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Biomedical subjects

J Torres

Publications and source records attributed to J Torres.

At least 73 records · Page 4Linked to original sources

In vitro and in vivo characterization of conantokin-R, a selective NMDA receptor antagonist isolated from the venom of the fish-hunting snail Conus radiatus.

The purification, characterization, and synthesis of conantokin-R (Con-R), an N-methyl-D-aspartate (NMDA) receptor peptide antagonist from the venom of Conus radiatus, are described. With the use of well defined animal seizure models, Con-R was found to possess an anticonvulsant profile superior to that of ifenprodil and dizocilpine (MK-801). With voltage-clamp recording of Xenopus oocytes expressing heteromeric NMDA receptors from cloned NR1 and NR2 subunit RNAs, Con-R exhibited the following order of preference for NR2 subunits: NR2B approximately NR2A > NR2C >> NR2D. Con-R was without effect on oocytes expressing the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR1 or the kainate receptor subunit GluR6. In mouse cortical neurons voltage-clamped at -60 mV, Con-R application produced a slowly developing block of inward currents evoked by 10 microM NMDA and 1 microM glycine (IC(50) = 350 nM). At 3 microM, Con-R did not affect gamma-aminobutyric acid- or kainate-evoked currents. Con-R prevented sound-induced tonic extension seizures in the Frings audiogenic seizure-susceptible mice at i.c.v. doses below toxic levels. It was also effective at nontoxic doses in CF#1 mice against tonic extension seizures induced by threshold (15 mA) and maximal (50 mA) stimulation, and it partially blocked clonic seizures induced by s.c. pentylenetetrazol. In contrast, MK-801 and ifenprodil were effective only at doses approaching (audiogenic seizures) or exceeding (electrical and pentylenetetrazol seizures) those required to produce significant behavioral impairment. These results indicate that the subtype selectivity and other properties of Con-R afford a distinct advantage over the noncompetitive NMDA antagonists MK-801 and ifenprodil. Con-R is a useful new pharmacological agent for differentiation between the anticonvulsant and toxic effects of NMDA antagonists.

Animals↗

Ultrastructural study of spermiogenesis and the spermatozoon in Catenotaenia pusilla, an intestinal parasite of Mus musculus.

The ultrastructure of spermiogenesis and the mature spermatozoon in Catenotaenia pusilla (Cestoda: Catenotaeniidae) is described. Spermiogenesis is characterized by the presence of a single axoneme which grows on the outside of a cytoplasmic extension at an angle of 45 degrees. Flagellar rotation and proximodistal fusion are produced in this process. The centrioles lack striated roots and an intercentriolar body. In the mature spermatozoon four different regions are described. The anterior extremity is capped by an apical cone and presents two helical crest-like bodies of unequal length. The axoneme, of the 9 + '1' pattern of the Trepaxonemata, presents a periaxonemal sheath. The cortical microtubules form a spiral pattern at an angle of about 40 degrees to the hypothetical spermatozoon axis. The nucleus is kidney- to horseshoe-shaped in cross section. Granules and proteinaceus walls are not observed in the spermatozoon of C. pusilla.

Animals↗

[Prevalence of hereditary hemochromatosis among healthy workers. Diagnostic value of transferrin saturation assay].

AIM: Hereditary hemochromatosis is the most common inherited disorder in white population (2-8 cases per 1000 habitants). Hemochromatosis is characterized by increased intestinal absorption of iron leading to its deposition into multiple organs. An early diagnosis and proper management with frequent phlebotomies are known to improve life expectancy and quality of life. Diagnosis is suggested by an elevated Transferrin saturation (TS) (more than 60%). METHOD: Prospective study of the level of TS among 1131 healthy workers, who came to the Security and Hygiene Official Centre for their annual revision had been undertaken. RESULTS: Twenty-wo workers had high TS; in 10 of them the increase of TS was confirmed on repeated determinations. Liver biopsy was performed in six (and refused by the other four), eventually a diagnosis of hemochromatosis was confirmed in three (in-group prevalence of 2.6 per 1000 people). CONCLUSIONS: In our experience, TS is the most appropriate initial screening test for detecting hereditary hemochromatosis in a normal population.

Adult↗

A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase.

Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue, located within the KIM. Upon phosphorylation of Ser(231), PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal-regulated kinase (ERK)1/2 and p38alpha were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases.

