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31.
Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells 总被引:2,自引:1,他引:2
p53 mutation is commonly associated with high-grade, high-stage human
urothelial carcinomas. Recent studies suggest that p53 mutation in low-
grade, low-stage bladder carcinomas may be correlated with the progression
of the disease. In the present study, we used antisense RNA methodology in
vitro to evaluate the significance of the loss of p53 function at an early
stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat
urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was
transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA
in antisense orientation. The transfection resulted in a significant
reduction in p53 mRNA expression and protein synthesis, in stimulation of
anchorage- dependent growth, and in acquisition of anchorage-independent
growth potential. Three such clones, when tested in athymic nude mice, all
formed muscle-invasive, high-grade transitional cell carcinomas at s.c.
injection sites. When cells were inoculated into an orthotopic site
(urinary bladder), one of two antisense transfectants tested formed bulky
tumors in the bladder in all seven nude mice and metastases to lungs in
three of the seven mice. Analysis of these cells revealed a decrease in the
expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene
product. Phosphorylation of Rb protein was not inhibited when the cells
were starved. No significant difference was observed in the expression of
p16 protein. In cell cycle analysis, all antisense transfectants tested
escaped from G1 arrest by starvation. Furthermore, secretion of interleukin
(IL)-6 into culture medium was increased significantly. Treatment with
anti-IL-6 antibody suppressed anchorage-dependent growth. This study
directly demonstrates that the loss of p53 function at an early stage of
urothelial carcinogenesis may result in acquisition of a malignant
phenotype by regulating IL-6 production as well as cell cycle related
genes.
相似文献
32.
We aimed to determine the oxidative stress status in placentas obtained from gestational (GDM) and type 1 (T1D) diabetic pregnancies. Malonaldehyde and protein carbonyls, two biomarkers of oxidative damage, were higher in T1D but not in GDM placentas. Also, higher reduced glutathione and lower oxidized glutathione levels and higher glutathione peroxidase activity were found in T1D but not in GDM placentas. These results suggest that T1D placentas may develop a protective antioxidant mechanism to overcome higher oxidative stress levels. 相似文献
33.
Gabriela Roncholeta De Freitas Giovana Aparecida Moura Ferraz Marcelo Gehlen Thelma L. Skare 《Primary Care Diabetes》2021,15(1):184-186
Dry eyes may be caused by impairment in the tear production or excessive tear evaporation and are associated with photophobia, red eyes, vision impairment, local pain and pruritus. It has been described that patients with Diabetes Mellitus (DM) may have a higher prevalence of dry eyes than normal population.This is a case control study of 120 patients with Diabetes Mellitus (DM) and 120 paired controls aiming to compare their prevalence of dry eyes (by the Schirmer test) and its severity (measured by OSDI or Ocular Surface Disease Index) as well as their association with diseases’ clinical variables.We found that 38.3% of DM patients had dry eyes, a prevalence that was higher than controls (p = 0.02). At univariate analysis, they were found to be more common in older individuals (p = 0.001) with type 2 diabetes (p = 0.001) and in those using metformin (p = 0.001). A multivariate linear regression showed that metformin use was the only independent variable associated with dry eyes. When patients with dry eyes with and without DM were compared, no differences in the symptom’s intensity were found. 相似文献
34.
35.
Hugo Figueiredo‐Ferraz Pedro R. Gil‐Monte Ester Grau‐Alberola Marta Llorca‐Pellicer Juan A. García‐Juesas 《Journal of Applied Research in Intellectual Disabilities》2012,25(5):455-463
Background The problem of mobbing has attracted a great deal of attention over the past few years. This concern has increased the study of the phenomena, which has resulted in many scientific publications. Mobbing has been characterized as an emerging risk at work. The aim of this study was to analyse the influence of some psychosocial factors at work – role clarity, interpersonal conflicts and social support – on mobbing and its consequences – that is, inclination towards absenteeism and psychosomatic disorders. Materials and methods The sample included 422 employees working with people with intellectual disabilities. Structural equation modelling (SEM) was used to test the hypotheses. Results The Hypothesized model showed an adequate fit to data, and all hypothesized relationships were significant. Conclusions The results of this study provide support for the mediator role of mobbing in the relationship between high role ambiguity, low social support and high interpersonal conflicts and psychosomatic disorders and inclination towards absenteeism. 相似文献
36.
