is a rare disease, the Registry is expected to benefit patients, improving the knowledge of this illness from the diagnostic, clinical, therapeutical and epidemiological viewpoint, and also supporting the laboratory and clinical research on FA aetiology, pathophysiology and therapy. Moreover, the Cytogenetics Department provides diagnosis through cytogenetic tests and collects blood samples of diagnosed patients, their parents and siblings for genetic tests and research. The RIAF is participating, through its coordinator and the physicians collaborating all over Italy, to some Italian and European research projects.

Adolescent↗
PubMed1998

Glycaemic control and cardiovascular risk factors in type 2 diabetes: a population-based study.

The objective of this study was to estimate the prevalence of poor glycaemic control and cardiovascular risk factors in an Italian population-based cohort of subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects (estimated completeness of ascertainment 80%), 1574 (80%) were investigated, and adherence to targets for control of the European NIDDM Policy Group assessed. Prevalence of poor glycemic control (HbA1c > = 8) was 47.7%. Obesity was present in 23.4% of the cohort, hypertension in 83.4%, hypertriglyceridaemia (>2.26 mM) in 19.3%, hypercholesterolaemia (>6.46 mM) in 25.5%, and low HDL-cholesterol (<0.90 mM in men and <1.03 mM in women) in 13.7%. Only 153 (9.7%) subjects were free from other disorders. Subjects were treated as follows: 26.2% exclusively by general practitioners; 13.3%, 69.9%, 10.9%, and 5.9% with diet, oral hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression analysis showed associations between HbA1c and fibrinogen (p < 0.001), total cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex, duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure were associated with HbA1c. In conclusion, this Italian population-based cohort of subjects with Type 2 DM showed a high prevalence of poor glycaemic control, high consumption of oral hypoglycaemic drugs, and an independent association between glycaemic control and cardiovascular risk factors (fibrinogen, total cholesterol, and triglycerides). The presence of obesity or hypertension was not significantly associated with glycaemic control.

Blood Glucose↗
PubMed1998

Congenital disorders sharing oxidative stress and cancer proneness as phenotypic hallmarks: prospects for joint research in pharmacology.

In spite of very distinct genotypic assets, a number of congenital conditions include oxidative stress as a phenotypic hallmark. These disorders include Fanconi's anaemia, ataxia telangiectasia, xeroderma pigmentosum and Bloom's syndrome, as well as two frequent congenital conditions: Down's syndrome and cystic fibrosis. Cancer proneness is a clinical feature shared by these disorders, while other manifestations include early ageing, neurological symptoms or congenital malformations. The onset of oxidative stress has been related to excess formation, or defective detoxification, of reactive oxygen species (ROS). This can arise from either the abnormal expression or inducibility of ROS-detoxifying enzymes, or by defective absorption of nutrient antioxidants. Resulting oxidative injury has been characterized through: (i) DNA, protein or lipid oxidative damage; (ii) excess ROS formation (in vitro and ex vivo); (iii) sensitivity to oxygen-related toxicity; (iv) improvement of cellular defects by either hypoxia or antioxidants; and (v) circumstantial evidence for in vivo oxidative stress (as e.g. clastogenic factors). Investigations conducted so far have been confined to individual disorders. Comparative studies of selected indicators for oxidative stress could provide further insights into the pathogenesis of each individual condition. Such a unified approach may have wide-ranging consequences for studies of ageing and cancer.

Aging↗
PubMed1998

Lack of relationship between the P1A1/P1A2 polymorphism of platelet glycoprotein IIIa and premature myocardial infarction.

BACKGROUND: The P1A1/P1A2 polymorphism of the platelet glycoprotein IIIa has been variably associated with an increased risk of coronary thrombosis. MATERIALS: We investigated the linkage between the P1A1/P1A2 polymorphism and the risk of myocardial infarction in 98 patients who suffered their first myocardial infarction at the age of 45 years or less and 98 well-matched control subjects without coronary artery disease. Lipid parameters were measured using conventional methods of clinical chemistry; P1A genotypes were determined by polymerase chain reaction and restriction enzyme digestion. RESULTS: There was no significant difference in the prevalence of P1A2-positive genotypes (either P1A1/P1A2 or P1A2/P1A2) between patients and control subjects (chi 2 = 0.66, d.f. = 1, P = 0.41). CONCLUSIONS: These results suggest that the P1A2 polymorphism of the platelet glycoprotein IIIa does not contribute to the genetic susceptibility to premature myocardial infarction.

Adult↗
PubMed1998

[Clinical considerations and therapeutic options in papillomatosis of common bile duct. Clinical case].

The Authors report a case of endoscopic treatment of common biliary tract papillomatosis. This therapeutic option derive by patient's clinical evaluation and clinical reports from literature. Agreeing with Cornud, we have opted for endoscopic conservative management with drainage of common biliary tract; furthermore endoscopic procedure permit, by an intensive follow-up, identification and management of possible recurrences. This approach, minimally invasive, is in our opinion the first option for the biliary papillomatosis management.

