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1.
Zhonghua Nei Ke Za Zhi ; 62(2): 169-175, 2023 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-36740407

RESUMO

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Neuropatias Diabéticas , Retinopatia Diabética , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/epidemiologia , Nomogramas , Estudos Transversais , Fatores de Risco , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações
2.
BMC Endocr Disord ; 22(1): 84, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365152

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. METHODS: Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. RESULTS: This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. CONCLUSIONS: These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome Metabólica , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Fator 2 Relacionado a NF-E2/genética , Sirtuína 1/genética
3.
Artigo em Chinês | MEDLINE | ID: mdl-32306685

RESUMO

As an emerging environmental pollutant, microplastics have attracted more and more attention for its influence on the ecological environment and human health. Due to its wide range of usage and production, difficult degradation and other characteristics, as well as the continuous and substantial increase in the use of plastic products, the number of plastic fragments in the environment continues to increase, which leads to the accumulation of microplastics in the environment and organisms, spread through the food chain, and ultimately poses a threat to human health. At the same time, in the plastic production, synthetic textile, and other industries, the incidence of workers related occupational diseases greatly increased. In this paper, the concept, classification, source, impact on biological and human health of microplastics are summarized, and propose solutions on the current situation of microplastics pollution in China, we hope this review could provide effective reference for further carry out risk assessment of microplastics pollution on human health and formulate legislation to control microplastics pollution.


Assuntos
Microplásticos/efeitos adversos , Poluentes Químicos da Água/efeitos adversos , China , Monitoramento Ambiental , Humanos
4.
Clin Radiol ; 74(5): 399-404, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30773226

RESUMO

AIM: To investigate whether hyperdense areas (HDAs) observed after endovascular treatment on multisection computed tomography (CT) are related to outcome. MATERIALS AND METHODS: Data on 82 patients with acute anterior circulation ischaemic stroke resulting from intracranial large artery occlusion were analysed retrospectively All patients underwent mechanical thrombectomy and/or emergency angioplasty, and partial or complete recanalisation was successfully achieved. C-arm CT was performed immediately after endovascular treatment for all patients. Clinical and radiological data were compared between patients with and those without HDA and between patients with good and those with poor outcomes. RESULTS: Compared with non-HDA patients, HDA patients were more likely to present with severe neurological deficits (admission National Institutes of Health Stroke Scale [NIHSS] score: 18 versus 16, p=0.037) and had a higher number of stent retriever passes performed (2.9±1.3 versus 1.4±1, p<0.001), longer onset-to-presentation times (229±78 versus 171±90 minutes; p=0.002), longer onset-to-recanalisation times (418±94 versus 331±105 minutes; p<0.001), and longer puncture-to-recanalisation times (103±47 versus 69±42 minutes; p=0.001). Fewer HDA patients had a good prognosis (35.7% versus 70%, p<0.001). Multivariate analysis showed the presence of HDAs was an independent negative prognostic factor (OR=0.208; p=0.002). CONCLUSION: HDAs on C-arm CT appear to be common in patients with acute ischaemic stroke who underwent successful endovascular treatment. HDA presence suggests a poor prognosis despite successful reperfusion.


Assuntos
Isquemia Encefálica/terapia , Trombólise Mecânica/métodos , Acidente Vascular Cerebral/terapia , Idoso , Angiografia Digital/métodos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Hemorragia Cerebral/patologia , Revascularização Cerebral/métodos , Angiografia por Tomografia Computadorizada/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/diagnóstico por imagem , Tecido Parenquimatoso/patologia , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Resultado do Tratamento
5.
Cell Mol Biol (Noisy-le-grand) ; 63(8): 7-9, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28886307

RESUMO

This case-control study aimed to investigate the association between PHLDB1 rs498872 polymorphism and the risk of glioma in a Chinese Han population. A total of 210 patients and 235 controls were enrolled in this study. The CT genotype and TT genotype were significantly associated with the risk of glioma (OR=1.48, 95%CI 1.00-2.19, P=0.05 and OR=2.40, 95%CI 1.06-4.10, P=0.03), respectively. In addition, T allele of PHLDB1 rs498872 polymorphism was significantly associated with an increased risk of glioma (OR=1.58, 95%CI 1.08-2.29, P=0.02). We also found that PHLDB1 rs498872 polymorphism was not associated with histology and tumor grade of glioma. In conclusion, this study found that PHLDB1 rs498872 polymorphism was significantly associated with glioma risk in Chinese Han population.


