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Biomedical subjects

J Arias

Publications and source records attributed to J Arias.

At least 55 records · Page 3Linked to original sources
PubMed1999

A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group.

The Spanish PETHEMA group designed a protocol for newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia (APL) in which induction and consolidation followed the original AIDA regimen, except for the omission of cytarabine and etoposide from consolidation. Induction consisted of 45 mg/m(2) all-trans retinoic acid (ATRA) daily until complete remission (CR) and 12 mg/m(2) idarubicin on days 2, 4, 6, and 8. Patients in CR received 3 monthly chemotherapy courses: idarubicin 5 mg/m(2)/d x 4 (course no. 1), mitoxantrone 10 mg/m(2)/d x 5 (course no. 2), and idarubicin 12 mg/m(2)/d x 1 (course no. 3). Maintenance therapy consisted of 90 mg/m(2)/d mercaptopurine orally, 15 mg/m(2)/wk methotrexate intramuscularly, and, intermittently, 45 mg/m(2)/d ATRA for 15 days every 3 months. Between November 1996 and December 1998, 123 patients with newly diagnosed PML/RARalpha-positive APL from 39 centers were enrolled. A total of 109 patients achieved CR (89%; 95% confidence interval [CI], 83 to 95), 12 died of early complications, and the remaining 2 were resistant. Consolidation treatment was associated with very low toxicity and no deaths in remission were recorded. Molecular assessment of response by reverse transcriptase-polymerase chain reaction (RT-PCR) showed conversion to PCR-negative in 48 of 99 (51%) and 82 of 88 patients (93%) after induction and consolidation, respectively. The 2-year Kaplan-Meier estimates of overall survival and event-free survival were 82% +/- 4% and 79% +/- 4%, respectively. For patients who achieved CR, the 2-year disease-free survival (DFS) was 92% +/- 3%. These data indicate that a significant reduction in toxicity might be obtained in APL using a less intensive consolidation without apparently compromising the antileukemic effect. These results also suggest a minor role for cytarabine and etoposide in the treatment of newly diagnosed PML/RARalpha-positive APL patients.

Adolescent↗
PubMed1999

Exposure to 2500 lux increases serum melatonin in Venezuelan equine encephalomyelitis.

When mice infected with the Venezuelan equine encephalomyelitis (VEE) virus were exposed to 2500 lux with a 12 h light: 12 h dark photoperiod, the serum levels of melatonin (MLT) remained constantly elevated. In mice exposed to 400 lux low levels of serum MLT were detected during the day and high levels during the night. An increase in the survival rate of the infected mice from 6 to 13 days after virus inoculation was also observed. The significant increment in the concentration of serum MLT produced by the high intensity light could be responsible for the longer survival rate of mice infected with the VEE virus.

Animals↗
PubMed1999

Genetic structure of brown trout, salmo trutta l., at the southern limit of the distribution range of the anadromous form

Genetic variation at 33 protein loci was investigated in 41 wild brown trout populations from four river basins in Galicia (northwest Spain) to analyse the amount and distribution of genetic diversity in a marginal area, located in the distribution limit of the anadromous form of this species. The genetic diversity detected within populations (H between 0 and 6%) lies within the range quoted for this species in previous reports. The Mino, the most southern river basin analysed, showed a significantly lower genetic diversity and the highest genetic differentiation among the river basins studied. The hierarchical gene diversity analysis showed high population differentiation in a restricted area (GST = 27%), mostly due to differences among populations within basins (GSC = 22%). The reduction of GST observed when the isolated samples were excluded from the analysis (GST = 17%) showed the importance of habitat fragmentation on the heterogeneity detected. Gene flow among populations was comparatively evaluated by three indirect methods, which in general revealed low figures of absolute number of migrants per generation, slightly higher than 1. The gene flow among basins reflected a positive relationship with geographical distance. This trend was confirmed by the significant correlation observed between geographical and genetic distances, including all population pairs, which suggests a component of isolation by distance in brown trout genetic structure. Nevertheless, the nonsignificant intrabasin correlation demonstrates the complexity of genetic relationships among populations in this species. The model of genetic structure in brown trout is discussed in the light of the results obtained.

Journal Article↗
PubMed1999

[Clinical-biological differences between invasive ductal carcinomas and breast lobular carcinomas. Preliminary results].

