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Biomedical subjects

R Martínez

Publications and source records attributed to R Martínez.

At least 19 recordsLinked to original sources

Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain.

In Drosophila, the products of the Polycomb group (Pc-G) of genes act as chromatin-associated multimeric protein complexes that repress expression of homeotic genes. Vertebrate Pc-G homologues have been identified, but the nature of the complexes they form and the mechanisms of their action are largely unknown. The Polycomb homologue M33 is implicated in mesoderm patterning in the mouse and here we show that it acts as a transcriptional repressor in transiently transfected cells. Furthermore, we have identified two murine proteins, Ring1A and Ring1B, that interact directly with the repressor domain of M33. Ring1A and Ring1B display blocks of similarity throughout their sequences, including an N-terminal RING finger domain. However, the interaction with M33 occurs through a region at the C-terminus. Ring1A represses transcription through sequences not involved in M33 binding. Ring1A protein co-localizes in nuclear domains with M33 and other Pc-G homologues, such as Bmi1. The expression of Ring1A at early stages of development is restricted to the neural tube, whereas M33 is expressed ubiquitously. Within the neural tube, Ring1A RNA is located at the rhombomere boundaries of the hindbrain. Taken together, these data suggest that Ring1A may contribute to a tissue-specific function of Pc-G-protein complexes during mammalian development.

3T3 Cells

[PCR study of bcl-2 rearrangement in autologous transplantation of peripheral stem cells in follicular non-Hodgkin's lymphoma].

OBJECTIVE: To value the usefulness of the bcl-2 rearrangement analysis by PCR in the study of the minimal residual disease in patients with follicular non-Hodgkin's B cell lymphoma (NHL) submitted to peripheral blood stem-cell transplantation (PSCT). PATIENTS AND METHOD: The study was done on 12 patients diagnosed with low grade B-cell NHL, who were entered in a program of myeloablative chemotherapy followed by rescue with progenitor cells obtained from peripheral blood. At the time of peripheral stem-cells (PSC) harvesting, 8 patients did not present medullar infiltration and four of them presented medullar infiltration according to conventional histological criteria. The study was done on DNA from samples taken from bone marrow and cells taken in the apheresis. The DNA samples were studied by PCR to determine the existence of the bcl-2 rearrangement. RESULTS: At the time of apheresis, 8 patients did not present medullar infiltration according to conventional histological criteria but 7 of them presented bcl-2/JH rearrangement. Most patients studied (10 out of 12) showed bcl-2/JH rearrangement (minimal residual disease) in apheresis products. However, in 2 of these 10 patients, such rearrangement was negative in the bone marrow samples obtained 3-6 and 12 months after transplantation. CONCLUSION: In some patients with follicular NHL submitted to PSCT, the bcl-2/JH rearrangement had negativized after transplantation, this implies that the tumoral cells present in apheresis products lost their clonogenic capacity and were not able to subsist in vivo and that the myeloablative polychemotherapy schedules are able to eradicate the t(14; 18) translocation bearing cells or, at least, to decrease their number in bone marrow to levels below those of PCR detection.

Adult

[Definitive diagnosis of pulmonary sequestration using magnetic resonance. Description of 3 cases].

Pulmonary sequestration is a congenital malformation in which the pulmonary parenchyma is isolated from the rest of the lung and receives irrigation. Traditionally this malformation has been diagnosed by arteriography, but in recent years the usefulness of magnetic resonance, a technique that can probably substitute for arteriography on many occasions, has been emphasized. We report 3 cases of intralobar pulmonary sequestration diagnosed by magnetic resonance, a procedure that provided adequate presurgical assessment. The magnetic resonance images were later shown to be consistent with anatomical findings.

Adolescent

[Berger's disease and acquired sensorineural hearing loss].

A relation between kidney and inner ear disease, specifically neurosensorial hearing loss, has been established. Likewise, the role of tonsillitis in certain glomerulonephritides is well known. A case of post-streptococcal mesangial glomerulonephritis with IgA deposit (Berger's disease) and neurosensorial hearing loss is reported. The absence of any relevant family or personal history suggests an immunological origin for both disorders.

Adult

Antioxidant action of estrogens in rat hepatocytes.