Assuntos
Neoplasias Encefálicas/genética , Predisposição Genética para Doença , Glioma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Frequência do Gene , Glioma/diagnóstico , Glioma/etnologia , Glioma/patologia , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Razão de Chances , Fatores de Risco
6.
Zhonghua Nei Ke Za Zhi ; 56(2): 127-129, 2017 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-28162183

RESUMO

The aim of the study was to explore the effect and its clinical relevance of short-term intensive insulin treatment on plasma concentrations of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and secretory phospholipase A(2) (sPLA(2)) in newly diagnosed type 2 diabetes mellitus (T2DM). Ninety newly diagnosed T2DM patients were recruited and received continuous subcutaneous insulin infusion (CSII) for about 2 weeks. After CSII, sPLA(2) levels [173.78 (80.95, 278.09) µg/L] were significantly decreased compared with the levels before [219.33 (130.03, 337.30) µg/L], P<0.01, while no statistic significant changes could be viewed in Lp-PLA(2) levels. Correlation analysis showed that the changes of Lp-PLA(2) and sPLA(2) were both positively correlated with the changes of homeostasis model assessment of insulin resistance(HOMA-IR)after CSII (r=0.537, 0.493 respectively, all P<0.05). The Lp-PLA(2) and sPLA(2) level reduction after CSII might help to protect the patients from diabetic macroangiopathy. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-10001618.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Adulto , Glicemia , China , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina/administração & dosagem , Insulina/farmacologia , Resistência à Insulina , Masculino , Pessoa de Meia-Idade
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 40(12): 909-914, 2017 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-29224300

RESUMO

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Reação em Cadeia da Polimerase/métodos , Infecções Respiratórias/etiologia , Viroses/diagnóstico , Viroses/virologia , Vírus/isolamento & purificação , Bactérias/genética , Infecções Bacterianas/epidemiologia , Humanos , Lactente , Pacientes Internados , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Vírus/genética
8.
Clin Exp Dermatol ; 40(1): 56-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25154629

RESUMO

BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of diseases of keratinization, characterized primarily by abnormal skin scaling over the whole body surface. Recently, ARCI has been designated to include the major forms of lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) and harlequin ichthyosis. The first two conditions are the most common major clinical subtypes, and both are caused principally by mutations in the transglutaminase 1 gene, TGM1, although other genes may be responsible in some cases. AIM: To identify the genetic mutations underlying LI in a Chinese family with LI, and to review all the known TGM1 mutations in Chinese patients with ARCI. METHODS: The proband had the severe classic LI phenotype, and was a member of a four-generation family with close blood relationships. We sequenced the DNA of the patients and close relatives. We also reviewed 13 Chinese patients with ARCI from 8 reported families, comprising 10 patients with LI, 2 with CIE and 1 with bathing suit ichthyosis. RESULTS: We characterized 14 different TGM1 mutations. Six of these were reported in other ethnic groups initially and later in Chinese patients, while the remaining eight were first described in Chinese patients. Of the latter, five have been reported only in Chinese patients, while the remaining three have also been reported in other ethnic groups. CONCLUSION: This study expands the current spectrum on TGM1 mutation and increases the knowledge of TGM1 mutation characteristics.


