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Biomedical subjects

J Delgado

Publications and source records attributed to J Delgado.

At least 55 records · Page 3Linked to original sources

Hepatitis C virus-related fibrosing cholestatic hepatitis after cardiac transplantation: is azathioprine a contributory factor?

We report a patient who acquired hepatitis C virus (HCV) infection at cardiac transplantation, developing fibrosing cholestatic hepatitis (FCH) with early liver failure and a fatal outcome. FCH is a recently described clinicopathological entity characterized by a cholestatic pattern of serum liver enzyme abnormalities, a progressive course leading to liver failure, and a pathological picture defined by periportal fibrosis, neutrophilic infiltrates and signs of histological cholestasis. Although it was initially described secondary to hepatitis B virus infection, it has also been recently related to HCV infection. Some histopathological features consistent with azathioprine hepatotoxicity like cholestasis, perisinusoidal fibrosis, veno-subocclusive lesions and nodular regenerative hyperplasia were also observed in this case. Therefore, a direct cytopathic effect of HCV and the concurrent pathogenic role of azathioprine hepatotoxicity may be involved in the development of this complication of transplantation.

Azathioprine↗

Modulation of GT-1 DNA-binding activity by calcium-dependent phosphorylation.

The analysis of pea rbcS-3A promoter sequence showed that BoxII was necessary for the control of rbcS-3A gene expression by light. GT-1, a DNA-binding protein that interacts with BoxII in vitro, is a good candidate for being a light-modulated molecular switch controlling gene expression. However, the relationship between GT-1 activity and light-responsive gene activation still remains hypothetical. Because no marked de novo synthesis was detected after light treatment, light may induce post-translational modifications of GT-1 such as phosphorylation or dephosphorylation. Here, we show that recombinant GT-1 (hGT-1) of Arabidopsis can be phosphorylated by various mammalian kinase activities in vitro. Whereas phosphorylation by casein kinase II had no apparent effect on hGT-1 DNA binding, phosphorylation by calcium/calmodulin kinase II (CaMKII) increased the binding activity 10-20-fold. Mass spectrometry analyses of the phosphorylated hGT-1 showed that amongst the 6 potential phosphorylatable residues (T86, T133, S175, T179, S198 and T278), only T133 and S198 are heavily modified. Analyses of mutants altered at T86, T133, S175, T179, S198 and T278 demonstrated that phosphorylation of T133 can account for most of the stimulation of DNA-binding activity by CaMKII, indicating that this residue plays an important role in hGT-1/BoxII interaction. We further showed that nuclear GT-1 DNA-binding activity to BoxII was reduced by treatment with calf intestine phosphatase in extracts prepared from light-grown plants but not from etiolated plants. Taken together, our results suggest that GT-1 may act as a molecular switch modulated by calcium-dependent phosphorylation and dephosphorylation in response to light signals.

Amino Acid Sequence↗

Rat liver lysosomal and mitochondrial activities are modified by anabolic-androgenic steroids.

PURPOSE: The aim of this study was to examine the separate and combined effects of an 8-wk treatment with high doses of 17alpha-alkylated anabolic-androgenic steroids (AAS) and exercise training on selected lysosomal and mitochondrial enzyme activities in rat liver. METHODS: Sedentary and treadmill-trained (25 m x min(-1), 45 min x d(-1), 5 d x wk(-1)) male rats were treated with fluoxymesterone, methylandrostanolone, or stanozolol (2 mg x kg body weight(-1), 5 d x wk(-1)) for 8 wk. RESULTS: Acid phosphatase, arylsulfatase, beta-glucuronidase, and beta-galactosidase activities were increased in liver homogenates of sedentary and trained AAS-treated rats. The mitochondrial respiratory chain activities rotenone-sensitive NADH-cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), and cytochrome oxidase (COX) showed a significant decrease in steroid-administered rats, whereas citrate synthase (CS), a matrix enzyme, exhibited no changes in activity, pointing to a selective effect of AAS on mitochondrial membrane complexes. In vitro studies in mitochondrial fractions isolated from the liver of control rats showed that COX and CS activities were insensitive to the AAS, whereas NCCR and SCCR activities were partly inhibited. On the other hand, the mean values of serum parameters related to hepatic function were within normal ranges in all the experimental groups of animals. CONCLUSIONS: The present data show that 8-wk ingestion of three different anabolic-androgenic steroids, either with or without concurrent exercise training, affects lysosomal hydrolases and mitochondrial respiratory chain electron transport in rat liver without modifying classical serum indicators of hepatic function.

Anabolic Agents↗

Chronic and acute exercise do not alter Ca2+ regulatory systems and ectonucleotidase activities in rat heart.

