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1.
BJOG ; 128(12): 1997-2002, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34021948

RESUMEN

We describe a successful surgical technique of abdominal trachelectomy and re-vaginoplasty for cervico-vaginal stenosis following unsuccessful uterovaginal anastomosis and vaginoplasty in a patient with congenital cervical and vaginal aplasia. After the surgical procedure, cervico-vaginal stenosis was resolved and periodic menstruation without dysmenorrhoea resumed. While long-term follow-up is essential to ensure successful pregnancy and delivery, we conclude that this novel surgical procedure is a promising alternative for improvement of the quality of life and normal sexual function, and for preservation of fertility in patients with cervical and vaginal aplasia.


Asunto(s)
Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/cirugía , Traquelectomía/métodos , Vagina/cirugía , Enfermedades Vaginales/cirugía , Adolescente , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Cuello del Útero/anomalías , Cuello del Útero/patología , Constricción Patológica/cirugía , Femenino , Humanos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Embarazo , Reoperación , Vagina/anomalías , Vagina/patología , Enfermedades Vaginales/etiología , Enfermedades Vaginales/patología
2.
Ecotoxicol Environ Saf ; 160: 316-327, 2018 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-29857236

RESUMEN

Environmental contaminant exposure can pose significant risks to human health. Therefore, evaluating the impact of this exposure is of great importance; however, it is often difficult because both the molecular mechanism of disease and the mode of action of the contaminants are complex. We used network biology techniques to quantitatively assess the impact of environmental contaminants on the human interactome and diseases with a particular focus on seven major contaminant categories: persistent organic pollutants (POPs), dioxins, polycyclic aromatic hydrocarbons (PAHs), pesticides, perfluorochemicals (PFCs), metals, and pharmaceutical and personal care products (PPCPs). We integrated publicly available data on toxicogenomics, the diseasome, protein-protein interactions (PPIs), and gene essentiality and found that a few contaminants were targeted to many genes, and a few genes were targeted by many contaminants. The contaminant targets were hub proteins in the human PPI network, whereas the target proteins in most categories did not contain abundant essential proteins. Generally, contaminant targets and disease-associated proteins were closely associated with the PPI network, and the closeness of the associations depended on the disease type and chemical category. Network biology techniques were used to identify environmental contaminants with broad effects on the human interactome and contaminant-sensitive biomarkers. Moreover, this method enabled us to quantify the relationship between environmental contaminants and human diseases, which was supported by epidemiological and experimental evidence. These methods and findings have facilitated the elucidation of the complex relationship between environmental exposure and adverse health outcomes.


Asunto(s)
Contaminantes Ambientales/toxicidad , Cosméticos/toxicidad , Dioxinas/toxicidad , Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Exposición a Riesgos Ambientales , Humanos , Hidrocarburos Fluorados/toxicidad , Metales/toxicidad , Plaguicidas/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Mapas de Interacción de Proteínas
3.
Mol Pharm ; 14(12): 4734-4740, 2017 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-28985076

RESUMEN

Intestinal permeation enhancers are a crucial component of many oral formulations, without which many drugs would show an insufficient absorption in the gut. The present study sought to provide a better understanding of the molecular interaction of such absorption enhancers with the intestine, by investigating the effect of the surfactant-like permeation enhancer dodecylmaltoside (DDM) on Caco-2 cells. The extent to which the action of DDM is apportioned between the para- and transcellular routes was addressed by examining the transport of relevant marker compounds ([3H]-mannitol and [3H]-propranolol, respectively). In the case of [3H]-mannitol, a robust permeation enhancement was achieved with 0.5 mM DDM (∼6-fold), whereas little effect was seen on the permeation of [3H]-propranolol. Concomitantly measured TEER values revealed a rapid onset of action of DDM with a swift recovery and complete restitution (>90%) within 4 h after washout. To localize the site(s) of action of DDM at the absorptive surface of Caco-2 cells, sulfo-NHS-SS-biotin, a membrane-impermeable compound, was applied apically. In the presence of 0.5 mM DDM, translocated biotin was found to be accumulated toward bicellular contacts, whereas no biotin permeation was observed in untreated control cells. Western blot analysis of DDM-treated and untreated Caco-2 cells revealed an interaction of DDM with specific tight junction associated proteins, resulting in a reduction of claudin-3 and -4 and also occludin, as well as a depletion of claudin-2 from lipid rafts. Collectively, the results presented provide a more in depth understanding of the molecular mechanism(s) underlying the permeation-enhancing actions of DDM.


