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1.
PLoS One ; 18(4): e0283370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37036870

RESUMO

Rain-fed pastoral systems are tightly connected to meteorological conditions. It is, therefore, likely that climate change, including changing atmospheric CO2 concentration, temperature, precipitation and patterns of climate extremes, will greatly affect pastoral systems. However, exact impacts on the productivity and carbon dynamics of these systems are still poorly understood, particularly over longtime scales. The present study assesses the potential effects of future climatic conditions on productivity and soil organic carbon (SOC) stocks of mowed and rotationally grazed grasslands in France. We used the CenW ecosystem model to simulate carbon, water, and nitrogen cycles in response to changes in environmental drivers and management practices. We first evaluated model responses to individual changes in each key meteorological variable to get better insights into the role and importance of each individual variable. Then, we used 3 sets of meteorological variables corresponding to 3 Representative Concentration Pathways (RCP 2.6, RCP 4.5 and RCP 8.5) for long-term model runs from 1975 to 2100. Finally, we used the same three RCPs to analyze the responses of modelled grasslands to extreme climate events. We found that increasing temperature slightly increased grasslands productivities but strongly reduced SOC stocks. A reduction in precipitation led to reductions of biomass and milk production but increased SOC. Conversely, doubling CO2 concentration strongly increased biomass and milk production and marginally reduced SOC. These SOC trends were unexpected. They arose because both increasing precipitation and CO2 increased photosynthetic carbon gain, but they had an even greater effect on the proportion of biomass that could be grazed. The amount of carbon remaining on site and able to contribute to SOC formation was actually reduced under both higher precipitation and CO2. The simulations under the three RCPs indicated that grassland productivity was increased, but that required higher N fertilizer application rates and also led to substantial SOC losses. We thus conclude that, while milk productivity may continue at current rates under climate change, or even increase slightly, there could be some soil C losses over the 21st century. In addition, under the highest-emission scenario, the increasing importance of extreme climate conditions (heat waves and droughts) might render conditions at our site in some years as unsuitable for milk production. It highlights the importance of tailoring farming practices to achieve the dual goals of maintaining agricultural production while safeguarding soil C stocks.


Assuntos
Carbono , Solo , Ecossistema , Pradaria , Mudança Climática , Dióxido de Carbono
2.
Support Care Cancer ; 29(7): 3585-3592, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33159221

RESUMO

PURPOSE: Misconceptions regarding activity and toxicity of therapeutic interventions are common among cancer patients. There is little knowledge about the factors that contribute to a more realistic perception by patients. METHODS: This pilot study was designed as a prospective questionnaire survey and included 101 therapy-naïve patients treated at the Division of Oncology, Medical University of Vienna. After obtaining written informed consent, patients' expectations about treatment aims, side effects and the satisfaction with their oncologic consultation were interrogated before the first treatment cycle by questionnaires. RESULTS: Of 101 patients, 53 (53%) were female and 67/101 (66%) were treated with curative attempt in an adjuvant or neo-adjuvant setting. The most common diagnoses were lung cancer (31%) and breast cancer (30%). Although 92% of patients were satisfied with the information given by their oncologist, palliative patients were more likely to declare that not everything was explained in an intelligible manner (p = 0.01). Patients with a first language other than German stated more often that their physician did not listen carefully enough (p = 0.02). Of 30 patients, 26 (87%) receiving chemotherapy with palliative intent believed that their disease was curable. Concerning adverse events, female patients anticipated more frequently hair loss (p = 0.003) and changes in taste (p = 0.001) compared to men. Patients under curative treatment were more likely to expect weight loss (p = 0.02) and lack of appetite (p = 0.01) compared to patients with palliative treatment intent. CONCLUSION: In conclusion, cancer patients were satisfied with the patient-doctor communication. This prospective study aggregated patients' concerns on side effects and the perception of therapeutic goals in therapy-naïve patients. Of note, the majority of patients treated in the palliative setting expected their treatment to cure the disease.


