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1.
Glob Chang Biol ; 20(6): 1929-42, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24464954

RESUMEN

Global climate models suggest enhanced warming of the tropical mid and upper troposphere, with larger temperature rise rates at higher elevations. Changes in fire activity are amongst the most significant ecological consequences of rising temperatures and changing hydrological properties in mountainous ecosystems, and there is a global evidence of increased fire activity with elevation. Whilst fire research has become popular in the tropical lowlands, much less is known of the tropical high Andean region (>2000 masl, from Colombia to Bolivia). This study examines fire trends in the high Andes for three ecosystems, the Puna, the Paramo and the Yungas, for the period 1982-2006. We pose three questions: (i) is there an increased fire response with elevation? (ii) does the El Niño- Southern Oscillation control fire activity in this region? (iii) are the observed fire trends human driven (e.g., human practices and their effects on fuel build-up) or climate driven? We did not find evidence of increased fire activity with elevation but, instead, a quasicyclic and synchronous fire response in Ecuador, Peru and Bolivia, suggesting the influence of high-frequency climate forcing on fire responses on a subcontinental scale, in the high Andes. ENSO variability did not show a significant relation to fire activity for these three countries, partly because ENSO variability did not significantly relate to precipitation extremes, although it strongly did to temperature extremes. Whilst ENSO did not individually lead the observed regional fire trends, our results suggest a climate influence on fire activity, mainly through a sawtooth pattern of precipitation (increased rainfall before fire-peak seasons (t-1) followed by drought spells and unusual low temperatures (t0), which is particularly common where fire is carried by low fuel loads (e.g., grasslands and fine fuel). This climatic sawtooth appeared as the main driver of fire trends, above local human influences and fuel build-up cyclicity.


Asunto(s)
Cambio Climático , Clima , Ecosistema , Incendios , Altitud , Bosques , Pradera , Humanos , América del Sur , Tundra
2.
Sci Data ; 11(1): 782, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013892

RESUMEN

We present a flora and fauna dataset for the Mira-Mataje binational basins. This is an area shared between southwestern Colombia and northwestern Ecuador, where both the Chocó and Tropical Andes biodiversity hotspots converge. We systematized data from 120 sources in the Darwin Core Archive (DwC-A) standard and geospatial vector data format for geographic information systems (GIS) (shapefiles). Sources included natural history museums, published literature, and citizen science repositories across 13 countries. The resulting database has 33,460 records from 6,821 species, of which 540 have been recorded as endemic, and 612 as threatened. The diversity represented in the dataset is equivalent to 10% of the total plant species and 26% of the total terrestrial vertebrate species in both hotspots. The dataset can be used to estimate and compare biodiversity patterns with environmental parameters and provide value to ecosystems, ecoregions, and protected areas. The dataset is a baseline for future assessments of biodiversity in the face of environmental degradation, climate change, and accelerated extinction processes.


Asunto(s)
Biodiversidad , Plantas , Ecuador , Animales , Colombia , Vertebrados , Sistemas de Información Geográfica , Ecosistema , Cambio Climático , Conservación de los Recursos Naturales , Clima Tropical
3.
Poult Sci ; 102(10): 102950, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37540949

RESUMEN

Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is associated with septicemia resulting in acute mortality with no premonitory signs in turkeys. Three SG isolates were obtained from clinical field cases of acute septicemia of commercial turkeys and used in three independent experiments. In Experiment 1, embryos were inoculated 25 d of embryogenesis with varying concentrations of SG1, SG2, or SG3. In Experiment 2, day of hatch, poults were inoculated with varying concentrations using different routes of administration of SG1, SG2, or SG3. In Experiment 3, day of hatch, poults were inoculated with only isolate SG1 using different paths. Poults were randomly selected for necropsy on d 8 and d 15 and sampled to collect spleen, heart, and liver for SG on d 21, the remaining poults were necropsied and cultured. Samples were plated on Columbia nalidixic acid and colistin agar (CNA) (40°C, 18-24 h). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed suspect colonies. Data were analyzed using the chi-square test of independence, testing all possible combinations to determine significance (P < 0.05). Weight data were subjected to ANOVA using JMP with significance (P < 0.05). No differences were found in BW or BWG on d 0, 8, 15, or 22. Splenomegaly, focal heart necrosis, and pericarditis were observed in all groups in experiments 1 through 3. In Experiment 3, only airsacculitis was observed in a negative control in separate isolation (P > 0.05). On d 21 of Experiment 3, increased (P < 0.05) recovery of SG from spleens were observed in co-housed negative controls, as well as poults challenged by oral gavage (P > 0.05 for d 7 and d 14). These results confirm numerous previous studies indicating that SG subsp. pasteurianus is a primary infectious microorganism that causes septicemia in young poults.