In order to know the biological differences between both histological types, we have analyzed some clinical and biological parameters in tissues of women having infiltrating carcinomas (247 ductal (IDCs) 17 and lobular (ILCs) of the breast. Our preliminary results led us to suggest the following. 1) In negative axillary lymph node involvement (N-) patients, ILCs were more frequently associated with diploidy and the existence of multiple foci; likewise, they had higher pS2 cytosolic levels than IDC; 2) in N+ patients, ILC were associated with multicentricity and had higher concentrations of progesterone receptors and 3) these findings could help to explain us the clinical and biological peculiarities, as well as, the clinical outcome of both histological types.

Adult↗
PubMed1999

Hepatic cytochrome oxidase in rats with microsurgical cholestasis or portocaval shunt.

AIMS: portocaval shunt and extrahepatic cholestasis are experimental models of chronic hepatic insufficiency of different etiology and histological characteristics, and which probably also differ in the mechanism of impairment of oxidative metabolism. To test this hypothesis we measured hepatic cytochrome oxidase. METHODS: cytochrome oxidase was assayed with a histochemical technique in three groups of Wistar rats: A (n = 8) control; B (n = 8) microsurgical extrahepatic cholestasis; and C (n = 8) end-to-side portocaval shunt. RESULTS: cytochrome oxidase activity was lowest in group B, both in the left middle (p = 0.00019) and in the inferior caudate (p = 0.00014) hepatic lobes, and was highest in group C in both hepatic lobes, especially in the left middle lobe (p = 0.0029). CONCLUSION: the decrease in cytochrome oxidase activity in the liver of rats with extrahepatic cholestasis and the increase in animals subjected to portal flow deprivation demonstrate the different nature of the impairment in hepatic oxidative metabolism in these two pathological conditions.

Animals↗
PubMed1998

Auxin-induced stress potentiates trans-activation by a conserved plant basic/leucine-zipper factor.

The promoter element activation sequence-1 (as-1) confers tissue-specific and signal-responsive transcription in plants. Hormone and chemical stress cues are thought to activate as-1-dependent transcription through specific basic/leucine-zipper proteins, termed TGA factors, that bind this element. We report here that a highly conserved TGA factor of tobacco, TGA1a, can selectively activate transcription in response to micromolar concentrations of auxin hormones or their analogs. This induction is chemically specific, as a range of other compounds tested at similar concentrations had little or no effect. Auxin was found to augment the trans-activation potential of TGA1a through carboxyl-terminal residues. The amino-terminal domain of TGA1a, by gain-of-function assays, was found to both constitutively activate transcription and maximize the response to auxin. Further evidence indicates that the trans-activation potential of this domain in TGA1a is repressed, under basal conditions, by carboxyl-terminal residues. Because TGA1a and endogenous TGA factors are stimulated by auxin only at concentrations that inhibited cell growth, this response is likely to involve chemical stress.

Basic-Leucine Zipper Transcription Factors↗
PubMed1998

Maintenance treatment with interferon alpha-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology).

The objectives of the present study were to investigate whether interferon alpha (IFN) maintenance could prolong response duration and survival in patients with multiple myeloma (MM) in objective response and to analyze the characteristics of relapse and subsequent survival. From January 1991 to November 1994, 92 patients from the Spanish Cooperative Group PETHEMA with MM in objective response after 12 courses of VCMP/VBAP chemotherapy were randomized to receive IFN maintenance vs no treatment until relapse. Prognostic factors at diagnosis were similar in both groups. IFN was administered at a starting dose of 3 mU/m2 three times per week. The IFN toxicity was moderate with granulocytopenia and fatigue being the most common adverse effects. Median duration of response from randomization until relapse was 13 months in the IFN group vs 7.7 months in the no treatment arm (P = 0.042). Median survival from randomization was 38.8 months for patients given IFN vs 32.7 months for those allocated to the no treatment arm (P = 0.12). Features at relapse were similar in patients who received IFN maintenance and in those assigned to no treatment. Finally, survival from relapse was identical in both groups. In summary, our results show a significant prolongation of response in patients maintained with IFN with no significant influence on survival. In addition, in our series features at relapse and subsequent outcome were similar in both groups.