The in vitro addition of 17 beta-estradiol (0-100 microM) to isolated rat hepatocytes efficiently prevented cellular lipid oxidation induced by the Fe(III)/ADP complex. 17 beta-estradiol was found to be less effective than its metabolic derivative 2-hydroxyestradiol. The presence of specific inhibitors of cytochrome P450 activity significantly diminished the antioxidant capacity of estradiol. These observations support the hypothesis that estradiol, in the micromolar range, inhibits iron-induced lipid peroxidation in liver cells by diverting reducing equivalents from the peroxidative process to its own metabolism.

Animals

Clinical experience with cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease.

Coimplants of adrenal medulla (AM) and peripheral nerve (PN) in animal models of Parkinson's disease (PD) have shown that AM cells survive longer, tend to show neuronal phenotype, and enhance sprouting of host fibers. Since 1987, our implants of perfused AM and fetal ventral mesencephalon (FVM) in PD patients have achieved varying degrees of clinical improvement. If the donor tissue determines the improvement, different types of implants should result in qualitatively and quantitatively different degrees of improvement. The purpose of this study is to determine whether or not the clinical course, improvement slope, and reduction of medication observed in PD patients who undergo tissue transplantation (Tx) depend on the donor tissue type. In a pilot study, four grade IV-V PD patients received implants of precoincubated autologous AM and intercostal nerve in the caudate nucleus (open surgery). Clinical assessment was based on international scales (UPD) as reported for Tx of FVM and perfused AM. There were no systemic or neurologic complications. Four years post-Tx, longer On phases and improved PD symptoms (ADL and motor-UPD) in On and Off persist in four cases, with reduced dyskinesias. Progress appears to be stepwise, starting within weeks of Tx (similar to AM and sooner than our FVM implants), followed by a period of stability and, after a second wave of improvement 12-18 months post-Tx (similar to FVM implants), continues to date. L-dopa medication has been reduced by more than 60% and dopamine agonist use has not resumed. We conclude that our recipients continue to be clinically better than prior to Tx. The course of recovery after co-Tx of AM and PN differs from that of FVM or AM implants. This fact may be related to the etiological factors that produce the improvement.

Adrenal Medulla

Galanin-like immunoreactivity in the sea cucumber Holothuria glaberrima.

Galanin, a neuropeptide of 29 amino acids originally purified from porcine small intestine, has been found in most vertebrate groups, where it is present in both the central and peripheral nervous systems. In this study, galanin-like immunoreactivity was detected in an invertebrate, the sea cucumber Holothuria glaberrima. In this organism, fibers and cells expressing galanin-like immunoreactivity were found in the enteric nerve plexuses of the esophagus, and large and small intestine, particularly in the serosal layer. Immunoreactivity was also found in the ectoneural portion of the radial nerve and in nervous elements within the body wall. Preabsorbtion tests indicated that the observed immunoreactivity was not due to cross-reactivity of the antibody with other peptides also found in the intestinal plexuses. The immunoreactivity to galanin was quantified in various tissues using radioimmunoassay and partially characterized with high performance liquid chromatography. These results show that although the holothurian peptide shows common immunological determinants with porcine galanin, it differs with regard to certain biochemical properties.

Animals

Autotransplantation of peripheral blood stem cells mobilized by G-CSF in hematological malignancies: evidence for rapid and long-term sustained hematopoietic reconstitution.

We assessed the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC), the efficacy of PBSC infusion in the rescue of hematopoiesis after high-dose chemotherapy in 22 adult patients with hematological malignancies, and the long-term quality of engraftment. Bolus subcutaneous injections of G-CSF (12 micrograms/kg/day) were administered for 6 days. A median of three leukaphereses resulted in the collection of a median of 5.45 X 10(8) mononuclear cells/kg, 4.52 X 10(6) CD34+ cells/kg, and 3.97 X 10(4) CFU-GM/kg. G-CSF (5 micrograms/kg daily) was administered after PBSC infusion until granulocyte recovery. The median time to attain a neutrophil level > 0.5 X 10(9)/L and a platelet count > 20 X 10(9)/ L was 11 days. The median follow-up in 17 survivors was 23.8 months. These patients have maintained a complete and stable graft and some of them with neoplastic recurrence tolerated further chemotherapy. These results confirm that mobilization of PBSC by G-CSF can be performed on an outpatient setting and used in heavily pretreated patients. G-CSF mobilized PBSC transplantation provides early and complete engraftment in most patients.