Assuntos
Predisposição Genética para Doença , Eritrodermia Ictiosiforme Congênita/genética , Mutação , Transglutaminases/genética , Adolescente , Povo Asiático , China , Feminino , Genes Recessivos , Genótipo , Humanos , Masculino
9.
Genet Mol Res ; 14(4): 17244-51, 2015 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-26681218

RESUMO

LIM domain kinase 1 (LIMK1), an actin-binding kinase, can phosphorylate and inactivate its substrates, and can regulate long-term memory and synaptic plasticity. Both ß-amyloid precursor protein (App) and presenilin (PS) are functional degeneration factors during early neuronal development, and are considered as potential factors that contribute to the development of Alzheimer's disease (AD). However, hardly any information is available about the distribution and expression of LIMK1. Thus, using the App and PS deficient mice, the role of LIMK1 was demonstrated in the absence of App and PS. Our results showed that LIMK1 was present in the nerve fiber layer and external plexiform layer of the olfactory bulb, as well as in the mitral cells and Purkinje cells of the cerebellum in App and PS deficient mice. Additionally, LIMK1 was concentrated in the granule cell layer of the olfactory bulb and cerebellum and LIMK1 positive cells were located in the CA1 region of the hippocampus. Our study indicates that there is a connection between LIMK1 and AD in the mouse model of AD. This might explain neurological problems such as cerebellar ataxia, impaired long-term memory, and impaired synaptic plasticity observed in AD.


Assuntos
Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Quinases Lim/metabolismo , Bulbo Olfatório/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Expressão Gênica , Heterozigoto , Imuno-Histoquímica , Quinases Lim/genética , Camundongos , Camundongos Transgênicos , Presenilinas/genética , Presenilinas/metabolismo
10.
Eur Rev Med Pharmacol Sci ; 27(7): 2751-2758, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37070874

RESUMO

OBJECTIVE: This study aims to investigate the allergens in children with allergic rhinitis (AR) and AR-related influencing factors. PATIENTS AND METHODS: The clinical data of 230 children with AR admitted to our hospital from June 2020 to June 2021 were retrospectively analyzed and included in the observation group. The clinical data of 230 healthy children during the same time period were included as the control group. All children had been tested for allergens using serum allergens, and the clinical data were collected by telephone questionnaires. Univariate and multivariate logistic regression were used to analyze the risk factors affecting AR. RESULTS: A total of 230 children with AR was included in this study, and some of them had two or more allergens. The proportion of house dust mite was the highest among the inhaled allergens, about 75.22%. Shrimp accounted for the highest proportion of food allergens, about 40.87%. Compared with the control group, the proportion of floating population, home heating, allergy history, asthma and other general information in the observation group was higher. At the same time, the proportion of environmental factors such as second-hand smoke, number of residents (≤ 3), daily ventilation and cleaning (no), domestic animals, domestic plants, decoration within 2 years, and living environment (rural) in the observation group was higher. In addition, the proportion of family factors such as delivery mode (cesarean section), family history of allergic rhinitis, parents' education level (middle school and above) in the observation group was higher (p < 0.05). Univariate logistic regression analysis showed that allergic history, asthma, second-hand smoke, floating population, number of residents, domestic animals, decoration within 2 years, delivery mode, and family history of allergic rhinitis were the risk factors affecting the incidence of AR in children (p < 0.05), and daily window ventilation and cleaning were the protective factors (p < 0.05). The multivariate logistic regression analysis showed that asthma, second-hand smoke, floating population, decoration within 2 years, family history of allergic rhinitis and domestic animals were independent risk factors for the occurrence of AR (p < 0.05), and daily ventilation and cleaning were protective factors for the occurrence of AR in children (p < 0.05). CONCLUSIONS: The proportion of house dust mite in inhalation allergens and shrimp in food allergens were the highest in AR children. The incidence of AR was closely related to asthma, second-hand smoke, floating population, decoration within 2 years, family history of AR and domestic animals, etc. Targeted measures could effectively prevent the occurrence and recurrence of AR. At the same time, daily ventilation and cleaning were the protective factors which could reduce the incidence and occurrence of AR in children.