Aged↗
PubMed1997

Resistance to apoptosis in Fanconi's anaemia. An ex vivo study in peripheral blood mononuclear cells.

Fanconi's anaemia (FA) is a rare autosomal recessive disease characterised by progressive pancytopoenia, a diverse assortment of congenital malformations, an increased sensitivity to reactive oxygen species and a predisposition to the development of malignancies. In the present study, we assessed the propensity to undergo apoptosis of peripheral blood mononuclear cells (PBMC) from Italian FA patients. Cells were challenged by 2-deoxy-D-ribose (dRib) or TNF-alpha plus cycloheximide as agents that induce apoptosis by interfering with cell redox status and mitochondrial membrane potential (MMP), and PBMC from FA patients resulted to be less prone to die than those from healthy subjects. The decreased susceptibility of FA cells to undergo apoptosis was also evident when another parameter highly correlated with the apoptotic process, i.e. MMP, was measured. Moreover, when N-acetylcysteine was added to dRib-treated PBMC, a strong protection was evident either in PBMC from control subjects or from FA patients. These data indicate that an alteration of unknown nature of the mechanisms favouring apoptosis is present in freshly collected cells from FA patients, and that such alteration could contribute to the pathogenesis of the disease, and particularly to the increased susceptibility to cancer.

Adolescent↗
PubMed1997

Comparison of incidence of insulin-dependent diabetes mellitus in children and young adults in the Province of Turin, Italy, 1984-91. Piedmont Study Group for Diabetes Epidemiology.

To document the incidence of IDDM in the Province of Turin (Italy) in the 8-year period 1984-91 in children (0-14 years) and young adults (15-29 years), in relation to age, sex, monthly-seasonal variability, calendar year and urban/rural area, (all newly diagnosed cases (502) were ascertained through primary and secondary data sources and completeness of ascertainment estimated with the two sample capture-recapture method (99% in childhood and 95% in young adults). The independent effect of age, sex, calendar year, and urban/rural area was estimated with a Poisson regression model. Age-specific incidence rates were 8.42/100,000 (95% CI 7.37-9.62) and 6.72/100,000 (95% CI 5.96-7.58), respectively, in the age groups 0-14 and 15-29 years. Sex differences were evident in young adults, with an almost 1.5-fold increased risk in men (8.37/100,000, 95% CI 7.21-9.71 vs 5.00/100,000, CI 4.09-6.10). Seasonal trend was evident in childhood. Predictors of incidence rates were age, place of residence and interaction between sex and age; no temporal trend was detected. No significant differences were found in the two age-groups with respect to glycaemia, glycosuria, ketonuria, and fasting C-peptide levels. In conclusion, this study shows sex differences in IDDM risk in young adults; 55% of incident cases occurring in young adults; an independent contribution of urban/rural differences to IDDM risk; no temporal trend in 1984-91; a seasonal pattern of incidence in children; no significant differences in clinical presentation between age groups.

Adolescent↗
PubMed1997

Heritability of cardiovascular risk parameters in subjects with increased susceptibility to non-insulin-dependent diabetes mellitus.

To evaluate the inheritance of cardiovascular risk parameters in subjects with increased susceptibility for non-insulin-dependent diabetes mellitus, we compared 25 pairs of healthy twins who were offspring of diabetic parents with 25 pairs without a parental history for type 2 diabetes mellitus (12 monozygotic and 13 dizygotic in each group). Environmental factors were also evaluated to avoid bias in the assessment of concordance. No significant difference was found in concordance between monozygotic and dizygotic twins for physical activity, diet, smoking, alcohol intake and living together or apart. Genetic analysis revealed a substantial heritability for weight, body mass index, percentage of body fat, lipoprotein(a), high density lipoprotein (HDL)- and HDL2-cholesterol, without significant differences between the two groups. We conclude that heritability of several cardiovascular risk parameters is not increased in subjects with increased susceptibility to type 2 diabetes mellitus.

Adult↗
PubMed1997

Apolipoprotein H levels in diabetic subjects: correlation with cholesterol levels.

