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1.
BMC Gastroenterol ; 22(1): 516, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36513968

RESUMO

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).


Assuntos
Neoplasias Colorretais , Recidiva Local de Neoplasia , Humanos , Cicatriz/complicações , Cicatriz/patologia , Neoplasias Colorretais/patologia , Metástase Linfática , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
2.
Clin Genet ; 94(1): 170-173, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29633245

RESUMO

We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in an infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus activating, a number of transcription factors including the mixed lineage leukemia 1 (MLL1). Taspase 1-deficient mice showed early lethality, skeletal abnormalities, and growth failure, which support a potentially causal role of TASP1 deletion in this infant. Furthermore, the infant reported here had many of the features seen in Wiedemann-Steiner syndrome which is caused by MLL1 defects. Such observation further supports that TASP1 is a novel disease-related gene that is associated with a disease phenotype overlapping with Wiedemann-Steiner syndrome as both are caused by defects in the same pathway.


Assuntos
Anormalidades Congênitas/genética , Deficiências do Desenvolvimento/genética , Endopeptidases/genética , Fácies , Deleção de Genes , Microcefalia/genética , Fenótipo , Hibridização Genômica Comparativa , Anormalidades Congênitas/diagnóstico , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Lactente , Masculino , Microcefalia/diagnóstico , Polimorfismo de Nucleotídeo Único , Síndrome
3.
Gut ; 66(11): 1975-1982, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-27507905

RESUMO

OBJECTIVE: Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening. DESIGN: Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50-74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs. RESULTS: In total, 19 291 eligible invitees were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates. CONCLUSIONS: The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used. TRIAL REGISTRATION NUMBER: NTR5385; Results.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Sangue Oculto , Idoso , Colonografia Tomográfica Computadorizada , Colonoscopia , Feminino , Seguimentos , Humanos , Técnicas Imunológicas/métodos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Projetos Piloto , Valor Preditivo dos Testes
4.
Gut ; 66(3): 438-445, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-26674360

RESUMO

BACKGROUND AND AIMS: Colonoscopy is the current reference standard for the detection of colorectal neoplasia, but nevertheless adenomas remain undetected. The Endocuff, an endoscopic cap with plastic projections, may improve colonic visualisation and adenoma detection. The aim of this study was to compare the mean number of adenomas per patient (MAP) and the adenoma detection rate (ADR) between Endocuff-assisted colonoscopy (EAC) and conventional colonoscopy (CC). METHODS: We performed a multicentre, randomised controlled trial in five hospitals and included fecal immonochemical test (FIT)-positive screening participants as well as symptomatic patients (>45 years). Consenting patients were randomised 1:1 to EAC or CC. All colonoscopies were performed by experienced colonoscopists (≥500 colonoscopies) who were trained in EAC. All colonoscopy quality indicators were prospectively recorded. FINDINGS: Of the 1063 included patients (52% male, median age 65 years), 530 were allocated to EAC and 533 to CC. More adenomas were detected with EAC, 722 vs 621, but the gain in MAP was not significant: on average 1.36 per patient in the EAC group versus 1.17 in the CC group (p=0.08). In a per-protocol analysis, the gain was 1.44 vs 1.19 (p=0.02), respectively. In the EAC group, 275 patients (52%) had one or more adenomas detected versus 278 in the CC group (52%; p=0.92). For advanced adenomas these numbers were 109 (21%) vs 117 (22%). The adjusted caecal intubation rate was lower with EAC (94% vs 99%; p<0.001), however when allowing crossover from EAC to CC, they were similar in both groups (98% vs 99%; p value=0.25). INTERPRETATION: Though more adenomas are detected with EAC, the routine use of Endocuff does not translate in a higher number of patients with one or more adenomas detected. Whether increased detection ultimately results in a lower rate of interval carcinomas is not yet known. TRIAL REGISTRATION NUMBER: http://www.trialregister.nl Dutch Trial Register: NTR3962.


