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1.
Ann Surg Oncol ; 29(6): 3911-3920, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35041098

RESUMO

BACKGROUND: The Tumor Location-Modified Laurén Classification (MLC) system combines Laurén histologic subtype and anatomic tumor location. It divides gastric tumors into proximal non-diffuse (PND), distal non-diffuse (DND), and diffuse (D) types. The optimum classification of patients with Laurén mixed tumors in this system is not clear due to its grouping with both diffuse and non-diffuse types in previous studies. The clinical relevance of the MLC in a Western population has not been examined. METHODS: A cohort study investigated 404 patients who underwent gastrectomy for gastric adenocarcinoma between 2005 and 2020. The classification of Laurén mixed tumors was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of clinicopathologic characteristics (chi-square). Survival analysis was performed using multivariable Cox regression. RESULTS: The ROC curve analysis demonstrated a slightly higher area under the curve value for predicting survival when Laurén mixed tumors were grouped with intestinal-type rather than diffuse-type tumors (0.58 vs 0.57). Survival, tumor recurrence, and resection margin positivity in mixed tumors also was more similar to intestinal type. Distal non-diffuse tumors had the best 5-year survival (DND 64.7 % vs PND 56.1 % vs diffuse 45.1 %; p = 0.006) and were least likely to have recurrence (DND 27.0 % vs PND 34.3 % vs diffuse 48.3 %; p = 0.001). Multivariable analysis demonstrated that MLC was an independent prognostic factor for survival (PND: hazard ratio [HR], 1.64; 95 % confidence interval [CI], 1.16-2.32 vs diffuse: HR, 2.20; 95 % CI, 1.56-3.09) CONCLUSIONS: The MLC was an independent prognostic marker in this Western cohort of patients with gastric adenocarcinoma. The patients with PND and D tumors had worse survival than those with DND tumors.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Estudos de Coortes , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
2.
BJOG ; 128(9): 1487-1496, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33629490

RESUMO

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.


Assuntos
Hemoglobinas/análise , Recém-Nascido Pequeno para a Idade Gestacional , Morte Perinatal , Nascimento Prematuro/epidemiologia , Natimorto/epidemiologia , Adulto , Países em Desenvolvimento , Índices de Eritrócitos , Feminino , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Fatores de Risco
3.
BMC Public Health ; 21(1): 952, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016085

RESUMO

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).


Assuntos
Cesárea , Países em Desenvolvimento , Criança , Feminino , Humanos , Pobreza , Gravidez , Gestantes , Cuidado Pré-Natal
4.
Ecol Lett ; 22(7): 1136-1144, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074933

RESUMO

Sodium is unique among abundant elemental nutrients, because most plant species do not require it for growth or development, whereas animals physiologically require sodium. Foliar sodium influences consumption rates by animals and can structure herbivores across landscapes. We quantified foliar sodium in 201 locally abundant, herbaceous species representing 32 families and, at 26 sites on four continents, experimentally manipulated vertebrate herbivores and elemental nutrients to determine their effect on foliar sodium. Foliar sodium varied taxonomically and geographically, spanning five orders of magnitude. Site-level foliar sodium increased most strongly with site aridity and soil sodium; nutrient addition weakened the relationship between aridity and mean foliar sodium. Within sites, high sodium plants declined in abundance with fertilisation, whereas low sodium plants increased. Herbivory provided an explanation: herbivores selectively reduced high nutrient, high sodium plants. Thus, interactions among climate, nutrients and the resulting nutritional value for herbivores determine foliar sodium biogeography in herbaceous-dominated systems.


Assuntos
Pradaria , Herbivoria , Sódio , Adaptação Fisiológica , Animais , Nitrogênio , Plantas , Solo
5.
BJOG ; 125(9): 1137-1143, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29094456

RESUMO

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.


Assuntos
Causas de Morte , Saúde Global/estatística & dados numéricos , Morte Materna/classificação , Complicações na Gravidez/mortalidade , População Negra/estatística & dados numéricos , República Democrática do Congo/epidemiologia , Países em Desenvolvimento , Feminino , Guatemala/epidemiologia , Humanos , Renda , Índia/epidemiologia , Quênia/epidemiologia , Morte Materna/etiologia , Mortalidade Materna , Paquistão/epidemiologia , Gravidez , Estudos Prospectivos , Sistema de Registros , População Branca/estatística & dados numéricos , Zâmbia/epidemiologia
6.
BJOG ; 125(2): 131-138, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28139875

RESUMO

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.


Assuntos
Algoritmos , Sistema de Registros , Natimorto/epidemiologia , África/epidemiologia , Ásia/epidemiologia , Países em Desenvolvimento , Feminino , Saúde Global , Guatemala/epidemiologia , Humanos , Serviços de Saúde Materno-Infantil , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Prospectivos
7.
BJOG ; 125(12): 1591-1599, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29782696

RESUMO

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.


