Search PubMed⌕ Search

Biomedical subjects

A Morales

Publications and source records attributed to A Morales.

At least 109 records · Page 6Linked to original sources
PubMed1998

Transcriptional regulation of the heavy subunit chain of gamma-glutamylcysteine synthetase by ionizing radiation.

Since glutathione (GSH) protects against oxidative stress, we determined the regulation of cellular GSH by ionizing radiation in human hepatoblastoma cells, HepG2. The levels of GSH increased in irradiated HepG2 due to a greater gamma-glutamylcysteine synthetase (gamma-GCS) activity, which was paralleled by gamma-GCS heavy subunit chain (gamma-GCS-HS) mRNA levels. Transcription of deletion constructs of the gamma-GCS-HS promoter cloned in a reporter vector was associated with activator protein-1 (AP-1), consistent with the DNA binding of AP-1 in nuclear extracts of irradiated HepG2. Hence, the transcriptional regulation of gamma-GCS by ionizing radiation emerges as an adaptive mechanism, which may be of significance to control the consequences of the oxidative stress induced by radiation.

Gene Expression Regulation, Enzymologic↗
PubMed1998

Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA. METHODS: Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts. RESULTS: Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells. CONCLUSION: Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.

Administration, Oral↗
PubMed1998

Oxidative stress: role of mitochondria and protection by glutathione.

Increasing evidence has unraveled a dual functional role of mitochondria as suppliers of the energy required for cell viability, and critical players in the pathway leading to cell death. Consequence of their physiological role in the oxidative phosphorylation is the generation of reactive oxygen species (ROS) as byproducts of the consumption of molecular oxygen in the electron transport chain. Superoxide anion and hydrogen peroxide produced during aerobic respiration are precursors of hydroxyl radical by the participation of transition metals. Glutathione (GSH) in mitochondria is the only defense available to metabolize hydrogen peroxide. A small fraction of the total cellular pool of GSH is sequestered in mitochondria by the action of a carrier that transports GSH from cytosol to the mitochondrial matrix. Recent evidence position mitochondria as subcellular targets of cytokines leading to overproduction of ROS induced by ceramide, a lipid intermediate of cytokine action. Chronic ethanol-fed cells are selectively depleted of GSH in mitochondria due to a defective operation of the carrier responsible for the transport of GSH from cytosol into the mitochondrial matrix. Its limitation sensitizes alcohol hepatocytes to the prooxidant effects of cytokines and prooxidants generated by the oxidative metabolism of ethanol. One of the mechanisms leading to the onset of selective defect in the mitochondrial transport of GSH induced by chronic ethanol exposure is mediated by decreased fluidity of the mitochondrial inner membrane. Its fluidization by SAM treatment normalizes the steady state levels of GSH in mitochondria contributing to withstand the oxidative stress derived by the oxidative metabolism of ethanol.

Animals↗
PubMed1998

Papillary-cystic neoplasm of the pancreas. A sex-steroid dependent tumor.

CONCLUSION: The rate of growth of a papillary-cystic tumor of the pancreas seemed to be enhanced by the concurrence of pregnancy. Progesterone receptors in the tumor were demonstrated by immunohistochemistry and by molecular biology methods. BACKGROUND: Papillary cystic tumor of the pancreas is extremely rare, occurring predominantly young females. Owing to the low frequency of the tumor, there is scarce information about the conditions that promote tumor growth. METHODS: In this report, we present the temporal association between very rapid growth of a papillary-cystic neoplasm and pregnancy. Clinicopathological, immunohistochemical, and molecular biology analyses were performed. RESULTS: A 21-yr-old woman was admitted because of recurrent epigastric abdominal pain associated with episodes of nausea and vomiting, and a history of an abdominal tumor of about 50 mm near the head of the pancreas, detected by ultrasound. On admission the patient had a flat, nontender abdomen without palpable masses. Laboratory analysis including hematologic and hepatic tests were strictly normal; only CA 19-9 (42 U/mL, normal 37 U/mL) was above normal values. One week after admission, an abdominal computerized axial tomography (CAT) scan revealed an 81.6-mm cystic mass localized in the head of the pancreas, and 1 wk later, in a laparotomy, a papillary-cystic neoplasm of 120 mm, limited to the head of the pancreas, was found. Three months later, in a routine follow-up visit, an 18-wk pregnancy was clinically diagnosed and confirmed by ultrasound exploration. The pregnancy continued without complications, and a normal male infant (3.7 kg) was born at 39 wk of gestation, by vaginal delivery. Eighteen months after tumor resection, the patient was asymptomatic and her child was in good health. We propose that progesterone affects tumor growth.

