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Biomedical subjects

G Torres

Publications and source records attributed to G Torres.

At least 19 recordsLinked to original sources

[Onset of Behçet's disease as meningoencephalitis and sudden blindness].

CASE REPORT: A 41-year-old man presented a clinical picture characterized by lymphocytic meningoencephalitis, visual loss in both eyes and transverse sinus thrombosis. This picture was treated with prednisone and anticoagulation. Fundus examination showed complete occlusive arteritis, periphlebitis, peripheral ischemia and perfusion macular defects affecting both eyes. The picture was suggestive of Behçet's disease. Azathioprine was added to the treatment without improvement in visual acuity. Four months later oral aphthous ulcers developed, confirming the suspected diagnosis. DISCUSSION: Behçet's disease may appear with the sudden onset of visual loss secondary to massive occlusive retinal vasculitis. The critical state of neuro-Behçet disease may delay the diagnosis. This combination of visual and neurological symptoms is associated with a poor visual prognosis (Arch Soc Esp Oftalmol 2002; 77: 275-278).

Adult↗

HIV-1 reverse transcriptase sequence in plasma and cerebrospinal fluid of patients with AIDS dementia complex treated with Abacavir.

OBJECTIVE: To assess HIV-1 RNA levels and the relationship between HIV-1 reverse transcriptase (RT) genotype from plasma and cerebrospinal fluid (CSF) during treatment with abacavir (Ziagen, ABC) or placebo in combination with stable background therapy (SBG) in subjects with AIDS dementia complex (ADC) (study CNA3001). DESIGN: One-hundred and five HIV-1 infected adults with ADC were randomized to receive either ABC (600 mg twice daily) or ABC-matched placebo (twice daily) in addition to SBG for 12 weeks. METHODS: Plasma and CSF were collected for population sequencing at baseline and week 12 (CSF optional). Sequences were analyzed for mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTI). RESULTS: Sixty out of sixty-seven subjects with baseline plasma HIV-RT sequence data harbored virus with > or = 1 NRTI-associated mutations; 50 out of 67 had the M184V mutation. At week 12, more subjects in the ABC group had plasma HIV-1 RNA < or = 400 copies/ml than the SBG group (46% versus 13%, P = 0.002). Non-response to ABC was associated with multiple baseline zidovudine (ZDV)/stavudine (d4T)-associated mutations. Baseline RT mutation patterns differed in 14 out of 21 (67%) paired samples from plasma and CSF. Four subjects experienced > 1 log10 copies/ml reductions in CSF HIV-1 RNA, two in the absence of reductions in plasma HIV-1 RNA and two with undetectable plasma HIV-1 RNA at baseline. CONCLUSIONS: Substantial decreases in plasma and CSF HIV-1 RNA following addition of ABC were not precluded by baseline HIV-1 NRTI-associated mutations, including the M184V mutation, but non-responders commonly harbored multiple ZDV/d4T-associated mutations. HIV-1 RNA responses and RT genotype appear to be discordant between CSF and plasma in some subjects.

AIDS Dementia Complex↗

Spatial distribution, cellular integration and stage development of Parkin protein in Xenopus brain.

Parkin is an ubiquitin-protein ligase molecule abundantly expressed in mammalian brains. Deletional mutations of Parkin protein produce a disease-related parkinsonian phenotype which is inherited with an autosomal recessive mode of transmission. To gain a greater insight into the evolutionary trajectory of the protein among vertebrate species, we describe here the (i) distribution pattern, (ii) sizing of specific fragments and (iii) embryonic development of Parkin in Xenopus laevis utilizing two antibodies to the N- and C-terminal sequence of the human Parkin protein. Parkin immunoreactivity was distributed in a heterogeneous fashion throughout the adult frog brain. The telencephalon, including the olfactory bulb, striatum and nucleus accumbens, harbored high numbers of Parkin-containing cells. High numbers of immunoreactive neurons were also present in discrete regions of the thalamus and hypothalamus. Relatively moderate expression of Parkin protein was noted in the nucleus anterodorsalis tegmenti, nucleus reticularis medius and torus semicircularis. The substantia nigra exhibited a distinctive heterogeneous pattern of Parkin-immunoreactivity, especially within presumptive dopamine neurons. The cerebellum also showed high expression of Parkin-positive material. Characterization of the subcellular distribution of the protein indicated both a cytoplasmic and nuclear integration of Parkin-immunoreactivity. This pattern of subcellular localization was similar to that observed in human brain material, perhaps reflecting distinct structural phosphorylation sites of the Parkin protein. Western blot analysis identified three specific bands with molecular weights varying from 50 to 65 kDa in adult Xenopus brain. However, studies on the temporal expression of Parkin during development showed a complete absence of cellular immunoreactivity which was especially conspicuous during late premetamorphic stages of frog development. These results suggest that the ubiquitination activity of Parkin is limited or non-existent during embryogenesis, but appears to assume a more functional role during adulthood as reflected by the high distribution pattern of the protein within major circuits of the amphibian brain.

