RESUMEN
In a 54-year-old woman with diabetes mellitus, hearing loss, muscle weakness and hypocalcemia, caused by idiopathic hypoparathyroidism, an A to G transition at the nucleotide position of 3243 (A3243G mutation) was found in the mitochondrial DNA from her leukocytes. Clinical features of diabetes mellitus and hearing loss in association with the A3243G mutation are compatible with a diagnosis of maternally inherited diabetes and deafness (MIDD). Although hypoparathyroidism is rarely seen in MIDD, we consider that hypoparathyroidism in this patient is a possible phenotype caused by the A3243G mutation of mitochondrial DNA.
Asunto(s)
ADN Mitocondrial/genética , Sordera/genética , Diabetes Mellitus/genética , Hipocalcemia/genética , Debilidad Muscular/genética , Mutación Puntual , Calcio/sangre , Análisis Mutacional de ADN , Cartilla de ADN/química , Sordera/sangre , Diabetes Mellitus/sangre , Femenino , Humanos , Hipocalcemia/sangre , Hipoparatiroidismo/sangre , Hipoparatiroidismo/genética , Persona de Mediana Edad , Debilidad Muscular/sangre , Hormona Paratiroidea/sangre , Linaje , FenotipoRESUMEN
Calponin has been implicated in the regulation of smooth muscle contraction. Basic calponin, one of the calponin isoforms, is expressed exclusively in smooth muscle cell (SMC)-rich tissues, and is considered to be a phenotypic marker of differentiated SMC. To define the molecular mechanism of SMC-specific gene transcription in humans, we isolated and characterized the 5'-flanking region of this gene. Sequence analysis revealed that several putative cis-acting elements were clustered within a 500-bp sequence upstream of the transcription start site. However, the 1.9-kb promoter region obtained herein lacked a completely matched consensus sequence of the CArG box that is commonly identified in the promoter region of other SMC-specific genes. A luciferase assay demonstrated that the 1.9-kb promoter region was sufficient to drive a basal transcriptional activity not only in human vascular smooth muscle cells (VSMC) but also in HeLa cells. In particular, the sequence between positions -1,906 and -867 had a significantly higher transcriptional activity in VSMC than in HeLa cells. In contrast, the promoter activity was drastically decreased between positions -327 and -257 in both types of cells. These results indicate that the sequence spanning from position -327 to -257 contains an essential domain involved in the basal transcriptional activity of the human basic calponin gene, and that the distal region of the 1.9-kb 5'-flanking sequence presented herein may play a pivotal role in the phenotypic modulation of VSMC.
Asunto(s)
Proteínas de Unión al Calcio/genética , Contracción Muscular/genética , Regiones no Traducidas 5'/genética , Secuencia de Bases , Regulación de la Expresión Génica/fisiología , Humanos , Proteínas de Microfilamentos , Datos de Secuencia Molecular , Proteínas Musculares/genética , Músculo Liso Vascular/fisiología , Regiones Promotoras Genéticas/genética , Isoformas de Proteínas/genética , Análisis de Secuencia de ADN , Transcripción Genética , CalponinasRESUMEN
Mucin-producing tumors (MPTs) of the pancreas are increasingly being recognized. To evaluate the appropriate surgical treatment and predict the prognosis of MPTs, we performed a retrospective clinicopathological study in 51 patients, 27 with benign tumors and 24 with borderline/malignant tumors. Three of the malignant tumors showed stromal invasion and lymph node metastasis on histological examination. Of the 24 patients with borderline/malignant tumors, 2 died of MPTs and 4 died of other diseases. At the last follow-up, 35 patients were alive and well. The 5-year postoperative survival rate was 90% for patients with benign tumors, and 78% of these with borderline/malignant tumors. Five of the patients with borderline/malignant tumors had multicentric tumors. Three of these patients underwent resection of the rest of the pancreas, 5, 6, and 8 years, respectively, after the first operation. Extended radical resection is required for malignant MPT with invasion of the pancreatic stroma. We prefer to perform pancreatogastrostomy or Imanaga's procedure to allow examination of the body and tail of the pancreas by endoscopic retrograde pancreatography after resection of the pancreatic head. Careful follow-up for a long period may be the most prudent approach for detecting multiple MPTs in the residual pancreas after surgical treatment.
Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirugía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Colangiopancreatografia Retrógrada Endoscópica , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutanenous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.