Assuntos
Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Colonoscopia/instrumentação , Centros Médicos Acadêmicos/estatística & dados numéricos , Idoso , Competência Clínica , Colonoscopia/efeitos adversos , Fezes/química , Feminino , Humanos , Imunoquímica , Masculino , Pessoa de Meia-Idade
5.
Tech Coloproctol ; 21(11): 887-891, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29149427

RESUMO

BACKGROUND: In January 2014, a national bowel cancer screening program started in the Netherlands. The program is being implemented in phases until 2019. Due to this program, an increase in patients referred for a colorectal resection for benign, but endoscopically unresectable polyps, is expected. So far, most resections are performed according to oncological principles despite no pre-operative histological diagnosis of malignancy. The aim of this study was to analyze the increase in referred patients during the first year of the screening program and to compare pathological results and clinical outcome of resections of patients undergoing resection for benign polyps before and after implementation of screening. METHODS: Patients referred for colorectal resection without biopsy-proven cancer between January 2009 and January December 2014 were identified from a prospectively maintained database. Patients with endoscopically macroscopic features of carcinoma were excluded. RESULTS: Seventy-six patients were included. Forty-seven patients (61.8%) were operated on in the 5 years prior to implementation of the screening program, and 29 patients (38.2%) were operated during the first year of implementation of the screening program. The overall malignancy rate before the introduction of the program was 14.1 and 6.6% after it had started (p = .469). All resections were performed laparoscopically; the conversion rate was 3.9% (n = 3). The overall mortality rate was 2.7% (n = 2), major complications (Clavien-Dindo > 3b) occurred in 11.8% (n = 9) of patients. The anastomotic leakage rate was 3.9% (n = 3). CONCLUSIONS: The number of patients referred for benign polyps tripled after introduction of the screening program. With an overall major morbidity and mortality rate of 11.8%, it seems valid to discuss whether an endoscopic excision with advanced techniques with or without laparoscopic assistance would be preferable in this patient group, accepting a 6.6% reoperation rate for additional oncological resection with lymph node sampling in patients in whom a malignancy is found on histological analysis of the complete polyp.


Assuntos
Pólipos do Colo/diagnóstico , Pólipos do Colo/cirurgia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia/efeitos adversos , Pólipos do Colo/patologia , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Países Baixos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
6.
Opt Express ; 22(16): 19235-41, 2014 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-25321008

RESUMO

We demonstrate for the first time the applicability of antenna-coupled field-effect transistors for the detection of terahertz radiation (TeraFETs) for multi-spectral imaging from 0.76 to 4.25 THz. TeraFETs were fabricated in a commercial 90-nm CMOS process and noise-equivalent powers of 59, 20, 63, 85 and 110 pW/√(Hz) at 0.216, 0.59, 2,52, 3.11 and 4.25 THz, respectively, have been achieved. A set of TeraFETs has been applied in raster-scan transmission and reflection imaging of pellets of sucrose and tartaric acid simulating common plastic explosives. Transmittance values are in good agreement with Fourier-transform infrared spectroscopy data. The spatial distribution of the components in the samples has been determined from the transmission data using principal component analysis.

7.
Intern Emerg Med ; 18(8): 2271-2280, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37700180

RESUMO

BACKGROUND: Data on effects of intra-gastric balloon (IGB) on metabolic dysfunction-associated steatotic liver disease (MASLD) are scarce, in part with contradictory results, and mainly obtained in tertiary care patients with diabetes and other comorbidities. We here explore effects of IGB in patients with MASLD referred to a first-line obesity clinic. METHODS: In this prospective cohort study, patients with at least significant fibrosis (≥ F2) and/or severe steatosis (S3) according to screening transient elastography (FibroScan®) were offered a second FibroScan® after 6 months lifestyle modification with or without IGB (based on patient preference). RESULTS: 50 of 100 consecutively screened patients (generally non-diabetic) qualified for repeated evaluation and 29 (58%) of those had a second FibroScan®. At baseline, at least significant fibrosis was present in 28% and severe steatosis in 91%. IGB was placed in 19 patients (59%), whereas 10 patients (41%) preferred only lifestyle modification (no differences in baseline characteristics between both groups). After 6 months, liver stiffness decreased markedly in the IGB group (median: from 6.0 to 4.9 kPa, p = 0.005), but not in the lifestyle modification only group (median: from 5.5 to 6.9 kPa, p = 0.477). Steatosis improved in both groups, (controlled attenuation parameter values; IGB, mean ± SD: from 328 ± 34 to 272 ± 62 dB/m, p = 0.006: lifestyle modification only, mean ± SD: from 344 ± 33 to 305 ± 43 dB/m: p = 0.006). CONCLUSION: Both steatosis and fibrosis improve markedly in overweight/obese patients with MASLD after 6 months IGB combined with lifestyle modification. Our results warrant further research into long-term effect of IGB in these patients.