Adult↗
PubMed1998

Selective glutathione depletion of mitochondria by ethanol sensitizes hepatocytes to tumor necrosis factor.

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha induces cell injury by generating oxidative stress from mitochondria. The purpose of this study was to determine the effect of ethanol on the sensitization of hepatocytes to TNF-alpha. METHODS: Cultured hepatocytes from ethanol-fed (ethanol hepatocytes) or pair-fed (control hepatocytes) rats were exposed to TNF-alpha, and the extent of oxidative stress, gene expression, and viability were evaluated. RESULTS: Ethanol hepatocytes, which develop a selective deficiency of mitochondrial glutathione (mGSH), showed marked susceptibility to TNF-alpha. The susceptibility to TNF-alpha, manifested as necrosis rather than apoptosis, was accompanied by a progressive increase in hydrogen peroxide that correlated inversely with cell survival. Nuclear factor kappaB activation by TNF-alpha was significantly greater in ethanol hepatocytes than in control hepatocytes, an effect paralleled by the expression of cytokine-induced neutrophil chemoattractant. Similar sensitization of normal hepatocytes to TNF-alpha was obtained by depleting the mitochondrial pool of GSH with 3-hydroxyl-4-pentenoate. Restoration of mGSH by S-adenosyl-L-methionine or by GSH-ethyl ester prevented the increased susceptibility of ethanol hepatocytes to TNF-alpha. CONCLUSIONS: These results indicate that mGSH controls the fate of hepatocytes in response to TNF-alpha. Its depletion caused by alcohol consumption amplifies the power of TNF-alpha to generate reactive oxygen species, compromising mitochondrial and cellular functions that culminate in cell death.

Animals↗
PubMed1998

Sertoli cell nuclear pore number changes in some stages of the spermatogenic cycle of the rat seminiferous epithelium.

In an earlier study we described changes in the number and distribution of nuclear pores during maturation of germ cells at given stages of the spermatogenic cycle; these changes were related to the activity of nucleus-cytoplasm transport. Similarly, the present work was performed by combining freeze-fracture techniques with Sertoli nuclei identification criteria, using fragments of tubules isolated by transillumination under stereomicroscopy. We studied the density of nuclear pores in freeze-fracture replicas of the Sertoli nuclear envelope at stages XIII-XIV-I compared with stages IX-XII. Pore counts were carried out on photographs of the platinum replicas using a digitalized morphometric board. The results were statistically analyzed using Student's t test. The difference in density (pore number/micron2 +/- SEM) was significant between stages IX-XII (8.25 +/- 0.63) and XIII-XIV-I (10.80 +/- 0.60). We postulate that this density appears to be increased at the time of increased metabolic requirements of the Sertoli cell.

Animals↗
PubMed1998

Web-based health care agents; the case of reminders and todos, too (R2Do2).

This paper describes efforts to develop and field an agent-based, healthcare middleware framework that securely connects practice rule sets to patient records to anticipate health todo items and to remind and alert users about these items over the web. Reminders and todos, too (R2Do2) is an example of merging data- and document-centric architectures, and of integrating agents into patient-provider collaboration environments. A test of this capability verifies that R2Do2 is progressing toward its two goals: (1) an open standards framework for middleware in the healthcare field; and (2) an implementation of the 'principle of optimality' to derive the best possible health plans for each user. This paper concludes with lessons learned to date.