Asunto(s)
Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Neoplasias del Conducto Colédoco/cirugía , Neoplasias Hepáticas/secundario , Siembra Neoplásica , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica , Neoplasias del Conducto Colédoco/diagnóstico , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Pruebas de Función Hepática , Persona de Mediana Edad , Neoplasias Pancreáticas/secundario , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: To understand the regulatory mechanism of platelet-derived growth factor beta-receptor gene expression. METHODS: A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5'-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at -67 or -94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at -67. Effects of the upstream sequence spanning -310 through -120 on heterologous gene promoters were also investigated. RESULTS: Multiple transcription start sites were observed in the 5'-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptional activity were identified by the functional promoter assay. One was the CCAAT motif at -67 which acts as a promoter itself, and the other was the upstream region spanning -310 through -210 which positively regulates the basal promoter activity. CONCLUSION: The basal promoter activity of the rat platelet-derived growth factor beta-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element.
Asunto(s)
Regiones Promotoras Genéticas/genética , Receptores del Factor de Crecimiento Derivado de Plaquetas/genética , Animales , Secuencia de Bases , Células Cultivadas , Regulación de la Expresión Génica , Genoma , Masculino , Datos de Secuencia Molecular , Músculo Liso Vascular/fisiología , Ratas , Ratas Sprague-Dawley , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Transcripción GenéticaRESUMEN
Apoptosis (programmed cell death) is observed in vascular smooth muscle cells (VSMC) in atherosclerotic lesions and stenotic lesions after injury, and modulates the cellularity of these lesions. It is recognized that cell growth and apoptosis are two linked processes. Platelet-derived growth factor (PDGF) induces VSMC proliferation and migration in vitro. We studied the effect of PDGF on apoptosis in VSMC. Cultured rat VSMC were treated with PDGF-AA or PDGF-BB. PDGF-BB induced cell death in cultured VSMC in a time- and dose-dependent manner, but PDGF-AA did not. Gel electrophoresis of genomic DNA and in situ DNA labeling confirmed that the cell death induced by PDGF-BB is apoptosis. PDGF-BB treatment reduced bcl-2 mRNA and bcl-xl mRNA expression, in contrast, induced bcl-xs mRNA expression, linked with the induction of apoptosis in cultured VSMC.
Asunto(s)
Apoptosis/fisiología , Músculo Liso Vascular/citología , Factor de Crecimiento Derivado de Plaquetas/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Becaplermina , División Celular/efectos de los fármacos , Células Cultivadas , Fragmentación del ADN , Expresión Génica , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-sis , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacologíaRESUMEN
A 71-year-old woman was admitted to hospital because of malaise and bloody stool. Laboratory findings consistently showed anemia (Hb 9.2 g/dl) and occult blood in the stool. Although barium series and endoscopy of the upper and lower intestinal tructs were carried out, there was no evidence of bleeding from the gastrointestinal tract 99mTcO4- scintigraphy, which was performed to exclude bleeding from Meckel's diverticulum, also did not locate a significant lesion. Angiographic imaging of the superior mesenteric arteries (SMA) was performed to exclude lesions such as small intestine tumors with extraluminal growth and vascular abnormalities such as A-V malformation and it revealed the round encasement of arteries in the peripheral SMA region, strongly suggestive of a small intestine tumor. Surgery was performed and an extraluminally protruding tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in size, are was diagnosed histologically as aberrant pancreas. The postoperative laboratory findings showed that the anemia had improved and occult blood was not detected in the stools. Although aberrant pancreas of the small intestine is a common benign tumor, it is a very unusual cause of bleeding from the alimentary tract.
Asunto(s)
Coristoma/complicaciones , Hemorragia Gastrointestinal/etiología , Enfermedades Intestinales/complicaciones , Intestino Delgado , Páncreas , Anciano , Femenino , HumanosRESUMEN
To investigate the underlying mechanisms of asymptomatic cerebrovascular damage, the diurnal change in blood pressure was evaluated in hypertensive patients with silent cerebral infarction (SCI). Sixty elderly hypertensive patients (age > or = 60 years) were matched with 40 middle-aged patients (age < or = 59 years) for sex and left ventricular mass index (LVMi). Lacunar lesions were evaluated by magnetic resonance imaging as SCI. The presence and the severity of SCI increased with age. In the middle-aged group, the presence of SCI was significantly related to 24-h blood pressure and LVMi evaluated by echocardiography. In elderly patients, the presence of SCI had no relationship with 24-h blood pressure or LVMi. The lowest level of nocturnal diastolic blood pressure showed a J-shaped relationship with the incidence of SCI in the elderly patients. These findings indicate that the hemodynamic characteristics underlying the development of SCI differ between middle-aged and elderly hypertensive patients. A different approach to the treatment of hypertension in the elderly appears necessary.