Assuntos
Alérgenos , Rinite Alérgica , Alérgenos/análise , Rinite Alérgica/epidemiologia , Humanos , Criança , Antígenos de Dermatophagoides/análise , Hipersensibilidade Alimentar/epidemiologia , Análise Multivariada
12.
Eur Rev Med Pharmacol Sci ; 24(13): 7433-7441, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32706083

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has become a common liver disorder caused by lipid accumulation and insulin resistance (IR). Acylcarnitines have become a new biomarker of IR. However, their roles in NAFLD are still poorly studied. Thus, we performed a targeted metabolomic analysis to study the level of plasma acylcarnitines in patients with NAFLD. MATERIALS AND METHODS: The levels of 34 plasma acylcarnitines were measured by a targeted metabolomic approach in NAFLD patients (n = 50) and in healthy control subjects (n = 50) by liquid chromatography-tandem mass spectrometry. Detailed demographic and clinical characteristics of all subjects were also analyzed. RESULTS: The clinical presentation of IR was identified in the NAFLD group but not in the healthy control group. Significant differences were found in the levels of several short-, medium- and long-chain acylcarnitines. A high degree of correlation (r>0.7) was found between even-numbered-carbon long-chain acylcarnitines in NAFLD patients. The area under the receiver operator characteristic of long-chain acylcarnitines, especially C20 (AUC=0.952), C16:1 (AUC=0.949) and C14:1OH (AUC=0.944) acylcarnitines, was greater in NAFLD patients than in healthy control subjects. CONCLUSIONS: The accumulation and disorders of acylcarnitines are associated with NAFLD. A positive correlation between even-numbered-carbon long-chain acylcarnitines was found, and these even-numbered-carbon long-chain acylcarnitines. could be used as potential novel screening markers for nonalcoholic fatty liver disease.


Assuntos
Carnitina/análogos & derivados , Metaboloma , Metabolômica , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Biomarcadores/sangue , Carnitina/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
13.
Gene Ther ; 16(8): 973-81, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19421232

RESUMO

Corneal neovascularization can reduce visual acuity. GA-binding protein (GABP) is a transcription factor that regulates the expression of target genes including vascular endothelial growth factor (VEGF) and roundabout4 (Robo4), which participate in pathologic angiogenesis. We assessed whether intraocular injection of the GABP gene affects the growth of new corneal blood vessels in a mouse ocular neovascularization model. Transfection of human GABPalpha and GABPbeta gene (GABPalpha/beta) into human conjunctival epithelial cells resulted in decreased VEGF and Robo4 expression. Three groups of mice underwent chemical and mechanical denudation of the corneal epithelium. Subsequently, two groups were administered subconjunctival injection of lipoplexes carrying plasmid DNA encoding for human GABPalpha/beta or an empty plasmid DNA at 1-week intervals. The third group served as an experimental control. In vivo delivery of human GABPalpha/beta into mouse neovascularized cornea reduced VEGF and Robo4 gene expression. Biomicroscopic examination showed that, at 1 week after one or two injections, GABPalpha/beta-treated eyes had significantly less neovascularized corneal area than did eyes treated with the empty vector. Histologic examination showed significantly less vascularized area and fewer blood vessels in the GABP-treated group at 1 week after injections. However, these angiosuppressive effects were weakened at 2 weeks after injections. Our results indicate that subconjunctival GABP gene delivery delays corneal neovascularization for up to 2 weeks in a mouse model of deliberate corneal injury.