Assuntos
Fígado Gorduroso , Balão Gástrico , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Sobrepeso , Estudos Prospectivos , Obesidade/complicações , Fibrose , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia
8.
J Chem Phys ; 129(1): 014110, 2008 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-18624473

RESUMO

Self-interaction is one of the most substantial problems in present-day density functional theory. A widely used approach to overcome this problem is the self-interaction correction proposed by Perdew and Zunger. However, the thus given functional not only depends on the orbitals explicitly but is also variant under unitary transformation of the orbitals. In this manuscript, we present a generalized version of the optimized effective potential equation which is able to deal with both problems in one go. Calculations for molecules exemplify the approach.


Assuntos
Teoria Quântica , Artefatos , Elétrons
10.
Fam Cancer ; 17(3): 371-380, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28936633

RESUMO

Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença/genética , Inquéritos e Questionários , Adulto , Idoso , Feminino , Aconselhamento Genético/métodos , Humanos , Masculino , Anamnese/métodos , Pessoa de Meia-Idade , Sistemas On-Line
11.
Aliment Pharmacol Ther ; 24(4): 669-77, 2006 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16827813

RESUMO

BACKGROUND: Serotonin and the 5-HT4 receptor play an important role in gastrointestinal motor and sensory functions. While 5-HT4 agonists are known for their prokinetics properties, the effect of 5-HT4 antagonists on upper gastrointestinal functions is largely unknown. AIM: To assess the effect of a 5-HT4 receptor antagonist (R216073) on gastric relaxation and visceral sensitivity in patients with functional dyspepsia. Secondly, the influence of a functional polymorphism in the gene encoding the serotonin transport protein on drug response was determined. METHODS: A double-blind, randomized, placebo-controlled, two-period crossover study was performed in 20 functional dyspepsia patients. The effect of a single dose of 2,000 mg R216073 on gastric relaxation and sensitivity was tested using three-dimensional ultrasonography and a nutrient drinktest. RESULTS: R216073 did not affect partial gastric volumes or upper abdominal sensations scored during three-dimensional ultrasonography (P > 0.05). The maximum tolerated volume or upper abdominal sensations induced by the drinktest were not affected by R216073 (P > 0.05). The serotonin transport protein promoter polymorphism was not associated with any of the end-points of the study. CONCLUSIONS: A single dose of R216073 had no effect on fundic relaxation, drinking capacity, or upper abdominal symptoms in patients with functional dyspepsia.


Assuntos
Dispepsia/fisiopatologia , Esvaziamento Gástrico/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Antagonistas do Receptor 5-HT4 de Serotonina , Adulto , Método Duplo-Cego , Feminino , Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sensação , Fatores de Tempo
12.
Oncogene ; 15(2): 237-44, 1997 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-9244359

RESUMO

The tumor suppressor protein p53 is a transcription factor frequently inactivated in human cancers. We have studied the DNA binding potential and the transcriptional activity of p53 variants and p53 protein complexes in in vitro transcription assays. p53 specific transcription was measured via introduction of radioactive UTP into G-free cassette transcripts regulated by promoter sequences containing p53 response elements. Latent and activated p53 fractions were prepared from insect cells infected with p53 encoding baculoviruses by chromatography on heparin columns. p53 fractions distinguishable by their specific DNA binding activities and their recognition by monoclonal antibody PAb421 were obtained. Specific DNA binding and binding to PAb421 are mutually exclusive. The C-terminus of p53 can be phosphorylated by casein kinase II, protein kinase C and cyclin dependent kinases. The antibody PAb421 binds within the PKC phosphorylation site of p53 and is able to activate DNA binding of latent p53 in vitro. Activation of p53 by PAb421 also results in enhanced transactivation in vitro. Dephosphorylation of latent p53 with phosphatase 2A does not change these properties. This suggests that a conformational change in the carboxyl terminal domain of p53 controls the transactivation potential of p53.