Amino Acid Motifs↗

The electron paramagnetic resonance characterisation of a copper-containing extracellular peroxidase from Thermomonospora fusca BD25.

The actinomycete Thermomonospora fusca BD25 contains a peroxidase with a high activity over a broad range of temperature and pH and a high stability against denaturing agents. Unusually this peroxidase (PO) is a non-haem enzyme. As prepared PO is characterised by two electron paramagnetic resonance (EPR) signals, detected at liquid helium temperature, a free radical signal (g=2.0045) and a broad signal at g=2.056. The peroxidase activity of the purified enzyme was assayed using H(2)O(2) and 2,4-dichlorophenol (DCP). The intensity of the free radical EPR signal correlated with the peroxidase activity in a variety of enzyme preparations. Furthermore, when DCP and H(2)O(2) were added to PO a significant increase of both the free radical signal and the broad signal at g=2.056 was observed. We associate the increase of the broad signal with the oxidation of the preparation since a similar increase can be achieved by the addition of ferricyanide. The high intensity of the broad signal in the ferricyanide treated PO allowed us to deconvolute the signal into several components using the difference in their relaxation characteristics: two distinct copper signals were detected, one of which was similar to a type 2 centre. Furthermore a symmetrical singlet was detected at g=2.059, consistent with the presence of an iron complex with a high degree of symmetry and weakly coordinated ligands.

Actinomycetales↗

Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides substrate specificity and retains ERK2 in the cytoplasm.

ERK1 and ERK2 associate with the tyrosine phosphatase PTP-SL through a kinase interaction motif (KIM) located in the juxtamembrane region of PTP-SL. A glutathione S-transferase (GST)-PTP-SL fusion protein containing the KIM associated with ERK1 and ERK2 as well as with p38/HOG, but not with the related JNK1 kinase or with protein kinase A or C. Accordingly, ERK2 showed in vitro substrate specificity to phosphorylate GST-PTP-SL in comparison with GST-c-Jun. Furthermore, tyrosine dephosphorylation of ERK2 by the PTP-SLDeltaKIM mutant was impaired. The in vitro association of ERK1/2 with GST-PTP-SL was highly stable; however, low concentrations of nucleotides partially dissociated the ERK1/2.PTP-SL complex. Partial deletions of the KIM abrogated the association of PTP-SL with ERK1/2, indicating that KIM integrity is required for interaction. Amino acid substitution analysis revealed that Arg and Leu residues within the KIM are essential for the interaction and suggested a regulatory role for Ser(231). Finally, coexpression of PTP-SL and ERK2 in COS-7 cells resulted in the retention of ERK2 in the cytoplasm in a KIM-dependent manner. Our results demonstrate that the noncatalytic region of PTP-SL associates with mitogen-activated protein kinases with high affinity and specificity, providing a mechanism for substrate specificity, and suggest a role for PTP-SL in the regulation of mitogen-activated protein kinase translocation to the nucleus upon activation.

Amino Acid Sequence↗

The reactions of copper proteins with nitric oxide.

Nitric oxide (NO) can act as a ligand for copper atoms and may also engage in redox chemistry with the metal once bound. Furthermore NO posses an unpaired electron which can couple with the unpaired electron on Cu2+. These properties have been exploited to probe the active sites of copper-containing enzymes and proteins. We review these studies. In addition to the use as a spectroscopic probe for the active site we draw attention to the rapid reactions of NO at the copper sites in Cytochrome c oxidase (CcO) and laccase. These reactions in CcO occur in the ms time range, at low NO concentrations and in the presence of oxygen and may therefore be of physiological relevance to the control of respiration. Finally we speculate on the wider role that NO may play in regulation of an important group of Type 2 copper containing enzymes.

Catalysis↗

Quantifying excess length of postoperative stay attributable to infections: a comparison of methods.

To quantify the net effect of deep surgical site infection (DSSI) on postoperative stay (POS) among patients who had undergone open heart surgery, and to assess the comparability of two methods, two observational studies were conducted: one on a retrospective cohort of 701 operated patients, and the other on a cohort of 31 infected patients versus a cohort of uninfected patients, with 1:1 matching. In addition to DSSI, a further three factors were identified by multivariate analysis as independent POS-related predictor variables. After internal validation of the multivariate model, excess POS attributable to DSSI amounted to 20.7 days (95% confidence interval [CI] 16.7-24.9). In contrast, excess length of stay attributable to DSSI among the matched pairs who survived infection (22) totaled 14.3 days (95% CI 3.2-25.4) and 26.5 days (mean and median differences). Multivariate techniques may prove a more appropriate and reliable analysis than matched-pair comparisons for the purpose of evaluating the extra stay and cost attributable to the nosocomial infections.

