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Biomedical subjects

A Melis

Publications and source records attributed to A Melis.

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

Transforming growth factor beta, fibrogenesis and hyperglycemia in patients with chronic pancreatitis.

UNLABELLED: It has been suggested that transforming growth factor beta (TGFb) mediates liver fibrosis, which can be monitored by the serum determination of the N-terminal peptide of type III procollagen (PIIIP) and laminin. Fibrosis is also an important phenomenon in patients with chronic pancreatitis (CP). In 23 patients with CP, 38 with liver cirrhosis (LC) and 20 healthy controls we compared the serum patterns of PIIIP, laminin and TGFb and assessed whether in CP these markers are correlated with exocrine and endocrine function. In patients with LC, PIIIP and laminin levels were significantly higher, whereas TGFb levels were significantly lower than those of controls. In CP patients, no significant variations were found for PIIIP and laminin, although levels were high in 7/23 and in 5/23 patients, respectively. TGFb levels in CP patients were higher than those in LC patients, levels being raised in 6/23 patients. In LC patients an inverse correlation was found between PIIIP and TGFb, whereas in CP patients, a direct correlation was found between TGFb and PIIIP. Moreover, in CP patients, there was also a positive correlation between TGFb and fasting serum glucose levels, while laminin was correlated with PABA test results. IN CONCLUSION: serum biochemical markers of liver fibrosis can be considered of limited value in assessing pancreatic fibrosis; in liver cirrhosis there may be a negative feed-back regulation between TGFb production and the fibrogenetic process; and in chronic pancreatitis TGFb appears to favor fibrosis on the one hand and the development of hyperglycemia on the other.

Adult↗
PubMed1996

S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial.

OBJECTIVES: To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). METHODS: Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases. RESULTS: After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups. CONCLUSIONS: These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials.

Adult↗
PubMed1995

Isolation of a differentially regulated splicing isoform of human NF-E2.

The transcription factor NF-E2 (nuclear factor erythroid 2), interacting via DNA motifs within regulatory regions of several hematopoietic genes, is thought to mediate the enhancer activity of the globin locus control regions. By screening a human fetal liver cDNA library with probes derived from mouse NF-E2, we have isolated a splicing variant of the NF-E2 gene (fNF-E2) that differs in the 5' untranslated region from the previously reported cDNA (aNF-E2). The fNF-E2 isoform is transcribed from an alternative promoter located in the 3' end of the first intron and joined by alternative splicing to the second and third exons, which are shared by both RNA isoforms. Although the two forms produce the same protein, they are expressed in different ratios during development. fNF-E2 is more abundant in the fetal liver and less abundant in the adult bone marrow compared to the previously described form. Their distribution apparently follows the differential expression of fetal and adult hemoglobins.

Alternative Splicing↗
PubMed1995

Hyperinsulinemia and hypertension. Do intestinal hormones play a role?

Gastric inhibitory polypeptide (GIP) is one of the strongest insulinotropic gut factors. Its secretion is induced by oral (but not intravenous) glucose and it has been implicated in the pathogenesis of hyperinsulinemic states (NIDDM, obesity). To determine its relevance to hypertension, 54 subjects were studied: 26 normotensives (12 with and 14 without family history of essential hypertension), and 28 essential hypertensive subjects. Plasma glucose, serum insulin (IRI), and GIP were evaluated after a mixed meal containing a total of 82 g of carbohydrates, and 2 g sodium chloride. Venous blood was collected at baseline and every 15 min during a 3-h period. Baseline levels of glucose, IRI, and GIP were comparable in the three groups. At 30 min, however, IRI and GIP were higher in normotensives with a family history of hypertension and in established hypertensive versus control subjects. Both in normotensive and in hypertensive groups, glucose, IRI, and GIP responses to the meal were significantly correlated. Our data suggest the contribution of altered GIP secretion in the pathogenesis of hyperinsulinemia in essential hypertension.

Adult↗
PubMed1995

Localization and characterization of a novel 20 kDa polypeptide in the chloroplast of the green alga Dunaliella salina.