Amino Acid Sequence↗

Immunodetection of Parkin protein in vertebrate and invertebrate brains: a comparative study using specific antibodies.

Parkin is an intracellular protein that plays a significant role in the etiopathogenesis of autosomal recessive juvenile parkinsonism. Using immunoblot methods, we found Parkin isoforms varying from 54 to 58 kDa in rat, mouse, bird, frog and fruit-fly brains. Immunocytochemical studies carried out in rats, mice and birds demonstrated multiple cell types bearing the phenotype for Parkin throughout telencephalic, diencephalic, mesencephalic and metencephalic brain structures. While in some instances Parkin-containing neurons tended to be grouped into clusters, the majority of these labeled nerve cells were widely scattered throughout the neuraxis. The topographical distribution and organizational pattern of Parkin within major functional brain circuits was comparable in both rats and mice. However, the subcellular localization of Parkin was found to vary significantly as a function of antibody reactivity. A consistent cytoplasmic labeling for Parkin was observed in rodent tissue incubated with a polyclonal antibody raised against the human Parkin protein and having an identical amino-acid sequence with that of the rat. In contrast, rodent tissue alternately incubated with a polyclonal antibody raised against a different region of the same human Parkin protein but having 10 mismatched amino-acid sequence changes with those of the rat and mouse, resulted in nuclear labeling for Parkin in rat but not mouse neurons. This difference in epitope recognition, however, was reversed when mouse brain tissue was heated at 80 degrees C, apparently unmasking target epitopes against which the antisera were directed. Collectively, these results show a high degree of conservation in the cellular identity of Parkin in animals as different as drosophilids and mammals and points to the possibility that the biochemical specificities of Parkin, including analogous functional roles, may have been conserved during the course of evolution.

Amino Acid Sequence↗

Expression of the HIV-1 co-receptors CCR5 and CXCR4 on placental macrophages and the effect of IL-10 on their expression.

The chemokine receptors CCR5 and CXCR4 play a key role in HIV-1 infection as co-receptors for viral entry. In the placenta, an important natural barrier to HIV, the expression and regulation of these receptors has yet to be elucidated. In this study, we determined the expression of CCR5 and CXCR4 co-receptors on placental macrophages (PM) and the effect of interleukin-10 (IL-10) on co-receptor expression. PM were isolated from term placentae of HIV-uninfected mothers and cultured for up to 11 days. The cells were stimulated with IL-10 for 24 h and stained with specific antibodies to CCR5, CXCR4, CD4, CD3, CD11c and CD14 for flow cytometry. Unstimulated PM expressed significantly more CCR5 than CXCR4. Expression of both co-receptors was upregulated by stimulation with IL-10 at 24 h post-stimulation. In vivo expression of these co-receptors from frozen sections revealed a higher percentage of CCR5 positive cells. This is the first study in which expression of both co-receptors is detected on the PM membrane. These results are consistent with previous studies performed in our laboratory where PM were readily infected by CCR5-using HIV strains but could not be productively infected by HIV strains that exclusively use CXCR4 as a co-receptor.

Acquired Immunodeficiency Syndrome↗

Is decreased HIV-1 infectivity of placental macrophages caused by high levels of beta-chemokines?

