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M Arellano

Publications and source records attributed to M Arellano.

28 records · Page 2Linked to original sources
PubMed1997

Regulation of CDK/cyclin complexes during the cell cycle.

The eukaryotic cell cycle is regulated by the temporal activation of different cyclin-dependent kinase (CDK)/cyclin complexes. Whilst the level of the catalytic subunit of the complex, the CDK, remains relatively constant through the cycle, the level of the cyclin subunit generally oscillates. Cyclins are synthesized, bind and activate the CDK and are then destroyed. In this review, we summarize the current knowledge of the regulation of the cell cycle by CDK/cyclin complexes with special emphasis on new developments in cyclin biosynthesis and destruction, the structural analysis of the CDK/cyclin complexes and the role of a set of inhibitors of CDK/cyclin complexes that are important for the coordination of the different stages of the cell cycle.

Animals↗
PubMed1997

5-Ethynyluracil (GW776): effects on the formation of the toxic catabolites of 5-fluorouracil, fluoroacetate and fluorohydroxypropionic acid in the isolated perfused rat liver model.

We studied the effects of 5-ethynyluracil (GW776), a potent inactivator of dihydropyrimidine dehydrogenase, on the metabolism of 5-fluorouracil (5-FU), in particular with respect to formation of the toxic compounds fluoroacetate (FAC) and 2-fluoro-3-hydroxypropionic acid (FHPA), using fluorine-19 nuclear magnetic resonance and the isolated perfused rat liver model. Livers were perfused with 5-FU alone at a dose of 15 mg kg(-1) body weight or with 5-FU + GW776 at doses of 15 mg 5-FU kg(-1) body weight and 0.5 mg GW776 kg(-1) body weight injected 1 h before 5-FU. All 5-FU was metabolized in experiments with 5-FU alone whereas unmetabolized 5-FU represented 94% of the fluorinated compounds measured in experiments with 5-FU + GW776. GW776 modulated both the catabolic and the anabolic pathways of 5-FU, the most striking effect being on the degradative pathway. The amount of 5-FU catabolites decreased by a factor of 27 in the presence of GW776. The modulator led to a decrease in alpha-fluoro-beta-alanine (FBAL) formation by a factor of approximately 110, while fluoride ion formation decreased by a factor of approximately 10. By strongly lowering the metabolism of 5-FU into FBAL, GW776 circumvented the transformation of FBAL into toxic FAC and FHPA. 5-FU anabolites increased by a factor of approximately 7 in the presence of GW776. The level of free fluoronucleotides and 5-fluorouridine-5'-diphosphate sugars was increased up to fivefold. No incorporation of 5-FU into RNA could be measured in experiments with 5-FU alone whereas, although low (0.1% of 5-FU injected dose), it was detectable in experiments with 5-FU + GW776. These results suggest that GW776 may be useful for attenuating the not very common but serious cardiotoxic and/or neurotoxic side-effects of 5-FU that are probably due to FBAL metabolites.

Animals↗
PubMed1997

Localisation of the Schizosaccharomyces pombe rho1p GTPase and its involvement in the organisation of the actin cytoskeleton.