Assuntos
Neoplasias/terapia , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Estudos Prospectivos
4.
Cell Death Dis ; 4: e635, 2013 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-23681230

RESUMO

We explored the activity of SIRT1 activators (SRT501 and SRT2183) alone and in combination with panobinostat in a panel of malignant lymphoid cell lines in terms of biological and gene expression responses. SRT501 and SRT2183 induced growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and reduction of c-Myc protein levels. PCR arrays revealed that SRT2183 leads to increased mRNA levels of pro-apoptosis and DNA-damage-response genes, accompanied by accumulation of phospho-H2A.X levels. Next, ChIP assays revealed that SRT2183 reduces the DNA-binding activity of both NF-κB and STAT3 to the promoter of GADD45G, which is one of the most upregulated genes following SRT2183 treatment. Combination of SRT2183 with panobinostat enhanced the anti-growth and anti-survival effects mediated by either compound alone. Quantitative-PCR confirmed that the panobinostat in combination with SRT2183, SRT501 or resveratrol leads to greater upregulation of GADD45G than any of the single agents. Panobinostat plus SRT2183 in combination showed greater inhibition of c-Myc protein levels and phosphorylation of H2A.X, and increased acetylation of p53. Furthermore, EMSA revealed that NF-κB binds directly to the GADD45G promoter, while STAT3 binds indirectly in complexes with NF-κB. In addition, the binding of NF-κB/STAT3 complexes to the GADD45G promoter is inhibited following panobinostat, SRT501 or resveratrol treatment. Moreover, the combination of panobinostat with SRT2183, SRT501 or resveratrol induces a greater binding repression than either agent alone. These data suggest that STAT3 is a corepressor with NF-κB of the GADD45G gene and provides in vitro proof-of-concept for the combination of HDACi with SIRT1 activators as a potential new therapeutic strategy in lymphoid malignancies.


Assuntos
Histona Desacetilases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Sirtuína 1/metabolismo , Acetilação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/química , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfoma/metabolismo , Linfoma/patologia , NF-kappa B/genética , Panobinostat , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Resveratrol , Fator de Transcrição STAT3/genética , Sirtuína 1/química , Estilbenos/farmacologia , Regulação para Cima/efeitos dos fármacos , Proteínas GADD45
5.
Leukemia ; 25(10): 1543-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21625235

RESUMO

Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b.i.d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Quinolonas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/farmacocinética , Recidiva , Fatores de Risco
6.
Rofo ; 181(3): 255-63, 2009 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-19229791

RESUMO

PURPOSE: The purpose of this study was to compare the diagnostic accuracy of whole-body MRI (WB-MRI) and bone scintigraphy (BS) for the screening of bone metastases for the first time in a large and homogeneous patient collective with breast cancer in a systematic and controlled study. MATERIALS AND METHOD: 213 breast cancer patients were evaluated for bone metastases under randomized, double-blinded and prospective conditions at two hospitals. All participants were examined by WB-MRI and BS over an average period of four days. The examinations were performed separately at two different locations. The WB-MRI protocol included T 1-TSE and STIR sequences. WB-MRI and BS were reviewed independently by experienced radiologists and nuclear medicine specialists in a consensus reading. RESULTS: In 66 % of cases bone metastases were excluded by both procedures, and bone metastases were detected concordantly in 2 % of cases. In 7 % of cases there were discrepant results: in 7 cases BS was false-positive when WB-MRI was negative. In 5 / 7 cases BS was negative when WB-MRI identified bone metastases. In 89 % of cases BS was uncertain when WB-MRI was true-negative. In 17 % of cases WB-MRI showed important (non-) tumor-associated findings. The sensitivity, specificity, positive and negative predictive value and diagnostic accuracy for WB-MRI were 90 %, 94 %, 82 %, 98 % and 99 % and for BS those were 40 %, 81 %, 36 %, 91 % and 93 %. CONCLUSION: It could be demonstrated that WB-MRI is superior to BS for detecting bone metastases in breast cancer patients. These results should be considered for the next version of the S 3 guideline "Diagnosis, Therapy and Follow-Up of Breast Cancer".


