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Biomedical subjects

C Costa

Publications and source records attributed to C Costa.

At least 109 records · Page 6Linked to original sources

Determination of copper and zinc levels in human hair: influence of sex, age, and hair pigmentation.

The Cu and Zn levels of both 607 men (1-85 y old) and 649 women (1-92 y old) were determined by atomic absorption spectrometry. Sex does not influence Cu (14.89 + or - 0.89 mu g/g and 15.26 + or - 0.79 mu g/g hair for males and females, respectively) and Zn contents (200.97 + or - 9.68 mu g/g for men and 209.81 + or - 9.49 mu g/g hair for women). Age influences Cu and Zn concentrations, but only significantly in females: Cu levels decrease over 60 y of age; whereas Zn levels increase significantly from age groups 2-5 to 20-40 years. Hair color influences Cu concentrations in both males and females. In males, white hair contains less Cu than black hair; in females, white hair's Cu levels are significantly lower than those of dark blond, red, light brown, and brown hair. There are no significant differences in Zn concentrations with respect to different hair colors, in either males or females.

Adolescent↗

Phosphorylation of Ga14p at a single C-terminal residue is necessary for galactose-inducible transcription.

Gal4p regulates expression of genes necessary for galactose catabolism in Saccharomyces cerevisiae. We have previously shown that phosphorylation of Gal4p requires both its DNA binding and transcriptional-activation functions and have suggested that phosphorylation occurs as a consequence of interaction with general transcription factors. In this study, we show that phosphorylation occurs rapidly on a limited fraction of overexpressed Gal4p present in a sodium dodecyl sulfate-extractable subcellular fraction while a significant fraction remains stably unphosphorylated. Taken together with our previous observations, we conclude that Gal4p is phosphorylated only if it becomes localized to the nucleus and is capable of both DNA binding and transcriptional activation. We demonstrate that Gal4p is multiply phosphorylated at both the C and N termini, and we identify the precise locations of three sites of phosphorylation at serines 691, 696, and 699. Of these sites, only serine 699 must be phosphorylated for galactose-inducible transcription to occur. Mutation of S-699 to alanine significantly impairs GAL induction by galactose in GAL80+ cells but does not affect transcriptional activation by Gal4p in gal80- cells. In gal80- cells, Gal4p phosphorylation, including that of serine 699, is stimulated by the presence of both galactose and glucose, indicating that phosphorylation at this site is not specifically activated by galactose. Serine 699 phosphorylation requires Gal4p's DNA binding function and is influenced by the function of the RNA polymerase II holoenzyme component Gal11p. These results suggest that a phosphorylation on Gal4p, likely resulting from interaction with the holoenzyme, modulates the induction process by regulating interaction between Gal4p and Gal80p.

Base Sequence↗

Pseudouridine for monitoring interferon treatment of patients with chronic hepatitis C.

Pseudouridine is a modified nucleoside derived from RNA catabolism; the concentration of this nucleoside is elevated in body fluids of both tumour-bearing and human immunodeficiency virus (HIV) infected patients. We used an HPLC procedure to evaluate the serum pseudouridine concentration in patients with chronic hepatitis C in an attempt to determine whether the nucleoside serum concentration was related to the response to alpha-interferon treatment. We found that: a) pseudouridine serum concentration was increased significantly in 76% (29/39) of patients with chronic hepatitis C at the time of diagnosis and before any therapeutic treatment; b) pseudouridine excretion was higher in patients affected by chronic hepatitis C with cirrhosis; c) there was a positive correlation between response to therapy and pseudouridine serum concentration in patients undergoing treatment with alpha-interferon; d) during one year of alpha-interferon treatment, the pseudouridine serum concentration remained within the normal range in responder patients. These results indicate that serum pseudouridine might be useful as a valuable biochemical marker with which to monitor chronic hepatitis C patients treated with alpha-interferon.

Adolescent↗

Electrochemical studies on nitrite reductase towards a biosensor.