Asunto(s)
Enfermedades de las Aves de Corral , Sepsis , Animales , Pollos , Proyectos Piloto , Sepsis/veterinaria , Streptococcus gallolyticus , Pavos
4.
Cir Pediatr ; 25(1): 4-8, 2012 Jan.
Artículo en Español | MEDLINE | ID: mdl-23113404

RESUMEN

INTRODUCTION: Thanks to the generalization of minimally invasive surgery in pediatric patients some classic techniques are being replaced. Inguinal hernia repair may be an example. MATERIAL AND METHODS: We present the technique and our first results in 10 patients treated by percutaneous laparoscopic assisted herniotomy. For this purpose we used an umbilical port, for a 5 mm camera and an optional 2 mm grasper. By laparoscopic guidance we make two inguinal punctures with a 20G needle that introduces a non absorbable suture that crosses the whole inguinal defect and allows it closure by extracorporeal knot tying. RESULTS: The ages ranged between 1 month and 8 years with a median age of 10 months. 50% of the patients were boys. 50% of the patients had previous diagnosis of inguinal bilateral hernia. 30% of patients presented a postoperatory diagnosis different from the previous one. The average time of intervention was 32 minutes in bilateral hernias, and 19 in the unilateral ones. Follow-up time was 6 months without complications. The aesthetic result was ideal. CONCLUSION: Percutaneous laparoscopic assisted herniotomy is an effective, simple and feasible option for inguinal hernia in chidren without a high rate of complications.


Asunto(s)
Hernia Inguinal/cirugía , Herniorrafia/métodos , Laparoscopía , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino
5.
New Phytol ; 189(4): 967-977, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21077887

RESUMEN

• We present the results from a litter translocation experiment along a 2800-m elevation gradient in Peruvian tropical forests. The understanding of the environmental factors controlling litter decomposition is important in the description of the carbon and nutrient cycles of tropical ecosystems, and in predicting their response to long-term increases in temperature. • Samples of litter from 15 species were transplanted across all five sites in the study, and decomposition was tracked over 448 d. • Species' type had a large influence on the decomposition rate (k), most probably through its influence on leaf quality and morphology. When samples were pooled across species and elevations, soil temperature explained 95% of the variation in the decomposition rate, but no direct relationship was observed with either soil moisture or rainfall. The sensitivity of the decay rate to temperature (κ(T)) varied seven-fold across species, between 0.024 and 0.169 °C⁻¹, with a mean value of 0.118 ± 0.009 °C⁻¹ (SE). This is equivalent to a temperature sensitivity parameter (Q10) for litter decay of 3.06 ± 0.28, higher than that frequently assumed for heterotrophic processes. • Our results suggest that the warming of approx. 0.9 °C experienced in the region in recent decades may have increased decomposition and nutrient mineralization rates by c. 10%.


Asunto(s)
Altitud , Hojas de la Planta/fisiología , Temperatura , Árboles/fisiología , Clima Tropical , Geografía , Humedad , Cinética , Perú , Lluvia , Suelo , Especificidad de la Especie , Factores de Tiempo
6.
Cir Pediatr ; 24(4): 237-40, 2011 Oct.
Artículo en Español | MEDLINE | ID: mdl-23155639

RESUMEN

INTRODUCTION: Minimally invasive surgery (CMI) for the treatment of malignant tumors in children begins to have a role for selected cases and reaches similar results than open surgery. We show our first two cases of Wilms tumor treated by laparoscopy describing patients and technique. MATERIAL AND METHODS: Three-year-old girl with macroscopic hematuria is diagnosed of 8 cm mass in the left kidney suggesting Wilms tumor. After 4 weeks of chemotherapy she went under laparoscopic nephroureterectomy. The histological result was Wilms tumor. Chemotherapy was completed seven more months. Five-year-old patient with abdominal pain is diagnosed of renal right mass suggesting Wilms tumor. After 4 weeks of chemotherapy the laparoscopic nephroureterectomy was performed. The histological result was Wilms tumor. Treatment was completes with postoperatory chemotherapy. RESULTS: After 1 year follow-up both patients have clinical and radiological absence of disease. CONCLUSION: The CMI in selected cases of Wilms tumor fulfills successfully the aims of the surgical treatment.