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/diagnóstico , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Cintilografia , Imagem Corporal Total/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/diagnóstico , Osso e Ossos/patologia , Neoplasias da Mama Masculina/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/secundário , Medronato de Tecnécio Tc 99m/análogos & derivados
7.
Bone Marrow Transplant ; 40(9): 843-50, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17724447

RESUMO

We retrospectively evaluated the outcome of reduced-intensity conditioning (RIC) followed by allogeneic hematopoietic stem cell transplantation (HCT) in 43 patients with myelodysplastic syndrome (MDS) or AML arising from MDS. All patients received fludarabine plus melphalan followed by an allogeneic HCT from an HLA-identical sibling (SIB: n=19) or unrelated donor (MUD: n=24). Median age was 58 years (range: 30-71). Diagnoses at transplantation were RA (n=8), RARS (n=1), RAEB (n=13), RAEB-T (n=6), or AML arising from MDS (n=15). Of 28 patients with MDS, two patients had low, 10 had intermediate-1, nine had intermediate-2 and seven had high-risk MDS by IPSS criteria. All patients initially engrafted with the median neutrophil recovery of 15 days (range: 9-27). The 2-year overall survival, disease-free survival, relapse and transplant-related mortality were 53.5% (CI 45.2-61.1), 51.2% (CI 43.3-58.5), 16.3% (CI 7.9-30.7) and 35.2% (26.4-45.7), respectively. Grade II-IV acute graft-versus-host disease occurred in 27 (63%) patients. There was no significant survival difference between SIB and MUD-HCT, but the relapse rate was higher among SIB donor recipients when compared to MUD (38.5 versus 7%, P=0.02). RIC with fludarabine plus melphalan was associated with durable disease control and acceptable toxicity in this high-risk cohort.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Melfalan/uso terapêutico , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adulto , Idoso , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Melfalan/toxicidade , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/prevenção & controle , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Vidarabina/uso terapêutico , Vidarabina/toxicidade
8.
Plant Biol (Stuttg) ; 7(1): 58-66, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15666215

RESUMO

Previous work has shown that the apparent quantum yield of CO2 fixation can be reduced for up to several minutes after prior exposure to darkness. In the work reported here, we investigated this phenomenon more fully and have deduced information about the underlying processes. This was done mainly by concurrent measurements of O2 and CO2 exchange in an oxygen-free atmosphere. Measurements of O2 evolution indicated that photochemical efficiency was not lost through dark adaptation, and that O2 evolution could proceed immediately at high rates provided that there were reducible pools of photosynthetic intermediates. Part of the delay in reaching the full quantum yield of CO2 fixation could be attributed to the need to build up pools of photosynthetic intermediates to high enough levels to support steady rates of CO2 fixation. There was no evidence that Rubisco inactivation contributed towards delayed CO2 uptake (under measurement conditions of low light). However, we obtained evidence that an enzyme in the reaction path between triose phosphates and RuBP must become completely inactivated in the dark. As a consequence, in dark-adapted leaves, a large amount of triose phosphates were exported from the chloroplast over the first minute of light rather than being converted to RuBP for CO2 fixation. That pattern was not observed if the pre-incubation light level was increased to just 3-5 micromol quanta m(-2) s(-1). The findings from this work underscore that there are fundamental differences in enzyme activation between complete darkness and even a very low light level of only 3-5 micromol quanta m(-2) s(-1) which predispose leaves to different gas exchange patterns once leaves are transferred to higher light levels.


Assuntos
Dióxido de Carbono/fisiologia , Escuridão , Helianthus/fisiologia , Fotossíntese/fisiologia , Helianthus/efeitos da radiação , Folhas de Planta/fisiologia , Folhas de Planta/efeitos da radiação , Ribulose-Bifosfato Carboxilase/fisiologia , Fatores de Tempo
9.
Plant Biol (Stuttg) ; 6(3): 242-53, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15143433