To assess the relationship between apolipoprotein H (apo H) plasma levels and lipid metabolism in diabetes mellitus, we have examined the correlation between apo H plasma concentration and the main plasma lipid levels in 127 non-insulin-dependent (NIDDM) and 118 insulin-dependent (IDDM) diabetes mellitus patients. The data are compared with those in 286 nondiabetics. Our data show a significant increase in plasma apo H in diabetic as opposed to nondiabetic subjects (NIDDM, 29.9 +/- 10.8 mg/dL; IDDM, 31.3 +/- 9.9; controls, 22.5 +/- 7.7; F = 53.3, P = .0001). The relation between plasma lipids and apo H was simultaneously evaluated in the three groups with inclusion of diabetes, sex, body mass index (BMI), and age as covariates in the model. This analysis showed a strong positive correlation (P = .0009) between apo H and total cholesterol, and a weaker positive correlation with triglycerides ([TGs] P = .016). The correlation between apo H and hemoglobin A1c (HbA1c) levels in diabetics (P = .03) highlights the importance of glycemic control for plasma levels of this apoprotein, which is highly glycated. Although the role of apo H in lipid metabolism is still uncertain, recent investigations on the possible relation between plasma apo H levels and increased plasma lipids and thrombotic risk could explain the increased atherosclerotic risk in diabetic patients.

Adult↗
PubMed1997

Characterization of the carbohydrate structures of apolipoprotein H through concanavalin A affinity chromatography.

Apolipoprotein H, also known as beta 2-Glycoprotein I, is a single chain highly glycosylated polypeptide of 326 amino acids. The carbohydrate content of apolipoprotein H is approximately 19% of the molecular weight. Some studies have described the main oligosaccharides forming the glycosylated chains but the carbohydrate inner structures of apolipoprotein H has not been investigated yet. This gap should be filled being glycosylation a very important process which is able to regulate the structure and the biological functions of proteins. Lectins are proteins which specifically bind carbohydrate structures. Affinity chromatography of glycoproteins on immobilized lectins, such as Concanavalin A (Con A), has been proved to be a useful method for oligosaccharide fractionation. N-Linked oligosaccharide structures were shown to interact with Con A according to their branching properties. In the present study, we analyzed the patterns of Con A elution of apolipoprotein H isolated from human plasma. Using Con A affinity chromatography we show that apolipoprotein H has a high degree of heterogeneity in its glycosylated structure. It allowed one to isolate two groups of apolipoprotein H molecules bearing biantennary and truncated hybrids and high mannose and hybrid oligosaccharides. Since Con A affinity chromatography allows fractionation of molecules differing in the extent of carbohydrate branching irrespective of the sialyl residues, we can conclude that mannose residues are masked with other sugars such as galactose-beta (1-4)N-acetylglucosamine, galactose-beta (1-3)N-acetyl-galactosamine and sialic acid linked alpha (2-6) to galactose or to N-acetylgalactosamine, or capped with sulfated residues. Thus, according to our results apolipoprotein H presents truncated hybryd or hybrid-type carbohydrate chains which bear few unmasked mannose residues as terminal sugar. Moreover, isoelectrofocusing of apolipoprotein H forms fractionated on Con A demostrates that weakly bound material presents a predominance of more acidic isoforms than that firmly bound to the lectin, indicating that weakly bound fractions contain molecules which are more negatively charged and that Con A is able to separate glycosylated forms which are not discriminated by isoelectrofocusing.

Apolipoproteins↗
PubMed1997

Characterization and representative structures of N-oligosaccharides bound to apolipoprotein H.

We studied the structure of N-linked carbohydrates bound to apolipoprotein H by a combination of two methods which make use of lectins. Digoxigenin-labelled lectins are used for the structural characterization of carbohydrate chains of glycoproteins. Concanavalin A lectin affinity chromatography was used to analyse apolipoprotein H according to the characteristics of its carbohydrate chain inner to sialic acid residues. Our results from digoxigenin-labelled lectins analysis showed that apolipoprotein H gave positive bands to SNA, DSA, GNA, PNA and AAA lectins. Apolipoprotein H gave a negative band when reacted with MAA lectin. When we applied apolipoprotein H onto the Concanavalin A lectin column no detectable amounts of protein were eluted with Concanavalin A buffer. After adding a buffer with low sugar concentration (10 mM glucoside) a large amount of apolipoprotein H was recovered. These molecules of apolipoprotein H weakly bound to the lectin. When a higher sugar concentration (500 mM mannoside) was added most of the sample applied was eluted. These molecules of apolipoprotein H firmly bound to the column having high affinity for the lectin. These results combined with those coming from the digoxigen-labeled lectins method enable us to understand the inner structure of carbohydrate chains with their outer branches. Molecules of apolipoprotein H which weakly bind to Concanavalin A could bear complex N-glycans organized in biantennary or truncated hybrid structures. Firmly bound apolipoprotein H referred to molecules rich in N-glycan hybrid structures. They have an outer branch belonging to the high mannose carbohydrate chains which explain the ability to bind to the column and an other main branch bearing the sequence galactose beta-(1-4)-N-acetylglucosamine beta-(1-2) mannose. Galactose could be the terminal sugar or, alternatively, be masked with sialic acid alpha-(2-6) terminally linked.

Amino Acid Sequence↗
PubMed1997

Qualitative analysis of the carbohydrate composition of apolipoprotein H.