Asunto(s)
Detergentes/farmacología , Glucósidos/farmacología , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Uniones Estrechas/efectos de los fármacos , Células CACO-2 , Humanos , Mucosa Intestinal/metabolismo , Manitol/farmacocinética , Permeabilidad/efectos de los fármacos , Propranolol/farmacocinética , Uniones Estrechas/metabolismo
6.
Dis Esophagus ; 25(6): 484-90, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22098187

RESUMEN

The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 ± 2.1, 8.0 ± 2.6, and 3.3 ± 1.3 per high-power field (mean ± standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 (P= 0.0086) and between Sections 2 and 3 (P < 0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 ± 52.4 µm, 149.6 ± 58.6 µm, and 199.5 ± 75.1 µm (mean ± SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant (P < 0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections (P < 0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus.


Asunto(s)
Unión Esofagogástrica , Microvasos/anatomía & histología , Adulto , Anciano , Enfermedades del Esófago/diagnóstico , Unión Esofagogástrica/anatomía & histología , Unión Esofagogástrica/irrigación sanguínea , Esofagoscopía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/anatomía & histología , Membrana Mucosa/irrigación sanguínea , Imagen de Banda Estrecha/métodos , Estudios Prospectivos
7.
Clin Nephrol ; 75(3): 251-4, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21329636

RESUMEN

Gadolinium (Gd)-based contrast media were introduced as alternatives to iodinated media for magnetic resonance imaging (MRI). Although originally thought to be non-nephrotoxic, Gd-based contrast media have recently been reported to be associated with acute kidney injury. The underlying mechanism of Gd-induced renal injury is not completely understood. We report an 80-year-old patient with buccal mucosa cancer for whom MRI with Gd-based contrast agent was conducted 3 times within 3 weeks. The patient developed rapid deterioration of preexisting renal insufficiency, and developed uremic symptoms and pulmonary edema. The patient was hemodialyzed 3 times. This resulted in improvement of renal function and clinical symptoms. This case emphasizes the potential nephrotoxicity of Gd-based contrast media and suggests that renal insufficiency, diabetes mellitus, old age and high dose of Gd-based contrast medium are risk factors for acute kidney injury.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Medios de Contraste/efectos adversos , Gadolinio DTPA/efectos adversos , Imagen por Resonancia Magnética , Neoplasias de la Boca/patología , Insuficiencia Renal/complicaciones , Lesión Renal Aguda/terapia , Anciano de 80 o más Años , Humanos , Masculino , Neoplasias de la Boca/complicaciones , Edema Pulmonar/inducido químicamente , Diálisis Renal , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Uremia/inducido químicamente
8.
Eur J Gynaecol Oncol ; 32(1): 73-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21446330

RESUMEN

OBJECTIVE: Some Japanese institutes have been performing a population screening program for cervix cancer involving the simultaneous use of Pap smear and colposcopy. This program may be a good model for evaluating the efficacy of Pap smears and colposcopy. METHODS & MATERIALS: The subjects included 2,000 women who underwent primary screening at the Kanagawa Health Service Association. RESULTS: 1) The incidence of ACF (atypical colposcopic findings) was 3.6%, whereas that of abnormal Pap smears (ASC-US and above) was 1.1%; 2) Of 88 women who showed abnormal findings on Pap smear and/or colposcopy, only three cases appeared abnormal in both methods, i.e., the two methods were complementary; 3) Colposcopy was more useful for detecting mild dysplasia than the Pap smear. However, colposcopy may possibly detect benign reparatory lesions; 4) The incidence of unsatisfactory colposcopic findings (UCF) was high (24.2%), whereas no unsatisfactory cases were found by Pap smear. CONCLUSIONS: The sensitivity of the Pap smear for detecting mild dysplasia is low, whereas that of colposcopy is high. However, colposcopy may not be suitable for primary screening due to its high UCF. The low sensitivity of Pap smears may be improved by repetition or adding ancillary HPV testing.


