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Biomedical subjects

P Gonzalez

Publications and source records attributed to P Gonzalez.

At least 55 records · Page 3Linked to original sources
PubMed1997

A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study.

BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD. METHODS: Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess the safety of the material in this patient population. In addition, as a surrogate marker of efficacy, each subject underwent a variety of exercise tests before and after HBOC-201 was given. RESULTS: All HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS: HBOC-201 was safely administered to patients with SCD who were not in crisis at the time of study. Furthermore, following infusion of the study material, subjects with SCD performed the identical aerobic exercise-induced workload with an increase in heart rate that was significantly less than the increase observed in the subjects who received an infusion of the saline placebo. These safety and surrogate efficacy data support the notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.

Adult↗
PubMed1996

Periventricular leukomalacia: risk factors revisited.

The dramatic improvement in neonatal care during the last decade did not succeed in reducing the incidence of periventricular leukomalacia (PVL), suggesting that prenatal events may be the main target for PVL prevention. The studied cohort included 753 very preterm infants born between 24 and 32 weeks of gestational age, admitted to the intensive care unit and surviving at least 7 days; 69 (9.2%) of these infants had a diagnosis of cystic PVL. The highest PVL frequency was observed among the infants born at 28 weeks of gestation (16%). Inflammatory prenatal events occurring during the last days or weeks before delivery and PVL occurrence are strongly correlated. Indeed, the combination of intra-uterine infection and premature rupture of membranes is associated with a very high risk (22%). Prolongation of pregnancy with tocolysis for more than 24 hours also carries a significant 8% risk of PVL. In contrast, chronic fetal distress of long duration, such as severe intra-uterine growth retardation and pre-eclampsia, is seldom followed by PVL (< 2% risk). Similarly, rapid unexpected deliveries entail a minimal PVL risk (4%). Experimental and epidemiological confirmations of these data would have an influence on the management of both the preterm onset of labour and the premature rupture of membranes.

Female↗
PubMed1996

Analysis of directions, responses, and consequences involving persons with mental retardation in employment and vocational training settings.

Parameters of direction-relevant stimuli (i.e., directness, complexity), types of responses, and consequences occurring in competitive worksites were compared with those in community vocational training sites. Direction sequences initiated by co-workers to 8 individuals with mental retardation were compared to those initiated by school personnel to 8 special education students in community-based vocational training. Results indicated that the majority of directions in either setting were direct/noncomplex; however, more indirect commands occurred in the employment setting. The types of responses to directions were proportionately similar in both groups. Only rarely were consequences contingent upon responses or lack thereof, particularly in the employment setting.

Adolescent↗
PubMed1995

Comparative study of elgodipine and nisoldipine on the contractile responses of various isolated blood vessels.

The effects of elgodipine, a new dihydropyridine derivative, were compared to those of nisoldipine on contractile responses in various isolated artery rings and on mechanical activity in portal vein segments. Arteries used were: rabbit aorta, mesenteric (fifth branch), femoral and basilar, and sheep coronary arteries. Elgodipine and nisoldipine (10(-16)-3 x 10(-6) M) produced a concentration-dependent inhibition of the contractile responses induced by high K+ (80 mM), 5-hydroxytryptamine (10(-5) M) or noradrenaline (10(-6) M or 10(-4) M) in all the arteries studied. The inhibitory effect of elgodipine was greater in mesenteric resistance vessels (IC50 = 8.0 +/- 2.1 x 10(-12) M and 2.0 +/- 0.5 x 10(-13) M for the depression of high K(+)- and agonist-induced contraction, respectively), and in coronary arteries (IC50 = 2.6 +/- 0.3 x 10(-10) M and 9.0 +/- 1.4 x 10(-8) M for the inhibition of high K(+)- and agonist-induced contraction, respectively). In addition, the action of elgodipine in peripheral resistance vessels and in the coronary artery was more prominent than in aorta or femoral arteries, and this tissue selectivity was more apparent for elgodipine than for nisoldipine. In rat portal vein elgodipine (IC50 = 6.5 +/- 0.9 x 10(-8) M) and nisoldipine (IC50 = 8.5 +/- 1.3 x 10(-8) M) reduced in a concentration-dependent manner the development of mechanical activity. Furthermore, contractile responses produced by the addition of Ca2+ (1-5 mM) to Ca(2+)-free high K+ solution were also concentration dependently inhibited by elgodipine. However, elgodipine did not modify noradrenaline-induced contractions attributed to intracellular Ca2+ release. The results of this study indicate that elgodipine has potent vasodilator properties and vascular selectivity. The mechanisms through which elgodipine relaxes vascular smooth fibres seem to be related to its ability to inhibit the entry of extracellular Ca2+ into the cell.