Adolescent↗

The Cryptosporidium "mouse" genotype is conserved across geographic areas.

A 298-bp region of the Cryptosporidium parvum 18S rRNA gene and a 390-bp region of the acetyl coenzyme A synthetase gene were sequenced for a range of Cryptosporidium isolates from wild house mice (Mus domesticus), a bat (Myotus adversus), and cattle from different geographical areas. Previous research has identified a distinct genotype, referred to as the "mouse"-derived Cryptosporidium genotype, common to isolates from Australian mice. Comparison of a wider range of Australian mouse isolates with United Kingdom and Spanish isolates from mice and cattle and also an Australian bat-derived Cryptosporidium isolate revealed that the "mouse" genotype is conserved across geographic areas. Mice are also susceptible to infection with the "cattle" Cryptosporidium genotype, which has important implications for their role as reservoirs of infection for humans and domestic animals.

Acetate-CoA Ligase↗

Neural networks for the biochemical prediction of bone mass loss.

Neural networks are specialized artificial intelligence techniques that have shown high efficiency in dealing with complex problems. Paradigms such as backpropagation have been successfully applied in a number of biomedical applications, but not in attempts to identify women at risk of postmenopausal osteoporotic complications. In this paper, several neural networks were trained using different combinations of biochemical variables as inputs. Bone densitometric measurements in Ward's triangle and in the spinal column were used as separate classification criteria (outputs) between slow and fast bone mass losers. The most parsimonious model with the best performance included plasma concentrations of estrone, estradiol, osteocalcin, parathyrin and urine concentrations of calcium and hydroxyproline (expressed as ratio to creatinine excretion) as input neurons; ten neurons in a single hidden layer; and one neuron in the output layer. Diagnostic efficiency was 76% in Ward's triangle and 74% in the spinal column; sensitivity was 70 and 81%, and specificity was 77 and 65%, respectively. Linear discriminant analysis showed a diagnostic efficiency of 66% in Ward's triangle and 64% in the spinal column, sensitivity was 55 and 86%, and specificity was 75 and 13%, respectively. We conclude that performance of the stepwise discriminant analysis was not superior to the neural networks.

Adult↗

Serologic IgG response to urease in Helicobacter pylori-infected persons from Mexico.

Helicobacter pylori urease is required to counteract acidity during colonization of the stomach, and has been suggested as a major immunodominant antigen. The aim of this study was to determine the anti-urease response in a representative national serologic survey in Mexico. The population surveyed included persons 1-90 years of age from all socioeconomic levels and geographic zones of the country. Helicobacter pylori status was determined by ELISA serology. The IgG anti-urease was studied by ELISA using a recombinant apoenzyme. We found that 2,930 of the 7,720 infected patients (38%) were seropositive for IgG urease. The rate of IgG anti-urease positivity increased with age; in children < 10 years old it was < 20% and in persons > 40 years old it was > 50%. Age and a region with a high level of development were risk factors for seropositivity, whereas gender, educational level, crowding, and socioeconomic level were not associated with seropositivity. In conclusion, in natural infection with H. pylori, the response to urease is poor, mainly during the first years of infection. This inconsistent immune response to the enzyme may favor persistence of infection. A vaccine eliciting a consistent anti-urease response might overcome immune evasion and enhance clearance of bacteria after exposure.

Adolescent↗

[The prognostic value of dobutamine echocardiography after an uncomplicated acute myocardial infarct].