RESUMO

Climate change affects plants in many different ways. Increasing CO(2) concentration can increase photosynthetic rates. This is especially pronounced for C(3) plants, at high temperatures and under water-limited conditions. Increasing temperature also affects photosynthesis, but plants have a considerable ability to adapt to their growth conditions and can function even at extremely high temperatures, provided adequate water is available. Temperature optima differ between species and growth conditions, and are higher in elevated atmospheric CO(2). With increasing temperature, vapour pressure deficits of the air may increase, with a concomitant increase in the transpiration rate from plant canopies. However, if stomata close in response to increasing CO(2) concentration, or if there is a reduction in the diurnal temperature range, then transpiration rates may even decrease. Soil organic matter decomposition rates are likely to be stimulated by higher temperatures, so that nutrients can be more readily mineralised and made available to plants. This is likely to increase photosynthetic carbon gain in nutrient-limited systems. All the factors listed above interact strongly so that, for different combinations of increases in temperature and CO(2) concentration, and for systems in different climatic regions and primarily affected by water or nutrient limitations, photosynthesis must be expected to respond differently to the same climatic changes.


Assuntos
Efeito Estufa , Fotossíntese/fisiologia , Transpiração Vegetal/fisiologia , Dióxido de Carbono/farmacologia , Clima , Modelos Biológicos , Fotossíntese/efeitos dos fármacos , Temperatura , Água/fisiologia
10.
Arch Pediatr Adolesc Med ; 155(12): 1323-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11732950

RESUMO

CONTEXT: Bronchiolitis is the most common lower respiratory tract infection in infancy. A recent Centers for Disease Control and Prevention report confirmed that hospitalization rates for bronchiolitis have increased 2.4-fold from 1980 to 1996. Controversies exist about optimal treatment plans. Milliman and Robertson recommend ambulatory care management; in case of hospitalization, the recommended length of stay is 1 day. OBJECTIVES: To relate actual practice variation for infants admitted with uncomplicated bronchiolitis to Milliman and Robertson's recommendations. DESIGN: Prospective observational study. SETTING: General care wards of 8 pediatric hospitals of the Child Health Accountability Initiative during the winter of 1998-1999. PATIENTS: First-time admissions for uncomplicated bronchiolitis in patients not previously diagnosed as having asthma and who were younger than 1 year. MAIN OUTCOME MEASURES: Respiratory rate, monitored interventions, attainment of discharge criteria goals, and length of stay. RESULTS: Eight hundred forty-six patients were included in the final analysis: 85.7% were younger than 6 months, 48.5% were nonwhite, and 64.1% were Medicaid recipients or self-pay. On admission to the hospital, 18.3% of the infants had respiratory rates higher than higher than 80 breaths per minute, 53.8% received supplemental oxygen therapy, and 52.6% received intravenous fluids. These proportions decreased to 1.9%, 33.8%, and 20.3%, respectively, 1 day after admission, and to 0.7%, 20.1%, and 8.6%, respectively, 2 days after admission. The average length of stay was 2.8 days (SD, 2.3 days). CONCLUSIONS: Milliman and Robertson's recommendations do not correspond to practice patterns observed at the hospitals participating in this study; no hospital met the Milliman and Robertson recommended 1-day goal length of stay. Administration of monitored intervention persisted past the second day of hospitalization.


Assuntos
Assistência Ambulatorial , Bronquiolite/terapia , Hospitalização , Guias de Prática Clínica como Assunto , Hidratação , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Avaliação de Processos e Resultados em Cuidados de Saúde , Oxigenoterapia , Padrões de Prática Médica , Estudos Prospectivos
11.
Eur J Endocrinol ; 145(2): 187-92, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11454515

RESUMO

BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.


Assuntos
Hidroxiprostaglandina Desidrogenases/genética , Hidroxiesteroide Desidrogenases/genética , Placenta/enzimologia , Gravidez/metabolismo , RNA Mensageiro/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2 , Adolescente , Adulto , Peso ao Nascer , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Humanos , Hidroxiprostaglandina Desidrogenases/biossíntese , Hidroxiesteroide Desidrogenases/biossíntese , Recém-Nascido , Trabalho de Parto Prematuro/enzimologia , Placenta/fisiologia , Segundo Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/genética , RNA Mensageiro/biossíntese , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Eur J Obstet Gynecol Reprod Biol ; 97(2): 163-7, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11451542

