Alpha128 Arg-->Ser (CGT-->AGT) spectrin mutation associated with severe neonatal elliptopoikilocytosis in Spain.
Explore the source record for details and available documents.
Anemia, Hemolytic↗
Biomedical subjects
R Alvarez
Publications and source records attributed to R Alvarez.
[Availability of permanent vascular access at the beginning of hemodialysis: role of the pre-dialysis consultation].
Explore the source record for details and available documents.
Adult↗
Isomerization of all-trans-retinol to cis-retinols in bovine retinal pigment epithelial cells: dependence on the specificity of retinoid-binding proteins.
In the retinal rod and cone photoreceptors, light photoactivates rhodopsin or cone visual pigments by converting 11-cis-retinal to all-trans-retinal, the process that ultimately results in phototransduction and visual sensation. The production of 11-cis-retinal in adjacent retinal pigment epithelial (RPE) cells is a fundamental process that allows regeneration of the vertebrate visual system. Here, we present evidence that all-trans-retinol is unstable in the presence of H(+) and rearranges to anhydroretinol through a carbocation intermediate, which can be trapped by alcohols to form retro-retinyl ethers. This ability of all-trans-retinol to form a carbocation could be relevant for isomerization. The calculated activation energy of isomerization of all-trans-retinyl carbocation to the 11-cis-isomer was only approximately 18 kcal/mol, as compared to approximately 36 kcal/mol for all-trans-retinol. This activation energy is similar to approximately 17 kcal/mol obtained experimentally for the isomerization reaction in RPE microsomes. Mass spectrometric (MS) analysis of isotopically labeled retinoids showed that isomerization proceeds via alkyl cleavage mechanism, but the product of isomerization depended on the specificity of the retinoid-binding protein(s) as evidenced by the production of 13-cis-retinol in the presence of cellular retinoid-binding protein (CRBP). To test the influence of an electron-withdrawing group on the polyene chain, which would inhibit carbocation formation, 11-fluoro-all-trans-retinol was used in the isomerization assay and was shown to be inactive. Together, these results strengthen the idea that the isomerization reaction is driven by mass action and may occur via carbocation intermediate.
Animals↗
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids.
The intracellular pathways and receptors mediating the effects of retinoic acid (RA) on the brown-fat-uncoupling-protein-1 gene (ucp-1) have been analysed. RA activates transcription of ucp-1 and the RA receptor (RAR) is known to be involved in this effect. However, co-transfection of an expression vector for retinoid-X receptor (RXR) increases the action of 9-cis RA but not the effects of all-trans RA on the ucp-1 promoter in brown adipocytes. Either RAR-specific ¿p-[(E)-2-(5,6,7,8,-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid¿ or RXR-specific [isopropyl-(E,E)-(R,S)-11-methoxy-3,7, 11-trimethyldodeca-2,4-dienoate, or methoprene] synthetic compounds increase the expression of UCP-1 mRNA and the activity of chloramphenicol acetyltransferase expression vectors driven by the ucp-1 promoter. The RXR-mediated action of 9-cis RA requires the upstream enhancer region at -2469/-2318 in ucp-1. During brown-adipocyte differentiation RXRalpha and RXRgamma mRNA expression is induced in parallel with UCP-1 mRNA, whereas the mRNA for the three RAR subtypes, alpha, beta and gamma, decreases. Co-transfection of murine expression vectors for the different RAR and RXR subtypes indicates that RARalpha and RARbeta as well as RXRalpha are the major retinoid-receptor subtypes capable of mediating the responsiveness of ucp-1 to retinoids. It is concluded that the effects of retinoids on ucp-1 transcription involve both RAR- and RXR-dependent signalling pathways. The responsiveness of brown adipose tissue to retinoids in vivo relies on a complex combination of the capacity of RAR and RXR subtypes to mediate ucp-1 induction and their distinct expression in the differentiated brown adipocyte.
Adipose Tissue, Brown↗
Posture-related changes of soleus H-reflex excitability.
We investigated whether the modulatory effects of segmental and descending inputs on the soleus H reflex are modified by postural conditions. Fourteen healthy volunteers received a transcranial magnetic stimulus (TMS) or percutaneous electrical stimulation of the posterior tibial nerve (PTN), preceding by 0 to 400 ms the elicitation of the soleus H reflex in supine, sitting, and standing positions. In all positions, TMS induced an early period of facilitation at interstimulus intervals (ISIs) ranging between 5 and 35 ms. In supine and sitting positions, there was a second period of facilitation at ISIs between 60 and 90 ms, which was absent or significantly reduced in the standing position. PTN induced a strong inhibition of the H reflex in all positions up to 125 ms. In supine and sitting positions, inhibition continued up to 400 ms, whereas it was significantly reduced or completely absent beyond 125 ms in the standing position. These results demonstrate posture-related differences in the modulatory effects of descending and segmental inputs on the excitability of the H-reflex circuit.