BACKGROUND AND PURPOSE: The identification of patients at risk for future events after an infarction is mandatory. The aim of this study was to assess the prognostic value of dobutamine stress echocardiography after an uncomplicated myocardial infarction. METHODS: One hundred and twenty five patients (mean age 65 +/- 11 years, males 82%) underwent dobutamine-echo within ten days after an uncomplicated myocardial infarction. Four myocardial responses were identified: a) negative; b) sustained improvement of myocardial contractility; c) initial improvement followed by worsening, and d) worsening at a distance or in the infarcted zone. RESULTS: Mean follow-up was 7.4 +/- 4.6 months. An adverse outcome occurred in 47 patients: non cardiac death in 3, cardiac death in 6, myocardial infarction in 5, angina in 21, congestive heart failure in 2, and in 10 patients revascularization. Cox regression analysis showed that worsening of contractility was the best predictor for adverse events (p < 0.0001, relative risk 2.8; 95% confidence interval: 1.7-4.5). Non-smoking and previous angina were also predictors of adverse events (p = 0.003 and p = 0.04, respectively). Similar results were obtained after excluding the revascularized patients. CONCLUSIONS: Sustained improvement of contractility in the infarcted region is not a predictor of adverse events. Asynergy at a distance or in the infarcted region during dobutamine echocardiography within ten days after an uncomplicated myocardial infarction predicts adverse cardiac events during follow-up. Therefore, dobutamine echocardiography could be used for risk stratification after acute myocardial infarction.

Aged↗

[Chronic exposure to environmental lead in Chilean infants. II: Effects on the psychomotor development].

BACKGROUND: Lactating children are specially susceptible to lead toxicity due to their underdeveloped nervous system, lower body mass, higher intestinal absorption and lower elimination rates. AIM: To determine the effects of lead exposure, comparing Chilean lactating children residing in rural areas with low lead exposure, and in urban areas with high lead exposure. MATERIAL AND METHODS: Newborns from public maternity hospitals of the rural locality of San Felipe and from Metropolitan Santiago, were recruited for the study. On admission to the study, umbilical cord and maternal blood samples were obtained and an inquiry about perinatal, sociohereditary and lead exposure history was done. Children were followed every 6 months until 24 months of age, measuring blood parameters and neurobehavioral development using Bayley scales. RESULTS: Three hundred twelve children from Santiago and 113 from San Felipe were studied. Maternal and children blood lead levels were higher in Santiago, but lower than those reported in other international studies. At 24 months of age, 4.5% of children from Santiago and 0.7% of children from San Felipe had levels over 10 micrograms/dl. No differences in neurobehavioral development were observed between children of both cities. At 24 months, scores of MDI scales were 91 in Santiago and 97 in San Felipe. The figures for PDI scale were 93 in Santiago and 93 in San Felipe. Main risk factors for a retarded neurobehavioral development were socieconomic level with a mean Odds ratio of 3.5 (0.99-12.4), made sex with an Odds ratio of 2.3 (1.09-5.07) and stimulation at home with an Odds ratio of 0.7 (0.53-0.82). CONCLUSIONS: In this cohort of children, no effect of lead levels on neurobehavioral development was found.

Analysis of Variance↗

[Amiodarone induced retrobulbar neuritis. Clinical case].

We report a 66 years old male, with an ophtalmologic history of long sightedness, admitted to the hospital due to paroxysmal atrial fibrillation crises in the context of a coronary heart disease. He was treated with i.v. amiodarone, receiving a total dose of 6 g in 72 hours. After the third day of treatment, the patient noticed a correction of his long sightedness and 24 h later, he complained of hlurred vision and orbital frontal headache. Visual field examination revealed a concentric retraction of visual field and a centrocecal scotoma in both eyes. Amiodarone was withdrawn and dexametasone treatment was begun. Three days after amiodarone discontinuation, sight improved and visual field returned to normal. Although retrobulbar neuritis has been associated to various drugs, amiodarone has not been considered as a possible agent.

Aged↗

Redescription of Eucoleus schvalovoj (Nematoda: Capillariidae), an oesophageal parasite of the Eurasian otter, Lutra lutra, in Spain.

Eucoleus schvalovoj Kontrimavichus, 1963 (Nematoda: Capillariidae) is redescribed. The original description of this species was brief and inadequate in that it was based on just a few specimens removed from the Eurasian otter, Lutra lutra (Linnaeus, 1758) in the Khabarovsk region, USSR. Detailed morphological study of several specimens of E. schvalovoj from the oesophagus of L. lutra from Spain revealed new characters, above all in males, and allows for a better characterisation of this species. Since its original description E. schvalovoj has only been recorded in Spain.

Animals↗

Chloride bound to oxidized cytochrome c oxidase controls the reaction with nitric oxide.

