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Biomedical subjects

C Martínez

Publications and source records attributed to C Martínez.

At least 19 recordsLinked to original sources

Development of the sexual reproductive cycle of Xanthophyllomyces dendrorhous.

Conditions inducing the development of holobasidia with terminal basidiospores in wild-type and astaxanthin mutant strains of Xanthophyllomyces dendrorhous were reexamined. Important factors for the development of holobasidia were the incubation temperature and the medium composition. A temperature of 9 degrees C was demonstrated to enhance holobasidia formation. Minimal growth medium with glucose as sole carbon source at concentrations between 80 and 120 mM, and ammonium nitrate with concentrations of 28 mM gave optimal results. A period of 20 or more days was needed for the formation of holobasidia with basidiospores. Additionally, mutant strains of X. dendrorhous were observed to have different abilities to produce holobasidia and strains obtained after protoplast fusion, which have been called fusant in this study, to have an increased capacity to form holobasidia.

Basidiomycota↗

Allogeneic transplantation of CD34(+) selected cells from peripheral blood from human leukocyte antigen-identical siblings: detrimental effect of a high number of donor CD34(+) cells?

Clinical results after T-cell-depleted allografts might be improved by modifying the graft content of progenitor and accessory cells. Although the association of the number of donor T cells with the clinical outcome has been studied extensively, the optimum number of progenitor cells that should be administered to patients is unknown. The characteristics of 84 consecutive human leukocyte antigen (HLA)-identical sibling transplants of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) were analyzed for their effect on clinical outcome. After a median follow-up of 24 months (range, 1-70 months), 50 patients remain alive (59.5%) and 34 have died (21 [25%] as a result of the transplant and 13 [15.5%] due to disease relapse). The median number of CD34(+) cells administered to the patients was 3.9 x 10(6)/kg (range, 1.2-14.3 x 10(6)/kg). A number of CD34(+) cells in the inoculum of 1 x 10(6)/kg to 3 x 10(6)/kg was associated with increased survival: 21 of 28 (75%) patients are alive, as compared with 29 of 56 (52%) patients receiving more than 3 x 10(6)/kg (actuarial probability 75% vs. 42%, respectively; P =.01). In the multivariate analysis, the independent prognostic variables for survival were CD34(+) cell dose 1 x 10(6)/kg to 3 x 10(6)/kg (RR = 4.8; P =.0008), sex-pairing match (RR = 3.2; P =.002), and early stage of disease (RR = 2.8; P =.007). From these results it appears that, in allo-PBT/CD34(+) from HLA-identical siblings, a number of CD34(+) cells in the inoculum between 1 x 10(6)/kg to 3 x 10(6)/kg is an important factor for better survival, and that higher CD34(+) cell doses might be associated with a poorer outcome.

Adolescent↗

Bcl-2 targets protein phosphatase 1 alpha to Bad.

The diverse forms of protein phosphatase 1 (PP1) in vivo result from the association of the catalytic subunit with different regulatory subunits. We recently have described that PP1alpha is a Ras-activated Bad phosphatase that regulates IL-2 deprivation-induced apoptosis. With the yeast two-hybrid system, GST fusion proteins, indirect immunofluorescence, and coimmunoprecipitation, we found that Bcl-2 interacts with PP1alpha and Bad. In contrast, Bad did not interact with 14-3-3 protein. Bcl-2 depletion decreased phosphatase activity and association of PP1alpha to Bad. Bcl-2 contains the RIVAF motif, analogous to the well characterized R/KXV/IXF consensus motif shared by most PP1-interacting proteins. This sequence is involved in the binding of Bcl-2 to PP1alpha. Disruption of Bcl-2/PP1alpha association strongly decreased Bcl-2 and Bad-associated phosphatase activity and formation of the trimolecular complex. These results suggest that Bcl-2 targets PP1alpha to Bad.

Amino Acid Sequence↗

Avalanches in one-dimensional piles with different types of bases.

We perform a systematic experimental study of the influence of the type of base on the avalanche dynamics of slowly driven 1D ball piles. The control of base details allows us to explore a wide spectrum of pile structures and dynamics. The scaling properties of the observed avalanche distributions suggest that self-organized critical behavior is approached as the "base-induced" disorder at the pile profile increases.

