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Biomedical subjects

R Gambino

Publications and source records attributed to R Gambino.

At least 19 recordsLinked to original sources
PubMed2002

Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima-media thickness in Italian type 2 diabetic patients.

BACKGROUND: Moderately elevated levels of homocysteine have been associated with an increased cardiovascular risk in type 2 diabetic patients. The role of methylenetetrahydrofolate reductase gene polymorphism is less clear. MATERIALS AND METHODS: We investigated the contribution of plasma homocysteine levels and the methylenetetrahydrofolate reductase gene polymorphism to the variability of carotid intima-media thickness in 124 consecutive Italian patients with type 2 diabetes mellitus. Fasting plasma homocysteine was measured by high-pressure liquid chromatography with an electrochemical detector; methylenetetrahydrofolate reductase genotypes were determined by polymerase chain reaction and restriction enzyme digestion. The carotid intima-media thickness was evaluated with high-resolution B-mode ultrasonography. RESULTS: Age, creatinine and plasma homocysteine levels showed a positive correlation with mean carotid intima-media thickness values, but only age and creatinine levels were still associated with mean carotid intima-media thickness values in the multivariate analysis. Plasma homocysteine levels were significantly higher in the patients bearing the 677T/677T genotype of the methylenetetrahydrofolate reductase polymorphism; mean carotid intima-media thickness values were not different in the three different methylenetetrahydrofolate reductase genotypes. CONCLUSION: In 124 Italian patients with type 2 diabetes mellitus, basal levels of plasma homocysteine, as well as methylenetetrahydrofolate reductase gene polymorphism, did not explain the variability of mean carotid intima-media thickness.

Aged↗
PubMed2001

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients.

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.

Adult↗
PubMed2001

Circulating E-selectin levels in chronic hepatitis C patients with normal or elevated transaminase before and after alpha-interferon treatment.

E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte adhesion to the endothelium and in the cellular immunological reactions. Expression of this molecule, in fact, is physiologically absent, but it becomes evident on sinusoidal lining cells during inflammatory liver disease. The aim of this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH-C) patients with persistently normal transaminase in comparison to patients with CH-C and elevated transaminase, and its changes during alpha-interferon therapy. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of both groups. Fifty-eight subjects were divided into 3 groups: group A included 18 patients with CH-C and persistently normal transaminase; group B 20 patients with CH-C and persistently elevated transaminase levels and group C included 20 healthy subjects, representing the control group. The first two groups were treated with r-IFN alpha at a dose of 6 MU 3 times a week for 3 months and followed-up with 3 MU 3 times a week for another 3 months. Serum baseline values of E-selectin in groups A and B were significantly higher than those in group C (P < 0.04), but there was no difference between groups A and B. Furthermore, there was a trend toward higher E-selectin values as histological severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values showed a moderate decrease in both groups, but only among responder patients; while E-selectin levels were unchanged in non responders. Immunohistochemical localization showed no staining for E-selectin in normal liver specimens, while there was a quite similar staining for E-selectin in the two groups of patients. In conclusion, this study shows that serum E-selectin levels in patients with CH-C and persistently normal transaminase are higher than in controls and they are associated with severity of liver disease. Liver of these patients express E-selectin molecules, suggesting an activation of the immune system almost identical to that of patients with CH-C and elevated transaminase. In both groups only responder patients showed a moderate decrease below baseline serum values.

Adult↗
PubMed2001

Successful treatment of hepatosplenic candidiasis in an elderly patient with acute myeloid leukemia using liposomal daunorubicin and fluconazole.

Fungal infections are an increasing cause of morbidity and mortality in patients with haematological malignancies. The organism most often responsible are Candida spp., particurarly Candida Albicans. This report describes our experience in a 63-year-old man who developed symptoms of hepatosplenic candidiasis caused by Candida tropicalis after treatment for acute myeloid leukaemia (AML). The fungal infection was successfully controlled using fluconazole, and the patient has been disease-free for more than 11 months after antileukemic chemotherapy without any recurrence of Candida infections. Our experience suggests that AML and chemotherapy associated fungal infections can be controlled with an appropriate therapeutic regimen.

Antibiotics, Antineoplastic↗
PubMed2000

Serum concentration of E-selectin in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.