The purpose of this investigation was to examine the effects of chronic and acute exercise on the main components involved in excitation-contraction coupling and relaxation in rat heart. Sixty male Wistar rats were divided into a sedentary (S) and three 12-wk treadmill-trained groups (T-1, moderate intensity; T-2, high intensity; T-3, interval running). After 12-wk, 15 rats from the S group and 15 rats from the T-2 group were subjected to a single treadmill-exercise session until exhaustion before being killed at 0, 24, or 48 h (acute exercise). The remaining animals were killed 48 h after the last standard exercise session (chronic exercise). The efficacy of the training programs was confirmed by an increase in treadmill endurance time and in skeletal muscle citrate synthase activity. None of the exercise programs modified heart weight or cardiac oxidative capacity. [(3)H]PN200-110 and [(3)H]ryanodine binding to cardiac homogenates indicated that the density of L-type and sarcoplasmic reticulum (SR) Ca(2+) channels was the same in S and trained rats. The SR Ca(2+)-ATPase activity was also unmodified. Finally, the activities of the ectoenzymes Mg(2+)-ATPase and 5'-nucleotidase, which are involved in degradation of extracellular nucleotides, were not affected by either of the running programs. After the acute exercise session, no changes were detected in either of the tested parameters in heart homogenates of S and T-2 animals. We conclude that neither treadmill-exercise training for 12 wk nor exhaustive exercise alters the density of Ca(2+) channels involved in excitation-contraction coupling or the SR Ca(2+)-ATPase and the ectonucleotidase activities in rat heart.

5'-Nucleotidase↗

[Epidemiology of dengue and hemorrhagic dengue in Santiago, Cuba 1997].

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.

Adolescent↗

Learning volleyball serves: a preliminary study of the effects of knowledge of performance and of results.

Recently, doubts have begun to surface about the emphasis that for years has been given to the variable knowledge of results in motor learning, and a view has been expressed that information on how an action has been made (knowledge of performance) may be of more use. This study compared the two types of information in learning a volleyball serve by eight subjects, who were given the two kinds of feedback at various points in the process. Analysis seems to show that knowledge of performance tends to be more effective for learning and that there may be interference across information if knowledge of results is provided after knowledge of performance.

Adolescent↗

High frequency of serious side effects from meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients.

Organic pentavalent antimonials are one of the mainstays of treatment for visceral leishmaniasis (VL). Few data are available on the toxicity and efficacy of these drugs at the dosing schedule recommended by the Centers for Disease Control and Prevention (CDC) (Atlanta, GA). We analyzed 25 VL episodes in human immunodeficiency virus (HIV)-infected patients who were treated with meglumine antimoniate (MA) at the CDC-recommended dose in southern Spain. Adverse effects were observed in 14 (56%) VL episodes. In 7 (28%), treatment with MA was permanently discontinued due to serious adverse effects that included acute pancreatitis, acute renal failure, and leukopenia. Three (12%) patients died during therapy due to severe acute pancreatitis attributable to MA. The dosing regimen of MA currently recommended for treating VL is associated with a high rate of serious side effects in HIV-1-infected patients.

Adult↗

[Impact of medical approach on the presentation form of AIDS defined by clinical episodes].

BACKGROUND: In recent years there has been a change in the opportunistic diseases incidence in HIV-infected patients. The change could be related to the use antiviral therapy and chemoprophylaxis strategies. The aim of the present study was to evaluate if medical intervention is able to modificate the clinical presentation of AIDS and the CD4+ lymphocyte counts at time of AIDS diagnosis. PATIENTS AND METHODS: The first AIDS-defining condition and the CD4+ count at time of AIDS diagnosis were analyzed in 95 HIV-infected patients who developed an AIDS-defining disease since April 1989 until March 1996, retrospectively reviewed. Patients who had been previously followed at an AIDS Unit were compared with those who had not. RESULTS: The frequency of Pneumocystis carinii pneumonia as the first AIDS-defining condition was lower in medically followed patients. Among this group, AIDS cases who received chemoprophylaxis with isoniazide showed a decrease in the rate of tuberculosis. No differences were found in CD4+ lymphocyte counts between both groups. CONCLUSIONS: As a result of medical intervention significant changes have occurred in the spectrum of initial AIDS-defining conditions in relation to medical intervention; a decrease in the frequency of Pneumocystis carinii pneumonia and tuberculosis have been found; however, the CD4+ lymphocyte counts at time of AIDS diagnosis are not modificated by medical intervention.

AIDS-Related Opportunistic Infections↗

Isolation of the Pichia pastoris PYC1 gene encoding pyruvate carboxylase and identification of a suppressor of the pyc phenotype.