Journal Article↗

A potential immune escape mechanism by melanoma cells through the activation of chemokine-induced T cell death.

The immune system attempts to prevent or limit tumor growth, yet efforts to induce responses to tumors yield minimal results, rendering tumors virtually invisible to the immune system [1]. Several mechanisms may account for this subversion, including the triggering of tolerance to tumor antigens [2, 3], TGF-alpha or IL-10 production, downregulation of MHC molecules, or upregulation of FasL expression [4, 5]. Melanoma cells may in some instances use FasL expression to protect themselves against tumor-infiltrating lymphocytes (TIL) [4, 5]. Here, we show another, chemokine-dependent mechanism by which melanoma tumor cells shield themselves from immune reactions. Melanoma-inducible CCL5 (RANTES) production by infiltrating CD8 cells activates an apoptotic pathway in TIL involving cytochrome c release into the cytosol and activation of caspase-9 and -3. This process, triggered by CCL5 binding to CCR5, is not mediated by TNFalpha, Fas, or caspase-8. The effect is not unique to CCL5, as other CCR5 ligands such as CCL3 (MIP-1alpha) and CCL4 (MIP-1beta) also trigger TIL cell death, nor is it limited to melanoma cells, as it also operates in activated primary T lymphocytes. The model assigns a role to the CXC chemokine CXCL12 (SDF-1alpha) in this process, as this melanoma cell-produced chemokine upregulates CCL5 production by TIL, initiating TIL cell death.

Apoptosis↗

MRI and CSF oligoclonal bands after autologous hematopoietic stem cell transplantation in MS.

OBJECTIVE: To analyze the MRI and CSF oligoclonal bands (OB) changes in patients with MS who underwent an autologous hematopoietic stem cell transplantation (AHSCT). BACKGROUND: AHSCT is evaluated as an alternative therapy in severe MS. In previous series of AHSCT for MS, data on MRI or OB outcome were limited or not provided. METHODS: Five patients with a median Kurtzke's EDSS score of 6.5, more than two attacks, and confirmed worsening of the EDSS in the previous year received an AHSCT. Hematopoietic stem cells were mobilized with cyclophosphamide (3 g/m2) and granulocyte colony-stimulating factor (5 microg/kg/d). The graft was T cell depleted by positive CD 34+ selection. Conditioning regimen included BCNU (300 mg/m(2)), cyclophosphamide (150 mg/kg in 3 days), and antithymocyte globulin (60 mg/kg in 4 days). MRI scans were scheduled at baseline and 1, 3, 6, and 12 months and OB analysis at baseline and 3 and 12 months post-AHSCT. RESULTS: Four patients had a stable or improved EDSS after a median follow-up of 18 months (range, 12 to 24 months). The fifth patient's condition deteriorated during AHSCT. She partially improved and remained stable after month 3 after AHSCT. The baseline CSF OB persisted 1 year after AHSCT. MRI studies after AHSCT showed no enhanced T1 lesions and no new or enlarging T2 lesions. The median percentage change of T2 lesion load was -11.8% (range, -26.6 to -4.0%). All patients had a decrease of corpus callosum area at 1 year (median, 12.4%; range, 7.8% to 20.5%) that did not progress in the two patients evaluated at 2 years after AHSCT. CONCLUSIONS: Although the persistence of CSF OB suggests the lymphocytes were not eliminated from the CNS, the follow-up MRI studies showed no enhanced T1 brain lesions and a reduction in the T2 lesion load that correlated with the clinical stabilization of MS after AHSCT.

Adult↗

[The effects of dust inhalation in slate industry workers].

BACKGROUND: Slate industries involve the risk of causing silicosis; these industries are now on the increase, which implies an increasing number of workers too. The effects of this type of mining on respiratory health are not yet known. SUBJECTS AND METHOD: A cross section study of active workers. Radiological and functional alterations, and their relation to risk factors, were assessed. RESULTS: A prevalence of 2.1% simple pneumoconiosis was found. The value of the FEV1 probed to be significantly related to smoking and to existence of nodulation of a 1/0 or higher profusion; these risk factors, when multiple regression is applied, work independently. CONCLUSION: Slate industry involves a risk of pneumoconiosis and other respiratory alterations.

