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Biomedical subjects

C Gonzalez

Publications and source records attributed to C Gonzalez.

At least 145 records · Page 8Linked to original sources
PubMed1995

Chemical modification of hammerhead ribozymes. Catalytic activity and nuclease resistance.

A systematic study of selectively modified, 36-mer hammerhead ribozymes has resulted in the identification of a generic, catalytically active and nuclease stable ribozyme motif containing 5 ribose residues, 29-30 2'-O-Me nucleotides, 1-2 other 2'-modified nucleotides at positions U4 and U7, and a 3'-3'-linked nucleotide "cap." Eight 2'-modified uridine residues were introduced at positions U4 and U7. From the resulting set of ribozymes, several have almost wild-type catalytic activity and significantly improved stability. Specifically, ribozymes containing 2'-NH2 substitutions at U4 and U7, or 2'-C-allyl substitutions at U4, retain most of their catalytic activity when compared to the all-RNA parent. Their serum half-lives were 5-8 h in a variety of biological fluids, including human serum, while the all-RNA parent ribozyme exhibits a stability half-life of only approximately 0.1 min. The addition of a 3'-3'-linked nucleotide "cap" (inverted T) did not affect catalysis but increased the serum half-lives of these two ribozymes to > 260 h at nanomolar concentrations. This represents an overall increase in stability/activity of 53,000-80,000-fold compared to the all-RNA parent ribozyme.

Animals↗
PubMed1995

Synthesis, deprotection, analysis and purification of RNA and ribozymes.

Improvements in the synthesis, deprotection and purification of oligoribonucleotides are described. These advances allow for reduced synthesis and deprotection times, while improving product yield. Coupling times are reduced by half using 5-ethylthio-1H-tetrazole (S-ethyltetrazole) as the activator. Base and 2'-O-t-butyldimethylsilyl deprotection with methylamine (MA) and anhydrous triethylamine/hydrogen fluoride in N-methylpyrrolidinone (TEA.HF/NMP), respectively, requires a fraction of the time necessitated by current standard methods. In addition, the ease of oligoribonucleotide purification and analysis have been significantly enhanced using anion exchange chromatography. These new methods improve the yield and quality of the oligoribonucleotides synthesized. Hammerhead ribozymes synthesized utilizing the described methods exhibited no diminution in catalytic activity.

Base Sequence↗
PubMed1995

The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

AIDS-Related Opportunistic Infections↗
PubMed1995

Cellular mechanisms of oxygen chemoreception in the carotid body.

The carotid bodies (CB) are arterial chemoreceptors that by sensing changes of arterial PO2, PCO2 and pH can initiate and modify ventilatory and cardiovascular reflexes in order to maintain PO2, PCO2 and pH within physiological levels. It is now generally accepted that the glomus or type I cells of the CB are the transducers of hypoxic stimuli, and relay chemosensory information to the brainstem via neurotransmitter release at synaptic contacts with afferent terminals of the carotid sinus nerve. This article reviews the mechanisms of the O2-sensing process at the cellular level. We consider first the transduction of the hypoxic stimulus, in which most of the experimental evidence currently favors a mechanism involving modulation of the electrical properties of type I cells. The last part of the article deals with the transmission of the stimulus between type I cells and afferent nerve terminals, and we present an overview on the issue of neurotransmission in the CB, summarizing the actions of the main neurotransmitters present in the organ.

Acetylcholine↗
PubMed1995

Fungemia in children infected with the human immunodeficiency virus: new epidemiologic patterns, emerging pathogens, and improved outcome with antifungal therapy.

We characterized 27 episodes of fungemia in 22 children infected with the human immunodeficiency virus (HIV). Fungemia in these patients presented as a community-acquired infection in the setting of outpatient total parenteral nutrition or intravenous antibiotic therapy through a chronically indwelling central venous catheter (CVC). Fungemia developed only in patients with CVCs (P < .001). Non-albicans Candida species, Torulopsis glabrata, Rhodotorula rubra, and Bipolaris spicifera constituted 52% of all causes. Fungemia was detected early, within a median of 2.4 days after the onset of new fever, which permitted prompt administration of amphotericin B (mean dosage, 0.7 mg/[kg.day]; median duration, 19 days). CVCs were removed in 23 (85%) of the episodes. We conclude that fungemia in HIV-infected children often presents as a community-acquired infection, is frequently due to newly emerging opportunistic fungi, and can be managed, with a high level of success (95% survival with no posttherapeutic sequelae), by early diagnosis, prompt initiation of amphotericin B therapy, and removal of the CVC.