Asunto(s)
Colposcopía , Detección Precoz del Cáncer , Prueba de Papanicolaou , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal , Femenino , Humanos
9.
Diabetologia ; 53(2): 341-5, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19911164

RESUMEN

AIMS/HYPOTHESIS: A 41-year-old woman undergoing simultaneous pancreas-kidney transplantation from an HLA-mismatched cardiac death donor abruptly developed overt hyperglycaemia under standard immunosuppressive therapy at 48 months after transplantation. Unexpectedly, we found insulitis in the transplanted pancreas and characterised the insulitis. METHODS: Pancreas graft biopsies were performed 3 years before and after the development of hyperglycaemia and the specimens were examined histologically. RESULTS: Insulitis was absent in the first biopsy, although oxidative DNA changes revealed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining were diffusely present both in islet cells and exocrine cells. No Ki67-positive proliferating cells were seen in the islets. Anti-glutamic acid decarboxylase antibody was undetectable 6 months earlier but increased to 6.3 U/l at the development of hyperglycaemia. The level of anti-insulinoma-associated protein 2 antibody was 18.5 U/l. Insulin secretion was severely suppressed and insulin therapy was resumed. In the second biopsy, although acute allograft rejection was minimal, insulin-positive beta cells were markedly reduced, and glucagon-positive alpha cells predominated. CD3-positive T lymphocytes, CD8-positive cytotoxic T lymphocytes and CD68-positive macrophages infiltrated around and into islets. The infiltrating cells expressed Fas ligand as well as granzyme B. More than 80% of islets were affected by insulitis. 8-OHdG-positive cells were also present in islets and exocrine tissue. The percentage of Ki67-positive cells in total islet cells was 1.5%. There were no TUNEL-positive apoptotic cells in the islet cells. CONCLUSIONS/INTERPRETATION: The histological features of insulitis in transplanted pancreas were consistent with common type 1 diabetes mellitus, but the clinical course of the recurrence appeared to be more rapid.


Asunto(s)
Diabetes Mellitus Tipo 1/diagnóstico , Hiperglucemia/diagnóstico , Trasplante de Riñón/patología , Trasplante de Páncreas/patología , Trasplante de Páncreas/fisiología , Adulto , Biopsia , Cadáver , Nefropatías Diabéticas/cirugía , Nefropatías Diabéticas/terapia , Femenino , Glucagón/análisis , Rechazo de Injerto/patología , Humanos , Hiperinsulinismo/patología , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Insulina/uso terapéutico , Secreción de Insulina , Complicaciones Posoperatorias/diagnóstico , Recurrencia , Diálisis Renal , Donantes de Tejidos , Adulto Joven
10.
Acta Psychiatr Scand ; 122(4): 319-25, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20626720

RESUMEN

OBJECTIVE: To examine secular trends in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) in a general Japanese population. METHOD: Four cross-sectional examinations were conducted among residents of a Japanese community aged >or=65 in 1985, 1992, 1998 and 2005. RESULTS: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). CONCLUSION: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Demencia Vascular/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Estudios Transversales , Demencia Vascular/diagnóstico , Femenino , Humanos , Japón/epidemiología , Masculino , Pruebas Neuropsicológicas , Dinámica Poblacional , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales
11.
Colorectal Dis ; 12(10 Online): e291-7, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20041914

RESUMEN

AIM: Autofluorescence imaging (AFI) is a novel technology for endoscopy, which enhances neoplastic lesions of the gastrointestinal tract. The aim of this investigation was to examine whether AFI colonoscopy can identify dysplasia in ulcerative colitis. METHOD: We examined 48 patients with ulcerative colitis by AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding lesions under conventional colonoscopy were observed by AFI. Those target areas were classified into low AF and high AF according to the colour under AFI colonoscopy. The grade of dysplasia was determined in the specimens obtained from the target areas. RESULTS: About 126 sites (35 protruding lesions and 91 flat areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas and to be low in 84 areas. The positive rate of dysplasia was higher in protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive dysplasia was not statistically different between lesions determined to be low AF (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in protruding lesions was significantly higher in low AF than in high AF (45.0%vs 13.3%, P = 0.043), while the value in flat lesions was not different between low AF and high AF (8.2%vs 0%, P = 0.3). CONCLUSIONS: Autofluorescence imaging colonoscopy seems to have a role for the detection of dysplaia in ulcerative colitis.