OBJECTIVES: High levels of soluble E-selectin have been reported in acute and chronic inflammatory disorders. Moreover, in some types of tumor elevated values have been found while in other types reduced levels have been reported. Our aims were to determine whether soluble E-selectin levels might be useful in monitoring the progression of chronic liver disease, including hepatocellular carcinoma. METHODS: Circulating soluble E-selectin was measured by an enzyme-linked immunosorbent assay in the sera of 18 patients with chronic hepatitis, 44 with liver cirrhosis, and 38 with hepatocellular-carcinoma-associated liver cirrhosis. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. RESULTS: Serum levels of soluble E-selectin were higher in the chronic hepatitis and liver cirrhosis patients than in the hepatocellular carcinoma patients and healthy controls. Levels in the hepatocellular carcinoma patients and controls were not significantly different. In the liver cirrhosis group, divided according to the Child-Pugh classification, soluble E-selectin decreased with disease severity. Similarly, in patients with liver cirrhosis who developed hepatocellular carcinoma, soluble E-selectin decreased as the disease progressed. Immunohistochemical localization showed strong membrane staining on endothelial cells in areas rich in inflammatory cells in severe chronic hepatitis. In some hepatocellular carcinoma tissues a marked E-selectin staining was observed on endothelial cells of tumor-associated small vessels. CONCLUSIONS: The results obtained suggest that high serum levels of soluble E-selectin are associated with chronic hepatitis and liver cirrhosis, and that levels decrease in liver cirrhosis patients as the disease progresses. Patients with hepatocellular carcinoma have different types of soluble E-selectin behaviour the significance of which requires further investigation.

Adult↗
PubMed2000

Localization and association to cytoskeleton of COLL1alpha mRNA in Paracentrotus lividus egg requires cis- and trans-acting factors.

COLL1alpha mRNA is asymmetrically distributed in the Paracentrotus lividus egg. Here we examine the involvement of the cytoskeleton in the localization process of collagen mRNA. The use of drugs such as colchicine and cytochalasin B reveals a perturbation of localization collagen mRNA. Moreover, the presence of specific cis-and trans-acting factors involved in cytoskeleton binding and the localization process was investigated. By Northwestern experiment we found that the 3'UTR of COLL1alpha mRNA is also able to bind two proteins of 54 and 40 kDa in a cellular fraction containing the cytoskeleton. Finally, we found that the protein of 54 kDa is LP54, a protein that binds the 3'UTRs of P. lividus maternal bep messengers and is necessary for their localization.

3' Untranslated Regions↗
PubMed2000

Platelet glycoprotein IIIa PlA1/A2 polymorphism and its relationship with diabetic nephropathy in type 2 diabetic patients.

OBJECTIVE: The increased prevalence of cardiovascular events in type 2-diabetic patients with micro- or macroalbuminuria is not completely explained by an excess of conventional risk factors for atherosclerosis. Genetic polymorphism within the platelet glycoprotein IIIa has been implicated in the etiology of acute coronary syndromes. We tested the hypothesis that the PI(A1/A2) polymorphism could in part account for the increased cardiovascular risk of type 2-diabetic patients with micro- or macroalbuminuria compared to normoalbuminuric diabetic patients. RESEARCH DESIGN AND METHODS: We have examined the PI(A1/A2) polymorphism of the platelet glycoprotein IIIa in type 2-diabetic patients: 94 with micro-, macroalbuminuria, and 94 with normoalbuminuria, matched for age, sex and body mass index. PI(A) genotypes were performed by polymerase chain reaction and restriction enzyme digestion. RESULTS: There was no significant difference in the prevalence of PI(A2)-positive genotypes (either PI(A1/A2) or PI(A2/A2)) in the two groups of patients (chi2 = 0.19, df = 1 , p = 0.66). CONCLUSIONS: These results suggest that carriage of the platelet glycoprotein IIIa PI(A2) allele does not contribute to explain the increased cardiovascular risk associated with micro- or macroalbuminuria in type 2 diabetes.

Aged↗
PubMed2000

Apolipoprotein H is increased in type 2 diabetic patients with microalbuminuria.