Animals↗
PubMed1995

N-acetylcysteine diminishes injury induced by balloon angioplasty of the carotid artery in rabbits.

The effect of N-acetylcysteine (NAC) on preventing or ameliorating the injury associated with percutaneous transluminal angioplasty was investigated in rabbits. Carotid artery angioplasty (CA) was performed on 8 control (vehicle-treated) rabbits and 7 rabbits treated with NAC, 250 mg/kg, administered orally in Nutrical paste for 10 days prior to and 10 days following CA. Single blind histologic evaluation of the angioplasty sites demonstrated a significant reduction in the incidence in vessel: 1) inflammation; 2) endothelial damage; 3) thrombus formation; 4) elastic lamina damage in the NAC rabbits. The percentage of control versus NAC treated animals exhibiting damage in each category were: inflammation: 75% vs 14%; endothelial damage: 88% vs 57%; thrombus formation: 88% vs 43%; laminal damage: 63% vs 14%. The results suggest that NAC treatment may be a valuable therapeutic agent in effectively preventing or reducing angioplasty-induced vessel damage.

Acetylcysteine↗
PubMed1995

Glyceraldehyde 3-phosphate dehydrogenase is an enzyme-crystallin in diurnal geckos of the genus Phelsuma.

Lenses from diurnal geckos, Phelsuma barbouri, Phelsuma madagascariensis grandis and Phelsuma serraticauda contain a prominent 37 kDa polypeptide (pi-crystallin) that is not present in lenses from the nocturnal geckos, Gekko gekko, Hemidactylus garnoti, Tarentola annularis, and Uroplatus henkeli. This protein was partially purified from P. serraticauda and was identified as glyceraldehyde 3-phosphate dehydrogenase (GAPD). The GAPDs, which constitute 14-24% of the lens soluble protein in the diurnal species, were highly active. The presence of this enzyme in the lenses of diurnal, but not nocturnal, geckos supports the hypothesis that the oxido-reductases found as enzyme-crystallins may function in providing protection against the increased oxidative stress to which diurnal species are exposed. These findings strongly support the concept that the recruitment of enzyme-crystallins is a selective response to changes in the visual environment.

Amino Acid Sequence↗
PubMed1995

The use of progestins for programming assisted reproductive cycles and gonadotropin-releasing hormone agonist flare-up protocols in older patients.

OBJECTIVES: To determine if the use of norethisterone acetate (NET) in the previous cycle affects the ovarian response to GnRH agonist (GnRH-a) in flare-up protocols and controlled ovarian hyperstimulation in older patients. DESIGN: Retrospective analysis of the outcome of the assisted reproductive technology (ART) cycle. PATIENTS: Eighty women > 37 years old undergoing controlled ovarian hyperstimulation (COH) for a ART cycle (GIFT, IVF, zygote intrafallopian transfer). Forty received NET during the luteal phase of the previous cycle for programming the procedure and 40 did not receive NET (control group). Gonadotropin-releasing hormone agonist in follicular phase (flare-up) protocols were administered to all the patients. MAIN OUTCOME MEASURES: Cycle outcome: amount of gonadotropins used, oocyte production and quality, fertilization, and pregnancy rates. Estradiol, FSH, and LH levels the first 3 days of COH in eight patients. RESULTS: There were no differences between both groups in the cycle outcome. Estradiol levels during the first 3 days of COH were higher in the patients that did not receive NET in the previous cycle. Follicle-stimulating hormone and LH levels were similar in both groups. CONCLUSIONS: The administration of NET in the previous cycle in patients > 37 years old does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins for COH.

Adult↗
PubMed1995

Evidence for independent recruitment of zeta-crystallin/quinone reductase (CRYZ) as a crystallin in camelids and hystricomorph rodents.

Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase expressed at very high levels in the lenses of two groups of mammals: camelids and some hystricomorph rodents. It is also expressed at very low levels in all other species tested. Comparative analysis of the mechanisms mediating the high expression of this enzyme/crystallin in the lens of the Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided evidence for independent recruitment of this enzyme as a lens crystallin in both species and allowed us to elucidate for the first time the mechanism of lens recruitment of an enzyme-crystallin. The data presented here show that in both species such recruitment most likely occurred through the generation of new lens promoters from nonfunctional intron sequences by the accumulation of point mutations and/or small deletions and insertions. These results further support the idea that recruitment of CRYZ resulted from an adaptive process in which the high expression of CRYZ in the lens provides some selective advantage rather than from a purely neutral evolutionary process.

