RESUMEN
A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is a rare case of a Japanese patient with autoimmune polyglandular syndrome type 3A (APS-3A) coexisting with autoimmune thyroid disease (AITD) and type 1 DM complicated by IgG4-RD. Bilateral submandibular gland resection was successfully performed without steroid therapy. We discuss the possibility that the immunological pathogenic mechanisms of APS-3A and IgG4-RD are related.
Asunto(s)
Enfermedades Autoinmunes , Diabetes Mellitus Tipo 1 , Enfermedad de Hashimoto , Enfermedad Relacionada con Inmunoglobulina G4 , Poliendocrinopatías Autoinmunes , Femenino , Humanos , Adulto , Persona de Mediana Edad , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/diagnóstico , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnósticoRESUMEN
Acute coronary syndromes are multifactorial and occur in response to inflammation, plaque rupture and subsequent thrombosis, progressive mechanical obstruction, and dynamic obstruction. Among potential biomarkers, much interest has focused on biomarkers of inflammation. The process that leads to eventual plaque erosion or rupture involves a number of inflammatory mechanisms, including endothelial dysfunction, leukocyte migration, extracellular matrix degradation, and platelet activation. We discuss herein blood levels of adhesion molecules, matrix metalloproteases, monocyte chemoattractant protein-1, and tissue factor and interferon-gamma production of circulating T cell in patients with acute coronary syndromes. These biomarkers are associated with not only formation and progression of atherosclerotic plaque but also incidence of coronary event.
Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etiología , Moléculas de Adhesión Celular/sangre , Quimiocina CCL2/sangre , Interferón gamma/sangre , Linfocitos T/fisiología , Biomarcadores/sangre , Humanos , Activación de Linfocitos , Activación de Macrófagos , Metaloproteinasas de la Matriz/sangreAsunto(s)
Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/prevención & control , Humanos , Hipertensión/tratamiento farmacológico , Factores de RiesgoRESUMEN
BACKGROUND: T cells in peripheral blood reflect the systemic inflammatory response in patients with heart failure (HF). In a rat model of HF, osteopontin is dramatically increased in the left ventricular myocardium, so the association between osteopontin and HF was examined in the present study. METHODS AND RESULTS: Peripheral blood was collected from 93 patients with heart disease and 38 controls. Left ventricular ejection fraction (LVEF) was calculated using a modified Simpson's rule. The 93 patients were classified into 3 classes according to the New York Heart Association (NYHA) functional classification. Osteopontin-expressing CD4+ T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) and the frequencies of osteopontin-expressing CD4+ T cells (%) were higher in patients with HF than in controls (800+/-554, 575+/-229, p=0.016 and 27.3+/-12.2, 16.7+/-10.0, p<0.001). Furthermore, the plasma osteopontin levels and the frequencies of osteopontin-expressing CD4+ T cells increased in proportion to the severity of the NYHA functional class. The frequencies of osteopontin-expressing CD4+ T cells were significantly correlated with LVEF (r=-0.336, p=0.0048) and log plasma brain natriuretic peptide levels (r=0.305, p=0.0025). CONCLUSIONS: Osteopontin expression of circulating CD4+ T cells and plasma osteopontin levels reflect the severity of HF. Osteopontin could be a new target in the assessment of HF.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/metabolismo , Osteopontina/metabolismo , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Insuficiencia Cardíaca/clasificación , Humanos , Masculino , Persona de Mediana Edad , Osteopontina/sangre , Pronóstico , Índice de Severidad de la Enfermedad , Volumen Sistólico/fisiologíaRESUMEN
Insulin receptor substrate-1 (IRS-1) is the major substrate of both the insulin receptor and the IGF-1 receptor. In this study, we created IRS-1 transgenic (IRS-1-Tg) mice which express human IRS-1 cDNA under control of the mouse IRS-1 gene promoter. In the IRS-1-Tg mice, IRS-1 mRNA expression was significantly increased in almost all tissues, but its protein expression was increased in very limited tissues (epididymal fat and skeletal muscle). IRS-1-Tg mice showed glucose intolerance and significantly enlarged epididymal fat mass, as well as elevated serum TNF-alpha concentrations. Importantly insulin signaling was significantly attenuated in the liver of IRS-1-Tg mice, which may contribute to the glucose intolerance. Our results suggest that excess IRS-1 expression may not provide a beneficial impact on glucose homeostasis in vivo.