Assuntos
Serviços de Saúde Materno-Infantil , Área Carente de Assistência Médica , Assistência Perinatal , Complicações na Gravidez/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adolescente , Adulto , Análise por Conglomerados , Países em Desenvolvimento , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Masculino , Mortalidade Materna , Gravidez , Complicações na Gravidez/mortalidade , Adulto Jovem
8.
Science ; 374(6568): 768-772, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34735227

RESUMO

Clonal hematopoiesis results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. We developed a technique that combines mosaic mutagenesis with color labeling of HSPCs to study how acquired mutations affect clonal fitness in a native environment. Mutations in clonal hematopoiesis­associated genes such as asxl1 promoted clonal dominance. Single-cell transcriptional analysis revealed that mutations stimulated expression of proinflammatory genes in mature myeloid cells and anti-inflammatory genes in progenitor cells of the mutant clone. Biallelic loss of one such immunomodulator, nr4a1, abrogated the ability of asxl1-mutant clones to establish clonal dominance. These results support a model where clonal fitness of mutant clones is driven by enhanced resistance to inflammatory signals from their mutant mature cell progeny.


Assuntos
Hematopoiese Clonal , Células-Tronco Hematopoéticas/fisiologia , Inflamação , Células Mieloides/fisiologia , Animais , Sistemas CRISPR-Cas , Citocinas/genética , Citocinas/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Mutação da Fase de Leitura , Genes p53 , Inflamação/genética , Mutação , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , RNA-Seq , Proteínas Repressoras/genética , Seleção Genética , Análise de Célula Única , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
9.
J Exp Med ; 155(4): 1120-23, 1982 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-6278048

RESUMO

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain's inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the "genetic distance" statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus.


Assuntos
Vírus AKR da Leucemia Murina/genética , Genes Virais , Vírus da Leucemia Murina/genética , Camundongos Endogâmicos AKR/genética , Alelos , Animais , Mapeamento Cromossômico , Enzimas de Restrição do DNA , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
10.
Nat Commun ; 11(1): 6036, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247130

RESUMO

Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.


Assuntos
Biomassa , Pradaria , Herbivoria/fisiologia , Nitrogênio/análise , Fósforo/análise , Intervalos de Confiança , Fertilizantes , Fatores de Tempo
11.
Science ; 291(5513): 2616-9, 2001 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-11283376

RESUMO

There is increasing evidence that areas of outstanding conservation importance may coincide with dense human settlement or impact. We tested the generality of these findings using 1 degree-resolution data for sub-Saharan Africa. We find that human population density is positively correlated with species richness of birds, mammals, snakes, and amphibians. This association holds for widespread, narrowly endemic, and threatened species and looks set to persist in the face of foreseeable population growth. Our results contradict earlier expectations of low conflict based on the idea that species richness decreases and human impact increases with primary productivity. We find that across Africa, both variables instead exhibit unimodal relationships with productivity. Modifying priority-setting to take account of human density shows that, at this scale, conflicts between conservation and development are not easily avoided, because many densely inhabited grid cells contain species found nowhere else.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , África Subsaariana , Anfíbios , Animais , Aves , Humanos , Mamíferos , Densidade Demográfica , Crescimento Demográfico , Serpentes
12.
Nat Commun ; 10(1): 4981, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672992

RESUMO

Soil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nmin are laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nmin across 30 grasslands worldwide. We find that realised Nmin is largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nmin only weakly correlates with realised Nmin, but contributes to explain realised net Nmin when combined with soil and climatic variables. We provide novel insights of global realised soil net Nmin and show that potential soil net Nmin data available in the literature could be parameterised with soil and climate data to better predict realised Nmin.

13.
Space Sci Rev ; 214(1)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-30713357

RESUMO

OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This article describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at level 100 A/2 and <180 ng/cm2 of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication among scientists, engineers, managers, and technicians.