RESUMO

OBJECTIVE: To investigate the maturation of the paracrine system's endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), endothelin-1 (ET-1) and adrenomedullin (AM) in human placenta during the 2nd and 3rd trimester of pregnancy. STUDY DESIGN: Placental tissue from 14 healthy women with normal pregnancy and from 13 patients giving birth to premature infants following premature labor was obtained. Messenger RNA expression was determined using quantitative TaqMan real-time PCR. RESULTS: Placental eNOS/GAPDH and ET-1/GAPDH mRNA expression significantly increased as a function of gestational age (r=0.63, P<0.001 and r=0.53, P=0.007, respectively). There was no change in gene expression of neither iNOS nor AM mRNA/GAPDH during gestation (r=0.02, P=0.75 and r=0.001, P=0.99, respectively). CONCLUSION: There is a maturation of eNOS and ET-1 in human placenta with gestation reflecting developmental changes of important paracrine endothelial and trophoblastic regulators. AM and iNOS show no maturation during pregnancy.


Assuntos
Endotelina-1/genética , Expressão Gênica , Óxido Nítrico Sintase/genética , Placenta/metabolismo , RNA Mensageiro/análise , Adrenomedulina , Adulto , Feminino , Idade Gestacional , Gliceraldeído-3-Fosfato Desidrogenases/genética , Humanos , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III , Peptídeos/genética , Placenta/química , Placenta/enzimologia , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Clin Endocrinol Metab ; 86(3): 1313-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11238526

RESUMO

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.


Assuntos
Expressão Gênica , Hidroxiprostaglandina Desidrogenases/genética , Hidroxiesteroide Desidrogenases/genética , Placenta/enzimologia , Pré-Eclâmpsia/enzimologia , 11-beta-Hidroxiesteroide Desidrogenases , Adolescente , Adulto , Peso ao Nascer , Cortisona/metabolismo , Feminino , Idade Gestacional , Humanos , Hidrocortisona/metabolismo , Recém-Nascido , Recém-Nascido Prematuro , Reação em Cadeia da Polimerase , Gravidez , Proteinúria , RNA Mensageiro/análise
14.
ScientificWorldJournal ; 1: 271-80, 2001 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-12806084

RESUMO

There is the concern among some countries that compliance costs with commitments under the Kyoto Protocol may be unacceptably high. There is also the concern that technical difficulties with the inclusion of land use, land-use change, and forestry activities in non-Annex I countries might lead to an effective exclusion of such activities from consideration under the Protocol. This paper is proposing a mechanism that addresses both these concerns. In essence, it is suggested that parties should be able to purchase fixed-price offset certificates if they feel they cannot achieve compliance through other means alone, such as by improved energy efficiency, increased use of renewable energy, or use of the flexible mechanisms in the Kyoto Protocol. These offset certificates would act as a price cap for the cost of compliance for any party to the Protocol. Revenues from purchase of the offset certificates would be directed to forest-based activities in non-Annex I countries such as forest protection that may carry multiple benefits including enhancing net carbon sequestration.


Assuntos
Fontes Geradoras de Energia/economia , Agricultura Florestal/economia , Efeito Estufa , Fidelidade a Diretrizes , Cooperação Internacional
15.
J Cell Biochem Suppl ; 34: 52-60, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10762015

RESUMO

Cancer chemoprevention trials can be directed at targeting established molecular mechanisms which contribute to neoplasia. One potential target is the ErbB/HER family of growth factor receptors with intrinsic tyrosine kinase activity. This group of four receptors mediates the action of multiple stromal ligands of the EGF/neuregulin family on the adjacent epithelium. Aberrant autocrine loops and overexpression of certain receptors, especially ErbB-2 (also called HER2 or Neu), play a role in fixation and propagation of oncogenic mutations. Here we concentrate on ErbB-2 and epithelial cancer and discuss current and future therapeutic strategies that may limit cancer, particularly in patients who are at high risk after removal of the primary tumor. Because ErbB-2 acts as a shared co-receptor, and its heterodimers are relatively potent receptor combinations, it offers selectivity that spares other routes of signal transduction. Immunotherapy, as well as gene therapy and tyrosine kinase inhibitors specific to ErbB-2 may join the ranks of effective chemopreventive agents.