Adult

[Antibiotic resistance to erythromycin, clindamycin and tetracycline of 573 strains of Streptococcus pyogenes (1992-1994)].

BACKGROUND: The aim of this study was to know the antibiotic resistence of Streptococcus pyogenes to erythromycine, clindamycine and/or tetracycline in community samples. The second aim was to determine the existence of multiresistant strains and to know the relationship between resistant strains, clinical samples and age of the patient. METHOD: A retrospective analysis was performed in all the strains of S. pyogenes isolated from January 1992 to December 1994. Antibiotic sensitivity was studied by MIC by the microdilution method using the Pasco semiautomatic system. RESULTS: During the study period 573 beta hemolytic streptococci were identified as S. pyogenes. The global resistance to erythromycine (2.8%), clindamycine (1.4%) and tetracycline (7.3%) remains at low levels but has significantly increased in the case of erythromycine (p < 0.05) and tetracycline (p < 0.05) over these 3 years. The incidence of strains resistant to clindamycine has also increased slowly although this rise is not significant. Five strains (0.9%) were not sensitive to the three antibiotics studied, 4 being isolated in the last trimester of 1994 in pharyngeal exudates. S. pyogenes resistant to erythromycine was most frequently isolated from cutaneous lesions and in pediatric patients (under the age of 14 years). CONCLUSIONS: These results confirm the trend towards an increase in the number of strains of S. pyogenes resistant to erythromycine, clindamycine and/or tetracycline, being most often found in cutaneous lesions and pediatric patients.

Anti-Bacterial Agents

Labelling pattern obtained by non-isotopic in situ hybridization as a prognostic factor in HPV-associated lesions.

In the study of infection of the lower female genital tract caused by human papillomavirus (HPV), one of the main concerns is the search for prognostic factors to predict the evolution of premalignant low- and high-grade squamous intraepithelial lesions. This study has evaluated the prognostic usefulness of the patterns of positive reaction obtained by non-isotopic in situ hybridization (NISH), referred to as diffuse, punctate, or mixed 'labelling patterns'. The study examined 141 vulvar and uterine cervical biopsy specimens that were positive for HPV by a NISH screening technique and that had the following histological diagnoses: low-grade squamous intraepithelial lesion (LSIL; n = 87); high-grade squamous intraepithelial lesion (HSIL, n = 40); and squamous cell carcinoma (SCC n = 14). Typing of all the specimens was carried out by NISH with DNA probes specific for HPV types 6/11 (low risk), 16/18 (high risk), and 31/33/51 (intermediate risk), and the labelling pattern observed in each specimen was recorded. Statistical analysis of the results showed that there was a significant difference in the distribution of labelling patterns, both by lesion diagnosis (P < or = 0.004) and by infecting viral type (P < or = 10(-6)). Lesions with a punctate or mixed pattern are considered more likely to undergo malignant evolution and consequently have a worse prognosis than lesions with a diffuse pattern.

Carcinoma, Squamous Cell

Growth enhancement in transgenic tilapia by ectopic expression of tilapia growth hormone.

The generation of transgenic fish with the transfer of growth hormone (GH) genes has opened new possibilities for the manipulation of growth in economically important fish species. The tilapia growth hormone (tiGH) cDNA was linked to the human cytomegalovirus (CMV) enhancer-promoter and used to generate transgenic tilapia by microinjection into one-cell embryos. Five transgenic tilapia were obtained from 40 injected embryos. A transgenic animal containing one copy of the transgene per cell was selected to establish a transgenic line. The transgene was stably transmitted to F1 and F2 generations in a Mendelian fashion. Ectopic, low-level expression of tiGH was detected in gonad and muscle cells of F1 transgenic tilapia by immunohystochemical analysis of tissue sections. Nine-month-old transgenic F1 progeny were 82% larger than nontransgenic fish at p = .001. These results showed that low-level ectopic expression of tiGH resulted in a growth acceleration in transgenic tilapia. Tilapia GH gene transfer is an alternative for growth acceleration in tilapia.

Animals

Transgenic rabbits as bioreactors for the production of human growth hormone.