BACKGROUND AND AIM: Serum apolipoprotein H (Apo H) levels are increased in hyperlipidemic subjects and type 2 diabetics, but unknown in microalbuminuria, another disorder with an increased cardiovascular risk. We looked to see whether increased Apo H levels are associated with microalbuminuria in type 2 diabetes. METHODS AND RESULTS: Serum Apo H was calculated in 20 normoalbuminuric and 17 microalbuminuric type 2 diabetics matched for age, sex, body mass index (BMI), glycosylated haemoglobin, plasma lipids and duration of diabetes, and also compared with 20 non-diabetic controls matched for age, sex, BMI and plasma lipids. Mean serum Apo H was significantly higher in the microalbuminuric patients (31.12 +/- 1.58 SEM vs 25.25 +/- 1.52 and 24.72 +/- 0.99 mg/dL, p = 0.003). CONCLUSION: Serum apo H levels are increased in type 2 diabetics with microalbuminuria.

Albuminuria↗
PubMed1999

Study of the glycosylation of apolipoprotein H.

Apolipoprotein H is a single chain polypeptide composed of 326 amino acids highly glycosylated. Its carbohydrate content is approximately 19% of the molecular weight. We show that it 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. Carbohydrate O-linked chains (mainly sialic acid) are alpha (2-6) linked to galactose or N-acetylgalactosamine. Galactose is also organised in O-linked chains and beta (1-4) linked to N-acetylglucosamine and beta (1-3) linked to acetylgalactosamine. Concanavalin A lectin was used to isolate two groups of apolipoprotein H molecules bearing biantennary and truncated hybrids and high mannose and hybrid oligosaccharides. Apolipoprotein H fails to bind lysine-Sepharose. Our results thus show that it presents truncated hybrid or hybrid-type carbohydrate chains which bear few unmasked mannose residues as a terminal sugar. Biochemical analysis of carbohydrate structures conducted on single isoforms separated through IEF revealed that no specific carbohydrate complex is bound to a single isoform.

Chromatography, Affinity↗
PubMed1999

Human lipoprotein lipase HindIII polymorphism in young patients with myocardial infarction.

We investigated the possibility that the DNA HindIII polymorphism of human lipoprotein lipase (LPL) is associated with the severity of coronary artery disease (CAD) determined by angiography in young patients who survived a myocardial infarction (MI). Conflicting studies have explored the relationship linking CAD severity to the HindIII restriction site polymorphism at the LPL gene locus, and to our knowledge, no data are available from Italy. The patients were aged less than 45 years (mean age, 40.1 +/- 3.9 years); 83 were male and four were female. The 87 case-patients had a Q-wave or non-Q-wave infarction (67.3% and 32.7%, respectively); the MI was anterior (50.5%), lateral (41.7%), or inferior (7.8%). Analysis of coronary angiograms showed the absence of critical stenosis in 13.8% and the presence of monovessel disease in 50.6% and multivessel disease in 35.6% of the case-patients. The allelic frequency of the HindIII H(-) and H(+) allele was 0.37 and 0.63, respectively. There was a striking association between the HindIII polymorphism and the number of diseased vessels. The patients with HindIII(+/+) genotypes were significantly more likely to have double- or triple-vessel disease and less likely to have no significantly diseased vessels. In this study, we demonstrated that the homozygous form of the LPL HindIII(+) allele increases the risk of multivessel disease by a factor of 4 in an Italian group of young MI survivors. This association was independent from the smoking status and a positive family history for CAD and hypertension, which are known to predict CAD severity. The discrepancies in the results of these studies are difficult to explain. The lack of homogeneity in the study populations (age at which CAD occurred, number of enrolled patients, and geographical origin) and differences in the assessment of CAD severity may account for these conflicting results.

Adult↗
PubMed1999

The binding of apolipoprotein H (beta2-Glycoprotein I) to lipoproteins.