Aged↗
PubMed1998

Role of vascular endothelial growth factor in the response to vessel injury.

In the post-embryonic life, physiological angiogenesis is tightly controlled. Angiogenesis also occurs in pathological circumstances such as tumor vessel proliferation, retinal neovascularization and ischemia. The development of collateral circulation is not only not deleterious, but life saving. Other cases such as neoplastic neovascularization are the basis of the continuous growth of tumors and metastases, and therefore constitute a target of therapeutical efforts. Among a list of molecules able to control angiogenesis, we emphasize the pivotal role of vascular endothelial growth factor (VEGF). VEGF is a potent mitogen for endothelial cells, but is devoid of mitogenic activity for other cell types. VEGF is a polypeptide with four main different isoforms that are remarkably different in terms of solubility and affinity for matrix proteins. VEGF interacts with two endothelial cell-specific tyrosine kinase receptors. The main interest of its study lies in VEGF's role in pathological angiogenic processes, where an increase in the VEGF mRNA expression has been consistently observed. An interesting example is the up-regulation of VEGF's and VEGF receptors' mRNA in a considerable number of human tumors and retina, where they have a critical role in the development of neovascularization. In recent work in our laboratory, we have found further potential interactions of VEGF with pathophysiological mechanisms, namely, the increase in VEGF gene expression under exposure to reactive oxygen species and the positive interaction between VEGF and erythropoietin. VEGF has outstanding possibilities for therapeutic applications aimed at inhibiting or favoring the development of new vessels.

Endothelial Growth Factors↗
PubMed1997

Changes of cytochrome oxidase activity in rat suprachiasmatic nucleus.

This paper evaluates the changes of cytochrome oxidase (CO) activity that take place in the suprachiasmatic nucleus (SCN) during the light-dark cycle. CO is a mitochondrial energy-generating enzyme used as a marker of neural oxidative metabolism. We measured CO activity using quantitative histochemistry calibrated with brain tissue standards and a computerized analysis image system. The results indicate that the CO enzyme activity changes on the basis of a circadian pattern, with the higher levels during the light phase (P < 0.0001). These changes are detected over a period of hours, in accordance with other studies on the possible short-term regulation of CO activity in the nervous system. It is, therefore, possible to apply this methodology to the study of the SCN and other brain areas which show functional rhythmicity.

Animals↗
PubMed1997

Portacaval shunt control animals: physiological consequences derived from the sham operation.

The portacaval shunt in the rat is a frequently used experimental model of portosystemic encephalopathy. Among other consequences of this surgical preparation is an important decrease in hepatic and testicular volume. Different sham-operation methods including a laparotomy were used as controls in each case. Given that the liver volume varies greatly in comparison to body weight in the sham-operated animals, this paper aims to evaluate the possible consequences of the sham operation. It concludes that control animals without manipulation, in addition to the respective controls of portacaval shunt, should be used in every case.

Analysis of Variance↗
PubMed1996

Adaptor-mediated recruitment of RNA polymerase II to a signal-dependent activator.

The second messenger cAMP stimulates the expression of a number of target genes via the protein kinase A-mediated phosphorylation of CREB at Ser-133 (Gonzalez, G. A., and Montminy, M. R. (1989) Cell 59, 675-680). Ser-133 phosphorylation enhances CREB activity by promoting interaction with a 265-kDa CREB binding protein referred to as CBP (Arias, J., Alberts, A., Brindle, P., Claret, F., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-228; Chrivia, J. C., Kwok, R. P., Lamb, N., Hagiwara, M., Montminy, M. R., and Goodman, R. H. (1993) Nature 365, 855-859). The mechanism by which CBP in turn mediates induction of cAMP-responsive genes is unknown but is thought to involve recruitment of basal transcription factors to the promoter. Here we demonstrate that CBP associates specifically with RNA polymerase II in HeLa nuclear extracts. This association in turn permits RNA polymerase II to be recruited to CREB in a phospho-(Ser-133)-dependent manner. As anti-CBP antiserum, which inhibits recruitment of CBP and RNA polymerase II to phospho-(Ser-133) CREB, attenuates transcriptional induction by protein kinase A in vitro, our results demonstrate that the CBP-RNA polymerase II complex is critical for expression of cAMP-responsive genes.

CREB-Binding Protein↗