Gene farming is one of the most promising areas in modern biotechnology. To assay the potential usefulness of transgenic rabbits as bioreactors, one call embryos were microinjected with a chimeric gene comprising 5' sequences from mouse whey acidic protein gene (mWAP) linked to the human growth hormone (hGH) gene. Transgenic animals were obtained and the presence of the foreign protein was detected in the milk and serum of these animals at levels of up to 50 micrograms ml-1 and 0.6 ng ml-1, respectively. Founder transgenics were able to transmit the microinjected gene to the first filial generation in a Mendelian fashion. These results showed that transgenic rabbits could constitute a suitable system for the rapid production of recombinant proteins in the milk of lactating females.

Animals

Differential constitutive expression of interferon genes in early mouse embryos.

Recent evidence suggests that several processes during mammalian embryogenesis may be regulated by IFNs or IFN-like molecules. With the use of MAPPing, the simultaneous presence of transcripts homologous to IFN-alpha, IFN-beta, IRF-1, and IRF-2 was examined in mouse embryos and in embryonal carcinoma (EC) P19 cells, which are equivalent to epiblast cells of the early postimplantation blastocysts. Transcripts for IFN-alpha, but not for IFN-beta, were detected as maternal transcripts in the ovulated oocyte and persisted over early embryogenesis. IRF-1 transcripts appeared only after the first cell cleavage in the two-cell stage embryo. IRF-2 transcripts were analyzed only in EC P19 cells and were found in both undifferentiated (D-) and differentiated (D+) cells. The IFN-alpha transcripts present in (D-) P19 cells were cloned and the partial cDNA sequences determined. Mu IFN-alpha A and a new Mu IFN-alpha species (Mu IFN-alpha 12) were isolated from (D-) P19 cells. The presence of constitutive IFN-alpha transcripts in early mouse embryos suggests a role for these molecules during embryogenesis.

Animals

Protective effect of estrogens and catecholestrogens against peroxidative membrane damage in vitro.

The antioxidant effects of natural estrogens (estrone, E1; 17 beta-estradiol), synthetic estrogens (17 alpha-ethynylestradiol, EE2; mestranol, MES; diethylstilbestrol, DES) and catecholestrogens (2-hydroxyestradiol; 4-hydroxyestradiol, 4-OHE2) on lipid peroxidation induced by different means in rat liver microsomes were investigated. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances. Prooxidants included Fe3+/ADP/reduced NADPH, Fe2+/ascorbate, tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2-amidinopropane) (AAPH). Estrogens and catecholestrogens decreased lipid peroxidation in all four systems tested. In the iron/ascorbate model it was shown that (i) 4-OHE2 and DES had analogous patterns of inhibition, irrespective of the presence of NADPH or the functional integrity of the microsomes, and (ii) the antioxidant activities of E1, EE2 and MES were dependent on the assay conditions with the activity being markedly higher when estrogen metabolism was favored. When peroxidation was initiated by the peroxyl radical generator AAPH, the inhibitory effects observed were least pronounced. Our data also showed that, in each of the systems, all inhibitors displayed the same order of inhibitory potency with DES and catecholestrogens being the most potent antioxidants under all experimental conditions used. The present results confirm earlier findings and point toward a link between estrogen metabolism and estrogen antioxidant activity. The data also indicate that estrogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-derived species being the most important modes of inhibition.

Animals

Effects of estrogens on the redox chemistry of iron: a possible mechanism of the antioxidant action of estrogens.

The preventive effects of estrogens on FeSO4-induced lipid peroxidation are closely correlated with their inhibition of Fe(II) oxidation during peroxidation. Estrogens affected the redox status of iron in aqueous solution with varying degrees of effectiveness. 2-Hydroxyestradiol substantially decreased the oxidation of Fe(II) and was the most potent Fe(III) reductant. Diethylstilbestrol and 4-hydroxyestradiol also exhibited reduction properties, whereas the phenolic estrogens 17 beta-estradiol, estrone, and 17 alpha-ethynylestradiol displayed slighter or no effects. Present results demonstrate that catecholestrogens and diethylstilbestrol directly alter the iron redox chemistry, this fact probably being involved in the antioxidant effects of these molecules.

Animals