A c-type hexaheme nitrite reductase (NiR) isolated from nitrate-grown cells of Desulfovibrio desulfuricans (Dd) ATCC 27774 catalyses the six-electron reduction of nitrite to ammonia. Previous electrochemical studies demonstrated that a simple electrocatalytic mechanism can be applied to this system (Moreno, C., Costa, C., Moura, I., LeGall, J., Liu, M. Y., Payne, W. J., Van Dijk, C. and Moura, J. J. G. (1992) Eur.J.Biochem. 212, 79-86). Its substrate specificity, availability and stability under ambient conditions makes this enzymatic system a promising candidate for use in a biosensor device. An electrochemical study of gel-immobilized Dd NiR on a glassy carbon electrode revealed both enzymatic activity and amperometric response to nitrite. In this study it was observed that the catalytic current density is a function of the nitrite concentration in solution and follows a characteristic Michaelis-Menten-type substrate dependence. Such a biosensor device (NiR-electrode) bears the option to be used for analytical determination of nitrite in complex media.

Biosensing Techniques↗

Biosynthesis of melanin from dopamine. An investigation of early oligomerization products.

Matrix-assisted laser desorption/ionization (MALDI) and fast-atom bombardment (FAB) mass spectrometry experiments were applied to the study of the early stages of the oligomerization reaction of dopamine with mushroom tyrosinase. Ultrafiltration was employed to remove the enzyme at various reaction times, to prevent possible attachment of the protein to the highly reactive intermediates. Two sets of five samples each, obtained at different reaction times, in one case immediately lyophilized and in the other left to react under an oxygen stream for 24 h before lyophilization, were compared. FAB showed the presence of various species and of these, that at m/z 305 increased in abundance with reaction time in immediately lyophilized set of samples only. Accurate mass measurements and tandem mass spectrometric experiments indicated the structure of a dopamine protonated dimer for this ion. MALDI measurements showed that all samples were composed of clusters of oligomers differing in degree of oligomerization. Oligomerization increases with reaction time, resulting in the formation of species at 2643-2911 Da. These clusters in turn were formed of species with a different degree of oxidation, detected in both sets of samples.

Dopamine↗

Primary biliary cirrhosis: lung involvement.

Sub-clinical lung impairment, mostly represented by a reduced diffusion of alveolar gases, is a recognised complication of advanced primary biliary cirrhosis. The aim of the study was to evaluate the prevalence and type of pulmonary involvement in primary biliary cirrhosis and the relationship between lung function abnormalities and selected epidemiological and clinical variables. Sixty-one patients with different stages of primary biliary cirrhosis consecutively seen in our outpatient clinic were evaluated. The advancement of primary biliary cirrhosis was characterised by the histological stage, the presence of signs of portal hypertension and the Mayo Risk Score: a Cox regression model using serum bilirubin and albumin levels, prothrombin time, age and degree of oedema as selected variables. We measured static and dynamic lung volumes, by means of a spirometer, and diffusing capacity for carbon monoxide. Rheumatological disorders were evaluated by an independent rheumatologist. No patient complained of respiratory symptoms. Airway obstruction was present in one patient. In 24 patients (39%) the alveolar diffusion capacity was reduced. We did not find any significant relationship between diffusing capacity and smoking habits, advancement of liver disease and concomitant Sjogren syndrome. Reduced diffusion capacity showed a significant correlation with the presence of complete or incomplete CREST syndrome (p < 0.01) and with the presence of circulating anti-centromere antibodies (p < 0.05). Alveolar diffusion capacity is frequently impaired in patients with primary biliary cirrhosis, usually in the absence of clinical manifestations. These alterations mostly affect patients with concomitant CREST syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relevance of intravenous cocaine use in relation to prevalence of HIV, hepatitis B and C virus markers among intravenous drug abusers in southern Italy.