Adult↗
DNA ploidy status and proliferative activity as markers of malignant potential in Barrett's esophagus: flow cytometric study using routinely paraffin-embedded tissue.
Regular endoscopic surveillance is recommended for patients with Barrett's esophagus to detect dysplasia and to diagnose carcinoma while it is in an early and possibly treatable stage. However, there are numerous unknown aspects regarding the natural history of dysplasia in this disease, and there is still a need for more accurate markers of risk of a malignant change. The aim of this study was to investigate the usefulness of DNA flow cytometry in Barrett's esophagus to define subgroups of patients showing similar histologic findings but with a different malignancy potential. Routinely formalin-fixed and paraffin-embedded tissues of 43 patients with Barrett's esophagus were processed for flow cytometric measurements (ploidy, proliferative index) and the results were compared with the histologic evolution observed in these patients. Only in the group of patients with "indefinite" dysplasia did we find statistically significant differences between the samples from patients with and without progression to more severe lesions (mean proliferative index of stable patients: 5.2% versus 8.3% in patients with progression, p = 0.001, Student's t-test). The presence in the flow cytometric analysis of a DNA aneuploid cell line is closely related to the presence of severe histologic alterations (i.e., high-grade dysplasia: p < 0.001, Fisher's exact test). Our results suggest that this procedure is at least capable of distinguishing between a real, although incipient, neoplastic process and morphologic changes of a reactive or reparative type. The increment in the tissue proliferative index could be an indicator of an early genomic instability which, with time, will develop into lesions with a more altered DNA content: aneuploidy.
Adenocarcinoma↗
Genetic variation in the renin-angiotensin system and athletic performance.
The D allele at the angiotensin-I-converting enzyme (ACE)-insertion/deletion polymorphism has been associated with an increased risk of developing several pathological processes, such as coronary heart disease and ventricular hypertrophy. Individuals with the DD genotype show a significantly increased left-ventricular mass in response to physical training, compared to the II genotype (which would be associated with the lowest plasma ACE levels) and the ID genotype. The II genotype has been linked to a greater anabolic response. In accordance with a role for ACE in the response to rigorous physical training, a higher frequency of the I allele has been reported to exist among elite rowers and high-altitude mountaineers. Sixty elite (professional) athletes (25 cyclists, 20 long-distance runners, and 15 handball players), and 400 healthy controls were genotyped for the DNA polymorphisms of the ACE, angiotensinogen (Ang) and angiotensin receptor type 1 (AT1) genes. Plasma ACE levels showed a strong correlation with the I/D genotype in our population. The I-allele occurred at a significantly higher frequency in athletes compared to controls (P = 0.0009). Gene and genotype frequencies for the Ang and AT1 polymorphisms did not differ between athletes and controls. Since the frequency of the ACE I allele was significantly increased among our elite athletes, we conclude that the ACE polymorphism represents a genetic factor that contributes to the development of an elite athlete.
Adult↗
Analysis of chromosome 6p in Spanish families with recessive polycystic kidney disease.
Several previous reports have suggested that autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in a single gene (the PKDH1 gene). Linkage analysis showed a positive linkage for polymorphic markers at the short arm of chromosome 6 (6p) in all families. PKHD1 has not been cloned. Recombinants in the critical region would permit the narrowing of the 6p interval containing the PKHD1 gene, thus facilitating the final identification (cloning) of this gene. Our study included 30 Spanish families. Each family consisted of both parents and at least two children, with at least one diagnosed with ARPKD by clinical and pathological parameters. DNA was obtained and 6p microsatellite markers were used to establish haplotypes for each family. A positive linkage to chromosome 6p was found for all families. In 2 cases, recombinants in the region containing the PKHD1 gene were found. These families will help narrow the size of the 6p region, facilitating the efforts to position and clone the PKHD1 gene. In conclusion, our analysis of Spanish ARPKD families confirms the lack of linkage heterogeneity. This suggests that mutations at a single locus on chromosome 6p21.1-p12 are responsible for the broad clinical spectrum of variable phenotypes.