The objective of this study was to determine the effect of beta-chemokine secretion on HIV infection of placental macrophages (HF) as compared to monocyte-derived macrophages (MDM). For this purpose, we measured chemokine production in supematants of LPS stimulated and unstimulated HF and MDM. LPS stimulated cultures produced 3 to 10 times higher levels of MIP-1alpha, MIP-1beta and RANTES than unstimulated cultures. The level of MIP-1beta was the highest of the three chemokines secreted upon stimulation of HF cells. Cell cultures were inoculated with HIV-BaL, a R5 virus, and tested for p24 antigen and chemokine production at days 5 and 10 post-infection (P.I.). We did not find significant differences in the level of chemokines produced by HIV-1-infected and uninfected MDM and HF cells. However, significant differences were found in p24 antigen released by unstimulated and LPS stimulated cells. In contrast to HF cells, MDM cultures showed a significant inhibition of p24 antigen production when cells were stimulated with LPS prior to infection. HF cells were less susceptible to HIV-1 infection than MDM, and chemokines produced by HF cells did not result in further inhibition of HIV-1 infection. We found that in contrast to MDM, decreased susceptibility HF cells to HIV infection is not due to increased levels of chemokines, but to decreased HIV-1 coreceptor expression.

CD4 Antigens↗

The Spectroscopic Orbit of the Planetary Companion Transiting HD 209458.

We report a spectroscopic orbit with period P=3.52433+/-0.00027 days for the planetary companion that transits the solar-type star HD 209458. For the metallicity, mass, and radius of the star, we derive [Fe/H&sqbr0;=0.00+/-0.02, M*=1.1+/-0.1 M middle dot in circle, and R*=1.2+/-0.1 R middle dot in circle. This is based on a new analysis of the iron lines in our HIRES template spectrum and also on the absolute magnitude, effective temperature, and color of the star, and it uses isochrones from four different sets of stellar evolution models. Using these values for the stellar parameters, we reanalyze the transit data and derive an orbital inclination of i=86&fdg;1+/-1&fdg;6. For the planet, we derive a mass of Mp=0.69+/-0.05 MJup, a radius of Rp=1.40+/-0.17 RJup, and a density of rho=0.31+/-0.07 g cm-3.

Journal Article↗

Gene transfer into the central nervous system using herpes simplex virus-1 vectors.

Manipulation of gene expression in developing or in mature central nervous systems (CNS) holds a promise for the resolution of many compelling neurobiological questions, including the feasibility of gene therapy to treat diseases of the brain. In this context, a number of viral vectors have been used in recent years to introduce and express genes into the CNS. This article discusses a gene transfer system based on the Herpes Simplex Virus-1 (HSV-1). We describe here the use of non-replicating, non-toxic HSV-1 vector, 8117/43, in a series of studies carried in our joint program. This vector proves further the utility of HSV-1 as a delivery vehicle to a number of distinct sites within the CNS.

Animals↗

Identification and distribution of Parkin in rat brain.

Mutations within the amino acid sequence of Parkin, the encoded protein of the parkin gene, appear to trigger the degeneration of dopaminergic neurons in the substantia nigra. Here, the presence and anatomical distribution of Parkin within the rat was examined. Immunoblot analysis of tissue homogenates showed two major bands at 50 and 44kDa. Within the brain, Parkin-containing neurons were identified in the basal ganglia, including the substantia nigra and caudate-putamen. Parkin was visualized in the raphe nucleus, which as in the substantia nigra, was closely localized to monoaminergic-encoding neurons. In addition, Parkin was detected in laminar structures such as the cortex and hippocampus; a substantial number of Parkin-immunoreactive neurons was seen in the cerebellum as well. Parkin therefore is widely distributed in brain pathways implicated in the pathology of Parkinson's disease.

Animals↗

[Relationship in cardiovascular reactivity to mental stress and early involvement of target organs in non-treated mild arterial hypertension. Hospitalet Study].