Asunto(s)
Neoplasias Renales/cirugía , Laparoscopía , Nefrectomía/métodos , Uréter/cirugía , Tumor de Wilms/cirugía , Preescolar , Femenino , Humanos
7.
Cir Pediatr ; 24(2): 109-11, 2011 Apr.
Artículo en Español | MEDLINE | ID: mdl-22097659

RESUMEN

UNLABELLED: INTRODUCION AND AIM: The enterostomy used in the treatment of Necrotizing Enterocolitis (NEC) causes many complications before and after its closure. The aim of this study was to examine the complications of closure aiming at determining the best timing for this operation. PATIENTS AND METHOD: Retrospective review patients (p) below 1500 g with NEC in whom the enterostomy was closed in the last seven years. P were divided into two groups: PC (planned closure after uncomplicated postoperative period) and CC (advanced closure due to stomal--excessive looses--or to parenteral nutrition complications--septicemia, liver dysfunction-). We compared the age at closure, time of enterostomy, weight gain and complications. RESULTS: Out of a total of 25 p requiring surgical treatment for NEC, 16 from the PC group and 9 from the CC group were included. The mean age at the moment of the closure were, respectively, 129 + 65 vs. 204 +/- 121 days (p < 0.05). Weight at closure was 2665 +/- 841 vs. 4665 +/- 2076 g (p < 0.05); the mean time with the enterostomy was 105 +/- 64 vs. 187 +/- 116 d (p < 0.05), and the weight gain was 1779 +/- 859 vs. 3693 +/- 2155 g (p < 0.05). After stomal closure, 7/16 p of the CC group (43%) and 2/9 of the PC group (22%) required reoperation due to severe complications (ns). In 4 of them, three of the CC group and one of the PC group, a new enterostomy was performed. CONCLUSIONS: In p with enterostomy-related complications, closure has often to be advanced and it is performed in deficient nutritional conditions. Severe complications after enterostomy closure required reoperation in 43% of the CC group and in 22% of the PC group. Although there was no statistically significant difference, the trend indicates an augmented risk in CC group. The timing for enterostomy closure should be chosen individually. At the time of indicating the closure, the high risk of complications, should be taken into account particularly in preterms with enterostomy-related problems.


Asunto(s)
Técnicas de Cierre de Herida Abdominal/normas , Enterocolitis Necrotizante/cirugía , Enterostomía/normas , Humanos , Recién Nacido , Estudios Retrospectivos , Factores de Tiempo
8.
Artículo en Inglés, Español | MEDLINE | ID: mdl-33191151

RESUMEN

PURPOSE: To describe the results of MRI (magnetic resonance image) guided ROLL (radioguided occult lesion localization) and SNOLL (sentinel node occult lesion localization) in the localization of residual disease after neoadjuvant chemotherapy for breast cancer, as well as assessing the surgical results obtained and disease free survival. METHODS: Prospective observational analysis of 132 patients with 136 tumors, treated with neoadjuvant chemotherapy at our hospital between 2011-2017. Residual disease was located presurgically with MRI guided ROLL/SNOLL technique. We analyzed technical aspects of localization, and variables corresponding to surgical procedures and events occurred during follow-up. RESULTS: The median tumor size was of 20.5mm (interquartilic range [IQR]: 14-28). The majority (96.3%) were invasive ductal carcinomas. Sentinel lymph node detection rate was 98.9%. Complete pathological response (CPR) in the breast was achieved in 58.1% of cases. The rate of affected margins in 89 cases operated by conservative surgery was 2.2%. With a median follow-up of 50 months (IQR: 37-61) we found a 7.4% rate of relapses. Of these, seven were loco-regional and three at distant sites. The estimated mean of disease-free survival time was 83.2 months (Confidence Interval [CI] 95%: 79.6-86.6). CONCLUSIONS: MRI guided ROLL/SNOLL is a great tool for breast cancer residual disease localization following neoadjuvant chemotherapy. In addition, this technique attains good loco-regional control of the diseases and has excellent surgical results.