Recent work with the green alga Dunaliella salina showed the presence of a approximately 20 kDa chloroplast protein that was recognized by polyclonal antibodies raised against the isolated LHC-II [Webb M.R. and Melis A. (1995) Plant Physiol. 107: 885]. In this report, a characterization of the approximately 20 kDa polypeptide is presented. It is shown that it is localized in the chloroplast envelope membrane of D. salina. The abundance of this protein is constant on a per cell basis and independent of the light regime during cell growth. The approximately 20 kDa polypeptide is easily degraded to a approximately 19 kDa product during sample preparation. A limited amino acid sequence of 21 residues from the free N-terminus of the approximately 19 kDa product was obtained. On the basis of this partial sequence, it was concluded that the approximately 20 kDa polypeptide is not a degradation product of a known LHC-II but rather a novel protein. The approximately 20 kDa polypeptide did not cross-react with antibodies raised against the Cbr (carotene biosynthesis-related) gene product and showed a different electrophoretic mobility from the latter. Light-shift experiments suggest that the approximately 20 kDa polypeptide is not an ELIP (early light-inducible protein). Possible functions of the approximately 20 kDa protein are discussed.

Amino Acid Sequence↗
PubMed1994

Photosystem II reaction center damage and repair cycle: chloroplast acclimation strategy to irradiance stress.

A daily occurrence in the life of a plant is the function of a photosystem II (PSII) damage and repair cycle in chloroplasts. This unique phenomenon involves the frequent turnover of D1, the 32-kDa reaction-center protein of PSII (chloroplast psbA gene product). In the model organism Dunaliella salina (a green alga), growth under low light (100 mol of photons per m2 per sec) entails damage, degradation, and replacement of D1 every 7 hr. Growth under irradiance stress (2200 micromol of photons per m2 per sec) entails damage to D1 every 20 min. The rate of de novo D1 biosynthesis under conditions of both low light and irradiance stress was found to be fairly constant on a per chloroplast or cell basis. The response of D. salina to the enhanced rate of damage entails an accumulation of photodamaged centers (80% of all PSII) and the formation of thylakoid membranes containing a smaller quantity of photosystem I (PSI) centers (about 10% of that in cells grown under low light). These changes contribute to a shift in the PSII/PSI ratio from 1.4:1 under low-light conditions to 15:1 under irradiance stress. The accumulation of photodamaged PSII under irradiance stress reflects a chloroplast inability to match the rate of D1 degradation or turnover with the rate of damage for individual PSII complexes. The altered thylakoid membrane organization ensures that a small fraction of PSII centers remains functional under irradiance stress and sustains electron flow from H2O to ferredoxin with rates sufficient for chloroplast photosynthesis and cell growth.

Journal Article↗
PubMed1993

Markers of hepatitis C virus infection in Sardinian blood donors: relationship with alanine aminotransferase levels.

Serum samples from 1,765 consecutive Sardinian blood donors, negative for hepatitis B surface antigen (HBsAg) and for antibodies to human immunodeficiency virus (HIV) (anti-HIV), were evaluated for the presence of antibodies to hepatitis C virus (anti-HCV) by second-generation ELISA. Anti-HCV was detected in 25 (1.45%) of the 1,765 donors examined. Anti-HCV was found in 15 of the 1,690 (0.9%) donors with normal alanine aminotransferase (ALT) and in 10 of the 75 (13%) donors with elevated ALT (P < 0.0001). Of the 15 anti-HCV-positive donors with normal ALT, only five (33%) were confirmed to be positive by second-generation RIBA, six (40%) were indeterminate, while four (27%) were RIBA negative. HCV RNA, as detected by polymerase chain reaction (PCR) using a set of primers from the 5'-noncoding region, was found in six of the 15 (40%) donors with normal ALT, including five RIBA positive and one indeterminant. Of the 10 anti-HCV-positive donors with elevated ALT, all were RIBA positive and eight (80%) had detectable HCV RNA. Thus, among ELISA-reactive donors, those with elevated ALT had a significantly higher probability of being positive for second-generation RIBA and HCV RNA compared to those with normal ALT levels (P = 0.028). None of the 65 donors with elevated ALT but negative for anti-HCV by ELISA had detectable serum HCV RNA, as compared to eight of 10 anti-HCV ELISA-positive donors (P < 0.0001). However, although negative for HBsAg, 12 of the 65 (18%) had serum HBV DNA by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Evidence for cortisol as the mineralocorticoid in the syndrome of apparent mineralocorticoid excess.