Assuntos
Ativação Transcricional , Proteína Supressora de Tumor p53/fisiologia , Animais , Sequência de Bases , DNA/metabolismo , Humanos , Dados de Sequência Molecular , Fosforilação , Proteína Quinase C/fisiologia , Spodoptera
13.
Cancer Epidemiol ; 39(3): 388-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25910865

RESUMO

BACKGROUND: The effectiveness of colorectal cancer screening programs based on the fecal immunochemical test (FIT) is influenced by program adherence during consecutive screening rounds. We aimed to evaluate the participation rate, yield, and interval cancers in a third round of biennial CRC screening using FIT and to compare those with the first and the second screening round. METHODS: A total of 3566 average-risk individuals aged 50-75 years were invited to participate in a third round of biennial FIT-based CRC screening. All FIT positives were recommended to undergo colonoscopy. We merged our data with the national cancer registry in the Netherlands to identify all non-screen-detected cancers in our cohort. RESULTS: Of the invitees, 2142 (60%) returned the FIT in this third screening round, compared to 56% in the second round and 57% in the first round. Overall, 153 of the third-round participants (7.1%) had a positive FIT result, versus 7.9% in the second round and 8.1% in the first round (P=0.05). Of all FIT positives, 123 (80%) underwent colonoscopy. Within this group, 33 persons had advanced neoplasia. The predictive value of FIT positivity for advanced neoplasia was 27% (33/123), compared to 42% in the second round and 54% in the first round - a significant decline (P<0.01). CONCLUSION: In an FIT-based screening program, participation rates remained stable over consecutive biennial screening rounds, while the FIT positivity rate and positive predictive value for advanced neoplasia gradually declined. Cancers in non-participants are significantly more advanced in staging than cancers in participants in the first round of screening.


Assuntos
Carcinoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Fezes/química , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Sangue Oculto , Sensibilidade e Especificidade
14.
Mol Cell Endocrinol ; 143(1-2): 143-54, 1998 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-9806359

RESUMO

p53 is a tumor suppressor which exerts its function through the regulation of genes mediating cell cycle arrest and the induction of apoptosis. Cellular survival and proliferation can be positively regulated through the action of cytokines. These signals act through the activation of cell surface receptors, and the phosphorylation of intracellular signaling components, e.g. members of the Stat family (signal transducers and activators of transcription). The signaling effects of p53 and the cytokine receptors on the cellular phenotype are counteracting. We investigated the influence of p53 on the transactivation potential of Stat5. p53 repressed the prolactin induction of the Stat5 mediated transcription of the beta-casein promoter-luciferase reporter gene, but did not affect IFN-gamma induced, Stat1 dependent transcription of the IRF-1 promoter. The inhibition was not due to a decrease in the cellular concentration of Stat5 or to interference with its specific DNA binding activity. No repression of the basal transcriptional activity of the beta-casein promoter was observed. p53 mutants defective in their DNA binding or oligomerization functions had only weak inhibitory effects, but a mutant of p53 in the transactivation domain, efficiently repressed Stat5 dependent induction. The repressive function of p53 on Stat5 activity is independent of the amino-terminal transactivation domain, but requires a functional DNA binding domain and the carboxyl-terminal domain. Our experiments show that p53 counteracts Stat5 mediated cytokine induction of gene transcription. The effect is specific for Stat5 and independent of p53 induced apoptosis.


Assuntos
Citocinas/genética , Proteínas de Ligação a DNA/genética , Proteínas do Leite , Transativadores/genética , Ativação Transcricional , Proteína Supressora de Tumor p53/genética , Animais , Células COS , Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Genes Supressores de Tumor , Mutação , Fator de Transcrição STAT5 , Transdução de Sinais/genética , Transativadores/metabolismo , Proteína Supressora de Tumor p53/metabolismo
15.
Mol Cell Endocrinol ; 183(1-2): 101-12, 2001 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-11604230