Frederico Figueiredo Amancio Maira Alves Pereira Felipe Campos de Melo Iani Lorena D'anuncia??o Jorge Luís Carvalho de Almeida Janer Aparecida Silveira Soares Marcela Lencine Ferraz Thiago Cardoso Vale José Roberto Lambertucci Mariangela Carneiro 《Revista do Instituto de Medicina Tropical de S?o Paulo》2014,56(3):267-270
Dengue is currently a major public-health problem. Dengue virus (DENV) is
classified into four distinct serotypes, DENV 1-4. After 28 years of absence, DENV-4
was again detected in Brazil in 2010 in Roraima State, and one year later, the virus
was identified in the northern Brazilian states of Amazonas and Pará, followed by Rio
de Janeiro and São Paulo. In Minas Gerais, the first confirmed case of DENV-4
occurred in the municipality of Frutal in 2011 and has now been isolated from a
growing number of patients. Although DENV-2 is associated with the highest risk of
severe forms of the disease and death due to the infection, DENV-4 has also been
associated with severe forms of the disease and an increasing risk of hemorrhagic
manifestations. Herein, the first fatal case of confirmed DENV-4 in Brazil is
reported. The patient was an 11-year-old girl from the municipality of Montes Claros
in northern Minas Gerais State, Brazil. She had idiopathic thrombocytopenic purpura
as a comorbid condition and presented with a fulminant course of infection, leading
to death due to hemorrhagic complications. Diagnosis was confirmed by detection of
Dengue-specific antibodies using IgM capture enzyme-linked immunosorbent assay and
semi-nested RT-PCR. Primary care physicians and other health-care
providers should bear in mind that DENV-4 can also result in severe forms of the
disease and lead to hemorrhagic complications and death, mainly when dengue infection
is associated with coexisting conditions. 相似文献
37.
Signal transduction by the platelet Fc receptor 总被引:6,自引:1,他引:6
We have evaluated the mechanism by which crosslinking human platelet Fc receptor (FcR) for IgG triggers platelet aggregation and the platelet release reaction. Platelet FcR was crosslinked by incubating purified human platelets with anti-FcRII monoclonal antibody and F(ab')2 anti- mouse Ig. The resultant [Ca2+]i increase, monitored by Fura-2 and measured in the absence of extracellular Ca2+, reached a peak of 750 +/- 50 nmol/L. The effects of cyclooxygenase inhibitors, aspirin and indomethacin, and a phospholipase A2 inhibitor, dibromoacetophenone, were examined. Regardless of the inhibitor, at least 25% of the [Ca2+]i increase remained. Thrombin (0.2 U/mL) stimulated an immediate [Ca2+]i increase that reached 1.95 +/- 0.8 mumol/L. The [Ca2+]i increase generated by thrombin was only slightly reduced by these inhibitors. Crosslinking the FcRII of platelets resulted in a fivefold increase in the production of [3H]inositol phosphates, (IP) which, in the absence of extracellular Ca2+ was insensitive to aspirin. The activation of a [Ca2+]i increase along with the measured increases in IP indicate that FcRII crosslinking leads to the activation of phospholipase C (PLC). In contrast to thrombin, platelet activation via FcRII depends to a large extent on arachidonic acid metabolites. However, neither cyclooxygenase nor phospholipase A2 inhibitors completely blocked FcRII-stimulated [Ca2+]i increase. These observations led us to propose that crosslinking of platelet FcRII initially activates PLC. 相似文献
38.
Giulia Marchetti Vítor Doria Ricardo André Orsini Ardengh Arthur Ferraz de Almeida Eloy Taglieri Otávio Micelli-Neto 《Scandinavian journal of gastroenterology》2020,55(8):995-1001
Abstract
Background and aims
Escalating an indication of EUS for diagnosis and treatment justifies the evaluation of the conditions associated with the adverse events (AE) and related deaths. The aim is to evaluate and compare the incidence of AE and deaths after diagnostic-EUS (D-EUS) and interventional-EUS (I-EUS). 相似文献39.
CL Sanchez CS Biskup S Herpertz TJ Gaber CM Kuhn SH Hood FD Zepf 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(10)
The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research. 相似文献
40.
Diesel exhaust particulates affect cell signaling,mucin profiles,and apoptosis in trachea explants of Balb/C mice
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Robson Seriani Mara de Souza Junqueira Alessandra Choqueta de Toledo Milton Arruda Martins Marcelo Seckler Adriano Mesquita Alencar Elnara Marcia Negri Luiz Fernando Ferraz Silva Thaís Mauad Paulo Hilário Nascimento Saldiva Mariangela Macchione 《Environmental toxicology》2015,30(11):1297-1308
Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) and to analyze the mucin profile (acid (AB+), neutral (PAS+), or mixed (AB/PAS+) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 μg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 μg/mL DEP treatment compared with the control. An increase in JNK phosphorylation was observed after 60 min of treatment with 50 μg/mL DEP compared with the control. We did not observe any change in the level of ERK1/2 phosphorylation after treatment with 50 μg/mL DEP. Other groups of tracheas were subjected to histological sectioning and stained with periodic acid‐Schiff (PAS) reagent and Alcian Blue (AB). The stained tissue sections were then subjected to morphometric analysis. The results obtained were compared using ANOVA. Treatment with 50 μg/mL DEP for 30 min or 60 min showed a significant increase (p < 0.001) in the amount of acid mucus, a reduction in neutral mucus, a significant reduction in mixed mucus, and greater vacuolization. Our results suggest that compounds found in DEPs are able to activate acid mucus production and enhance vacuolization and cell signaling pathways, which can lead to airway diseases. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 1297–1308, 2015. 相似文献