Assuntos
Neoplasias/metabolismo , Neoplasias/terapia , Receptor ErbB-2/metabolismo , Inibidores Enzimáticos/uso terapêutico , Epitélio/patologia , Terapia Genética/métodos , Humanos , Imunoterapia/métodos , Imunotoxinas/uso terapêutico , Neoplasias/patologia , Neurregulinas/metabolismo , Receptor ErbB-2/efeitos dos fármacos , Receptor ErbB-2/genética , Transdução de Sinais
16.
Adv Cancer Res ; 77: 25-79, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10549355

RESUMO

Carcinoma, cancer of epithelial cells, is a major cause of morbidity and mortality in Western societies. Clonal fixation and propagation of oncogenic genetic changes, sporadically accumulating in epithelial cells, depend on growth factors and their surface receptors. One of the large families of receptors is that of the ErbB tyrosine kinases, which bind multiple neuregulins and other epidermal growth factor-like molecules. Certain ErbB members and their ligands are involved in human cancers of various origins. However, most of the clinical data relate to ErbB-2, a protein whose overexpression in subsets of carcinomas can predict poor prognosis. Although no ligand has so far been assigned to ErbB-2, recent biochemical evidence implies that this oncoprotein operates as a shared receptor subunit of other ErbBs. Several biochemical attributes enable ErbB-2 to act as an epithelial cell amplifier of stroma-derived growth factor signals: It delays ligand dissociation, enhances coupling to the mitogen-activated protein kinase pathway, and impedes the rate of receptor downregulation. The realization that ErbB-2 is a master regulator of a signaling network that drives epithelial cell proliferation identifies this protein as a target for cancer therapy. Indeed, various ErbB-2-directed therapeutic approaches, including immunological and genetic therapies, demonstrate promising clinical potential.


Assuntos
Neoplasias/genética , Neoplasias/terapia , Receptor ErbB-2/fisiologia , Receptores de Fatores de Crescimento/fisiologia , Transdução de Sinais , Evolução Biológica , Genes erbB-2 , Terapia Genética , Humanos , Imunoterapia , Receptor ErbB-2/genética
17.
J Clin Endocrinol Metab ; 84(8): 2755-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10443674

RESUMO

The objective of the present study was to examine the impact of preeclampsia on the relation of leptin and neuropeptide Y (NPY) gene expression in human placenta. A second goal was to monitor the change of leptin messenger RNA (mRNA) with increasing gestational age. Placental tissue was obtained from 17 premature deliveries, 18 term deliveries, and 10 mothers with preeclampsia. Gene expression of leptin, NPY, and two housekeeping genes (beta-actin and glyceraldehyde-3-phosphate dehydrogenase was quantified using real-time PCR. The leptin/beta-actin mRNA ratio was significantly higher in specimens of patients with preeclampsia than in those of gestational age-matched controls (0.63+/-0.23 vs. 0.09+/-0.04 relative U (RU); P = 0.03). NPY/beta-actin mRNA was significantly reduced in the preeclampsia group (0.003+/-0.001 vs. 0.026+/-0.008 RU in controls; P = 0.01). The NPY/leptin ratio was 0.11+/-0.09 for preeclamptic placenta samples and 1.7+/-0.6 RU for the controls (P = 0.02). The leptin/beta-actin ratio was significantly lower in placenta from premature deliveries than in term deliveries (0.02+/-0.004 vs. 0.12+/-0.05 RU; P = 0.01). Similar results were obtained for normalization to glyceraldehyde-3-phosphate dehydrogenase mRNA. Our data suggest an increase of placental leptin production with gestational age. In patients with preeclampsia, elevated leptin expression goes along with suppressed NPY expression. This resembles hypothalamic regulation.