14.
Cancer Res ; 47(9): 2468-73, 1987 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-3032423

RESUMO

The in vitro transformation of normal T-lymphocytes by human T-cell leukemia/lymphoma virus (HTLV-I) is possible utilizing cocultivation techniques. We now report on a quantitative assay for HTLV-I transformation. Transformed cell lines were produced by cocultivation of either preactivated (phytohemagglutinin and T-cell growth factor) or nonactivated peripheral blood mononuclear cells with an equal number of lethally irradiated HTLV-I-positive donor cells (MT-2). After 14 days in liquid culture, transformed cells were plated in a 2-layer soft agarose system with or without T-cell growth factor (TCGF). Colony formation among 50 normal controls was observed at varying efficiencies with a mean number of 179 colonies (range, 6-599) in the presence of TCGF (up to a 2-log difference). The day 14 T-cell cultures demonstrated relatively low colony-forming efficiencies (less than or equal to 0.1%) and enhanced colony formation in the presence of TCGF. Day 14 after cocultivation was chosen for this assay based on a dose-response relationship between colony formation and the virus-positive donor cell inoculum and the known kinetics of colony growth of normal activated T-cells. An analysis of individual colonies indicated that they were of target cell origin and HTLV-I positive. Recombinant beta-interferon in increasing concentrations caused a decrease in colony formation as measured in this assay. Long-term cell cultures (2-18 months) showed higher colony-forming efficiencies (up to 1.0%) which were not enhanced by TCGF. The ability to quantitatively evaluate transformation via colony counts will provide an opportunity to study differences in transforming efficiencies attributable to varying target cells, donor cells, or blocking factors such as interferons, drugs, or anti-HTLV-I antibodies.


Assuntos
Transformação Celular Viral , Deltaretrovirus , Linfócitos T/microbiologia , Linhagem Celular , Ensaio de Unidades Formadoras de Colônias , Antígenos HLA/análise , Humanos , Interleucina-2/farmacologia , Cariotipagem , Linfócitos T/análise , Linfócitos T/efeitos dos fármacos , Fatores de Tempo
16.
Oncogene ; 15(3): 265-74, 1997 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-9233761

RESUMO

The inappropriate activation of protein-tyrosine kinases (PTKs) has been associated with initiation and progression of several types of human cancers. We therefore postulated that immortalization by DNA tumor viruses results in the induction of PTKs fundamental to these processes. An RT-PCR-based screen was thus used to identify PTKs that were abundantly expressed in HPV-18-immortalized epithelial cells and HPV-containing carcinoma cell lines. One of the genes isolated in this screen was the focal adhesion kinase (FAK; pp125FAK), a cytoplasmic protein kinase that is activated in v-src transformed cells or by stimulation with mitogenic polypeptides. FAK also becomes catalytically active upon integrin engagement with extracellular matrix proteins, such as fibronectin. We found that FAK expression and activity were significantly elevated in HPV-18 E6/E7-immortalized human genital epithelial cells relative to their primary cell counterparts. Protein expression and tyrosine phosphorylation of the putative FAK substrate, paxillin, were also notably increased upon HPV-18 immortalization of genital epithelial cells and in HPV-containing cervical carcinoma cell lines. Most significantly, these cells expressed markedly higher levels of both intracellular and extracellular fibronectin, thus providing a mechanism for activation of FAK and increased tyrosine phosphorylation of paxillin. These findings suggest a role for the integrin/FAK-mediated signaling pathway in cervical carcinogenesis and represent one of the first demonstrations of a tyrosine kinase whose activity is elevated following viral immortalization.


Assuntos
Moléculas de Adesão Celular/metabolismo , Transformação Celular Neoplásica , Transformação Celular Viral , Colo do Útero/citologia , Genes src , Papillomaviridae/genética , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Neoplasias do Colo do Útero/patologia , Moléculas de Adesão Celular/biossíntese , Células Cultivadas , Colo do Útero/patologia , Proteínas do Citoesqueleto/biossíntese , Epitélio/fisiologia , Feminino , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Humanos , Queratinócitos/citologia , Queratinócitos/fisiologia , Papillomaviridae/fisiologia , Paxilina , Fosfoproteínas/biossíntese , Fosforilação , Reação em Cadeia da Polimerase , Vírus 40 dos Símios/genética , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/fisiopatologia
17.
Gene ; 116(2): 223-30, 1992 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-1321778

RESUMO

We have cloned and determined the nucleotide (nt) sequence of a 6.5-kb genomic DNA fragment containing the rat MyoD gene (encoding a muscle regulatory factor, MyoD). Mouse fibroblasts transfected with this DNA display a high degree of conversion to a muscle phenotype, suggesting that this genomic clone contains sufficient sequence information to allow the production of the rat MyoD protein in these cells. The 6.5-kb genomic fragment contains the complete coding region of MyoD, distributed over three exons, plus 2.3 kb of 5'-noncoding sequence and 1.4 kb of 3'-noncoding sequence. Based on RNase protection assays, the major transcription start point of MyoD is located 210 nt 5' to a methionine start codon and 26 nt 3' to a TAAATA motif which bears similarity to a consensus recognition sequence (TATA) utilized by eukaryotic RNA polymerase II transcription complexes. The high degree of identity between the amino acid sequence of rat MyoD and the MyoD proteins isolated from other vertebrates indicates that this muscle regulatory protein has been evolutionarily conserved.