The specific binding of digoxigenin-labeled lectins to carbohydrate moieties is used to characterize the carbohydrate chains bound to apolipoprotein H. Our results show that apolipoprotein H is rich in sialic acid linked alpha(2-6) to galactose or N-acetylgalactosamine. Sialic acid is not alpha(2-3)-linked to galactose. Galactose is beta(1-4)-linked to N-acetylglucosamine and beta(1-3)-linked to N-acetylgalactosamine. High-mannose N-glycan chains are barely detectable. After N-glycosidase F treatment the molecular weight is substantially reduced. The main band is 32,500 daltons. Carbohydrate O-linked chains, which are mainly represented by sialic acid, are alpha(2-6)-linked to galactose or N-acetylgalactosamine. Galactose is also organized in O-linked chains and it is beta(1-4)-linked to N-acetylglucosamine and beta(1-3)-linked to acetylgalactosamine. Biochemical analysis of carbohydrate structures reveals that no specific carbohydrate complex is bound to a single isoform.

Acetylgalactosamine↗
PubMed1997

Influence of APOH protein polymorphism on apoH levels in normal and diabetic subjects.

Apolipoprotein (apo)H (also known as beta 2 glycoprotein-I) is a glycoprotein synthesized by liver cells and it is present in the blood associated with plasma lipoproteins. APOH displays a genetically determined structural polymorphism: three alleles (APOH*1, APOH*2, APOH*3) at a single locus on chromosome 17 code for different isoforms, and population studies have shown that APOH*2 is the most frequent allele. This paper assesses the relation between APOH phenotypes and plasma apoH levels in a population composed of 278 healthy subjects (243 H2/2, 32 H3/2, 2 H3/3, 1 H2/1; allele frequencies APOH*1 0.002, APOH*2 0.934, APOH*3 0.064) and 245 diabetics (212 H2/2, 30 H3/2, 3 H3/3; allele frequencies APOH*2 0.927 and APOH*3 0.073). Determination of apoH levels by competitive ELISA gave a mean value of 26.3 +/- 9.8 mg/dl for all subjects, 22.6 +/- 7.7 in normals vs 30.6 +/- 10.3 in diabetics (p = 0.0001), and 23.0 +/- 7.9, 19.3 +/- 5.4 and 18.5 +/- 3.5 mg/dl for H2/2, H3/2 and H3/3 in normals and 31.1 +/- 10.1, 28.2 +/- 10.8 and 15.7 +/- 9.0 mg/dl in diabetics, respectively. ANCOVA of the adjusted data revealed a significant difference in apoH levels for the three phenotypes in both the normal subjects (p = 0.01) and the diabetics (p = 0.02). ANCOVA of the whole samples of subjects, controlling for diabetes as well as age, sex and total cholesterol, indicated a substantial effect of phenotype, independent of the other variables (p = 0.0007).

Adult↗
PubMed1997

L-methionine induces stage-dependent changes of differentiation and oxidative activity in sea urchin embryogenesis.

This study was to investigate developmental toxicity of some selected low molecular weight antioxidants, by utilising sea urchin embryos and gametes as model system. Sea urchin embryos or sperm were exposed at different developmental stages to L-methionine or some selected low molecular weight antioxidants: a) N-acetylcysteine; b) L-carnosine; c) L-homocarnosine, and d) L-anserine. L-methionine displayed developmental toxicity at levels > or = 10(-5) M, whereas the other agents tested were mostly active at levels > or = 10(-4) M. When embryos were exposed to 10(-4) M L-methionine or N-acetylcysteine at different developmental stages, the most severe effects were exerted by early exposures (0 to 2 hr after fertilisation), whereas later exposures turned to lesser or no effects. Cytogenetic analysis of L-methionine-exposed embryos showed a significant mitogenic effect and increase of mitotic aberrations. Fertilisation success was decreased by L-methionine (10(-6) M to 10(-3) M) added at the moment of fertilisation, with increasing developmental and cytogenetic abnormalities in the offspring. The formation of reactive oxygen species in embryos and gametes was determined by: a) analysing the DNA oxidative product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and b) luminol-dependent chemiluminescence. The results showed that: 1) 8-OHdG levels were increased during embryogenesis; 2) fertilisation was associated with a double-wave luminol-dependent chemiluminescence emission; 3) luminol-dependent chemiluminescence was maximal in cleavage, declining down to zero in plutei, and 4) an embryotoxic L-methionine or N-acetylcysteine level (10(-4) M) turned to a decrease in reactive oxygen species formation. The data suggest that L-methionine- or N-acetylcysteine-induced developmental toxicity is confined to early stages. A role for oxidative activity is suggested in modulating cell differentiation and embryogenesis, consistent with antioxidant-induced damage to early life stages.

8-Hydroxy-2'-Deoxyguanosine↗