9.
J Gynecol Obstet Hum Reprod ; 50(5): 102004, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33242678

RESUMEN

OBJECTIVE: To determine the feasibility,tolerability, and safety of the ultrasound assessment of tubal patency using foam as contrast. METHODS: This was a prospective multicenter study of 915 infertile nulliparous women scheduled for sonohysterosalpingography with foam instillation (HYFOSY) for tubal patency testing as a part of the fertility workup. Clinical and sonographic data were recorded into a web-shared database. Tubal patency, cervical catheterization, pain during the procedure and post-procedural complications were collected. Patients reported discomfort or pain experienced during the procedure with a visual analogue scale (VAS) score. RESULTS: Nine hundred fifteen women were included in the final analysis. Median age was 34 (range, 21-45) years and median body mass index was 23 (range, 16-41) kg/m2. Of 839 women, only 8(0.95 %) cases were abandoned due to impossibility of introducing the intracervical catheter. Most of the cervical os were easily cannulated with either paediatric nasogastric probes or special catheter for intrauterine insemination / sonohysterosalpingography 688/914(75.3 %). With a median instillation of 4 mL (range 1-16) of foam, both tubes were identified in 649/875 (70.9 %) patients, while unilateral patency was observed in 190/875 (20.8 %). Only 36/875 (3.9 %) of the women had bilateral tubal obstruction. The median VAS score for perception of pain during HyFoSy examination was 2 (range 0-10), and only 17 (1.9 %) of women reported severe pain (VAS ≥ 7). Pain was unrelated to tubal patency or tubal blockage. Unexpectedly, difficult cervical catheterizations that needed tenaculum, were more likely associated with mild pain during procedure [nasogastric probe group 176/289 (70.9 %) vs. insemination catheter group 166/399 (41.6 %) vs. tenaculum group 190/218(87.2 %) p < 0.001]. Finally, among 915 patients, we only noticed 3 (0.32 %) complications of the technique: two vasovagal episodes and a mild urinary infection. CONCLUSION: HYFOSY is a feasible, well-tolerated and safe technique for the evaluation of tubal patency in infertile women.


Asunto(s)
Enfermedades de las Trompas Uterinas/diagnóstico por imagen , Pruebas de Obstrucción de las Trompas Uterinas/métodos , Trompas Uterinas/diagnóstico por imagen , Ultrasonografía/métodos , Útero/diagnóstico por imagen , Adulto , Índice de Masa Corporal , Cateterismo/efectos adversos , Cateterismo/instrumentación , Cateterismo/métodos , Cuello del Útero , Medios de Contraste , Estudios de Factibilidad , Femenino , Fase Folicular , Humanos , Infertilidad Femenina , Persona de Mediana Edad , Dimensión del Dolor , Dolor Asociado a Procedimientos Médicos/etiología , Estudios Prospectivos , España , Ultrasonografía/efectos adversos , Cremas, Espumas y Geles Vaginales , Adulto Joven
10.
Science ; 284(5413): 499-502, 1999 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-10205060

RESUMEN

Cytokine and proto-oncogene messenger RNAs (mRNAs) are rapidly degraded through AU-rich elements in the 3' untranslated region. Rapid decay involves AU-rich binding protein AUF1, which complexes with heat shock proteins hsc70-hsp70, translation initiation factor eIF4G, and poly(A) binding protein. AU-rich mRNA decay is associated with displacement of eIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of hsp70 by heat shock, down-regulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 all result in hsp70 sequestration of AUF1 in the perinucleus-nucleus, and all three processes block decay of AU-rich mRNAs and AUF1 protein. These results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Respuesta al Choque Térmico , Ribonucleoproteína Heterogénea-Nuclear Grupo D , Complejos Multienzimáticos/metabolismo , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/metabolismo , Ubiquitinas/metabolismo , Regiones no Traducidas 3' , Proteínas Portadoras/metabolismo , Núcleo Celular/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Citoplasma/metabolismo , Factor 4G Eucariótico de Iniciación , Proteínas del Choque Térmico HSC70 , Células HeLa , Ribonucleoproteína Nuclear Heterogénea D0 , Humanos , Leupeptinas/farmacología , Factores de Iniciación de Péptidos/metabolismo , Proteínas de Unión a Poli(A) , Complejo de la Endopetidasa Proteasomal , Unión Proteica , Proto-Oncogenes Mas , ARN Mensajero/genética , Transfección
11.
An Sist Sanit Navar ; 42(1): 49-54, 2019 Apr 25.
Artículo en Español | MEDLINE | ID: mdl-30895967