RESUMO

The signal transducers and activators of transcriptions (Stats) are central mediators of cytokine responses especially in hematopoietic cells. The detailed molecular mechanisms of Stat activation, particularly the role of post-translational modifications and co-operation with cellular transcription factors are subject to intense investigation. The phosphorylation of a tyrosine residue in the carboxyl terminal domain is a common characteristic for the biologically active state of all known Stats. We studied the biological potential of purified recombinant murine Stat5a and Stat5b. These proteins were expressed in Sf9 insect cells upon infection with Stat5 encoding baculoviruses. We also obtained the tyrosine phosphorylated, activated forms of the Stat5 proteins by expressing the tyrosine kinase Janus kinase2 (Jak) in the same cells through co-infection with a kinase encoding virus. After purification, only the tyrosine phosphorylated form was able to bind specifically in vitro to the Stat5 DNA response element. This activated form of Stat5 is also able to support specific cell free in vitro transcription of a gene with a Stat5 response element in its promoter region. The recombinant purified Stat5 proteins were treated with the tyrosine specific protein phosphatase or with potato acidic phosphatase, which removes phosphate groups from serine and tyrosine residues. Phosphatase treatment resulted in the loss of specific DNA binding ability. This property could be restored by an in vitro reaction with recombinant, purified EGF or PDGF receptor kinases. Tyrosine rephosphorylation in vitro also restored the transactivation potential of Stat5. This modification is, therefore, a sufficient prerequisite for transcriptional induction by Stat5.


Assuntos
Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Proteínas do Leite , Transativadores/metabolismo , Ativação Transcricional , Animais , Células COS , Cromatografia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/isolamento & purificação , Receptores ErbB/metabolismo , Genes Reporter , Proteínas de Fluorescência Verde , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microinjeções , Fosforilação , Proteínas Tirosina Fosfatases/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT5 , Transativadores/genética , Transativadores/isolamento & purificação , Tirosina/metabolismo
16.
Neurogastroenterol Motil ; 14(1): 97-105, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11874558

RESUMO

The motor mechanisms responsible for transpyloric flow of gastric contents are still poorly understood. The aim of our study was to investigate the relationship between luminal pressures and gastric wall motion and between gastroduodenal pressure gradients and pressure waves, and ante- and retro-grade transpyloric flow. In eight healthy volunteers, intraluminal pressures were recorded from the antrum and proximal duodenum. Transpyloric flow was monitored simultaneously using duplex ultrasonography, before, during and after ingestion of 300 mL meat soup. Transpyloric emptying occurred as sequences of alternating periods of emptying-reflux-emptying. Approximately one-third of the sequences were not associated with peristalsis. The antroduodenal pressure gradients were significantly lower during nonperistaltic-related emptying than during peristaltic-related emptying (0.15 (0-0.3) kPa, and 1.7 (0.2-2.0) kPa, respectively [mean plus minus (range)], P < 0.005). The duration of emptying episodes not associated with peristalsis were significantly longer than those associated with peristalsis at (6.5 (3-8.7) s and 4.4 (2-6) s, respectively, P=0.059). Manometry detected only 56% of the antral contractions seen on ultrasound. We concluded that gastric emptying of a low-calorie liquid meal occurs both during peristaltic and nonperistaltic antral activity. In spite of lower antroduodenal pressure gradients, the emptying episodes were longer for nonperistaltic emptying, which is likely to be caused by low pyloric resistance. Considerable flow seems to occur without peristalsis during gastric emptying of a low-calorie, liquid meal in humans.


Assuntos
Dieta Redutora , Duodeno/fisiologia , Alimentos Formulados , Alimentos , Esvaziamento Gástrico/fisiologia , Período Pós-Prandial/fisiologia , Adulto , Análise de Variância , Jejum/fisiologia , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Intubação Gastrointestinal , Masculino , Peristaltismo/fisiologia , Pressão , Antro Pilórico/fisiologia , Estatísticas não Paramétricas , Ultrassonografia Doppler/métodos
17.
Neurogastroenterol Motil ; 16(3): 315-24, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15198654

RESUMO

The objective of this study was to develop an analytical method to describe the three-dimensional (3-D) geometry of the gastric antrum, gastric fundus and the whole stomach. The Fourier series method was used to simulate the organ surface geometry obtained from a 3-D ultrasound system. Data generated from eight antrums and three whole stomachs, at pressures of approximately 7 cm H(2)O, were used for lumen curvature calculations. The principal curvatures spatial distributions were non-homogeneous in the gastric antrum, gastric fundus and the stomach due to their complex geometry. The maximum longitudinal principal curvature in the antrum, fundus and total stomach were, respectively, 0.460 +/- 0.066, 0.583 +/- 0.087 and 1.123 +/- 0.328, whereas the maximum circumferential curvature were 1.192 +/- 0.090, 3.649 +/- 1.574 and 8.444 +/- 3.424, respectively. The present study provides an analytical tool for characterizing the complex 3-D geometry of an organ-like the human stomach reconstructed by clinical imaging modalities. Providing an average tension for the stomach does not reflect the large variation in tension throughout the stomach wall.