Assuntos
Neovascularização da Córnea/terapia , Fator de Transcrição de Proteínas de Ligação GA/genética , Técnicas de Transferência de Genes , Animais , Córnea , Neovascularização da Córnea/genética , Modelos Animais de Doenças , Humanos , Injeções Intraoculares , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular , Receptores Imunológicos/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Science ; 251(4995): 796-9, 1991 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-1990442

RESUMO

Transfer of a normal Chinese hamster X chromosome (carried in a mouse A9 donor cell line) to a nickel-transformed Chinese hamster cell line with an Xq chromosome deletion resulted in senescense of these previously immortal cells. At early passages of the A9/CX donor cells, the hamster X chromosome was highly active, inducing senescence in 100% of the colonies obtained after its transfer into the nickel-transformed cells. However, senescence was reduced to 50% when Chinese hamster X chromosomes were transferred from later passage A9 cells. Full senescing activity of the intact hamster X chromosome was restored by treatment of the donor mouse cells with 5-azacytidine, which induced demethylation of DNA. These results suggest that a senescence gene or genes, which may be located on the Chinese hamster X chromosome, can be regulated by DNA methylation, and that escape from senescence and possibly loss of tumor suppressor gene activity can occur by epigenetic mechanisms.


Assuntos
Sobrevivência Celular/genética , Transformação Celular Neoplásica/genética , Níquel/farmacologia , Cromossomo X/efeitos dos fármacos , Animais , Fusão Celular , Linhagem Celular Transformada , Transformação Celular Neoplásica/induzido quimicamente , Deleção Cromossômica , Cricetinae , Cricetulus , Hipoxantina Fosforribosiltransferase/genética , Camundongos
15.
Gynecol Oncol Rep ; 25: 27-29, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29977987

RESUMO

•A young lady with uterine sarcoma had a successful delivery 3 years after diagnosis.•Local recurrence occurred after 8 years.•Ultrasound and endometrial biopsy can be used in the follow-up of these patients.•Patients should be counselled on risk of late recurrence.

16.
Mol Biol Cell ; 6(12): 1819-32, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8590808

RESUMO

NG2 is a chondroitin sulfate proteoglycan that is expressed on dividing progenitor cells of several lineages including glia, muscle, and cartilage. It is an integral membrane proteoglycan with a core glycoprotein of 300 kDa. In the present study we have characterized three molecular forms of the NG2 core protein expressed by different cell lines. Many cell lines that express the full length 300-kDa NG2 core protein also release a 290-kDa form into the medium. This species lacks the cytoplasmic domain but contains almost the entire ectodomain. Two core protein species, the intact 300-kDa form and a truncated 275-kDa form, are expressed at the surface of an NG2-transfected cell line U251NG52. The 275-kDa species lacks the cytoplasmic domain and at least 64 amino acids of the ectodomain. Mild trypsinization of B49 cells also generates the 275-kDa species, suggesting that this component is produced by proteolysis of the 300-kDa form. Conversion of the 300-kDa species to the 275-kDa form in U251NG52 cells is stimulated by reagents such as phorbol esters, which activate protein kinase C. Phorbol esters are also known to induce expression of metalloproteinases such as collagenase and stromelysin, which could be responsible for cleavage of the 300-kDa core protein. Although B49 cells do not spontaneously produce the truncated 275-kDa species, use of monoclonal antibodies against NG2 to block the interaction between NG2 and type VI collagen results in the appearance of the 275-kDa component in these cells. Thus the interaction between NG2 and type VI collagen, which contains a Kunitz-type proteinase inhibitor sequence in the alpha 3 chain, may protect the proteoglycan against proteolysis. This is consistent with the observed deficiency of U251NG52 cells in anchoring type VI collagen at the surface.


Assuntos
Antígenos/biossíntese , Processamento de Proteína Pós-Traducional , Proteoglicanas/biossíntese , Tripsina/metabolismo , Animais , Anticorpos Monoclonais , Antígenos/análise , Antígenos/metabolismo , Northern Blotting , Neoplasias Encefálicas , Linhagem Celular , Membrana Celular/metabolismo , Glioma , Humanos , Immunoblotting , Cinética , Metionina/metabolismo , Peso Molecular , Proteoglicanas/análise , Proteoglicanas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Proteínas Recombinantes/análise , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Radioisótopos de Enxofre , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica , Transfecção , Células Tumorais Cultivadas
17.
Mol Biol Cell ; 7(12): 1977-93, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8970159