Amino Acid Sequence↗
PubMed1994

Assignment of the zeta-crystallin gene (CRYZ) to human chromosome 1p22-p31 and identification of restriction fragment length polymorphisms.

zeta-Crystallin is a lens protein that has been associated with autosomal dominant congenital cataracts in guinea pigs and thus is a candidate for human congenital cataracts. We have assigned the zeta-crystallin gene (CRYZ) to human chromosome 1 using a Southern panel of 17 human-mouse somatic cell hybrids and regionally localized it to 1p22-p31 by fluorescence in situ hybridization. Five restriction fragment length polymorphisms were identified by analyzing the DNA from 10 unrelated, unaffected individuals. Our results will permit evaluation of its role in human cataractogenesis.

Alleles↗
PubMed1994

Organization of the human zeta-crystallin/quinone reductase gene (CRYZ).

zeta-Crystallin is a protein highly expressed in the lens of guinea pigs and camels, where it comprises about 10% of the total soluble protein. It has recently been characterized as a novel quinone oxidoreductase present in a variety of mammalian tissues. We report here the isolation and characterization of the human zeta-crystallin gene (CRYZ) and its processed pseudogene. The functional gene is composed of nine exons and spans about 20 kb. The 5'-flanking region of the gene is rich in G and C (58%) and lacks TATA and CAAT boxes. Previous analysis of the guinea pig gene revealed the presence of two different promoters, one responsible for the high lens-specific expression and the other for expression at the enzymatic level in numerous tissues. Comparative analysis with the guinea pig gene shows that a region of approximately 2.5 kb that includes the promoter responsible for the high expression in the lens in guinea pig is not present in the human gene.

Amino Acid Sequence↗
PubMed1994

Zeta-crystallin: a lens-specific promoter and the gene recruitment of an enzyme as a crystallin.

A novel enzyme with quinone oxidoreductase activity has undergone gene recruitment in certain mammals, acquiring a second function as the lens structural protein zeta-crystallin. Here we show that recruitment of this enzyme crystallin can be explained by the lens specificity of an alternative promoter which does not require host-specific factors. The strong lens preference of this promoter is apparent in both cultured cell transfections and in transgenic mice. While proximal regions of the promoter have some activity in the brain of transgenic mice this is abolished by the addition of more distal regions. The minimal active promoter is differentially footprinted by extracts from lens and non-lens cells. Deletion within the major region footprinted in lens, ZPE (zeta protected element), abolishes promoter function. This is the first example of a lens-specific promoter in an enzyme crystallin gene and the first demonstration of gene recruitment by this mechanism.

Animals↗
PubMed1994

The effects of experimental fasciolosis on bilirubin metabolism in the rat.

The effects of subclinical fasciolosis at various stages of its development on bilirubin metabolism were investigated in rats. Studies were carried out at 3 (initial lesions), 6 (parenchymal degeneration), and 11 weeks (biliary localization of the parasite) after infection with an oral dose of 20 metacercariae of Fasciola hepatica. Both bile flow and bile acid secretion were significantly reduced by Weeks 3 and 6 postinfection, while a significantly increased bile flow was found in the 11-week group. Serum concentration of unconjugated bilirubin was elevated at 3-6 weeks postinfection and that of conjugated bilirubin and the esterified/total bilirubin ratio increased in all infected rats. Biliary excretion of bilirubin mono- and diconjugates was maximally increased by 3-6 weeks, remaining elevated at 11 weeks. No significant change in the biliary diconjugate/monoconjugate ratio was found in any of the groups. UDP-glucuronosyltransferase activity was reduced by Weeks 3 and 6. This was accompanied by a significantly lowered liver cytochrome P450 concentration and an elevation in hepatic heme oxygenase activity. Blood hemoglobin concentration was significantly reduced and reticulocyte count increased by 6 and 11 weeks. Our results indicate that enhanced bilirubin production, cholestasis, and a reduced conjugating activity could be responsible for the changes in plasma and bile pigment composition during the acute stage of fasciolosis. Hemolysis and a high bilirubin excretion are maintained when the parasite migrates into the biliary ducts.

Animals↗
PubMed1994

Case-finding of pulmonary tuberculosis on admission to a penitentiary centre.

SETTING: The prison population is considered to be at high risk of tuberculosis infection and illness. Therefore, a tuberculosis prevention and control program was put into effect upon the opening of a penitentiary center in Barcelona whose inmates suffered a high prevalence of intravenous drug use (IVDU) (48.4%) and HIV-1 infection (36.0%). OBJECTIVE: To ascertain the prevalence of tuberculosis infection and pulmonary tuberculosis detected on admission to jail among those prisoners who had no history of tuberculosis; and to study as predictors of tuberculosis infection and illness the variables age, IVDU and HIV-1 infection. DESIGN: Cross-sectional study. RESULTS: Of the 729 prisoners studied, 56.2% were considered infected with Mycobacterium tuberculosis. Age was the only variable associated with the infection, with an Odds Ratio (OR) of 1.017 per year (Confidence Interval [CI] 95% = 1.006-1.029) (P = 0.004). The rates of HIV-1 and M. tuberculosis co-infection, which may run between 18.9% and 21.7%, reached 42.8% in the IVDU. A 2.7% prevalence of pulmonary tuberculosis was observed. The most accurate logistic regression model for pulmonary tuberculosis diagnosis (P = 0.09) includes the variables tuberculosis infection (OR = 13.00; CI 95% = 1.7-98), IVDU (OR = 2.60; CI 95% = 0.66-7.81) and age (OR = 1.05; CI 95% = 0.99-1.11). CONCLUSION: Given the high prevalences observed, we propose the activation and maintenance of programs designed to seek out and identify cases of M. tuberculosis infection and illness within the prison population.