The Schizosaccharomyces pombe rho1p GTPase directly activates the (1-3) beta-D-glucan synthase and participates in the regulation of cell wall growth and morphogenesis in this fission yeast. Indirect immunofluorescence experiments using rho1p tagged with hemagglutinin have revealed that rho1p was located at the growing tips during interphase and at the septum prior to cytokinesis, localising to the same areas as actin patches. In S. pombe cdc10-129 mutant cells, arrested in G1, HA-rho1p accumulates at one tip whereas in cdc25-22 mutants, arrested in G2, HA-rho1p accumulates at both tips. In tea1-1 and tea2-1 cdc11-119 mutant cells, HA-rho1p is localised to the new growing tips. Overexpression of different rho1 mutant alleles caused different effects on cortical actin patch distribution, (1-3) beta-D-glucan synthase activation, and sensitivity to cell wall specific antifungal drugs. These results indicate that multiple cellular components are activated by rho1p. Overexpression of the dominant negative rho1T20N allele was lethal as was the rho1+ deletion. Moreover, when rho1+ expression was repressed in actively growing S. pombe, cells died in about 10 to 12 hours. Under these conditions, normal cell morphology was maintained but the level of (1-3) beta-D-glucan synthase activity decreased and the actin patches disappeared. Most cells lysed after cytokinesis during the process of separation, and lysis was not prevented by an osmotic stabiliser. We conclude that rho1p localisation is restricted to growth areas and regulated during the cell cycle and that rho1p is involved in cell wall growth and actin cytoskeleton organisation in S. pombe.

Actins↗
PubMed1997

[Disability in the private pension system in Chile].

BACKGROUND: The degree of disability of workers ascribed to the private allowances system in Chile, is judged by Medical Commissions that apply norms that establish percentages of incapacity, without considering prognosis. AIM: To communicate the causes of disability among Chilean workers ascribed to the private allowances system, their mortality and to correlate the causes of death with diagnoses. SUBJECTS AND METHODS: We analyzed 13,456 consecutive cases judged between August 1990 and April 1992. Mortality was registered up to 12 months after judgment. RESULTS: Total incapacity was determined in 4,158 cases (30.9%), partial incapacity in 1,340 (9.9%) and minor incapacity in 7,958 (59.1%). Osteoarticular diseases were the main cause of disability in 4,460 patients (33.1%) and 77.8% of patients with malignant tumors were considered as having total incapacity. Mortality was 17% among subjects with total incapacity, 1.5% among those with partial disability and 1% among those with minor disability. The cause of death was related to the main disabling disease in 94% of subjects with total incapacity and 66.6% of those with partial incapacity. CONCLUSIONS: Osteoarticular diseases are the main cause of inability among workers ascribed to a private pension system.

Chile↗
PubMed1996

Rho 1 GTPase activates the (1-3)beta-D-glucan synthase and is involved in Schizosaccharomyces pombe morphogenesis.

The Schizosaccharomyces pombe Cdc42 and Rho1 GTPases were tested for their ability to complement the cwg2-1 mutant phenotype of a decrease in (1-3)beta-D-glucan synthase activity when grown at the non-permissive temperature. Only Rho1 is able to partly complement the defect in glucan synthase associated with the cwg2-1 mutation. Moreover, overexpression of the rho1 gene in wild-type S.pombe cells causes aberrant morphology with loss of polarity and cells with several septa. Under this condition (1-3)beta-D-glucan synthase activity is increased four times, but is still dependent on GTP. When S.pombe is transformed with constitutively active rho1 mutant alleles (rho1-G15V or rho1-Q64L), cells stop growing and show a very thick cell wall with hardly any septum. Under this condition the level of (1-3)beta-D-glucan synthase activity is at least 20 times higher than wild-type and is independent of GTP. Neither cdc42+ nor the cdc42-V12G or cdc42-Q61L constitutively active mutant alleles affect (1-3)beta-D-glucan synthase activity when overexpressed in S.pombe. Cells overproducing Rho1 are hypersensitive to inhibitors of cell wall biosynthesis or to cell wall degrading enzymes. We conclude that Rho1 GTPase directly activates (1-3)beta-D-glucan synthase and regulates S.pombe morphogenesis.

Cell Cycle Proteins↗
PubMed1996

Characterization of cwl1+, a gene from Schizosaccharomyces pombe whose overexpression causes cell lysis.