The purpose of this study was to analyze the relationship between intravenous (i.v) drug use practices and the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in 146 heterosexual male i.v. drug users (IVDUs) attending a methadone-maintainance treatment program in Catanzaro, Southern Italy. One hundred and forty-six heterosexual male IVDUs attending a methadone-maintainance treatment program in Catanzaro were interviewed in order to obtain the following information: age, number of drug injections (calculated by multiplying the mean number of daily injections by 365 and then by the number of years of injections), number of injection equipment-sharing partners in the last year, number of sexual partners in the last year and possible IV cocaine use. Their sera were studied for the presence of antibodies to HIV, HBV and HCV by commercial enzyme-linked-immuno-sorbent assays run in duplicate. HIV positive samples were confirmed by Western Blot assay. Sixteen per cent of IVDUs were anti-HIV positive, 40% were anti-HBc positive and 68% were anti-HCV positive. Twenty-three per cent were seronegative and 12% were seropositive for all 3 viral markers. Multiple logistic analysis of HIV, HBV and HCV seropositivities in relation to age, number of drug injections, i.v. cocaine use and presence of injection equipment-sharing partners in the last year, showed that: a) older age (more than 27 years) was significantly associated with all 3 viral infections (mainly with HIV); b) i.v. cocaine use was associated with HBV, but even more with HIV; c) injection equipment-sharing partners in the last year was directly associated with HCV and inversely with HIV. No significant association was observed with the number of drug injections and the number of sexual partners. In conclusion, this study: a) demonstrates a difference of prevalence for HIV, HBV and HCV serum markers in this group of IVDUs from Catanzaro, Southern Italy; b) underlines the importance of i.v. cocaine use in the spreading of HIV; c) emphasizes the need of preventive strategies.

Adolescent↗

Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations.

Transgenic mice expressing the P-enolpyruvate carboxykinase (PEPCK)/human insulin chimeric gene have been obtained as a model to study the feasibility of gene therapy for diabetes. These transgenic animals were healthy and normoglycemic and expressed human insulin in a physiologically regulated manner, mainly in the liver. Streptozotocin-treated transgenic mice had high levels of human insulin immunoreactivity in serum and showed a significant decrease (up to 40%) in glycemia compared with streptozotocin-treated control mice. The expression of genes involved in liver glucose metabolism, such as glucokinase, pyruvate kinase, and PEPCK, which is markedly altered by diabetes, was significantly recovered in transgenic mice treated with streptozotocin. In addition, the activity of both glucokinase and glycogen synthase, and the content of glucose 6-phosphate and glycogen, were normal in the liver, even when transgenic animals were treated with diabetogenic doses of streptozotocin. These results constitute an indication in vivo that diabetes gene therapy is possible, by means of the production of insulin in extrapancreatic tissues.

Animals↗

Laser desorption ionization mass spectrometry in the study of natural and synthetic melanins. II--Serotonin melanins.

Various biosynthetic melanins obtained by enzymic oxidation of serotonin with polyphenol oxidase from Psalliota campestris mushroom or potato, and with tyrosinase from Sepia officinalis or from Sigma were studied by means of laser desorption ionization mass spectrometry. Various oligomeric clusters were evidenced, proving that the examined melanins are composed of sets of different oligomers, the production of which strongly depends on the enzyme reaction. While serotonin melanins obtained with polyphenol oxidase from potato showed wide species distribution with molecular weights ranging from 2008 to 13,000 Da, the same melanins obtained from mushroom showed oligomer distributions from 1505 to 9000 Da. Serotonin melanins prepared with tyrosinase from Sepia showed oligomers from 1636 to 18,000 Da. A dopa-melanin obtained with mushroom polyphenol oxidase showed oligomer species from 1709 to 17,874 Da. Comparison of molecular weight distributions of the various oligomer sets in serotonin melanins with those in tyrosine melanins revealed clear differences, which are investigated and discussed.

Agaricus↗

Deflazacort in Duchenne dystrophy: study of long-term effect.

A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P < 0.01), in rising from a chair, Gower's maneuver, and walking (P < 0.0025) after 6 months of treatment. After 1 year, all the above changes remained significantly improved and the MRC index was significantly better (P < 0.05) in the treated group. After 2 years, a significant change was found in the MRC index: higher scores in walking, chair rising (P < 0.02), and grade and time of Gower's maneuver (P < 0.05) were found. The mean time for loss of ambulation for the treated group after we started the trial was 33.2 +/- 9 months; for the placebo group it was 20.5 +/- 11 months (deflazacort vs. placebo group, P < 0.05) [corrected]. Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group. Side effects were mild, consisting of moderate weight gain and slight behavioral changes.