The hypothesis that cortisol is the functioning mineralocorticoid in the syndrome of apparent mineralocorticoid excess was tested by suppressing its secretion with dexamethasone. The subjects were two siblings with the type 2 form of this syndrome in which the defect in the peripheral metabolism of cortisol lies predominantly in ring A reduction but not in 11 beta-hydroxy dehydrogenation of cortisol to cortisone. Low dosage dexamethasone improved the hypokalemia within several days and hypertension was corrected after 3 weeks of treatment. Mineralocorticoid manifestations remained in remission during 10 yr of therapy with the synthetic glucocorticoid during which normal growth and development were restored. The effectiveness of dexamethasone supports the hypothesis that cortisol is the functioning mineralocorticoid in the AME syndrome.

Adolescent↗
PubMed1992

Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Polymerase chain reaction analysis for specific HTLV-1 sequences from cerebrospinal fluid and peripheral blood cells in Sardinian multiple sclerosis patients.

Using polymerase chain reaction and specific primers, we found no gag and env sequences of HTLV-1 in DNA samples from peripheral blood mononuclear cells of 26 multiple sclerosis (MS) patients with relapsing-remitting, relapsing-progressive and progressive course from onset of the disease, and from 8 patients affected with other neurological diseases (OND). A Positive signal for the gag region was found in DNA samples from cerebrospinal fluid mononuclear cells (CSFMC) of 6/17 (27.3%) MS patients (either with relapsing-remitting, or relapsing-progressive and progressive course from onset of the disease), and in 2/11 (18.2%) CSFMC OND samples. Positive hybridization for the env sequence was evident in 2/11 (18.2%) CSFMC from OND and none of MS samples. The finding of positive hybridization for gag and env sequences in a few samples of CSFMC may be related to the presence in the CSF of a great number of activated cells, which could express cross-reacting sequences of endogenous retrovirus.

Adolescent↗
PubMed1992

Abnormalities of erythrocyte sodium transport systems in Bartter's syndrome.

The basic tubular alteration present in Bartter's syndrome is still a subject of controversy. The possibility that a generalized defect in the transmembrane ion transport underlies the disease has been extensively investigated. Previous evaluations of cellular sodium metabolism in Bartter patients showed extremely variable findings. We have examined in the red blood cells of two patients with Bartter's syndrome the intracellular Na+ and K+ concentrations, the activity of the ouabain-sensitive Na+/K+ pump, furosemide-sensitive Na+/K+ cotransport, Na+/Li+ countertransport and the rate constant of Na+ and K+ passive permeability. We have compared these values with those of healthy subjects and patients with chronic hypokalemia produced by conditions other than Bartter's syndrome. Ouabain-sensitive Na+/K+ pump activity was decreased in both patients, whereas Na+/Li+ countertransport was activated. One of the patients also exhibited markedly decreased intraerythrocyte K+ concentration and decreased furosemide-sensitive Na+/K+ cotransport. The other had increased Na+/K+ cotransport activity and Na+ passive permeability. Intracellular Na+ and passive permeability to K+ were normal in both subjects. Neither oral potassium supplementation (100 mEq/day) nor indomethacin treatment (150 mg/day) could correct these abnormalities. Our results are partially consistent with previous observations and indicate the existence of heterogenous abnormalities of erythrocyte sodium transport systems in patients with Bartter's syndrome which are not a consequence of chronic hypokalemia.

Adult↗
PubMed1992

Influence of acetyl-carnitine on some mitochondrial enzymic activities in the human cerebral tissue in conditions of acute hypoxia.