Antifungal Agents↗
PubMed1995

Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis.

This study evaluated intravitreous and plasma ganciclovir and foscarnet concentrations after intravenous administration in AIDS patients with cytomegalovirus (CMV) retinitis and retinal detachment. Undiluted vitreous samples were prospectively obtained from 60 eyes (52 patients) at the time of pars plana vitrectomy. Thirty-three plasma samples (from 27 patients in the initial group of 52) were obtained simultaneously during surgery on 33 eyes. High-pressure liquid chromatography showed the mean vitreous ganciclovir concentrations in patients on induction and maintenance therapy were, respectively, 4.74 +/- 1.49 microM (n = 24) and 3.29 +/- 1.84 microM (n = 30; P = .005). Simultaneous plasma ganciclovir concentrations were less than the vitreous concentrations in 78% of the patients. The mean intravitreous foscarnet concentrations in patients receiving induction dosages were 189 +/- 177 microM (n = 5) versus 163 +/- 167 microM (n = 4; P > .20) for those receiving maintenance therapy. The foscarnet vitreous plasma concentration ratio averaged 1.43. Current drugs and doses for CMV retinitis result in borderline or progressively subtherapeutic concentrations.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The use of the Expressed Emotion Index as a predictor of outcome in first admitted schizophrenic patients in a French speaking area of Switzerland.

A 5 year prospective study of 44 first admission schizophrenic patients was conducted in Geneva, in order to evaluate the prognostic value of Expressed Emotion (EE). The predictive power of the EE index was tested on 3 variables of outcome: relapse rates, social adaptation and hospital stays. The EE index and the outcome measures tended to be associated. After the third year, patients living with high EE relatives were significantly more maladjusted and relapsed more than those living with low EE relatives. At intake, the patients presenting more premorbid features lived in high EE households. Our results show that initial measure of EE in a first episode cohort is predictive of outcome over a five-year period. This may not be causal, as it cannot be excluded that poorer premorbid functioning alone may result in poorer outcome, and may also elicit high EE in the relative.

Expressed Emotion↗
PubMed1995

Effects of fluoride and cholera and pertussis toxins on sensory transduction in the carotid body.

The regulation of the chemoreceptor cell function by G proteins has been studied by measuring the release of 3H-labeled catecholamines ([3H]CA) in carotid bodies (CBs) treated with fluoride, cholera toxin (CTX), and pertussis toxin (PTX). Fluoride augmented the basal release of [3H]CA in a dose- (5-20 mM) and Ca(2+)-dependent manner. Nisoldipine (1 microM) and ethylisopropyl amiloride (EIPA; 10 microM) inhibited this effect by approximately 60%, and both drugs combined inhibited it in full. BAY K 8644 (1 microM) doubled the effect of fluoride. The effects of fluoride on the stimulus-evoked release of [3H]CA varied with the type of stimulus and the duration of the treatment. Simultaneous application of fluoride with the stimulus increased by five times the release evoked by hypoxia and by two times that by K+ and dinitrophenol (DNP). Preincubation with fluoride for 1 h caused an inhibition (approximately 70%) of the release evoked by high K+ and veratridine, whereas that evoked by DNP and low PO2 was still augmented (approximately 2 times). Preincubation (4 h) of the CBs with CTX (3 micrograms/ml) reduced by 54% the release of [3H]CA evoked by 35 mM K+ but did not affect that evoked by low PO2 or DNP. A similar treatment with PTX (1 microgram/ml) affected only the release of [3H]CA evoked by DNP, reducing it by 65%. The data show that fluoride, CTX, and PTX have different effects on the release of [3H]CA evoked by high external K+, DNP, and low PO2, indicating that the stimulus-secretion coupling process for each stimulus is differently regulated by G proteins.

Animals↗
PubMed1995

Low birth weight and genital infections. An incident case-referent study.