RESUMO

The transmembrane proteoglycan NG2 is able to interact both with components of the extracellular matrix and with the actin cytoskeleton. An examination of the distribution of NG2 during cell spreading suggests that NG2 can associate with two distinct types of actin-containing cytoskeletal structures, depending on the nature of the stimulus derived from the substratum. On fibronectin-coated dishes, cell surface NG2 associates exclusively with stress fibers developing within the cell. On poly-L-lysine-coated dishes, cell surface NG2 is associated with radial processes extending from the cell periphery. Spreading on fibronectin/poly-L-lysine mixtures, as well as on matrix components such as laminin, tenascin, and type VI collagen, produces cells with mosaic characteristics, i.e., NG2 is associated with both types of structures. NG2-positive radial processes are distinct from a second population of radial structures that contain fascin. NG2-positive extensions appear to be individual self-contained units (filopodia), whereas fascin is associated with actin ribs within sheets of membrane (lamellipodia). NG2- and fascin-positive structures are often localized to opposite poles of spreading cells, suggesting a possible role for the two classes of cellular extensions in the establishment of cell polarity during morphogenesis or migration. Time lapse imaging confirms the presence of lamellipodia on the leading edges of migrating cells, while numerous filopodia are present on trailing edges.


Assuntos
Actinas/metabolismo , Antígenos/metabolismo , Proteínas de Transporte/metabolismo , Movimento Celular , Proteínas dos Microfilamentos/metabolismo , Proteoglicanas/metabolismo , Animais , Compartimento Celular , Membrana Celular , Citoesqueleto , Fibronectinas/farmacologia , Humanos , Microscopia de Vídeo/métodos , Polilisina/farmacologia , Ratos , Células Tumorais Cultivadas
18.
Cancer Res ; 50(3): 669-76, 1990 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-2404574

RESUMO

Rats were fed the peroxisome proliferator ciprofibrate (0.025%), and the effects on the expression, modification, and localization of seven domain-specific integral proteins of the rat hepatocyte plasma membrane were assessed using a combination of immunoblotting, -precipitation, and -fluorescence. Ciprofibrate caused the down-regulation of five of the plasma membrane proteins (the epidermal growth factor receptor, the asialoglycoprotein receptor, HA 321, HA 4, and dipeptidylpeptidase IV) and induced the expression of a more basic, lower-Mr isoform of the basolateral plasma membrane protein CE 9. Pulse labeling, chemical deglycosylation, and 125I-wheat germ lectin blotting suggested that the ciprofibrate-induced isoform of CE 9 differed in the posttranslational modification of its oligosaccharides and contained more sialic acid. These changes in hepatocyte surface differentiation were first observed between Days 1 and 5 on the ciprofibrate-containing diet, coincident with other aspects of the pleiotropic response of the hepatocyte to peroxisome proliferators, e.g., the induction of the Mr 78,000 peroxisome proliferation-associated protein. The effects were reversed within 2-3 weeks upon removal of ciprofibrate. The three other peroxisome proliferators tested, di(2-ethylhexyl)phthalate, clofibrate, and Wy-14,643, were found to exert most of these same effects on the expression and modification of the hepatocyte plasma membrane proteins, but the compounds differed in relative potency. The ciprofibrate-induced decreases in the concentrations of the epidermal growth factor receptor, the asialoglycoprotein receptor, HA 321, and HA 4 were similar to the selective down-regulation of these proteins observed transiently during the period of hepatocyte proliferation following two-thirds hepatectomy. Other compounds frequently used in studies of liver enzyme induction and carcinogenesis, the antioxidants ethoxyquin and butylated hydroxyanisole and the liver tumor promoter phenobarbital, were not as effective as ciprofibrate or two-thirds hepatectomy at causing the down-regulation of these proteins. The induction of the lower-Mr isoform of the basolateral plasma membrane protein CE 9 was not observed following two-thirds hepatectomy or upon the feeding of the antioxidants or phenobarbital but was specific to the feeding of the peroxisome proliferators.