RESUMEN

BACKGROUND: The present study aims to evaluate the safety and effectiveness of the Boussignac continuous positive airway pressure device (CPAPB) when used during the transportation of infants under three months of age with bronchiolitis. METHODS: Transversal analytical observational study of four years duration. Data was collected on 25 infants who needed inter-hospital transportation to the reference Paediatric Intensive Care Unit (PICU), with CPAPB and Helmet interface. The epidemiological characteristics of the transportation and evolution in the PICU were registered, as well as the cardiorespiratory gastronomic parameters prior to transfer and on arrival at the PICU. RESULTS: The median level of continuous airway pressure (CPAP) used during the transfer was 7 cm H2O (6-7.25). No patient required endotracheal intubation during transportation, while one patient required this during the first six hours of admission in the PICU. The following cardiorespiratory parameters presented a statistically significant improvement on arrival at the PICU: modified Wood-Downes score [8.40 (2.1) vs 5.29 (1.68)], respiratory frequency [60.72 (12.73) vs 47.28 (10.31)], cardiac frequency [167.28 (22.60) vs 154.48 (24.83)] and oxygen saturation [92.08 (5.63) vs 97.64 (2.27)]. CONCLUSIONS: Application of CPAPB proved to be a safe method of respiratory support in infants under three months of age. Its use during transportation brought an improvement in cardiorespiratory parameters.


Asunto(s)
Bronquiolitis/terapia , Presión de las Vías Aéreas Positiva Contínua/instrumentación , Unidades de Cuidado Intensivo Pediátrico , Transporte de Pacientes/métodos , Diseño de Equipo , Femenino , Humanos , Lactante , Recién Nacido , Intubación Intratraqueal/métodos , Masculino
12.
Mol Cell Biol ; 19(6): 4167-81, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10330157

RESUMEN

Gcd10p and Gcd14p were first identified genetically as repressors of GCN4 mRNA translation in Saccharomyces cerevisiae. Recent findings indicate that Gcd10p and Gcd14p reside in a nuclear complex required for the presence of 1-methyladenosine in tRNAs. Here we show that Gcd14p is an essential protein with predicted binding motifs for S-adenosylmethionine, consistent with a direct function in tRNA methylation. Two different gcd14 mutants exhibit defects in cell growth and accumulate high levels of initiator methionyl-tRNA (tRNAiMet) precursors containing 5' and 3' extensions, suggesting a defect in processing of the primary transcript. Dosage suppressors of gcd10 mutations, encoding tRNAiMet (hcIMT1 to hcIMT4; hc indicates that the gene is carried on a high-copy-number plasmid) or a homologue of human La protein implicated in tRNA 3'-end formation (hcLHP1), also suppressed gcd14 mutations. In fact, the lethality of a GCD14 deletion was suppressed by hcIMT4, indicating that the essential function of Gcd14p is required for biogenesis of tRNAiMet. A mutation in GCD10 or deletion of LHP1 exacerbated the defects in cell growth and expression of mature tRNAiMet in gcd14 mutants, consistent with functional interactions between Gcd14p, Gcd10p, and Lhp1p in vivo. Surprisingly, the amounts of NME1 and RPR1, the RNA components of RNases P and MRP, were substantially lower in gcd14 lhp1::LEU2 double mutants than in the corresponding single mutants, whereas 5S rRNA was present at wild-type levels. Our findings suggest that Gcd14p and Lhp1p cooperate in the maturation of a subset of RNA polymerase III transcripts.