AIDS-Related Opportunistic Infections↗
PubMed1994

Protective effect of S-adenosyl-l-methionine on liver damage induced by biliary obstruction in rats: a histological, ultrastructural and biochemical approach.

In human and experimental CCl4-liver damage, S-adenosyl-l-methionine-synthetase and/or the intrahepatic content of S-adenosyl-l-methionine, are diminished and in human cirrhosis phospholipid methyltransferase is markedly reduced. Therefore the aim of this study was to investigate the effect of S-adenosyl-l-methionine administration on liver damage induced by 15-day bile duct ligation. Liver damage was analyzed by histological, ultrastructural and biochemical techniques. Biliary obstruction produced an increase in collagen content, dilation of the bile canaliculi and disorganization of mitochondria. These effects were not observed in the bile-duct-ligated group receiving S-adenosyl-l-methionine. Biochemical results showed that bile duct ligation increased serum bilirubins, and alkaline phosphatase and gamma-glutamyl transpeptidase activities. These effects were prevented significantly by S-adenosyl-l-methionine. On the other hand, glycogen content in the liver was depleted while lipid peroxidation was increased by biliary obstruction, S-adenosyl-l-methionine administration prevented these effects. In the bile-duct-ligated group, hepatocyte and erythrocyte plasma membrane Na+/K+ and Ca(2+)-ATPase were lower than in the control group (p < 0.05). Administration of S-adenosyl-l-methionine preserved ATPase activities. The exogenous S-adenosyl-l-methionine supply is probably responsible for restoring transmethylation lost in liver diseases.

Analysis of Variance↗
PubMed1994

Environmental risk factors for acquisition of Mycobacterium avium complex in persons with human immunodeficiency virus infection.

A case-control study was done to determine risk factors for Mycobacterium avium complex (MAC) disease in persons infected with human immunodeficiency virus (HIV) with < 50 CD4+ cells/mm3. In univariate analysis, cases (n = 83) had lower CD4+ cell counts than controls (n = 177) (median, 10 vs. 17/mm3; P < .001) and were more likely to have consumed hard cheese (odds ratio [OR], 5.44; 95% confidence interval [CI], 1.61-18.4) but were less likely to have taken daily showers (OR, 0.55; 95% CI, 0.33-0.94). In multivariate analysis, CD4+ cell count < 25/mm3 (OR, 3.58; 95% CI, 1.71-7.49) and consumption of hard cheese (OR, 5.63; 95% CI, 1.58-20.1) remained associated with disease, while daily showering (OR, 0.58; 95% CI, 0.28-0.88) remained protective. Increased risk for MAC disease in persons with HIV infection and low CD4+ cell counts is not associated with exposure to water or a variety of other environmental sources but may be associated with consumption of hard cheese.

AIDS-Related Opportunistic Infections↗
PubMed1994

Comparative analysis of the zeta-crystallin/quinone reductase gene in guinea pig and mouse.

zeta-Crystallin is a novel nicotinamide adenine dinucleotide phosphate:quinone reductase, present at enzymatic levels in various tissues of different species, which is highly expressed in the lens of some hystricomorph rodents and camelids. We report here the complementary DNA (cDNA) cloning of zeta-crystallin from liver libraries in guinea pig (Cavia porcellus), where zeta-crystallin is highly expressed in the lens, and in the laboratory mouse (Mus musculus), where expression in the lens occurs only at enzymatic levels. A 5' untranslated sequence different from the one previously reported for the guinea pig lens cDNA was found in these clones. We also report the isolation of genomic clones including the complete guinea pig zeta-crystallin gene and the 5' region of this gene in mouse. These results show the presence of two promoters in the guinea pig zeta-crystallin gene, one responsible for expression at enzymatic levels and the other responsible for the high expression in the lens. The guinea pig lens promoter is not present in the mouse gene. This is the first example in which the recruitment of an enzyme as a lens crystallin can be explained by the acquisition of an alternative lens-specific promoter.

Amino Acid Sequence↗