Assuntos
Imageamento Tridimensional/métodos , Estômago/anatomia & histologia , Ultrassonografia , Adulto , Algoritmos , Feminino , Análise de Fourier , Humanos , Processamento de Imagem Assistida por Computador , Masculino
18.
J Pain Symptom Manage ; 22(3): 791-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11532592

RESUMO

Chronic pain is a widespread, difficult problem facing clinicians. This study assessed the current medical management of a general population of patients with chronic pain in 12 family medicine practices located throughout the state of Wisconsin. Medical record audits were conducted on a sample of 209 adults. Sixty-seven percent were female with an average age of 53 years. The most common pain diagnoses included lumbar/low back (44%), joint disease/arthritis (33%), and headache/migraine (28%) pain. The most frequently prescribed opioids were oxycodone/acetaminophen (31%), morphine ERT (19%), Tylenol #3 (15%), and hydrocodone/acetaminophen (14%). Depression/affective disorders were reported in 36% of the patient charts, anxiety/panic disorders (15%), drug abuse (6%), and alcohol abuse (3%). Written drug contracts were utilized by 42% (n = 31) of the practitioners, pain scales 25% (n = 29), and urine toxicology screens 8% (n = 6). This study suggests that primary care practitioners have unique opportunities to identify and successfully treat patients with chronic pain.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor/tratamento farmacológico , Atenção Primária à Saúde , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Amostragem
19.
Water Res ; 35(3): 720-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11228970

RESUMO

Groundwater samples from six wells of a former gas plant site were characterised using chemical, microbial and ecotoxicological methods. Degradation studies were performed in batch-culture under aerobic conditions with the groundwater samples containing their autochthonous microflora and original contaminant mixture. The highest O2-consumption (3 mmol 100 ml-1), combined with BTEX (8.3 mg l-1) and naphthalene (171.3 mg l-1) degradation, as well as formation of organic acids was found after N- and P-supplementation with the highest contaminated groundwater sample. The other highly polluted groundwater sample showed no activity obviously because of the toxicity of some compounds. The major part of the PAHs and BTEX was eliminated in the assays with the low contaminated groundwater samples. The results indicate that the microbial degradation capacity and thereby the natural attenuation capacity in each groundwater differ and cannot be assessed simply by chemical, microbial and toxicological data. Additionally activity tests with authentic groundwater samples with and without nutrient supplementation are recommended.


Assuntos
Microbiologia da Água , Purificação da Água/métodos , Abastecimento de Água , Dióxido de Carbono/análise , Cromatografia Gasosa-Espectrometria de Massas , Alemanha , Concentração de Íons de Hidrogênio , Microquímica , Naftalenos , Oxigênio/análise , Consumo de Oxigênio , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise
20.
Psychiatr Serv ; 52(6): 838-40, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11376238

RESUMO

A total of 684 primary care physicians in Wisconsin participated in a survey designed to explore their experiences of consulting with and referring patients to mental health care professionals. The respondents indicated that they had only moderate access to mental health care professionals, and even less access when a patient was covered by Medicare or Medicaid or had no insurance. Physicians in group practices that included at least one mental health professional reported having better access to care than those in practices that did not include mental health services. Perceived access to mental health care services was not related to community size or to a managed care setting.


Assuntos
Serviços Comunitários de Saúde Mental/organização & administração , Acessibilidade aos Serviços de Saúde , Transtornos Mentais/terapia , Médicos de Família , Encaminhamento e Consulta , Comunicação , Medicina de Família e Comunidade/estatística & dados numéricos , Humanos , Medicina Interna/estatística & dados numéricos , Relações Interprofissionais , Pediatria/estatística & dados numéricos , Padrões de Prática Médica , Wisconsin
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