Asunto(s)
Colitis Ulcerosa/patología , Neoplasias del Colon/diagnóstico , Colonoscopía/métodos , Fluorescencia , Mucosa Intestinal/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Colonoscopía/instrumentación , Femenino , Humanos , Aumento de la Imagen , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto Joven
12.
Clin Nephrol ; 74(2): 154-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20630137

RESUMEN

A 59-year-old male presented at our hospital with disturbance of consciousness. He had severe neurological disturbances associated with uremia caused by severe renal insufficiency. Cranial computed tomography (CT) was normal on admission. FLAIR-weighted MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe. Repeated hemodialysis resulted in improvement of the clinical symptoms and blood chemistry, and normalization of the MRI findings. Although the patient was discharged without neurological deficit, he had to be maintained on regular intermittent hemodialysis due to persistent renal failure. These reversible neuroradiological abnormalities may have been caused by reversible brain edema, but other pathoetiological factors should be also considered, such as abnormalities of cerebral metabolism and effects of uremic toxins.


Asunto(s)
Encefalopatías Metabólicas/etiología , Edema Encefálico/etiología , Encefalopatía Hipertensiva/complicaciones , Uremia/complicaciones , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/terapia , Edema Encefálico/diagnóstico , Edema Encefálico/terapia , Humanos , Encefalopatía Hipertensiva/diagnóstico , Encefalopatía Hipertensiva/terapia , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Diálisis Renal , Síndrome , Tomografía Computarizada por Rayos X , Uremia/diagnóstico , Uremia/terapia
13.
Dis Esophagus ; 23(8): 627-32, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20545974

RESUMEN

Endocytoscopy has the potential to reduce the need for histologic examination of biopsy specimens in cases of esophageal squamous cell carcinoma. Up to now, two types of endocytoscope have been used: the probe type and the integrated type. In this study we examined the utility of a newly developed endocytoscope, the 'GIF-Y0002,' which has a single lens allowing consecutive magnification from the conventional endoscopy level up to ×380. Using the GIF-Y0002, we examined 24 examples of normal esophageal mucosa to clarify the appearance of the microvasculature of the normal squamous epithelium in vivo. We also examined 11 cases of esophageal cancer in the same way, employing methylene blue as a vital dye to stain the surface cells. In normal squamous epithelium, we clarified the relationship between the subepithelial capillary network, IPCLs and subepithelial venules. With methylene blue staining, we observed typical squamous cells (low nuclear density and low N/C ratio without nuclear abnormality). When cancerous lesions were observed using lower-power magnification, we were able to visualize their microvascular architecture to the same extent as when conventional magnifying endoscopy was used. Furthermore, at higher magnification, we were able to visualize the features of blood flow in both superficial and advanced cancer. Methylene blue staining revealed an increase of nuclear density in all cases of cancer. The pathologist agreed to omit biopsy histology in 81.8% (9/11) of cancer cases considering the nuclear density and nuclear abnormality. The GIF-Y0002 provides information on cell abnormality in addition to the features revealed by currently available magnifying endoscopy.


Asunto(s)
Carcinoma de Células Escamosas , Endoscopios Gastrointestinales , Neoplasias Esofágicas , Esofagoscopía/instrumentación , Microscopía , Biopsia , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/ultraestructura , Colorantes , Endoscopios Gastrointestinales/estadística & datos numéricos , Endoscopios Gastrointestinales/tendencias , Diseño de Equipo , Neoplasias Esofágicas/irrigación sanguínea , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/ultraestructura , Estudios de Evaluación como Asunto , Humanos , Azul de Metileno , Microscopía/estadística & datos numéricos , Microscopía/tendencias , Estadificación de Neoplasias , Neovascularización Patológica/diagnóstico
14.
J Clin Pharm Ther ; 35(4): 401-8, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20831543

RESUMEN

BACKGROUND AND OBJECTIVE: The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. METHODS: Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group. RESULTS AND DISCUSSION: Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women. CONCLUSIONS: The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Tiazolidinedionas/administración & dosificación , Adiponectina/sangre , Fosfatasa Alcalina/sangre , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Esquema de Medicación , Dislipidemias/metabolismo , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Japón , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pioglitazona , Posmenopausia , Tiazolidinedionas/uso terapéutico
15.
Mutat Res ; 819-820: 111690, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32120136