Asunto(s)
Proteínas de Unión al ADN , Proteínas Fúngicas/fisiología , Proteínas Quinasas/fisiología , ARN de Transferencia de Metionina/fisiología , Proteínas de Unión al ARN/fisiología , Proteínas Represoras/fisiología , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Alelos , Secuencia de Aminoácidos , Northern Blotting , Mapeo Cromosómico , Clonación Molecular , Cruzamientos Genéticos , Eliminación de Gen , Humanos , Modelos Genéticos , Datos de Secuencia Molecular , Mutagénesis , Fenotipo , Plásmidos , Biosíntesis de Proteínas , S-Adenosilmetionina/genética , Análisis de Secuencia de ADN , Factores de Tiempo , ARNt Metiltransferasas
15.
Oncogene ; 35(27): 3535-43, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-26522726

RESUMEN

Breast cancer is the leading cause of cancer-related deaths among women. Approximately 75% of breast cancers are estrogen receptor-α (ERα) positive, underscoring the dependence of cancer cells on estrogen for growth and survival. Patients treated with endocrine therapy often develop resistance, either de novo or acquired, which in some cases is caused by aberrations within the growth factor signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) has emerged as a critical node in estrogenic signaling. We have previously shown that mTORC1 can phosphorylate and activate ERα on S167 via its effector-the 40S ribosomal S6 kinase 1 (S6K1). Presently, we have uncovered a direct link between mTORC1 and ERα. We found that ERα binds to regulatory-associated protein of mTOR (Raptor) and causes it to translocate to the nucleus upon estrogen stimulation. In addition, we identified mTOR as the kinase that phosphorylates ERα on S104/106 and activates transcription of ER target genes. Our findings show a direct link between mTORC1 and ERα, which further implicates mTORC1 signaling in the pathogenesis of ER-positive breast cancer and provides rationale for FDA-approved use of mTORC1 inhibitors in combination with endocrine agents for treatment of this disease.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Receptor alfa de Estrógeno/metabolismo , Estrógenos/farmacología , Complejos Multiproteicos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transporte Activo de Núcleo Celular/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Antagonistas de Estrógenos/farmacología , Receptor alfa de Estrógeno/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Células MCF-7 , Diana Mecanicista del Complejo 1 de la Rapamicina , Microscopía Fluorescente , Complejos Multiproteicos/genética , Fosforilación/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Interferencia de ARN , Proteína Reguladora Asociada a mTOR , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/genética , Tamoxifeno/farmacología
17.
Genetics ; 148(3): 1007-20, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9539420

RESUMEN

In Saccharomyces cerevisiae, expression of the transcriptional activator GCN4 increases at the translational level in response to starvation for an amino acid. The products of multiple GCD genes are required for efficient repression of GCN4 mRNA translation under nonstarvation conditions. The majority of the known GCD genes encode subunits of the general translation initiation factor eIF-2 or eIF-2B. To identify additional initiation factors in yeast, we characterized 65 spontaneously arising Gcd- mutants. In addition to the mutations that were complemented by known GCD genes or by GCN3, we isolated mutant alleles of two new genes named GCD14 and GCD15. Recessive mutations in these two genes led to highly unregulated GCN4 expression and to derepressed transcription of genes in the histidine biosynthetic pathway under GCN4 control. The derepression of GCN4 expression in gcd14 and gcd15 mutants occurred with little or no increase in GCN4 mRNA levels, and it was dependent on upstream open reading frames (uORFs) in GCN4 mRNA that regulate its translation. We conclude that GCD14 and GCD15 are required for repression of GCN4 mRNA translation by the uORFs under conditions of amino acid sufficiency. The gcd14 and gcd15 mutations confer a slow-growth phenotype on nutrient-rich medium, and gcd15 mutations are lethal when combined with a mutation in gcd13. Like other known GCD genes, GCD14 and GCD15 are therefore probably required for general translation initiation in addition to their roles in GCN4-specific translational control.


Asunto(s)
Proteínas de Unión al ADN , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Genes Fúngicos , Genes Reguladores , Biosíntesis de Proteínas , Proteínas Quinasas/genética , ARN de Hongos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Oxidorreductasas de Alcohol , Aminohidrolasas , Clonación Molecular , Epistasis Genética , Factor 2 Eucariótico de Iniciación/metabolismo , Factor 2B Eucariótico de Iniciación , Eliminación de Gen , Genes Dominantes , Genes Recesivos , Prueba de Complementación Genética , Meiosis , Mutagénesis , Fenotipo , Pirofosfatasas , ARN Mensajero , Factores de Transcripción/genética , Transcripción Genética
18.
Clin Cancer Res ; 1(3): 343-9, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9815990

RESUMEN

Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors.