Assuntos
Proteínas Musculares/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular/genética , Clonagem Molecular , Fibroblastos/fisiologia , Humanos , Dados de Sequência Molecular , Músculos/citologia , Proteína MyoD , Ratos , Homologia de Sequência do Ácido Nucleico , Transcrição Gênica
18.
Neuropsychologia ; 20(6): 661-8, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-7162588

RESUMO

The Seashore Rhythm Tests, Form A and Form B, and the Timbre Test, Form A were administered to 90 strongly right-handed subjects placed in one of three WAIS Verbal-Performance IQ discrepancy groups. Some dissociation of performance on these tests was expected. As predicted, for the Rhythm Test Form A the High Performance group obtained significantly lower scores than the Equal group, which in turn had reliably lower scores than the High Verbal group. Converse predictions of group differences on Rhythm Test Form B were not confirmed. However, the predicted superiority of the High Performance group over the High Verbal group on Timbre Test Form A was found though the Equal group performed as well as the High Performance group. Thirty per cent of the High Performance group obtained scores on Rhythm Test Form A below the clinical cutoff of this test as opposed to only 6% of the Equal group and 0% of the High Verbal group.


Assuntos
Inteligência , Discriminação da Altura Tonal , Percepção do Tempo , Aprendizagem Verbal , Adulto , Dominância Cerebral , Feminino , Humanos , Masculino , Música , Escalas de Wechsler
19.
Int J Radiat Oncol Biol Phys ; 10(9): 1697-701, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6207157

RESUMO

Since 1981 we have received 50 tumor samples from 10 different sites; over half were breast or ovary. Of the 27 that were considered suitable for cloning, 11 produced colony formation and 6 of these were drug tested. One ovarian granulosa cell tumor and its xenograft (V7) were tested against several cytotoxic agents. During a period of 16 months, sensitivity to cisplatin was relatively stable but sensitivity to vinblastine was markedly changed when the original tumor cells and original cells stored in liquid nitrogen were compared with xenograft cells. These changes may be related to patient treatments prior to tumor sample collection. This xenograft V7 exhibited chromosome karyotype and iso-enzyme Glucose-6-phosphate dehydrogenase consistent with it being of human origin. Gross histology of original tumor and xenograft were similar. Chemosensitization in vivo of a breast xenograft (Hx99) to melphalan by misonidazole was investigated. Misonidazole at a total dose of 0.5 g/kg given prior to melphalan (14 mg/kg) was an effective chemosensitizer.


Assuntos
Antineoplásicos/uso terapêutico , Ensaio de Unidades Formadoras de Colônias , Neoplasias/tratamento farmacológico , Transplante Heterólogo , Ensaio Tumoral de Célula-Tronco , Animais , Bleomicina/uso terapêutico , Cisplatino/uso terapêutico , Sinergismo Farmacológico , Etoposídeo/uso terapêutico , Feminino , Tumor de Células da Granulosa/tratamento farmacológico , Humanos , Melfalan/uso terapêutico , Metotrexato/uso terapêutico , Camundongos , Misonidazol/uso terapêutico , Transplante de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Vimblastina/uso terapêutico
20.
Int J Radiat Oncol Biol Phys ; 12(11): 1997-2002, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3771318

RESUMO

Specific absorption rate (SAR) and tissue temperature were measured for a total of 83 treatments in 33 patients who received local hyperthermia treatment for cancer. The patients were grouped into three categories according to tumor size. Hyperthermia was induced by 13.56 MHz electromagnetic energy applied using capacitive coupling. A method is described for evaluating SAR from the tissue temperature traces at any time in the treatment when a step change is made in applied power. The method is possible only if the temperature traces are free from interference and the total power delivered to the patient is monitored. Mean values of SAR ranged from 4.6 to 89 W kg-1 depending on the treatment site. Satisfactory heating was achieved for superficial tumors, with temperatures greater than 42 degrees C being recorded in 69% of treatments. For axillary nodes only 4% of treatments exceeded 42 degrees C. For cervix tumors an idealized tumor model was used to estimate tumor temperature from the temperature and SAR measured in the adjacent normal tissue. From the model it appears necessary either to raise the systemic temperature to 40 degrees C or to increase the SAR by at least a factor of 4 to obtain a temperature of 42 degrees C in a typical tumor. Measurements of SAR and temperature are essential for feedback control of computer models which, in principle, could provide a complete distribution of temperature during a hyperthermia treatment. Furthermore, measured SAR provides a direct comparison of the power deposition from different treatment machines in a clinical environment. The data presented form a basis for comparison with the clinical use of other heating systems.


Assuntos
Hipertermia Induzida , Neoplasias/terapia , Absorção , Temperatura Corporal , Humanos
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