Following previous research on human tissue in conditions of acute and massive hypoxia, in the present work the authors compared the cellular enzymic response to oxidative stress in normoxic (perifocal) and hypoxic (focal) areas in human brain affected by regional acute vasculopathies. Two homogeneous groups of patients were selected following strict clinical inclusion/exclusion criteria. The groups of patients were treated with a placebo or acetyl-carnitine at same doses and following randomized, double-blind procedures. The focal areas showed a significant functional damage in lactate, pyruvate and succinate dehydrogenases and in the cytochrome oxidase activity when compared with the enzymic capacities of perifocal areas (normoxic as controls). The pretreatment with acetyl-carnitine antagonized the above-mentioned enzymic damage by a protective action linked to the endocellular energy restoration. In accordance with these data, the therapeutic role played by acetyl-carnitine in the cerebral focal hypoxia appeared to be a determinant for the cell survival mainly in the reversible phase of oxidative damage.

Acetylcarnitine↗
PubMed1991

Serum insulin, insulin sensitivity, and erythrocyte sodium metabolism in normotensive and essential hypertensive subjects with and without overweight.

Increased insulin circulating levels and perturbations of intracellular sodium metabolism have been reported in essential hypertensive patients, leading to postulate their involvement in the pathophysiology of the disease. In-vitro studies have shown that insulin modulates the activity of some transmembrane sodium transporters. The aim of this investigation was to assess in subjects with essential hypertension and/or overweight, the levels of fasting serum insulin, the activity of sodium transporters and their possible relationships. In 18 lean normotensive, 12 overweight normotensive, 18 untreated lean essential hypertensive, and 16 untreated overweight essential hypertensive subjects, we measured the fasting levels of blood glucose and serum insulin, and calculated the glucose/insulin ratio as an index of sensitivity to insulin. In addition, in the red blood cells of these subjects, we evaluated the maximal rate of ouabain-sensitive Na/K pump, furosemide-sensitive outward Na/K cotransport, Nai/Lio countertransport, and the constant rate of passive permeability to Na. When compared to lean normotensive, overweight normotensive, lean hypertensive, and overweight hypertensive subjects exhibited significantly higher fasting insulin levels, with lower glucose/insulin ratio. No significant difference was found in the activity of Na/K pump, Na/K cotransport, and passive permeability to Na. The Nai/Lio exchange was significantly increased in both hypertensive groups. Mean blood pressure correlated positively and independently with body mass index and fasting insulinemia, and inversely with the glucose/insulin ratio. No relationships were found between blood pressure, fasting insulin levels or glucose/insulin ratio and the activity of sodium transport systems. We conclude that hyperinsulinemia and insulin resistance are associated with essential hypertension independently of overweight. These data lend support to the hypothesis that insulin is involved, concurrently with other factors, in the pathogenesis of essential hypertension in both lean and obese subjects.

Biological Transport↗
PubMed1991

Occupational exposure to lead and blood cholesterol in glucose-6-phosphate dehydrogenase deficient and normal subjects.

The effect of chronic lead poisoning on blood cholesterol levels of 148 patients, admitted to the Institute of Occupational Medicine of the University of Cagliari (Italy), was studied in connection with the genetic pattern of Glucose-6-Phosphate Dehydrogenase (G6PD) activity. The erythrocyte G6PD activity of twenty-six patients was genetically deficient. Multiple regressions were elaborated including the following in the model as independent variables: age, Quetelet index and blood lead or urinary lead in the 24 hours following 15 mg/Kg of i.v. calcium ethylen-diamine-tetracetate (EDTA) (PbUEDTA), expressed as a ratio with body weight (PbUEDTA/Kg). Dependent variables were alternatively, total cholesterol, cholesterol esters, LDL and HDL cholesterol. The analysis showed that G6PD deficient subjects have generally lower intercepts, but only for HDL the difference approached the statistical significance. Lead poisoning affected blood cholesterol of G6PD deficient subjects differently from normal ones: while total cholesterol and LDL tended to decrease in both, positive slopes were observed for cholesterol esters in G6PD deficient and for HDL in G6PD normal subjects.