BACKGROUND: It has been previously reported that an exaggerated response of blood pressure to mental stress tasks is associated to an increased cardiovascular risk. The objective of this cross-sectional study, with sequential inclusion of subjects who met the inclusion criteria, was to asses the relationships between the response of blood pressure and heart rate to two different mental stress tasks and early target organ-damage, defined as abnormalities in the echocardiogram and/or an increase of urinary albumin excretion (UAE) or microalbuminuria, in untreated mild hypertensive subjects. SUBJECTS AND METHODS: Two hundred and eleven subjects aged 18 to 65 years (56% males) with mild hypertension (SBP between 140-180 mmHg and/or DBP between 90-105 mmHg) were included in Hospitalet Study. One hundred and thirty seven of them accepted to participate in the study of cardiovascular reactivity. Two different tasks were applied in the same day: a stressful interview (SI) and a mental arithmetic stress tasks (MAST). An echocardiogram of good quality was obtained in 123 cases (89.8%) and 24 h UAE was measured in 108 cases (78.8%). RESULTS: The prevalence of left ventricular hypertrophy was 21.1% (95% CI = 14.3-29.4) and the prevalence of microalbuminuria was 15.7% (95% CI = 9.4-24.4%). After adjusting for the baseline blood pressure, a significant correlation was observed between increase of systolic BP during SI and UAE (r = 0.21; p = 0.03) and between increase of diastolic BP during SI and relative wall thickness (r = 0.32; p < 0.005). When we analyzed the changes of BP during MAST, a significant correlation was observed between increase of diastolic BP (adjusted for baseline diastolic BP) and left atrial size (r = 0.21; p = 0.02). We did not find any significant correlation between the increases of BP (systolic or diastolic) during MAST or increases of heart rate during both tasks and left ventricular mass index or UAE. CONCLUSIONS: A weak correlation was observed between cardiovascular reactivity of blood pressure during mental stress tasks and early target organ damage in mild hypertension. We did not find any relationship between the response to heart rate during the tasks and early target organ damage.

Adult↗

Cocaethylene synthesis in Drosophila.

Cocaethylene is an active cocaine metabolite that targets mammalian neural reward pathways and thus contributes to the reinforcing and addictive properties of ethanol and cocaine. Using gas chromatography-mass spectrometry, we find that fruit flies (Drosophila melanogaster) possess a cellular mechanism through which cocaine can be converted to cocaethylene, presumably via ethanol-sensitive enzymes. These findings illustrate the striking similarity of gene products in humans and flies, which might reflect a homologous role in the metabolic inactivation of cocaine. Further, this conservation of metabolic steps suggests that Drosophila can be used to study cellular, molecular and biochemical processes leading to polydrug abuse and addiction.

Animals↗

Detection of fluoxetine in brain, blood, liver and hair of rats using gas chromatography-mass spectrometry.

This study reports the measurements of fluoxetine in discrete brain regions, blood, liver and hair of male rats injected with 10 mg/kg fluoxetine HCl for 15 consecutive days. Concentrations of the antidepressant were obtained by gas chromatography-mass spectrometry (GC-MS) methodology. In brain, fluoxetine levels were unevenly distributed, with the raphé nucleus containing the highest amounts relative to the hypothalamus or striatum. Fluoxetine was also measured in blood and liver roughly paralleling those ratios described in previous rodent studies. Of potential interest, fluoxetine was found to accumulate in rat hair after chronic treatment. Detection of fluoxetine in hair by GC-MS could be used as a marker for probative analyses.

Animals↗

Behavior and drug measurements in Long-Evans and Sprague-Dawley rats after ethanol-cocaine exposure.

Long-Evans and Sprague-Dawley rats show differential behavioral responses to cocaethylene, a metabolite derived from the simultaneous ingestion of ethanol and cocaine. Such differences may also be manifested when these outbred strains are exposed to ethanol and cocaine. To test this hypothesis, both strains were fed an ethanol-diet (8.7% v/v) in conjunction with cocaine (15 mg/kg) injections for 15 days. The following parameters were evaluated: (a) ethanol consumption, (b) cocaine-induced behavioral activity, (c) blood ethanol levels, (d) blood, liver, or brain cocaine and cocaethylene levels, and (e) liver catalase and esterase activity. We found that Long-Evans rats drank significantly more of the ethanol diet relative to the Sprague-Dawley line during the first few days of the test session. This rat phenotype also differed significantly from the Sprague-Dawley line in terms of behavioral activity after cocaine administration. Blood ethanol levels did not differ between strains. Similarly, we failed to detect strain-dependent differences in blood, liver, or brain cocaine levels as measured by gas chromatography/mass spectrometry. Cocaethylene levels, however, were higher in blood and brain of Long-Evans relative to Sprague-Dawley cohorts. Although the ethanol-cocaine regimen produced a marked suppression of catalase and esterase activity compared with control-fed rats, this suppression was roughly equivalent in both rat phenotypes. These data are discussed in the context of genotypic background and vulnerability to polysubstance abuse.