Asunto(s)
Tejido Adiposo/patología , Epidídimo/patología , Resistencia a la Insulina/fisiología , Fosfoproteínas/biosíntesis , Tejido Adiposo/metabolismo , Animales , Epidídimo/metabolismo , Glucosa/metabolismo , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Proteínas Sustrato del Receptor de Insulina , Hígado/metabolismo , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/metabolismo , Fosfoproteínas/genética , Regiones Promotoras Genéticas , ARN Mensajero/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismoAsunto(s)
Vasoespasmo Coronario/complicaciones , Infarto del Miocardio/etiología , Arteritis/complicaciones , Enfermedad de la Arteria Coronaria/complicaciones , Trombosis Coronaria/etiología , Humanos , Mutación , Óxido Nítrico Sintasa de Tipo III/genética , Inactivadores Plasminogénicos/fisiología , Agregación PlaquetariaRESUMEN
BACKGROUND: Plaque instability in patients with unstable angina (UA) is associated with stimulated CD4+ T cells, so the present study investigated whether there is a relationship among plaque instability, osteopontin and CD4+ T cells. METHODS AND RESULTS: Peripheral blood mononuclear cells were collected from 51 consecutive patients with UA, 60 patients with stable angina (SA), and 39 patients with chest pain syndrome (CPS). Osteopontin-producing CD4+ T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) were measured by ELISA and were higher in patients with UA (792.0 +/- 316.7) than in those with SA (626.0 +/- 195.0, p < 0.005) or CPS (594.7 +/- 239.4, p < 0.005). The frequency (%) of osteopontin-producing CD4+ T cells was higher in patients with UA (26.7 +/- 13.3) than in those with SA (19.5 +/- 11.1, p < 0.05) or CPS (16.6 +/- 9.0, p < 0.005). Furthermore, the plasma osteopontin level correlated with the frequency of osteopontin-producing CD4+ T cells (r = 0.327, p = 0.0004), as did the high-sensitivity C-reactive protein level (r = 0.360, p = 0.0002). CONCLUSIONS: The plasma osteopontin levels are elevated in patients with UA, accompanied by an increase in the number of osteopontin-production of circulating CD4+ T cells. Circulating CD4+ T cells may play a role through osteopontin in the pathophysiology of UA.
Asunto(s)
Angina Inestable/sangre , Linfocitos T CD4-Positivos/metabolismo , Sialoglicoproteínas/sangre , Anciano , Angina Inestable/patología , Angina Inestable/fisiopatología , Proteína C-Reactiva/análisis , Linfocitos T CD4-Positivos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , OsteopontinaAsunto(s)
Retinopatía Diabética/etiología , Retinopatía Diabética/prevención & control , Antagonistas Adrenérgicos beta/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Animales , Antihipertensivos/administración & dosificación , Biomarcadores/sangre , Retinopatía Diabética/diagnóstico , Hemoglobina Glucada/análisis , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
BACKGROUND: Connective tissue disease, which is an inflammatory condition represented by C-reactive protein (CRP), is a risk factor for ischemic heart disease. The aim of the present study was to examine if there is a relationship between connective tissue disease and coronary spastic angina, and whether the inflammatory condition was associated with ischemic heart disease, even in patients with connective tissue disease. METHODS AND RESULTS: The study group comprised 73 consecutive patients with connective tissue disease who were admitted to the Department of Cardiovascular Medicine between April 2000 and March 2003. Of the 73 patients, 38 (19 men, 19 women) were diagnosed as having an ischemic heart disease (7 patients acute coronary syndrome, 19 patients coronary spastic angina, 12 patients stable exertional angina). In the present study, 19 (50.0%) of the 38 patients of ischemic heart disease were diagnosed as having coronary spastic angina. In the same study period, 151 (38.7%) of 390 patients with ischemic heart disease (without connective tissue disease) were diagnosed as having coronary spastic angina. The frequency of the patients with coronary spastic angina tended to be higher in patients with connective tissue disease than in patients without connective tissue disease. Among the study patients, serum CRP concentrations (mg/dl) were higher in patients with acute coronary syndrome (1.50 +/- 1.19, n=7) and those with coronary spastic angina (1.06 +/- 1.78, n=19) than in those with non-ischemia (0.35 +/- 0.40, n=35, p<0.05). CONCLUSIONS: Coronary spastic angina is a frequent complication in patients with connective tissue disease and the inflammatory condition is associated with coronary spastic angina and unstable angina in patients with connective tissue disease.