Artificial Intelligence↗
PubMed1998

Analysis of airborne radon in an ultra-low background experiment.

The contribution of 222Rn to the background in a low background experiment with a germanium detector has been estimated. We have also checked the efficacy of a standard radon cleaning system. The cleaning reduces the radon concentration two orders of magnitude with respect to the air in the laboratory. The residual 222Rn represents at most 12.5% of the background in the low energy region, a value low enough for the purpose of our experiment. A detailed study of the radioactive background is presented.

Air Pollutants, Radioactive↗
PubMed1998

Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction.

Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated in more than 3700 patients (with a total of 1631 years of exposure worldwide). Safety and tolerability data were analysed from a series of double-blind, placebo-controlled studies and from 10 open-label extension studies of sildenafil in the treatment of erectile dysfunction. A total of 4274 patients (2722 sildenafil, 1552 placebo; age range 19-87 y) received double-blind treatment over a period of up to six months' duration, and 2199 received long-term, open-label sildenafil for up to 1 y. The most commonly reported adverse events (all causes) were headache (16% sildenafil, 4% placebo), flushing (10% sildenafil, 1% placebo), and dyspepsia (7% sildenafil, 2% placebo) and they were predominantly transient and mild or moderate in nature. These adverse events reflect the pharmacology of sildenafil as a phosphodiesterase type 5 inhibitor. No cases of priapism were reported. The rate of discontinuation due to adverse events (all causes) was comparable for patients treated with sildenafil (2.5%) and placebo (2.3%). In open-label extension studies, 90% of patients completed long-term sildenafil treatment, with only 2% withdrawing due to adverse events. Sildenafil is a well-tolerated oral treatment for erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Developments in bladder cancer monitoring.

The exclusive reliance on standard urinary cytology and cystoscopy for early diagnosis and monitoring of bladder cancer is now challenged by innovative techniques. A variety of urine tests employing immunostaining promise to enhance the value of cytological examination. Detection of tumor-associated antigens and substances present in the urine of patients harboring bladder cancer has reached a high degree of sophistication. Laboratory-based tests offer the possibility of early prediction of recurrence with a significant degree of accuracy. Equally exciting is the availability of rapid urine tests (point-of-care) that offer better sensitivity and specificity than cytology, deliver immediate results and provide an indication of the degree of tumor differentiation.

Journal Article↗
PubMed1998

[Correlation between myocardial perfusion and coronary angiography].

Determining the severity of coronary heart disease is of great importance to the cardiologist. There is a very good correlation between the severity of coronary heart disease and perfusion abnormalities to the myocardium as determined by radioisotope studies. We present our experience with forty (40) cases of ischemic heart disease diagnosed with sestamibi and its correlation with the obstruction of the coronary arteries by angiography. There is good correlation between the sestamibi findings and the coronary artery angiography obstructions and our findings concur with those published in the literature, which is between 75-85%.

Adult↗
PubMed1998

Technetium-99m-labeled anti-EGF-receptor antibody in patients with tumor of epithelial origin: I. Biodistribution and dosimetry for radioimmunotherapy.