Assuntos
Hipotálamo/fisiologia , Neuropeptídeo Y/genética , Placenta/metabolismo , Proteínas/genética , RNA Mensageiro/análise , Adulto , Feminino , Idade Gestacional , Humanos , Leptina , Pré-Eclâmpsia/metabolismo , Gravidez
18.
Leuk Lymphoma ; 34(1-2): 185-90, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10350348

RESUMO

Allogeneic peripheral blood stem cell transplantation (allo PBSCT) is a recognized treatment modality for hematological malignancies resistant to conventional chemoradiotherapy. The post-transplant immune-mediated graft-versus-leukemia effect has major curative potential. In this case presentation, the allogeneic approach to resistant recurrent primary central nervous system (CNS) lymphoma using peripheral blood stem cells from an HLA identical sibling after immuno-suppressive non-myeloablative conditioning, was examined clinically. The patient in question had relapsing refractory primary CNS lymphoma and is the first to be treated with this modality. She developed early skin and liver-localized grade II graft-versus-host disease after allo PBSCT, which then responded to short-term treatment. Chimeric studies at the time showed 100% donor cells and repeated magnetic resonance imaging of the brain revealed gradual shrinkage of the tumor. Three months after transplant the cerebral mass was no longer evident and currently, 30 months after transplantation, the patient continues to be disease free. The absence of any signs of malignancy suggests the development of a durable graft-versus-lymphoma effect in this brain tumor and indicates that this effect may be achieved even after non-myeloablative conditioning.


Assuntos
Neoplasias Encefálicas/terapia , Efeito Enxerto vs Tumor , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B/terapia , Adulto , Neoplasias Encefálicas/imunologia , Feminino , Humanos , Linfoma de Células B/imunologia , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Transplante Homólogo
19.
Tree Physiol ; 19(9): 551-562, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12651529

RESUMO

The efficiency with which trees use water is a major determinant of growth under water-limited conditions. We investigated whether increased access to water and nutrients alters water-use efficiency in Pinus radiata D. Don. Intrinsic transpiration efficiency, defined here as the ratio of CO(2) assimilated and water transpired at a given vapor pressure deficit, is determined by the difference between ambient atmospheric CO(2) concentration (c(a)) and leaf intercellular CO(2) concentration (c(i)). The mean value of c(i)/c(a) can be inferred from an analysis of carbon isotope discrimination (Delta) in wood samples. A total of 117 trees, growing at sites with widely varying soil and climatic conditions in Australia and New Zealand, were cored and distinct annual rings were analyzed for their carbon isotope ratio, and correlated with rainfall during the July-June growing season in the year in which the wood was grown. Where possible, carbon isotope ratios were compared for different years within the same trees. The c(i)/c(a) ratio decreased with decreasing water availability, suggesting that intrinsic transpiration efficiency increased with decreasing water availability. An increase in growing season rainfall of 900 mm resulted in an increase in Delta of about 2.0 per thousand, corresponding to a decrease in intrinsic transpiration efficiency of approximately 24%. A stronger relationship was obtained when carbon isotope discrimination was expressed as a function of the ratio of rainfall to potential transpiration. Carbon isotope discrimination was also negatively correlated with mean annual vapor pressure deficit at different sites. In contrast, nutrient availability had no significant effect on carbon isotope discrimination.

20.
Eur J Obstet Gynecol Reprod Biol ; 76(2): 189-91, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9481573

RESUMO

Leiomyomatosis peritonealis disseminata (LPD) is a rare disease characterised by the presence of multiple smooth muscle tumour nodules throughout the peritoneal cavity. Approximately 50 cases of LPD have been reported to date in the world literature. There is a very high association with excess exogenous and endogenous female gonadal steroids, specifically oestrogen and progesterone. LPD has been described almost only in premenopausal women and is mostly asymptomatic. Four cases of malignant transformation of this disease have been reported. We report a case of a patient with prolonged exposure to oral contraceptives, operated because of hypermenorrhea and 'myoma in statu nascendi'. A metastasing myomatous tumour was suspected during the operation. LPD was diagnosed by intraoperative histological examination. Abdominal hysterectomy was performed. Five months later a second laparotomy had to be done because of an ovarian endometriosis tumour of about 10 cm size. A bilateral salpingo-oophorectomy and omentectomy were performed.


Assuntos
Endometriose/complicações , Leiomiomatose/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adulto , Anticoncepcionais Orais/efeitos adversos , Endometriose/patologia , Tubas Uterinas/cirurgia , Feminino , Humanos , Histerectomia , Intestinos/patologia , Leiomiomatose/complicações , Leiomiomatose/cirurgia , Músculo Liso/patologia , Omento/patologia , Ovariectomia , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/cirurgia
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