Adult↗

Involvement of K(ATP) channels in diethylstilbestrol-induced relaxation in rat aorta.

The estrogens prevent cardiovascular diseases that among other effects could be related to the modulation of the vascular tone via modifying ionic channel permeability. ATP-sensitive K(+) (K(ATP)) channels seem to be involved in diethylstilbestrol-induced relaxation in isolated rat aorta precontracted by noradrenaline (30 nM), since the effect is inhibited by glibenclamide (1--10 microM), and 1 mM tetraethylammonium, but not by 30 mM tetraethylammonium or paxilline. The antiestrogen tamoxifen, the inhibitor of protein kinase A, Rp-cAMPS, and the inhibitor of ornithine decarboxylase, difluoromethylornithine, antagonized diethylstilbestrol-induced relaxation. The association of glibenclamide with these compounds separately did not modify the effect of glibenclamide alone on diethylstilbestrol-induced relaxation. Functional K(ATP) channels are present in rat aorta, since diazoxide induced relaxation sensitive to glibenclamide. Papaverine, dibutyryl cyclic AMP and spermine relaxed isolated rat aorta although this was not sensitive to glibenclamide. The relaxation to forskolin was antagonized by glibenclamide. We conclude that diethylstilbestrol-induced relaxation in rat aorta is related to the modulation of K(ATP) channels. Cyclic AMP-dependent mechanisms and polyamine synthesis may mediate this modulation.

Animals↗

The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings.

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens.

Actuarial Analysis↗

High frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population.

OBJECTIVE: To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS: CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS: The frequency for CYP2C9 mutated alleles is higher among the Spanish subjects analysed than that reported for other Caucasian individuals: CYP2C9*2, 0.143 and CYP2C9*3, 0.162 (P = 0.0001). Nearly 10% of the individuals studied are expected to metabolise deficiently CYP2C9 substrates. CONCLUSION: In some Caucasian populations the impact of the CYP2C9 polymorphism may be much higher than that estimated from genotyping studies published to date.

Adult↗

Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma.

We analyzed the prognostic factors for a successful mobilization and peripheral blood stem cell collection in a series of 57 consecutive patients with multiple myeloma (MM); a new scoring system to predict an adequate mobilization in this subset of patients was also constructed. A total of 221 aphereses were performed in 57 patients with MM. The median time from diagnosis to mobilization was 12 months (range 4-120). Only one line of chemotherapy was administered before mobilization to 36 patients and two or more to 21. The median number of alkylating chemotherapy cycles was 6 (2-33). Two patients were mobilized in complete remission, 32 in partial response, and 23 in stable/progressive disease. Significant adverse prognostic factors for collecting 2.5 x 10(6) CD34+cells/kg or more were: a period of at least 12 months from diagnosis, at least six cycles of alkylating agents, and a plasma cell infiltration of 20% or more prior to mobilization. Patients with three risk factors had a probability of only 0.38 (95% CI 0.3-0.9) for adequate mobilization. Ten patients failed to mobilize; a period from diagnosis of 12 months or more and female sex were unfavorable factors. Patients with two risk factors had a probability of 0.50 (95% CI 0.2-0.8) for failing the mobilization procedure. These findings indicate that MM patients must be mobilized early in the course of the disease, with minimal disease burden before severe hematopoietic progenitor cell injury due to cumulative therapy.

Adult↗

Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution.

The prognosis of patients relapsing after an autologous transplant (autoSCT) is very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility of curing some of these patients, at the cost, however, of a high transplant related mortality (TRM). The aim of this study was to analyze the outcome of 14 consecutive patients with hematologic malignancies, from a single institution, who underwent alloSCT for progressive disease after autoSCT. Patients had relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten patients received HLA-identical related peripheral blood progenitor cells, three patients underwent matched-unrelated donor marrow transplants, and one patient received a mismatched related transplant. Conditioning regimens consisted of total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high-dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months, 95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent disease. Three patients remain alive and in complete remission at the time of this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers the possibility of a sustained control of the disease in some patients who relapse after an autoSCT. However, the procedure is associated with a high transplant-related mortality. Better results might be obtained by carefully selecting patients and by reducing the intensity of the preparative regimen.