Assuntos
Clofibrato/análogos & derivados , Ácido Clofíbrico/análogos & derivados , Fígado/metabolismo , Glicoproteínas de Membrana/metabolismo , Microcorpos/efeitos dos fármacos , Anticorpos Monoclonais , Receptor de Asialoglicoproteína , Western Blotting , Clofibrato/farmacologia , Ácido Clofíbrico/farmacologia , Dietilexilftalato/farmacologia , Receptores ErbB/metabolismo , Ácidos Fíbricos , Imunofluorescência , Ponto Isoelétrico , Pirimidinas/farmacologia , Receptores Imunológicos/metabolismo , Sialoglicoproteínas/metabolismo
19.
Biol Psychiatry ; 46(12): 1665-71, 1999 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-10624548

RESUMO

BACKGROUND: Abnormalities in types of neurotransmitter signaling that are coupled with phosphoinositide-specific phospholipase C (PLC) have previously been reported in brains from patients with schizophrenia. PLC, a main component of this pathway, may be affected in schizophrenia. METHODS: We immunoquantified PLC beta 1, gamma 1 and delta 1 in the left prefrontal cortex and superior temporal cortex, nucleus accumbens and amygdala, and in the right superior temporal cortex of postmortem brains obtained from a total of 19 patients with schizophrenia and a total of 27 controls. RESULTS: PLC beta 1 immunoreactivities were increased in the particulate fraction from the prefrontal cortex (by 64%), although they were decreased in the particulate fraction from the left superior temporal cortex (by 28%), as compared with the values in controls. There was no difference in PLC beta 1 immunoreactivities in the nucleus accumbens, the amygdala or the right superior temporal cortex between schizophrenic patients and controls. PLC gamma 1 and delta 1 immunoreactivities did not differ between the two groups in any of the regions studied. CONCLUSIONS: Changes in PLC beta 1 immunoreactivities in the prefrontal and superior temporal cortex of patients with schizophrenia may reflect abnormalities in neurotransmissions via receptors that are coupled with the Gq alpha-PLC beta 1 cascade.


Assuntos
Fosfatidilinositóis/metabolismo , Córtex Pré-Frontal/enzimologia , Esquizofrenia/enzimologia , Lobo Temporal/enzimologia , Fosfolipases Tipo C/metabolismo , Tonsila do Cerebelo/enzimologia , Western Blotting , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/enzimologia
20.
Biol Psychiatry ; 43(4): 254-62, 1998 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9513734

RESUMO

BACKGROUND: We examined possible abnormalities in neural structural proteins that may underlie morphometric changes reported in the left superior temporal cortices (Brodmann's area 22) of schizophrenics. METHODS: Particulate proteins of the superior temporal cortices taken at autopsy from 11 schizophrenic and 9 control brains were fractionated by gel electrophoresis. Target proteins, identified by reading their amino acid sequences, were immunoquantified using the specific antibody. RESULTS: Amino acid sequences of the 150-kDa proteins on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, which were significantly increased on the left side of schizophrenic superior temporal cortices, revealed that they were proteolytic fragments of the alpha subunit of fodrin, a major cytoskeletal protein underlying the plasma membrane. Immunoquantification using the specific antibodies against alpha and beta subunits of fodrin indicated that there exist concomitant decreases in the full-length 240-kDa form and increases in the 150-kDa form of alpha-fodrin with no changes of the 235-kDa form of beta-fodrin in the left superior temporal cortices of the schizophrenic brains. CONCLUSIONS: The findings may be a possible molecular basis for linking morphometric changes to neurochemical pathophysiology in schizophrenia.


Assuntos
Química Encefálica/fisiologia , Proteínas de Transporte/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Esquizofrenia/metabolismo , Lobo Temporal/metabolismo , Idoso , Aminoácidos/análise , Western Blotting , Eletroforese em Gel de Poliacrilamida , Córtex Entorrinal/metabolismo , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/metabolismo
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