RESUMEN

The serine/threonine kinase AKT, also known as protein kinase B (PKB), is the major substrate to phosphoinositide 3-kinase (PI3K) and consists of three paralogs: AKT1 (PKBα), AKT2 (PKBß) and AKT3 (PKBγ). The PI3K/AKT pathway is normally activated by binding of ligands to membrane-bound receptor tyrosine kinases (RTKs) as well as downstream to G-protein coupled receptors and integrin-linked kinase. Through multiple downstream substrates, activated AKT controls a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. In human cancers, the PI3K/AKT pathway is most frequently hyperactivated due to mutations and/or overexpression of upstream components. Aberrant expression of RTKs, gain of function mutations in PIK3CA, RAS, PDPK1, and AKT itself, as well as loss of function mutation in AKT phosphatases are genetic lesions that confer hyperactivation of AKT. Activated AKT stimulates DNA repair, e.g. double strand break repair after radiotherapy. Likewise, AKT attenuates chemotherapy-induced apoptosis. These observations suggest that a crucial link exists between AKT and DNA damage. Thus, AKT could be a major predictive marker of conventional cancer therapy, molecularly targeted therapy, and immunotherapy for solid tumors. In this review, we summarize the current understanding by which activated AKT mediates resistance to cancer treatment modalities, i.e. radiotherapy, chemotherapy, and RTK targeted therapy. Next, the effect of AKT on response of tumor cells to RTK targeted strategies will be discussed. Finally, we will provide a brief summary on the clinical trials of AKT inhibitors in combination with radiochemotherapy, RTK targeted therapy, and immunotherapy.


Asunto(s)
ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Terapia Molecular Dirigida/métodos , Neoplasias/terapia , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/genética , Proteínas Quinasas Dependientes de 3-Fosfoinosítido/metabolismo , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Daño del ADN , Reparación del ADN/efectos de los fármacos , ADN de Neoplasias/metabolismo , Rayos gamma/uso terapéutico , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Neoplasias/enzimología , Neoplasias/genética , Neoplasias/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Resultado del Tratamiento , Proteínas ras/genética , Proteínas ras/metabolismo
16.
J Neurol Neurosurg Psychiatry ; 80(4): 366-70, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18977814

RESUMEN

OBJECTIVE: To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population. METHODS: A total of 828 subjects without dementia, aged 65 years or over, were followed-up prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging. RESULTS: The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes. CONCLUSIONS: Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable.


Asunto(s)
Demencia/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/mortalidad , Recolección de Datos , Demencia/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Enfermedad por Cuerpos de Lewy/epidemiología , Enfermedad por Cuerpos de Lewy/mortalidad , Masculino , Escalas de Valoración Psiquiátrica , Factores Sexuales , Análisis de Supervivencia
17.
Diabetes Metab Res Rev ; 25(4): 344-50, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19330879

RESUMEN

BACKGROUND: Postprandial hyperglycemia and hyperlipidemia are frequently associated with type 2 diabetes mellitus. The aim of the present study is to investigate the clinical determinants of postprandial glycemia and lipemia, especially serum high-molecular weight adiponectin. METHODS: Twenty-seven diabetic patients treated with diet alone and 13 healthy volunteers took liquid test meal containing 53 g carbohydrate and 47 g lipid, dosed with nonradioactive isotope (13)C-acetate. Venous blood and breath samples were obtained for 180 min after the meal. Gastric emptying was evaluated by peak excretion time of (13)CO(2) in the breath samples. Delayed gastric emptying was defined as peak excretion time > 2.5 h (mean + 2 SD in the healthy volunteers). RESULTS: Diabetic patients showed delayed insulin secretion, postprandial hyperglycemia and hyperlipidemia compared with control. Postprandial glycemic increases significantly correlated with enhanced gastric emptying. Serum high-molecular weight adiponectin correlated with postprandial glycemic increases at 30 and 60 min after meal (r = 0.42, p < 0.05; r = 0.37, p < 0.05, respectively). Serum high-molecular weight adiponectin also correlated with gastric emptying (versus peak excretion time r = - 0.58, p < 0.05). In addition, diabetic patients with delayed gastric emptying showed the suppressed postprandial glycemia with lower serum high-molecular weight adiponectin than those with normal gastric emptying. On the other hand, postprandial increases in serum triglyceride were not related to serum high-molecular weight adiponectin or gastric emptying, but significantly related to liver function test (serum transaminases) and body mass index. CONCLUSIONS: Early postprandial glycemic increases were related to elevated serum high-molecular weight adiponectin, which might be associated with enhanced gastric emptying.