From a Schizosaccharomyces pombe genomic library we have isolated the gene cwl1+ that causes cell lysis when it is overexpressed in the absence of an osmotic stabilizer. Southern hybridization showed that cwl1+ exists as a single copy in the S. pombe genome. The cwl1+ gene nucleotide sequence revealed a putative open reading frame of 924 bp encoding a polypeptide of 308 amino acids with a calculated Mt of 27000. The cwl1+ DNA hybridizes to a major RNA transcript of 1.5 kb whose 5' end maps at a position 452 bp upstream from the predicted translation start. Comparison of the amino acid sequence with those included in the current databases, showed no significant similarity to any known sequences. Cells overexpressing the cwl1+ gene under the control of the S. pombe nmt inducible promoter displayed a reduced cell wall content, were unable to separate after division and lysed drastically in the absence of osmotic stabilizer. Disruption of the cwl1+ gene caused no noticeable phenotype.

Amino Acid Sequence↗
PubMed1994

[Cardiotoxicity of 5-fluorouracil: a question of formulation].

The cardiotoxicity of 5-fluorouracil (FU) was attributed to degradation compounds present in the injected vials, fluoroacetaldehyde (Facet) and fluoromalonaldehydic acid (FMald). These compounds are formed with time in the basic medium necessary to solubilize FU. FU-NaOH vials were much less cardiotoxic than FU-Tris vials on the isolated perfused rabbit heart model since, in FU-Tris vials, Facet and FMald are stored in stable "depot" forms, which are adducts with Tris, whereas, in FU-NaOH vials, they are extensively chemically transformed. Cardiotoxic fluoroacetate (FAC), arising from Facet metabolization, was found in urine of patients, with a ratio FAC/FU catabolites 10-30 fold lower in patients treated with FU-NaOH than in those treated with FU-Tris.

Animals↗
PubMed1991

[Biological value of protein from leaves of Atriplex suberecta].

The study of Atriplex suberecta leaf protein concentrate has been included within our work line entitled "Biological value of the leaf protein of Atriplex" amino acid profile and chemical score. In order to evaluate nitrogen retention, net protein utilization (NPU), true digestibility (TD) and biological value (BV) data were obtained. Weight gain was studied after determining net protein ratio (NPR) and relative net protein ratio (RNPR) with the following results: CS = 96, calculated for sulphur amino acids; NPU = 60 +/- 4.00; TD = 76 +/- 5.20; BV = 87; NPR = 3.34 +/- 2.50 and RNPR = 88%, which enable us to infer that its protein is of good quality. These data, therefore, should indicate that the product studied could be a good complement for cereals, considering its high lysine content (CS superior to 100).

Amino Acids↗
PubMedDate not supplied

[A ketogenic diet: is this a valid alternative in refractory epilepsy].

INTRODUCTION: The ketogenic diet was first used in refractory epilepsy of childhood in the early 1920s. It was forgotten when new antiepileptic drugs were introduced, but recently has been used again. Although its efficacy in the treatment of epilepsy, in some patients, is beyond doubt, its mechanism of action is still not clear. There are three types of diet: the classical diet with a proportion of 4:1 of long chain fatty acids, with MCT oil and with modified MCT oil. OBJECTIVE: To present a protocol recently designed in our hospital. We include the type of diet, form of onset, subsequent follow up of complications, clinical and electroencephalographic response and side effects seen in the patients. PATIENTS AND METHODS: Introduction of the ketogenic diet with MCT oil in six patients aged between 2 and 11 years, with various types of epilepsy, all resistant to treatment, who had been unsuccessfully treated for 28 months in one case and between 4 and 6 months in the others. We evaluated the response on the criteria of Huttenlocher and Panic electroencephalograms. RESULTS: Two of the patients improved with good control of their disorder and the EEG became normal. No serious side effects were seen apart from gastrointestinal symptoms which improved when the quantity of MCT oil was reduced. CONCLUSIONS: In patients with drug resistant epilepsy it is convenient to have a guideline for treatment using a ketogenic diet. It is also useful to have a multi disciplinary team for management, follow up to detect late side effects and obtain the cooperation of the patient s family in following the protocol.

Child↗