Anti-Inflammatory Agents, Non-Steroidal↗

The influence of color, age, and sex on the content of zinc, copper, nickel, manganese, and lead in human hair.

The hair of 132 healthy subjects between 6 and 40 yr old living in the Veneto region in Italy was analyzed by means of HPLC method in order to determine the presence of zinc, copper, nickel, manganese, and lead. The collected samples were subdivided on the basis of age (6-11 and 19-40 yr), and sex and color (black, red, brown, and blond). From the data some evident differences were emphasized. In female hair the content of metals was higher than in male hair independently of color. Blond hair gave the lowest concentration values of the elements studied independently of sex. The maximum amount of the metals was found generally in black hair, followed by red and brown hair. Age seems to have a different influence, with the copper element decreasing appreciably in brown and blond female hair as the age of the subjects increased.

Adolescent↗

Ribavirin treatment for chronic hepatitis D: a pilot study.

To assess whether therapy with Ribavirin may affect the course of chronic delta hepatitis, nine Italian patients with this disease received the drug orally at a dosage of 15 mg/kg daily for 16 weeks. At the end of the therapy period, all patients were followed for 12 additional months. Seven patients completed the trial. Two patients were withdrawn: one developed hemolytic anemia, and the other intractable itching. At the end of treatment HD viremia was reduced in one patient, had cleared in another, and was unchanged in the remaining five patients. None of the patients decreased their alanine transferase (ALT) levels by more than 50%. At the doses given in this study. Ribavirin did not show significant antiviral effects in chronic hepatitis D, and was not effective in reducing the biochemical markers of liver inflammation and necrosis.

Adult↗

[An estimate of the prevalence of dementia and Alzheimer's disease in Portugal].

The authors projected to the Portuguese population the data on prevalence of dementia and Alzheimer's disease obtained respectively by Hofman et al. and Rocca et al through reanalyses of European epidemiological studies conducted or published between 1980 and 1990. The projection relies on the fact that the results of these reanalyses are extensive to all European countries. With this projection which is based on the Portuguese population census of 1991 the numbers of about 92.470 demented patients and about 48.706 Alzheimer's patients are obtained for Portugal. The authors think that, until systematic epidemiological studies of dementia and Alzheimer's disease are available in Portugal, the data now provided are useful for the planning of the care of these patients.

Adult↗

Electrochemical studies of the hexaheme nitrite reductase from Desulfovibrio desulfuricans ATCC 27774.

The electron-transfer kinetics between three different mediators and the hexahemic enzyme nitrite reductase isolated from Desulfovibrio desulfuricans (ATCC 27774) were investigated by cyclic voltammetry and by chronoamperometry. The mediators, methyl viologen, Desulfovibrio vulgaris (Hildenborough) cytochrome c3 and D. desulfuricans (ATCC 27774) cytochrome c3 differ in structure, redox potential and charge. The reduced form of each mediator exchanged electrons with nitrite reductase. Second-order rate constants, k, were calculated on the basis of the theory for a simple catalytic mechanism and the results, obtained by cyclic voltammetry, were compared with those obtained by chronoamperometry. Values for k are in the range 10(6)-10(8) M-1 s-1 and increase in the direction D. desulfuricans cytochrome c3-->D. vulgaris cytochrome c3-->methyl viologen. An explanation is advanced on the basis of electrostatic interactions and relative orientation between the partners involved. Chronoamperometry (computer controlled) offers advantages over cyclic voltammetry in the determination of homogeneous rate constants (faster, more accurate and better reproducibility). Direct, unmediated electrochemical responses of the hexaheme nitrite reductase were also reported.

Cytochrome c Group↗

Laser desorption ionization mass spectrometry in the study of natural and synthetic melanins. I--Tyrosine melanins.

Nine synthetic, biosynthetic and natural tyrosine melanins, together with dopa and catechol melanins, have been studied by means of laser desorption ionization mass spectrometry. The results obtained have shown that all the melanins under study consist of homogeneous sets of oligomers and have led to definitive information on their molecular weight distribution (from 500 to 30,000 Da). A deeper analysis of the spectra, in terms of mass differences among the various oligomers, allowed the identification of some monomeric units, identical or analogous to those already proposed in the literature.

Lasers↗