We have cloned and characterized a gene encoding pyruvate carboxylase from the methylotrophic yeast Pichia pastoris. Disruption of this gene produced inability to grow in minimal medium with glucose as carbon source and ammonium as nitrogen source. Growth was possible with aspartate or glutamate as nitrogen source. The gene PpPYC1 expressed from its own promoter was able to rescue the phenotype of Saccharomyces cerevisiae mutants devoid of pyruvate carboxylase. In a P. pastoris strain carrying a disrupted PpPYC1 gene we have isolated spontaneous mutants able to grow in non-permissive conditions. In a mutant strain grown in glucose several enzymes sensitive to catabolite repression were derepressed. The strain also had elevated levels of glutamate dehydrogenase (NAD) both in repressed and derepressed conditions.

Amino Acid Sequence↗

Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease.

The aims of this study were to analyze the mortality directly attributable to chronic viral hepatitis in HIV-1 infected patients and to investigate the influence of hepatitis virus infections on the survival of this population. A cohort of 328 HIV-1 infected, antiretroviral-treated patients, followed up from 1989 to 1996, was investigated in the study. The median follow-up period of the cohort was 120 weeks. The median baseline CD4 + cell count of the cohort was 303 cells/mm3. Hepatitis C virus, hepatitis B virus and hepatitis D virus infections were present in 214 (65%), 16 (4.9%) and 9 (2.7%) patients, respectively. Sixty-seven (20.4%) subjects died but there was no information on the vital status of 36 patients (11%). The causes of mortality were AIDS in 49 (73%), liver failure in 3 (4.5%) and other causes in 15 (22.4%). The cohort was divided into two groups for survival analysis, the groups consisting of persons infected by a hepatitis virus and persons without hepatitis virus infection. There was no difference in survival between the two groups (p = 0.31, log-rank). It is concluded that mortality among HIV-1/hepatitis virus coinfected patients with moderate to severe immunosuppression is mostly due to AIDS, and that the survival of these subjects is not influenced by the presence of hepatitis virus infections, particularly hepatitis C virus.

Adult↗

Cervical cerclage: an alternative for the management of placenta previa?

OBJECTIVE: Our purpose was to determine whether cervical cerclage reduces the maternal and neonatal morbidity in women with placenta previa. STUDY DESIGN: Thirty-nine pregnant women with an initial diagnosis of placenta previa at 24 to 30 weeks' gestation were randomly assigned to cervical cerclage (n = 19) or conservative management (n = 20). Subjects were followed up until delivery. Primary outcome measure was gestational age at delivery. Secondary outcome measures were prolongation of pregnancy, number of patients bleeding after being randomly assigned, units of blood transfused, birth weight, hospital stay and costs, and admission to neonatal intensive care unit. Statistical significance was calculated by the Student t test, Fisher's exact probability test, and the chi2 with Yates' correction factor. RESULTS: No statistically significant differences were observed between the two groups studied. CONCLUSION: Cervical cerclage does not appear to be an adequate alternative for the management of placenta previa.

Adult↗

Flux calculation using metabolic control constraints

Prediction of metabolic fluxes requires the knowledge of reaction stoichiometry and the overall reaction kinetics including various regulatory mechanisms. Lacking the complete reaction kinetics, one often uses available flux measurements or other constraints to calculate the intracellular fluxes. In this article, we show that the flux constraints derived from the dynamic metabolic control theory can be used instead of the kinetics to calculate the fluxes. This approach provides a possibility of predicting the flux distribution in a genetically modified organism using the flux control coefficients and the fluxes determined from the host or the parent strains. It shows that the regulatory constraints can be expressed in terms of the flux control coefficients. This result gives new significance to the flux control coefficients and provides new incentives to determine the flux control coefficients systematically.

Journal Article↗

A microsatellite genetic linkage map for zebrafish (Danio rerio).

We have constructed a zebrafish genetic linkage map consisting of 705 simple sequence-length polymorphism markers (SSLPs). The map covers 2350 centimorgans (cM) of the zebrafish genome with an average resolution of 3.3 cM. It is a complete map in genetic mapping terms (there is one linkage group for each of the 25 chromosomes), and it has been confirmed by somatic-cell hybrids and centromere-mapping using half-tetrad analysis. The markers are highly polymorphic in the zebrafish strains used for genetic crosses and provide a means to compare genetic segregation of developmental mutations between laboratories. These markers will provide an initial infrastructure for the positional cloning of the nearly 600 zebrafish genes identified as crucial to vertebrate development,and will become the anchor for the physical map of the zebrafish genome.

Animals↗