UNLABELLED: Accurate estimation of biodistribution and absorbed dose to normal organs and tumors is important for immunoscintigraphic studies and radioimmunotherapy treatment planning. METHODS: Four patients (3 men, 1 woman; mean age 54.8 +/- 9.2 yr; range 42-64 yr) were administered 3 mg of anti-human epidermal growth factor receptor (anti-hEGF-r) antibody (ior egf/r3), radiolabeled with 99mTc activity of 39.5 +/- 1.1 mCi (range 38.5 mCi-40.7 mCi) by intravenous bolus infusion. After administration, blood and urine samples were collected from three patients up to 24 hr after injection. Whole-body anterior and posterior scans were obtained at 5 min and 1, 3, 5 and 24 hr after injection. Using a computer program, regions of interest were drawn over the heart, liver, spleen, bladder and tumor to measure the activity in the source organs at each scanning time. Time-activity curves for each source organ were then fitted to monoexponential or biexponential functions by nonlinear least squares regression using the flexible polyhedrals method, which adequately fit our data with the correlation coefficient of 0.985 +/- 0.013, and were integrated to determine organ residence times. The mean absorbed doses to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the methods developed by the Medical Internal Radiation Dose Committee. The effective dose equivalent and effective dose were calculated as prescribed in ICRP Publication Nos. 30 and 60. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-hEGF-r antibody were best-fit by a two-compartment model in all patients with a distribution half-life (t(1/2alpha)) of 0.207 hr +/- 0.059 hr (mean +/- s.d., n = 3) and an elimination half-life (t(1/2beta)) of 13.9 hr +/- 2.2 hr. Among the various organs, significant accumulation of the radiolabeled antibody was found in the liver (48.5% +/- 4.4%, mean +/- s.d.), heart (3.50% +/- 0.17%) and spleen (3.1% +/- 1.8%) at 5 min postadministration. These values were reduced to 3.2% +/- 0.4%, 0.1% +/- 0.01% and 0.1% +/- 0.1%, respectively, at 24 hr. Mean cumulative urinary excretion of 99mTc-labeled anti-hEGF-r antibody was 4.6% +/- 0.6% at 24 hr postinjection. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean +/- s.d., n = 4) were: whole body 0.017 +/- 0.002; gallbladder wall 0.074 +/- 0.007; spleen 0.136 +/- 0.076; and liver 0.267 +/- 0.036. The effective dose equivalent and effective dose estimates for adults were 0.041 +/- 0.008 rem/mCi and 0.027 +/- 0.004 rem/mCi administered. CONCLUSION: This feasibility study indicates that 99mTc-labeled anti-hEGF-r antibody (ior egf/r3) can be used safely; this analysis provides a dosimetric framework for future studies. This monoclonal antibody, labeled with 188Re, could possibly permit a successful regional radioimmunotherapy of tumors of epithelial origin.

Adult↗
PubMed1998

Relative efficacy of various exogenous glycosaminoglycans in providing a bladder surface permeability barrier.

PURPOSE: To investigate the relative efficacy of heparin (H), pentosanpolysulfate (PPS) and hyaluronic acid (HA) in preventing the absorption of 14C labeled urea in protamine pretreated bladders compared with saline pretreated control bladders. MATERIALS AND METHODS: Control Group - Rabbit bladders were pretreated with phosphate buffered saline (PBS) followed by instillation of 14C-urea. Radioactivity was determined in blood, bladder and fluid drained from the bladder. Protamine Group - Bladders were pretreated with of PBS followed by protamine sulfate. The bladders were then treated with 14C-urea and radioactivity determined as above. GAG Groups - Bladders were pretreated with saline and protamine as described above followed by instillation of: Group 3A - HA, Group 3B - H and Group 3C - PPS. The bladders were then treated with 14C-urea and radioactivity determined as described above. RESULTS: Protamine treated bladders demonstrated significantly more radioligand uptake in bladder tissue compared with control bladders. There was no significant difference in radioligand uptake in bladders treated with PPS and H compared with control. While not significantly different, there was considerably more radioligand concentration in the blood of rabbits with bladders treated with protamine and protamine-HA compared with those of control rabbits and those treated with protamine-PPS and protamine-H. CONCLUSIONS: Exogenous GAG's are effective in providing an epithelial permeability barrier in protamine pretreated bladders. There is a difference in the relative efficacy of the various GAG's in producing this effect.