In an attempt to elucidate the potential association between genital infections and low birth weight (LBW) births, 51 women with LBW neonates were identified and compared to 51 women with normal birthweight (NBW) neonates. Both groups were matched according to age and parity. All women were subjected to interviews regarding socioeconomic background and obstetric history. The were examined clinical and tested regarding serum haemoglobin, malaria parasitaemia, syphilis and HIV serology. Cultures were taken from the vagina, endocervix, amniotic fluid and from various sites of newborn, including the conjunctivae and the stomach and from the interior of the placenta. Whilst socioeconomic background factors did not differ among cases and referents, previous neonatal death did. Significant differences were also found in mid-upper-arm circumference (OR 3.08) and body mass index (OR 6.00). The prevalence of alleged risk factors according to the antenatal card was similar among cases and referents. Birthweight < 2,000 g was significantly more often associated with chorioamnionitis than birthweight between 2,000 and 2,499 g (OR 5.46). Bacteriological findings did not show significant differences in cases and referents. Haemoglobin values and prevalence of malaria parasitaemia were similar as was the neonatal mortality. It is concluded that LBW births is difficult to predict by use of alleged risk factors in existing antenatal cards.

Adolescent↗
PubMed1995

Concordance in diagnosis of diabetic retinopathy by fundus photography between retina specialists and a standardized reading center. Mexico City Diabetes Study Retinopathy Group.

Proper detection and adequate laser therapy of diabetic retinopathy (DR) using guidelines established by landmark studies is important to prevent blindness. We analyzed the agreement between diagnostic classification of DR as determined by certified retina specialists compared with standardized readings of fundus photographs performed by the Fundus Photograph Reading Center (FPRC) of the University of Wisconsin. Color fundus stereophotographs of seven standard fields of each eye of 15 diabetics were sent to FPRC and to 11 retina specialists practicing in Mexico City and representing the major health care institutions. These centers are sites for training programs in ophthalmology. In addition, leading specialists in private practice were invited to participate. Their diagnostic criteria were surveyed. Information was collected using a specially designed form on which the investigator entered his/her diagnostic classification using his/her clinical judgment. Mean overall percent agreement was 74%. Kappa statistic, which corrects for chance agreement, was between 0.29-0.87 with a mean of 0.53. Weighted kappa measuring level of disagreement was between 0.34-0.90, mean 0.57. Data were analyzed separately for macular edema and for this end point the weighted kappa statistic was 0.68. Based on conventional interpretation of the kappa statistic, these mean values are in the range of fair agreement. However, since there is a significant discrepancy in the concordance level observed, there is a need for promoting further applications of internationally accepted diagnostic criteria to assure optimal therapy.

Adult↗
PubMed1995

[Stability and predictive role of emotions, expressed by families in the development of a cohort of schizophrenic patients in the course of 5 years].

A prospective study of 44 first admission schizophrenic patients was conducted in Geneva, in order to evaluate the prognostic value of Expressed Emotion (EE), as well as its stability. The predictive power of the EE index was tested on three variables of outcome: relapse rate, social adaptation and hospital stay. At intake, the patients presenting more premorbid features lived in high EE households. The EE index and the outcome measures tended to be associated. After the third year, patients living with high EE relatives were significantly more maladjusted and relapsed more than those living with low EE relatives. The EE index was stable during the five years. Our results show that initial measure of EE in a first episode cohort is predictive of outcome over a five year period. This may not be causal as it cannot be excluded that poorer premorbid functioning alone may result in poorer outcome, and may also elicit high EE in relative.

Adult↗
PubMed1994

Ear disease in children with cystic fibrosis.

OBJECTIVE: To assess otitis media in children with cystic fibrosis. DESIGN: Prospective prevalence survey. SETTING: Otolaryngology and cystic fibrosis/pulmonology outpatient clinics, Children's Hospital of Pittsburgh (Pa), a regional referral center. PATIENTS: Seventy patients, aged 4 months to 17 years, with documented cystic fibrosis who presented to the cystic fibrosis/pulmonary clinic with scheduled appointments were asked to volunteer for the study. The 70 patients recruited represent approximately one fourth of the children younger than 17 years with cystic fibrosis who were followed up by the cystic fibrosis/pulmonary clinic. INTERVENTION: Ear, nose, and throat examination including pneumatic otoscopy, with tympanometry when indicated; relevant history taking. MAIN OUTCOME MEASURE: Presence or absence of otitis media. RESULTS: Seven (10%) of the 70 patients had unilateral or bilateral otitis media. CONCLUSIONS: Children with cystic fibrosis have a low prevalence of otitis media compared with normal children.

Acute Disease↗