Asunto(s)
Enfermedades del Tejido Conjuntivo/complicaciones , Vasoespasmo Coronario/etiología , Anciano , Angina Inestable/etiología , Biomarcadores , Proteína C-Reactiva/análisis , Enfermedades del Tejido Conjuntivo/sangre , Enfermedades del Tejido Conjuntivo/inmunología , Vasoespasmo Coronario/sangre , Vasoespasmo Coronario/inmunología , Femenino , Humanos , Inflamación/sangre , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/complicaciones , Subgrupos de Linfocitos T/metabolismoRESUMEN
OBJECTIVE: To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications. RESEARCH DESIGN AND METHODS: The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21-B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion. RESULTS: The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA(1c) than in those with normal HbA(1c) (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01). CONCLUSIONS: Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.
Asunto(s)
Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Diabetes Mellitus Tipo 2/orina , Angiopatías Diabéticas/diagnóstico , 8-Hidroxi-2'-Desoxicoguanosina , Anciano , Albuminuria/orina , Biomarcadores/orina , Arteria Carótida Común/patología , Creatinina/orina , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/orina , Retinopatía Diabética/clasificación , Esquema de Medicación , Femenino , Humanos , Insulina/administración & dosificación , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Túnica Íntima/patología , Túnica Media/patologíaRESUMEN
The left ventricular ejection fraction (LVEF) is one of the major prognostic factors after acute myocardial infarction (AMI) and matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for extracellular collagen degradation and remodeling. The present study investigated whether the concentration of serum MMP-1 was associated with the LVEF after AMI. Blood was sampled on admission, and at 24 h, 3 days, 7 days, 2 weeks and 4 weeks in 24 patients with their first AMI. Left ventriculography was performed 4 weeks after the onset of AMI and the LVEF was calculated by center line method. MMP-1 concentrations were higher at 7 days and at 2 weeks than on admission (p<0.001), and at 7 days (r=-0.655, p=0.0005) and at 2 weeks (r=-0.636, p=0.0008) were negatively correlated with the LVEF. The patients with AMI were divided into high and low LVEF groups according to the results of left ventriculography. Although there were no differences in the clinical characteristics between the 2 LVEF groups, the MMP-1 concentrations at 24 h (p<0.01), 7 days (p<0.01) and 2 weeks (p<0.05) were lower in the high LVEF group than in low LVEF group. A high concentration of MMP-1 at the subacute phase after AMI predicts advanced left ventricular remodeling.
Asunto(s)
Metaloproteinasa 1 de la Matriz/sangre , Infarto del Miocardio/fisiopatología , Función Ventricular Izquierda , Remodelación Ventricular , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico por imagen , Concentración Osmolar , Pronóstico , Radiografía , Volumen Sistólico , Factores de TiempoAsunto(s)
Baños , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Ingestión de Alimentos , Ejercicio Físico , Insulina/administración & dosificación , Autocuidado , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Esquema de Medicación , Ingestión de Alimentos/fisiología , Ejercicio Físico/fisiología , Humanos , Insulina/farmacocinética , Cuerpos Cetónicos/sangreAsunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Glucemia , Enfermedad Crónica , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Humanos , Insulina/efectos adversos , Calidad de Vida , Conducta de Reducción del RiesgoAsunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Automonitorización de la Glucosa Sanguínea , Angiopatías Diabéticas/prevención & control , Esquema de Medicación , Humanos , Hipoglucemia/etiología , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Inyecciones Subcutáneas , Insulina/efectos adversos , Sistemas de Infusión de Insulina , Obesidad/etiología , Obesidad/prevención & controlRESUMEN
A 78-year-old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 x 10 mm. Microscopically, the nodule was ill-defined and composed of atypical spindle-shaped and pleomorphic tumor cells. The spindle-shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.