Adult↗
PubMed1990

Evidence for a direct and non-receptor-mediated action of 5HT2 antagonists on transmembrane cation transport systems.

Changes in transmembrane sodium fluxes have been reported in normotensive and in hypertensive subjects after ketanserin administration. In this study, the effects of the serotonergic system on transmembrane sodium transport mechanisms have been investigated in vitro. In erythrocytes drawn from ten healthy subjects, we studied the effects of serotonin (5HT) on the Na/K pump, Na/K cotransport, Na/Li countertransport, and passive permeability of Na. No significant changes were found. A direct, non-receptor-mediated action of ketanserin was then suspected, and the effects of two concentrations of ketanserin (5 x 10(-8) and 5 x 10(-7) M) were evaluated in erythrocytes from 12 normal volunteers. Both concentrations of ketanserin significantly decreased the activity of the Na/K pump and increased the activity of Na/Li countertransport. Na/K cotransport and passive permeability were not affected. Indirect evidence of the action of ketanserin on sodium transmembrane fluxes came from other experiments. In the red blood cells taken from five normal subjects and incubated for 2 hours in a plasma pool, we evaluated the changes in intracellular sodium concentration induced by the presence of 5HT or ketanserin. A significant decrease in intracellular sodium concentration occurred only with ketanserin. This study indicates that ketanserin has a direct influence on transmembrane sodium fluxes. If this action were also present in other cells, it might contribute to the actions of the drug at vascular, nervous, and renal tubular levels.

Adult↗
PubMed1990

Adjustments of photosystem stoichiometry in chloroplasts improve the quantum efficiency of photosynthesis.

The efficiency of photosynthetic electron transport depends on the coordinated interaction of photosystem II (PSII) and photosystem I (PSI) in the electron-transport chain. Each photosystem contains distinct pigment-protein complexes that harvest light from different regions of the visible spectrum. The light energy is utilized in an endergonic electron-transport reaction at each photosystem. Recent evidence has shown a large variability in the PSII/PSI stoichiometry in plants grown under different environmental irradiance conditions. Results in this work are consistent with the notion of a dynamic, rather than static, thylakoid membrane in which the stoichiometry of the two photosystems is adjusted and optimized in response to different light quality conditions. Direct evidence is provided that photosystem stoichiometry adjustments in chloroplasts are a compensation strategy designed to correct unbalanced absorption of light by the two photosystems. Such adjustments allow the plant to maintain a high quantum efficiency of photosynthesis under diverse light quality conditions and constitute acclimation that confers to plants a significant evolutionary advantage over that of a fixed photosystem stoichiometry in thylakoid membranes.

Journal Article↗
PubMed1990

Effects of ketanserin on transmembrane sodium transport in erythrocytes.

Ketanserin, an antagonist of 5-HT2-serotonergic and alpha 1-adrenergic receptors, has come into use for the therapy of mild to moderate arterial hypertension. Quite recent observations have shown changes in transmembrane sodium (Na) transport after the acute administration of high doses of this drug to normal subjects. It is well known that some of these transport systems have an altered activity in essential hypertension. We evaluated the effects of long-term (3 months) administration of ketanserin (40-80 mg/day) on Na and potassium (K) intracellular concentrations and transmembrane fluxes in red blood cells (RBCs) from 12 essential hypertensive patients. In addition the present study describes the in vitro effects of two different concentrations of the drug (5 x 10(-8) and 5 x 10(-7) M) on erythrocytes in normal subjects. In the first study, both systolic and diastolic blood pressure were significantly lowered by the treatment with ketanserin (from 165/103 to 143/89; p less than 0.001). Na and K intraerythrocyte concentrations fell markedly during ketanserin administration (both p less than 0.001). A marked decrease in Na,K-pump activity (p less than 0.001) and an increase in Na,lithium(Li)-countertransport function (p less than 0.001) were observed. Na outward cotransport, Na leak, and K leak were not modified by the therapy. Direct correlation was found between the fall in mean blood pressure and in Na and K intraerythrocyte concentration (respectively, p less than 0.01 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