The reaction of nitric oxide (NO) with oxidized fast cytochrome c oxidase was investigated by stopped-flow, amperometry, and EPR, using the enzyme as prepared or after "pulsing." A rapid reduction of cytochrome a is observed with the pulsed, but not with the enzyme as prepared. The reactive species (lambdamax = 424 nm) reacts with NO at k = 2.2 x 10(5) M-1 s-1 at 20 degreesC and is stable for hours unless Cl- is added, in which case it decays slowly (t1/2 approximately 70 min) to an unreactive state (lambdamax = 423 nm) similar to the enzyme as prepared. Thus, Cl- binding prevents a rapid reaction of NO with the oxidized binuclear center. EPR experiments show no new signals within 15 s after addition of NO to the enzyme as prepared. Amperometric measurements show that the pulsed NO-reactive enzyme reacts with high affinity and a stoichiometry of 1 NO/aa3, whereas the enzyme as prepared reacts to a very small extent (<20%). In both cases, the reactivity is abolished by pre-incubation with cyanide. These experiments suggest that the effect of "pulsing" the enzyme, which leads to enhanced NO reactivity, arises from removing Cl- bound at the oxidized cytochrome a3-CuB site.

Animals↗

Infection with CagA+ Helicobacter pylori strains as a possible predictor of risk in the development of gastric adenocarcinoma in Mexico.

Helicobacter pylori strains possessing the Cag pathogenicity island have been associated with increased gastric inflammation and with duodenal ulcer. In contrast, studies on the association of cagA+ H. pylori infections and gastric cancer have shown conflicting results. The aim of our study was to determine whether H. pylori and CagA status are associated with gastric cancer in Mexico. We selected serum samples from 3 geographic areas with gastric cancer mortality rates per 100,000 inhabitants of 2.5 (low risk), 4.5 (medium risk) and 6.4 (high risk). H. pylori infection was determined by the detection of antibodies to H. pylori whole cell antigen by an enzyme-linked immunosorbent assay (ELISA). To study the prevalence of infection with cagA+ strains, serum IgG antibodies to CagA were determined by ELISA using a recombinant CagA antigen. Of the 2,775 individuals studied, 1,931 were H. pylori seropositive and 1,710 had antibodies against CagA. The risk for gastric cancer in the 3 populations studied increased proportionally as infection with cagA+ strains increased (p < 0.001 for trend). H. pylori infection also showed association with gastric cancer (p < 0.05). Individuals seropositive for CagA, but seronegative for H. pylori whole cell antigen, were more frequent in areas with higher gastric cancer rates (p < 0.01). These results support the possible role of CagA(+) status as predictor of risk for gastric adenocarcinoma in Mexico; this is in agreement with results in European and American populations, but contrary to studies in some Asian countries.

Adenocarcinoma↗

A common mechanism for the interaction of nitric oxide with the oxidized binuclear centre and oxygen intermediates of cytochrome c oxidase.

The reactions of nitric oxide (NO) with fully oxidized cytochrome c oxidase (O) and the intermediates P and F have been investigated by optical spectroscopy, using both static and kinetic methods. The reaction of NO with O leads to a rapid (approximately 100 s-1) electron ejection from the binuclear center to cytochrome a and CuA. The reaction with the intermediates P and F leads to the depletion of these species in slower reactions, yielding the fully oxidized enzyme. The fastest optical change, however, takes place within the dead time of the stopped-flow apparatus (approximately 1 ms), and corresponds to the formation of the F intermediate (580 nm) upon reaction of NO with a species that we postulate is at the peroxide oxidation level. This species can be formulated as either Fe5+ = O CuB2+ or Fe4+ = O CuB3+, and it is spectrally distinct from the P intermediate (607 nm). All of these reactions have been rationalized through a mechanism in which NO reacts with CuB2+, generating the nitrosonium species CuB1+ NO+, which upon hydration yields nitrous acid and CuB1+. This is followed by redox equilibration of CuB with Fea/CuA or Fea3 (in which Fea and Fea3 are the iron centers of cytochromes a and a3, respectively). In agreement with this hypothesis, our results indicate that nitrite is rapidly formed within the binuclear center following the addition of NO to the three species tested (O, P, and F). This work suggests that nitrosylation at CuB2+ instead of at Fea32+ is a key event in the fast inhibition of cytochrome c oxidase by NO.

Electron Transport Complex IV↗