Absorption↗
PubMed1998

Physiological changes in the juvenile euryhaline teleost, the tilapia Oreochromis hornorum, injected with E. coli-derived homologous growth hormone.

Growth is a complex process in fish. This study was designed to test the effect of different levels of recombinant tilapia growth hormone (tiGH) injected intraperitoneally in juvenile hybrid tilapia Oreochromis hornorum. Tilapia GH cDNA was cloned from hybrid O. hornorum tilapia. The mature protein was expressed in E. coli under regulation of the phage T7 promoter. The E. coli-derived tiGH was partially purified to 67% purity and, following renaturation, was shown to be biologically active in in vivo and in vitro assays. Recombinant tiGH stimulated extracellular matrix synthesis as shown by 35S-sulfate uptake in ceratobranchial cartilage explants. Zero, 0.1, 0.5 and 2.5 µg tiGH/g body weight (gbw) were injected in tilapia, and the effects on the growth-promoting action, hepatosomatic index (HSI), and mRNA insulin-like growth factor (IGF) induction were measured. A significant increase in the body weight (P < 0.05) and length (P < 0.01) was observed in tilapia receiving 0.5 µg tiGH/gbw. However, tilapia receiving 0.1 and 2.5 µg tiGH/gbw did not show an increase in body weight and length with respect to the control group receiving BSA injections. Binding sites for the recombinant tiGH were identified in the liver. Consistent with its somatotropic actions, the IGF mRNA induction was observed in the groups injected with 0.1 and 0.5 µg tiGH/gbw (P < 0.05). No significant increase in the HSI was detected in the injected groups when compared to the control group. These results demonstrated that the injection of biologically active E. coli-derived tiGH produces physiological changes in juvenile tilapia that ultimately resulted in a growth-promoting action only at a dose of 0.5 µg tiGH/gbw.

Journal Article↗
PubMed1998

[Cholestatic hepatitis associated with piroxicam use. Case report].

Most nonsteroidal antiinflammatory drugs can produce hepatotoxicity. We report a 22 years old female who presented with an acute cholestatic hepatitis after a prolonged period of piroxicam use. Hepatitis was attributed to this drug since all markers for hepatitis virus (A, B, C, E, Epstein Barr, Cytomegalovirus and Herpex Simplex) were negative, autoimmune markers were negative, serum iron and ceruloplasmin were normal, there was a temporal relationship between the administration of piroxicam and the hepatitis, the histological picture was compatible with this etiology and the patient had a favorable evolution after the discontinuance of the drug. This type of hepatotoxicity is not common but it must be born in mind when patients must receive nonsteroidal antiinflammatory drugs for prolonged periods.

Adult↗
PubMed1998

[Late onset epileptic crisis and cerebrovascular disease].

INTRODUCTION: Stroke is the most frequent cause of epilepsy in adults, specially in those over 60 years old. Our aim was to analyze the etiologic relevance of stroke among the different etiologies of late onset seizures and to evaluate the clinical characteristics of the subgroup of patients with late onset seizures associated to stroke. PATIENTS AND METHODS: Patients aged over 20 who were admitted to the Neurology or Neurosurgery departments in our hospital for a first-ever seizure over a period of five years were identified retrospectively. The total number of patients included was 248. RESULTS: The most frequent etiologies were stroke (26.2%), tumors (26.2%), unknown (24.6%) and chronic alcohol intake (18.5%). Stroke was the most frequent etiology in patients over 60 (50%). Five of the 65 patients with stroke related seizures had suffered an intracranial hemorrhage and the rest had ischemic lesions. Seven patients had clinically silent infarctions. Seizures were generalized in 60% of the cases. Nearly in all the patients lesions were placed close to the cortex and mainly in carotid artery territory. CONCLUSIONS: Late onset seizures are due to a lesion in the brain in an important number of cases. Stroke is the most prevalent cause and this prevalence increases with age. A complete diagnostic procedures is warranted in this patients.

Adult↗