Asunto(s)
Neoplasias del Ojo/patología , Fibrinolisina/metabolismo , Glicoproteínas , Inhibidores de Crecimiento/fisiología , Neoplasias Pulmonares/secundario , Melanoma/patología , Hormonas Testiculares/fisiología , Animales , Hormona Antimülleriana , Arginina , División Celular , Neoplasias del Ojo/terapia , Femenino , Inhibidores de Crecimiento/genética , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Masculino , Melanoma/terapia , Ratones , Ratones SCID , Conductos Paramesonéfricos/fisiología , Mutagénesis Sitio-Dirigida , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Serina , Hormonas Testiculares/genética , Transfección , Células Tumorales Cultivadas
19.
Ecancermedicalscience ; 9: 605, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26715942

RESUMEN

Benign multicystic mesothelioma is a rare tumour that originates from the abdominal peritoneum with a predisposition to the pelvic peritoneum. It typically affects women of reproductive age. There have been less than 200 cases of this rare neoplasia reported to date. We present the case of a 35-year-old woman who was referred to our centre because of the detection of a peritoneal carcinomatosis during a gynaecological exam. A diagnostic laparoscopy was performed. The findings included multiple cysts appearing as 'a bunch of grapes' occupying the omentum. Biopsies were taken during the surgery and the results showed benign multicystic peritoneal mesothelioma. Benign multicystic mesothelioma can simulate other conditions, such as malignant ovarian tumours or cystic lymphangioma. It is often diagnosed accidentally during surgery performed for another reason. The diagnosis is interoperative, observing multicystic structures grouped as a 'bunch of grapes' containing clear fluid with thin walls made of connective tissue. Immunohistochemistry confirmed mesothelial origin. Surgery is considered the treatment of choice and is based on the removal of the cysts from the abdominal cavity. Hyperthermic intraperitoneal chemotherapy can be considered as a primary treatment in patients with recurrences or even as a part of primary treatment associated with surgery. Survival at 5 years is 100% and invasive or malignant progression is extraordinary. The treatment approach should be multidisciplinary, and the patient should be referred to a referral centre.

20.
Eur J Cell Biol ; 78(9): 657-64, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10535308

RESUMEN

Human C4b-binding protein (C4BP) is an important regulator of the complement system that also binds and inactivates the anticoagulant vitamin K-dependent protein S. These two activities are performed by two distinct polypeptides of 70 kDa and 45 kDa known as alpha and beta chains, respectively. C4BP is present in plasma in various isoforms with different alpha/beta composition. We report here that C4BPbeta, but not C4BPalpha, is expressed in adult human ovary. Expression of C4BPbeta was detected in all ovarian biopsies analyzed (n = 15), independently of age and phase of the menstrual cycle. In situ hybridization and immunostaining analyses on cryostat sections demonstrated expression of C4BPbeta in both regressing corpus luteum and corpus albicans, but not in the follicles, the corpus luteum, the ovary stroma or the vascular cells. In addition, we noted that the expression pattern of the C4BPbeta mRNA resembles that described for the connective tissue that invades the degenerating corpus luteum and causes a progressive fibrosis that gradually converts it into a scar, the corpus albicans. RT-PCR and immunostaining analyses of primary cultures derived from human ovaries demonstrated the presence of fibroblast-like cells that express C4BPbeta. As a whole, these data suggest a role for the C4BPbeta in human ovary during the healing and scar resorption processes that leads to the formation of the corpus albicans and its replacement by ovarian stroma.


Asunto(s)
Proteínas Inactivadoras de Complemento , Glicoproteínas , Ovario/metabolismo , Receptores de Complemento/metabolismo , Adulto , Anciano , Células Cultivadas , Cuerpo Lúteo/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Inmunohistoquímica , Microscopía Confocal , Persona de Mediana Edad , Ovario/anatomía & histología , Proteína S/metabolismo , ARN/metabolismo , Receptores de Complemento/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Distribución Tisular
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