Beta2-glycoprotein I has a high affinity for triglyceride-rich particles, activates lipoprotein lipase, and is also defined as an apolipoprotein H. Previous studies have shown that apolipoprotein H is a regular structural component of the major classes of lipoproteins. In view of these findings, we analyzed the interactions of apolipoprotein H with lipoproteins in the fasting plasma of eight normal, seven hypertriglyceridemic, and seven hypercholesterolemic subjects. After rate-zonal, density gradient ultracentrifugation, apolipoprotein H was little distributed among the different density fractions, and most of it was recovered in the last fraction that contained the lipoprotein-free plasma. A small percentage (4-13%) of the apolipoprotein H associated with plasma lipoproteins was detected at the density ranging from 1.090 to 1.225 g/ml. This result means that apolipoprotein H is little associated with lipoproteins.

Case-Control Studies↗
PubMed1999

Apolipoprotein H is not affected by in vitro glycosylation.

Increased nonenzymatic glycosylation of all major classes of apolipoproteins has been demonstrated in diabetes. In this work we deal with the in vitro nonenzymatic glycosylation of apolipoprotein H, whose role in lipid metabolism is still poorly understood and whose levels increase in diabetes. Apolipoprotein H was isolated from human plasma and purified through a combination of affinity chromatography and continuous elution electrophoresis. The in vitro glycosylation was performed by incubating purified apolipoprotein H with high concentration of glucose. Our results indicate that the in vitro nonenzymatic glycosylation has no effect on the physical properties of apolipoprotein H, despite the fact that this apolipoprotein contains a high number of lysine residues. Since the in vitro concentration of glucose was far higher than the levels normally found in diabetic subjects, it is unlikely for apolipoprotein H to become glycosylated in diabetes.

Blotting, Western↗
PubMed1999

Is immobilization associated with an abnormal lipoprotein profile? Observations from a diverse cohort.

OBJECTIVE: The potential effects of ethnicity, gender, and adiposity on the serum lipid profile in persons with spinal cord injury (SCI) were determined. SUBJECTS: Subjects with SCI were recruited during their annual physical examination from Rancho Los Amigos Medical Center, Downey, California. Sedentary able-bodied controls were Bridge and Tunnel Officers of the Triboro Bridge and Tunnel Authority of the New York City metropolitan area. METHODS: Serum lipid profiles were investigated in 320 subjects with SCI and compared to those obtained from 303 relatively sedentary able-bodied controls. Serum lipid studies were obtained in the fasting state. Data were collected between 1993 and 1996. All lipid determinations were performed by the same commercial laboratory. MAIN OUTCOME MEASURES: The dependent variables were the values from the lipid profile analysis. The independent variables consisted of study group, gender, ethnic group, age, duration of injury, and anthropometric measurements. RESULTS: The serum high-density lipoprotein cholesterol (HDL-c) level was reduced in the SCI compared with the control group (mean+/-SEM) (42+/-0.79 vs 47+/-0.67 mg/dl, P<0.0005). The serum HDL-c level was significantly lower in males with SCI than males in the control group (39+/-0.83 vs 45+/-0.70 mg/dl, P<0.0001), but not for females (51+/-1.54 vs 54 1.52 mg/dl, n.s.). Within the subgroups for whites and Latinos, HDL-c values were also lower in subjects with SCI than in controls (whites: 41+/-1.02 vs 46+/-0.86 mg/dl, P<0.0001; Latinos: 37+/-1.53 vs 42+/-1.59 mg/dl, P<0.05), but not for African Americans (49+/-1.56 vs 51+/-1.27 mg/dl, n.s.). African Americans had higher HDL-c values than whites or Latinos (SCI: 49+/-1.56 vs 41+/-1.02 or 37+/-1.53 mg/dl, P< 0.0001; controls: 51+/-1.27 vs 46+/-0.86 mg/dl, P<0.01 or 42+/-1.59 mg/dl, P<0.0005). In persons with SCI, the serum HDL-c values were inversely related to body mass index and estimated per cent body fat (r=0.27, P<0.0001). CONCLUSION: In white and Latino males, but not in females or African Americans, immobilization from SCI appears to be associated with lower HDL-c values than in controls.

Adult↗
PubMed1999

Phosphorylation-dependent regulation of skeletogenesis in sea urchin micromere-derived cells and embryos.