Adolescent↗
Measurement of proton release and uptake by analogs of bacteriorhodopsin.
Proton release and subsequent uptake by several forms of bacteriorhodopsin (bR), including 4-keto analogs of wild-type (WT) and D96N and D85N mutants as well as the 9-demethylretinal analog of WT and D96N mutants, have been measured using a highly sensitive electrochemical technique. Release and uptake of protons by bR in membrane patches on a tin oxide electrode produce a current transient whose amplitude is proportional to the rate of pH change at the electrode surface. Profiles of proton release by the analogs vs. pH are substantially different from the profiles of the native proteins.
Bacteriorhodopsins↗
Microtubule binding to Smads may regulate TGF beta activity.
Smad proteins are intracellular signaling effectors of the TGF beta superfamily. We show that endogenous Smad2, 3, and 4 bind microtubules (MTs) in several cell lines. Binding of Smads to MTs does not require TGF beta stimulation. TGF beta triggers dissociation from MTs, phosphorylation, and nuclear translocation of Smad2 and 3, with consequent activation of transcription in CCL64 cells. Destabilization of the MT network by nocodazole, colchicine, or a tubulin mutant disrupts the complex between Smads and MTs and increases TGF beta-induced Smad2 phosphorylation and transcriptional response in CCL64 cells. These data demonstrate that MTs may serve as a cytoplasmic sequestering network for Smads, controlling Smad2 association with and phosphorylation by activated TGF beta receptor I, and suggest a novel mechanism for the MT network to negatively regulate TGF beta function.
Activin Receptors, Type I↗
Serum inhibin B determination is predictive of successful testicular sperm extraction in men with non-obstructive azoospermia.
Recent work indicates that serum inhibin B is a useful marker of spermatogenesis and inhibin B production sufficient to maintain detectable serum concentrations in adults depends on spermatogenic activity. The purpose of the present study was to investigate the usefulness of serum inhibin B measurement to predict the success of testicular sperm extraction (TESE) in 17 men with nonobstructive azoospermia to be treated by intracytoplasmic sperm injection (ICSI) (group 1). Two additional groups were used as positive controls; group 2 comprised 22 infertile men having obstructive azoospermia, and group 3, which included 29 semen donors having normal seminal parameters. Follicle stimulating hormone (FSH) was significantly higher (P < 0.01) and inhibin B significantly lower (P < 0.001), in group 1 as compared with groups 2 and 3. Serum inhibin B concentrations were significantly higher (P < 0.001) among successful TESE men as compared with those having failed TESE. In contrast, no differences were detected between these two groups with respect to serum FSH or testicular size. In addition, serum inhibin B but not FSH discriminated between successful and failed TESE in group 1 subjects as compared with control groups. According to the receiver operating characteristics curve analysis, the best inhibin B value for discriminating between successful and failed TESE was >40 pg/ml (sensitivity 90%, specificity 100%). It is concluded that inhibin B measurement is a useful non-invasive predictor of spermatogenesis and thus, all azoospermic males should have serum inhibin B concentrations determined in addition to FSH measurement and karyotyping prior to undergoing TESE.
Adult↗
Interaction of D-600 with the transmembrane domain of the sarcoplasmic reticulum Ca(2+)-ATPase.
Experiments were performed to determine whether the organic Ca(2+) channel blocker D-600 (gallopamil), which penetrates into muscle cells, affects sarcoplasmic reticulum (SR) Ca(2+) uptake by directly inhibiting the light SR Ca(2+)-ATPase. We have previously shown that at 10 microM, D-600 inhibits LSR ATP-dependent Ca(2+) uptake by 50% but has no effect on ATPase activity (21). These data suggest that the SR Ca(2+)-ATPase might be a potential target for D-600. The ATPase activity of the enzyme is associated with its hydrophilic cytoplasmic domain, whereas Ca(2+) binding and translocation are associated with the transmembrane domain (18). In the present experiments, we determined which of the two domains of the ATPase is affected by D-600. Thermal inactivation experiments using the SR Ca(2+)-ATPase demonstrated that D-600 decreased the thermal stability of Ca(2+) transport but had no effect on the stability of ATPase activity. In addition, D-600 at a concentration of 160 microM did not have any leaking effect of Ca(2+) on the Ca(2+)-loaded SR. Thermal denaturation profiles of SR membranes revealed that D-600 interacts directly with the transmembrane domain of the Ca(2+)-ATPase. No evidence for interaction with the nucleotide domain was obtained. We conclude that the Ca(2+) blocker D-600 inhibits the SR Ca(2+) pump specifically by interacting with the transmembrane Ca(2+)-binding domain of the Ca(2+)-ATPase.