Adult↗

[Tuberculosis notification from 1987 to 1999 for the public health area of the community of Valencia (Spain)].

OBJECTIVE: Under notification of tuberculosis (TB) is common worldwide but has hardly been studied in Spain. The objective of this study was to determine how many cases of TB are reported in our health care area. MATERIAL AND METHOD: Between 1987 and 1999 we carried out a direct study of the incidence and reporting of TB cases in our area (106,632 inhabitants on the census). Cases were taken from mandatory notification, pathology and bacteriology files and were then reviewed. RESULTS: Of the 410 TB cases diagnosed, 378 were residents of the area (annual incidence: 27/100,000 inhabitants), 223 of whom were reported (54%). Forty-eight patients were under 15 years of age. Sixty-seven percent of the pediatric cases and 53% of the adult cases were reported (n.s.). Of the 78 cases with HIV co-infection, only 32% were reported, in contrast with 60% of HIV-negative cases (p < 0.001). Of the 300 cases with pulmonary involvement, 56% were reported, versus 50% of those with exclusively extrapulmonary involvement (n.s.). For the 149 with positive Ziehl-Neelsen stain, 61% were reported, in contrast with 51% of those who were smear negative (n.s.). Diagnosis was based on clinical signs in 65 cases (16%), 51% of which were reported, versus 55% of those in which diagnosis was based on bacteriology or histology consistent with TB (n.s.). Overall under notification tended to decrease during the study period (r = 0.73, p < 0.005). Under notification also tended to decrease for patients with pulmonary involvement (r = 0.83, p < 0.0001) and for those with positive Ziehl-Neelsen staining of sputum (r = 0.79, p< 0.001). Likewise, under notification also decreased for HIV negative patients (r = 0.74, p < 0.02) but not significantly so for HIV positive patients r = 0.44, n.s.). CONCLUSIONS: Direct quantification of cases revealed a significant degree of under notification that is tending to decrease. Under notification is greatest for HIV-positive patients and is not changing. No differences were seen for smear positive and smear negative patients, by pulmonary or extra-pulmonary involvement, for clinical versus laboratory diagnosis, or for patients who were younger or older than 15 years of age. Reporting should be improved so that measures to decrease the incidence of TB can be taken.

AIDS-Related Opportunistic Infections↗

[Clinical outcome and health related quality of life in patients undergoing coronary angioplasty with balloon or stent. A prospective multicenter study].

INTRODUCTION AND OBJECTIVES: Clinical outcome and health related quality of life after coronary angioplasty with stent or balloon are insufficiently studied in routine practice. The aim of the present study was to assess the impact of angioplasty on the clinical results and quality of life in real clinical practice. PATIENTS AND METHODS: All the consecutive patients undergoing angioplasty with stent or balloon attending two Spanish tertiary hospitals from October, 1997 to July, 1998 were evaluated at baseline and one year after discharge from hospital with a structured clinical questionnaire and the generic SF-36 quality of life questionnaire. RESULTS: Three hundred ninety-seven patients with a mean age of 63 years were included in the study. A stent (or stent plus balloon) was implanted in 342 patients and angioplasty with a single balloon was performed in 55 patients. More advanced coronary disease and suboptimal lesions for treatment were found in patients treated with only balloon. At one year of follow up the total mortality was 6% and 54% of the patients were free of angina. Mean baseline scores of the SF-36 questionnaire were remarkably low (35 for physical health and 45 for mental health). At one year the scores achieved levels similar to those of the general Spanish population matched for age and sex (45 for physical health and 52 for mental health). Independent predictors of quality of life at one year were the following: baseline quality of life, age, sex, comorbidity, previous hospitalizations, hospital where the patient was attended, symptoms at admission and late angina. CONCLUSIONS: a) After percutaneous myocardial revascularization the mean quality of life achieved was similar to that of the general population; b) different clinical subgroups did not achieve these levels, although improvement was similar to that of the remaining subgroups

Adult↗