Animals↗

Splenic vein aneurysm: is it a surgical indication?

Splenic vein aneurysms are rare and are usually caused by portal hypertension. Symptoms are unusual, but may include rupture or abdominal pain. Diagnosis can usually be made either by means of duplex ultrasonography or computed tomography scanning. Treatment varies from noninvasive follow-up to aneurysm excision. We report an expanding splenic vein aneurysm in a young woman with abdominal and back pain and no history of portal hypertension. She was treated with aneurysm excision and splenectomy.

Abdominal Pain↗

Determinants of left ventricular mass in untreated mildly hypertensive subjects: hospitalet study in mild hypertension.

The objectives of this cross-sectional study were to identify the determinants of left ventricular mass in untreated mildly hypertensive subjects at the Hypertension Unit, Department of Internal Medicine, Red Cross Hospital, Hospitalet de Llobregat, Barcelona, Spain. One hundred seventy-one untreated mildly hypertensive subjects, with a mean age of 41.1+/-11.8 years (from 18 to 65 years) were sequentially visited in our Unit; 54% were men. Echocardiographic measurements of good quality were obtained in 142 subjects (83%). Two-dimensional guided M-mode echocardiograms were used and left ventricular mass was estimated according to the Penn convention. Left ventricular mass (LVM) was analyzed as a continuous variable. In the bivariate analysis, the variables that significantly correlated with LVM were patient's height (r = 0.42, P<.0005), weight (r = 0.47, P< or =.0005), heart rate (r = -0.22, P = .01), HDLc (r = -0.30, P = .002), hematocrit (r = -0.28, P = .001), urinary sodium excretion (r = 0.23, P = 0.012), and different measurements from the ambulatory blood pressure profile for 24 h. By means of multiple regression analysis, a maximum of 41.2% of LVM variability could be explained from the factors registered in our study. The final model included age, gender, patient's weight, and diastolic night load from ambulatory blood pressure monitoring. When added to different models, weight and diastolic night load showed a similar strength in predicting left ventricular mass. In untreated patients with mild hypertension, traditional factors such as blood pressure levels explain a maximum of 41.2% of LVM variability. More knowledge is needed about factors that may alter cardiac morphology in the evolution of hypertensive patients.

Adolescent↗

Correlation of parathyroid scanning and anatomy in 261 unselected patients with sporadic primary hyperparathyroidism.

BACKGROUND: Despite abundant literature on parathyroid scanning with technetium 99m-labeled cationic complexes, comprehensive clinical reports that unequivocally correlate scanning findings with the anatomy of parathyroid glands in extensive and homogeneous cohorts of patients are lacking. METHODS: We analyzed the records of patients with sporadic primary hyperparathyroidism who had had a preoperative scan with either 99mTc-labeled sestamibi or 99mTc-labeled tetrofosmin at our institution and who were cured after a bilateral surgical neck exploration procedure. RESULTS: In 261 patients, 710 normal and 347 abnormal glands (1494 +/- 2626 mg), including 15 glands within the mediastinum, were identified. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of scanning were 82%, 98%, 91%, 94%, and 94%, respectively, in 197 patients with uniglandular disease and 53%, 98%, 98%, 60%, and 72%, respectively, in 64 patients with multiglandular disease. False-positive uptakes were encountered in 17 patients (7%), 3 false-positive uptakes being within the mediastinum. If the unilateral approach had been followed, guidance with preoperative scanning would have significantly increased the number of effective unilateral neck exploration procedures (164 patients (63%) vs 78 patients (30%); P < .001). One abnormal gland would also have been neglected in 28 patients (11%). CONCLUSIONS: Preoperative scanning would limit neck exploration procedures in two thirds of patients with sporadic primary hyperparathyroidism but may also increase the risk of failure in the most challenging cases.

Adult↗