Adenosine Triphosphatases↗
Maintenance chemotherapy in advanced ovarian cancer.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Inhibitory tagging in inhibition of return is affected in schizophrenia: evidence from the stroop task.
L. J. Fuentes, A. B. Vivas, and G. W. Humphreys (1999b) showed that stimulus processing is affected when stimuli are presented to locations subject to inhibition of return. They argued that activated representations of stimuli presented at inhibited locations are disconnected from their associated responses through an "inhibitory tagging" mechanism occurring in inhibition of return. In the present research, the authors asked whether such a mechanism is affected in people with schizophrenia. Healthy adults and patients with schizophrenia performed a Stroop task in an inhibition of return paradigm. Healthy adults showed a reduction in the Stroop interference when stimuli were presented at inhibited locations, a result that agrees with the inhibitory tagging mechanism hypothesis and replicates previous findings. However, patients with schizophrenia did not show such a reduction, a result suggesting that they have a deficit in inhibitory processing occurring in inhibition of return.
Adult↗
Study of primary drug resistance of Mycobacterium tuberculosis from two hospitals in Tenerife, Canary Islands, Spain (1990-1997)
Explore the source record for details and available documents.
Antitubercular Agents↗
Co-existence of hereditary spherocytosis and a new red cell pyruvate kinase variant: PK mallorca.
BACKGROUND AND OBJECTIVE: A partial red blood cell (RBC) pyruvate-kinase (PK-R) deficiency was found in a patient with concomitant hereditary spherocytosis (HS) and chronic hemolytic anemia. Clinical, biological and molecular studies were performed in the patient, his parents and a brother, in order to characterize the specific PK-R gene mutation and the inheritance mechanism of the transmission of both red cell defects in this particular family. DESIGN AND METHODS: Conventional biological studies were used to identify the PK-LR gene mutation responsible for hereditary transmission of PK-R deficiency and HS. The family study was completed with genotypic and RBC membrane protein analyses in the patient and his family. RESULTS: Molecular study of the PK deficiency was performed in all the family members and demonstrated a heterozygous condition for the 1516 G->A (506Val->Ile) mutation at the PK-LR gene in both the patient and his mother. Since this mutation has not been reported previously, it is provisionally named PK "Mallorca". The study of RBC membrane proteins demonstrated the existence of partial band 3 and protein 4.2 deficiencies in the propositus and his father but not in the mother and brother, who were also studied. These results support the dominant mode of inheritance of HS and PK-LR gene in this family. INTERPRETATION AND CONCLUSIONS: HS and PK deficiency are not exceptional in Spain. The co-existence of both RBC defects in the same patient, however, is very rare; only a few cases have been described to date. Our findings suggest that performing an elementary RBC enzyme survey in all patients with HS would help to determine the real frequency of this apparently rare association.
Amino Acid Substitution↗
[The prolonged administration of intravenous immunoglobulins as a treatment for refractory fistulous Crohn's diseases].
Fistulating Crohn's disease is present in 17-35% of non-surgically treated patients and in up to 45% of surgically treated ones. Among the several therapeutic alternatives for this disease is intravenous immunoglobulin administration. We present a 28-year-old woman with refractory fistulating Crohn's disease who improved after prolonged immunoglobulin administration (32 months).
Adult↗
[Prognostic factors for survival following transarterial chemoembolization in advanced hepatocellular carcinoma].
The efficacy of transarterial chemoembolization in the palliative treatment of non-resectable hepatocellular carcinoma is controversial. To determine the possible existence of clinical and analytical variables with independent predictive value for survival related to the tumor and the treatment given, a multivariate analysis in a series of 111 patients who underwent transarterial chemoembolization was carried out. Overall actuarial survival was 54%, 31% and 24% at 1, 2 and 3 years respectively. Child-Pugh score (p < 0.05), tumor size (p < 0.05) and arterial occlusion after intraarterial chemotherapy (p < 0.05) reached independent predictive value. The group of patients in whom two or three of these factors were simultaneously present had a very poor prognosis with a survival of 20% and 0% at 1 and 2 years respectively, compared with 60%, 50% and 37% at 1, 2 and 3 years respectively in the group with one or none of these factors (p < 0.01). Grouping on the basis of these variables may be useful in the design of future controlled prospective studies that aim to determine the efficacy of transarterial chemoembolization.
Adult↗