Asunto(s)
Adiponectina/sangre , Diabetes Mellitus Tipo 2/sangre , Vaciamiento Gástrico/fisiología , Periodo Posprandial/fisiología , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Insulina/sangre , Masculino , Valores de Referencia
18.
Dis Esophagus ; 22(6): 505-12, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19302209

RESUMEN

We examined whether endocytoscopic observation of esophageal squamous cell carcinoma can replace the histologic examination of biopsy specimens. In a basic investigation, we examined 57 iodine-unstained areas in the resected specimens of the esophagus from 28 individuals. The endocytoscopic findings were graded from 0 to 3 in tandem with observations of the iodine staining. For endocytoscopic observation, we sprayed 1% methylene blue or toluidine blue as a vital dye on the surface of the esophageal mucosa, allowing 15-20 s for sufficient staining. One endoscopist observed the target lesions and decided their endocytoscopic type classification. Histological diagnoses were made by two pathologists who were unaware of the endoscopic findings. We then compared the endocytoscopic diagnosis and conventional histological diagnosis. In an in vivo investigation, we examined 71 lesions of esophageal squamous cell carcinoma. Two endoscopists diagnosed the type classification in consultation with a pathologist with regard to 'nuclear density,''nuclear abnormality,' and 'whether biopsy histology could have been omitted on the basis of endocytoscopic findings.' For the in vivo observation, we utilized XEC120U (higher magnification type [x1100]), XEC300F (lower magnification type [x450]), and XGIF-Q260EC1 (lower magnification type [x450]) instruments. In the basic investigation, among the 11 areas classified as Type 1, 10 (91%) were category 1 by the Vienna classification. Among the 39 lesions classified as Type 3, 36 (92%) were category 4 or 5. The sensitivity of endocytoscopy for malignant lesions (Vienna classification categories 4 and 5) was 94.7%, if Type 3 was considered malignant. The specificity was 84.2% according to the same criteria. In the in vivo observation, two endoscopists diagnosed more than 90% of esophageal squamous cell carcinomas as neoplasms using each type of endocytoscope. With regard to nuclear density, the pathologist considered it to be increased in 98% of cases with the XEC120U, in 94% with the XEC300F, and in 93% with the XGIF-Q260EC1. With regard to nuclear abnormality, the positivity rate was 90% with the XEC120U, 78% with the XEC300F, and 80% with the XGIF-Q260EC1. As to whether or not biopsy histology examination was considered necessary, the pathologist made a 'Yes' judgment for 84% of cases observed with the XEC120U, 66% with the XEC300F, and 67% with the XGIF-Q260EC1. Cancerous lesions diagnosed as Type 3 by both endoscopists using the XEC120U accounted for 46 (90.2%) of the 51 cases. Among these 46 cases, biopsy histology was considered unnecessary by the pathologist in 43 (93.5%). We believe that endocytoscopic observation has the potential to reduce the extent of histologic examination of biopsy specimens in cases corresponding to Types 1 and 3 of our classification.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Esofagoscopía/métodos , Núcleo Celular/patología , Endoscopios Gastrointestinales , Diseño de Equipo , Humanos , Procesamiento de Imagen Asistido por Computador , Microscopía Confocal , Sensibilidad y Especificidad
19.
Kyobu Geka ; 62(2): 149-51, 2009 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-19202937

RESUMEN

A 49-year-old female suffered from increasing dyspnea from 2004. She had undergone mitral valve replacement with Carpentier-Edwards 1st-generation standard porcine bioprosthesis due to mitral stenosis 22-years ago. The echocardiography and catheterization showed mitral stenosis and, regurgitation. Re-replacement of the mitral prosthetic valve with ATS (27 mm) valve and tricuspid annuloplasty with Edwards MC3 Ring were successfully performed. There was no case who underwent so long post operative period after initial implantation of fragile prosthetic valve.


Asunto(s)
Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Estenosis de la Válvula Mitral/cirugía , Animales , Femenino , Humanos , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/cirugía , Falla de Prótesis , Reoperación , Porcinos , Factores de Tiempo , Resultado del Tratamiento
20.
Oncogene ; 38(13): 2435, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30518873

RESUMEN

In Figure 4C, it was identified that the Histone H3 and α-Tubulin purification control blots for YES and LYN overexpressing cells were duplicated. The original Histone H3 control blot was found and confirmed the published results, however, the α-Tubulin control blot was not found. This error was determined to not impact the scientific findings of this figure. The authors regret this error.

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