Asunto(s)
Trastornos Cerebrovasculares/patología , Hipertensión/patología , Anciano , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Infarto Cerebral/etiología , Infarto Cerebral/patología , Trastornos Cerebrovasculares/etiología , Ritmo Circadiano/fisiología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
A 70-year-old man was admitted to our hospital for further evaluation of recurrent fever, which had begun in October 1994. The patient had 5 to 7 days without fever, and then 2 to 3 days of fever. He had headaches during the febrile periods. On admission, he had abnormal pyramidal, extrapyramidal, and celebellar signs, and nuchal rigidity during the febrile period. However, these neurological abnormalities were completely absent during the afebrile period. Examination of cerebrospinal fluid revealed pleocytosis of mononuclear cells. During the febrile period, pleocytosis was associated with high levels of IgG, IL-6, TNF-alpha, and PGE2 in the cerebrospinal fluid. Administration of indomethacin prevented the fever, which suggests that abnormal production of cytokines in the cerebrospinal fluid contributes to fever in Mollaret meningitis.
Asunto(s)
Citocinas/líquido cefalorraquídeo , Meningitis Aséptica/líquido cefalorraquídeo , Anciano , Fiebre/líquido cefalorraquídeo , Humanos , Masculino , RecurrenciaRESUMEN
Autonomic nervous function in elderly essential hypertensive patients was investigated by power spectral analysis of heart rate variability. Fifty-seven essential hypertensive patients participated in this study. They were divided into two groups: the middle-aged group (age < or = 59 years, n = 30) and the elderly group (age > or = 60 years, n = 27). All examinations were performed during hospitalization. Power spectral analysis of R-R interval was performed from Holter electrocardiogram every 10 min by the maximum entropy method to obtain the low frequency band (LFB; 0.04 to 0.15 Hz), which is an index of both sympathetic and parasympathetic nervous activity. Twenty-four-hour blood pressure measurement was performed by the cuffoscillometric method to evaluate the nocturnal decrease in blood pressure. Nondipper patients were defined as those whose nocturnal decrease in systolic blood pressure was < 10% of daytime blood pressure. Both LFB and HFB were significantly lower in elderly hypertensive patients than in middle-aged patients (P < .001 and P < .05, respectively). Elderly nondipper patients had further reduced power spectral densities throughout the day. Both LFB and HFB showed a negative correlation with age. However, the age-related decline of power densities was more prominent in dipper patients and was not statistically significant in nondipper patients. These findings indicate that the nondipper phenomenon is superimposed on age-related attenuation of autonomic nervous function in essential hypertension.
Asunto(s)
Envejecimiento/fisiología , Sistema Nervioso Autónomo/fisiopatología , Hipertensión/fisiopatología , Anciano , Presión Sanguínea/fisiología , Ritmo Circadiano , Electrocardiografía Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procesamiento de Señales Asistido por ComputadorRESUMEN
A 90-year-old man fell into a marsh and was rescued 18 hours later. When he was admitted to our emergency room, physical examination revealed no remarkable findings except for many abrasions on his skin. Laboratory examination revealed a serum CPK level of 46, 904 IU/L, which had further increased to 84,678 IU/L by the following day. Oliguria developed on the second day, along with an increase in serum creatinine to 5.5 mg/dt. Hemodialysis was considered for the treatment of acute renal failure, but his renal function recovered soon by the continuation of conservative fluid therapy. Fluid therapy may be an effective and easy treatment for acute renal failure due to the crush syndrome, even in very old patients.
Asunto(s)
Síndrome de Aplastamiento/terapia , Fluidoterapia , Lesión Renal Aguda/complicaciones , Anciano , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
Association between angiotensin-converting enzyme (ACE) gene polymorphism and essential hypertension in a Japanese population with the same socioeconomic background was investigated. Insertion-deletion (I/D) polymorphism of the ACE gene located on intron 16 was detected by polymerase chain reaction. Association between ACE gene polymorphism and family history of essential hypertension as well as the development of vascular damage in eye fundi were also investigated. Variation at ACE loci did not contribute to essential hypertension and the vascular damages in eye fundi. These results suggest that the ACE gene was not directly responsible for essential hypertension in this particular Japanese population with the same socioeconomic background.