Sea urchin embryo micromeres when isolated and cultured in vitro differentiate to produce spicules. Although several authors have used this model, almost nothing is known about the signaling pathways responsible for initiating skeletogenesis. In order to investigate the potential involvement of phosphorylation events in spiculogenesis, the effect of inhibitors of protein kinases and phosphatases on skeleton formation was studied. Results obtained using both cultured micromeres and embryos revealed that protein tyrosine kinase and phosphatase inhibitors blocked skeleton formation, but not serine/threonine phosphatase inhibitors. The inhibitors showed a dose-dependent effect and when removed from micromere or embryo culture, spicule formation resumed. Inhibition of tyrosine phosphatases resulted in an increase in the tyrosine phosphorylation level of two major proteins and a modest decrease in the expression of the mRNA coding for type I fibrillar collagen. These findings strongly suggest that tyrosine phosphorylation and dephosphorylation is required for micromere differentiation and for normal skeletogenesis during sea urchin embryo development.

Animals↗
PubMed1999

Role of lipid, apolipoprotein levels and apolipoprotein E genotype in young Italian patients with myocardial infarction.

BACKGROUND AND AIM: Studies of young patients with acute myocardial infarction (AMI) have demonstrated that conventional risk factors are usually responsible for their premature atherosclerosis. No account has yet been published of the risk profile of young Italians surviving an AMI. In this study, the conventional risk factors, lipids and apolipoproteins, and apolipoprotein E (APOE) allele distribution were evaluated in 98 consecutive AMI survivors (94 males, 4 females) aged 40.1 +/- 3.9 for at least three months after their acute event. These survivors were matched for age, sex, body mass index and presence of diabetes mellitus with 98 controls selected from subjects admitted to the same hospital for other reasons. METHODS AND RESULTS: Lipid profiles and APOE polymorphism were determined in both groups. Coronary angiography during hospitalization showed the absence of critical stenosis in 6.6% of the survivors, mono-vessel disease in 57.7%, and multi-vessel disease in 35.5%. The survivors had a higher frequency of smoking, hypertension, family history for coronary artery disease (CAD) and dyslipidemia, and a much greater frequency of 3 or more risk factors than the controls: Odd ratios (OR) 7.4, 95% confidence interval (CI) 2.5-18.6, p = 0.0000. Significant differences were found between the groups for triglycerides (p = 0.000002), total cholesterol (p = 0.003), LDL-cholesterol (p = 0.012), HDL-cholesterol (p = 0.0002), apolipoprotein AI (p = 0.00001), and Apolipoprotein B (p = 0.000001). No differences were observed in APOE allele distribution (APOE*4 0.11 vs 0.08, APOE*3 0.86 vs 0.89, APOE*2 0.03 vs 0.03), nor in lipid profile when both higher risk genotype (E3/4, E4/4, E2/4) and lower risk genotype groups (E2/2, E2/3, E3/3) were analysed. OR were calculated as measures of the association of the E4-positive genotypes with AMI. They indicated a non-significant increase in risk of AMI when the survivors were compared with the controls (OR 1.78, 95% CI 0.84-3.70, p = 0.13). CONCLUSIONS: This study provides further evidence that conventional coronary risk factors are usually present in young AMI patients. The APOE*4 allele was associated with a 1.8 non-significant increase in the risk of AMI in our group with premature CAD. Comparison with controls showed that the presence of three or more risk factors sharply increased the probability of premature CAD and that hyper-triglyceridemia is an independent risk factor. The data on APOE polymorphism are less certain and a larger study is needed.

Adult↗
PubMed1998

Temporal-spatial expression of two Paracentrotus lividus cell surface proteins.

The temporal expression of two cell surface proteins, called BEP1 and BEP4, during Paracentrosus lividus embryonic development was studied. These proteins are found in both monomeric and dimeric forms in egg and embryos and we have established that their specific form is related to their being in the cytoplasm or on the cell surface. The spatial distribution of BEP1 and BEP4 proteins in eggs and embryos was established by whole mount immunohistochemistry. These proteins are located in the animal part of unfertilized and fertilized eggs; thereafter they are much less represented in structures derived from the vegetal cells of the embryo such as the micromeres of the 16 cell stage, the primary mesenchyme of blastula and the gut of gastrula. At the prism stage BEP1 and BEP4 proteins are present to some ectodermal parts and thereafter, at the pluteus stage, to the oral region.

Animals↗