Asunto(s)
Hipertensión/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Secuencia de Bases , Femenino , Humanos , Hipertensión/etnología , Japón , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
A 67-year-old woman with idiopathic orthostatic hypotension was presented. The patient started to experience faintness on standing since 1993. During a physical examination, her systolic blood pressure fell from 148 to 50 mmHg on standing. Blood pressure responses to the mental arithmetic test and hyperventilation stress were normal. However, cold pressor test failed to increase blood pressure. These observations, with the finding that phase IV response on Valsalva's maneuver was absent, indicate afferent sympathetic nervous dysfunction. Peripheral neuropathy including diabetes mellitus and involvement of central nervous system such as multiple system atrophy were excluded. Holter ECG examination revealed a 3.9 second sinus arrest and bradycardia (total beats 88901/day). the blunted responses of the heart rate to atropine as well as isoproterenol further suggested the presence of sick sinus syndrome. Amezinium administration significantly improved her orthostatic hypotension and eliminated sinus arrest. These findings indicate that sympathetic nervous dysfunction could account for at least a part of the sick sinus syndrome in this patient.
Asunto(s)
Hipotensión Ortostática/complicaciones , Síndrome del Seno Enfermo/etiología , Sistema Nervioso Simpático/fisiopatología , Anciano , Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Femenino , Humanos , Piridazinas/uso terapéutico , Síndrome del Seno Enfermo/tratamiento farmacológico , Simpatomiméticos/uso terapéuticoRESUMEN
The nucleotide and deduced amino acid sequences of human basic and acidic calponins were determined. The basic calponin cDNA from human aorta (1496 bp) contained a single open reading frame (ORF) which encodes 297 amino acids (33,169 Da). The acidic calponin cDNA from human kidney (1607 bp) contained a single ORF which encodes 329 amino acids (36,412 Da). Basic calponin mRNA was expressed in only smooth muscle tissues, but acidic calponin mRNA was expressed in non-smooth muscle tissues as well as smooth muscle tissues. Fluorescent in situ hybridization revealed that basic and acidic calponin genes localize in 19p13.1-13.2 and 1p21-22 of human chromosomes, respectively.
Asunto(s)
Proteínas de Unión al Calcio/genética , Secuencia de Aminoácidos , Aorta/metabolismo , Secuencia de Bases , Proteínas de Unión al Calcio/química , Mapeo Cromosómico , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 19/genética , Clonación Molecular , Cartilla de ADN/genética , ADN Complementario/genética , Humanos , Hibridación Fluorescente in Situ , Riñón/metabolismo , Proteínas de Microfilamentos , Datos de Secuencia Molecular , Músculo Liso/metabolismo , Sistemas de Lectura Abierta , Distribución Tisular , CalponinasRESUMEN
Autonomic nervous function was evaluated by means of power spectral analysis of heart rate variability in hospitalized dipper (n = 31) and non-dipper (n = 31) essential hypertensive subjects. Twenty-four-hour blood pressure (BP) measurement was performed by the cuff-oscillometric method to evaluate the nocturnal decrease of BP. The non-dipper subjects were defined as those whose nocturnal decrease of systolic BP was < 10% of daytime BP. Power spectral analysis of RR interval was performed from Holter ECG every 10 minutes by the maximum entropy method to obtain the low-frequency band (LFB, 0.04 to 0.15 Hz), which is an index of both parasympathetic and sympathetic nervous activities, and the high frequency band (HFB, 0.15 to 0.4 Hz), which reflects parasympathetic nervous activity. LFB and HFB were averaged every hour to obtain hourly LFB and HFB values. Total LFB and total HFB were calculated as the mean values of 24 hourly averaged LFBs and HFBs. Both LFB and HFB were significantly lower in non-dipper hypertensives than in dipper subjects throughout the day. In dipper hypertensives, LFB showed a nocturnal decrease, whereas HFB was significantly increased during the nighttime. However, these diurnal changes in LFB and HFB were significantly blunted in non-dipper subjects. These findings indicate that non-dipper hypertensive subjects were characterized with a decreased physiological circadian fluctuation on autonomic functions compared with dipper subjects. This alteration in the autonomic nervous function may explain the non-dipper phenomenon in essential hypertension.