RESUMEN
We report that complexes of giant DNA molecules with histone H1 proteins form a pearl necklace-like structure when the complexes are prepared by natural dilution from a high-salt solution (2 M NaCl) to a low-salt solution (0.2 M and 50 mM NaCl). We performed real-time observations on the conformational changes of individual T4 phage DNA (166 kb) molecules in bulk solution by fluorescence microscopy. To identify H1-binding regions on individual DNA molecules, we also performed immunofluorescence microscopic observations on the DNA-H1 complex spread on a glass surface. It was found that histone H1 binds DNA in a highly co-operative manner and is accompanied by local folding of the DNA. On the basis of the experimental observations and a theoretical simulation, we propose a self-assembling mechanism for the pearling structure.
Asunto(s)
ADN Viral/química , Histonas/química , Bacteriófago T4/química , ADN Viral/ultraestructura , Sustancias Macromoleculares , Microscopía Fluorescente , Modelos Moleculares , Conformación de Ácido NucleicoRESUMEN
We report a case of advanced gastric cancer with multiple liver metastases and peritoneal dissemination. The patient was effectively treated with high-dose 5'-DFUR. A 52-year-old patient with advanced gastric cancer and multiple liver metastases, who showed a high serum level of CEA and CA19-9 underwent simple D1 gastrectomy. Thereafter, he received per os 1,200 mg/day of 5'-DFUR intermittently (5 days a week) and TAI every four months postoperatively. The serum levels of both CEA and CA19-9 fell dramatically to within the normal range and were maintained thereafter until the present. The size and number of the liver metastases dramatically decreased, judging from CT and angiography findings.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/administración & dosificación , Floxuridina/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/secundario , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patologíaRESUMEN
A case of acute thrombocytopenia associated with post-streptococcal acute glomerulonephritis is described. The patient showed a mild glomerulonephritis and a remarkable increase of platelet-associated immunoglobulin G (PAIgG). The relation between the mild degree of glomerulonephritis and the high PAIgG value is discussed.
Asunto(s)
Antiinflamatorios/uso terapéutico , Glomerulonefritis/complicaciones , Glomerulonefritis/microbiología , Prednisolona/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/etiología , Infecciones Estreptocócicas , Enfermedad Aguda , Antiinflamatorios/administración & dosificación , Preescolar , Esquema de Medicación , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulinas/sangre , Masculino , Recuento de Plaquetas , Prednisolona/administración & dosificación , Factores de TiempoRESUMEN
The clinical triad of Septo-optic dysplasia (SOD) comprises the absence of the septum pellucidum, congenital optic nerve dysplasia, and multiple endocrine defects. An incomplete form of SOD has been recognized, with two of the three elements. We present two cases of SOD in incomplete form.
Asunto(s)
Nervio Óptico/anomalías , Hipófisis/anomalías , Tabique Pelúcido/anomalías , Glándulas Suprarrenales/diagnóstico por imagen , Niño , Humanos , Recién Nacido , Masculino , Síndrome , UltrasonografíaRESUMEN
BACKGROUND & AIMS: Chronic alcoholic pancreatitis occurs in only a limited number of heavy drinkers. Other factors than alcohol are necessary for the occurrence of chronic alcoholic pancreatitis. The aim of this study was to examine whether pancreatic duct obstruction resulted in increased alcohol-induced parenchymal cell damage. METHODS: Four groups of adult mongrel dogs were used. In group A, 2. 0 g . kg-1 . day-1 of ethanol was administered via a gastric cannula. In group O, after ligation of the minor pancreatic duct, a polyethylene tube was inserted transduodenally into the major duct. In group AO, the protocols used in groups A and O were combined. Laparotomy was repeated after 3 months in each group. RESULTS: Three of the 9 dogs in group AO had pancreatic calculi in the main pancreatic duct. Moderate interlobular fibrosis, parenchymal cell loss, and inflammatory cell infiltration resembling human chronic alcoholic pancreatitis were observed in group AO. Little change was observed in groups A and O. Exocrine function assessed by secretin test in group AO was significantly reduced. Total protein, hexosamine, and calcium contents of the pancreatic juice in group AO were significantly increased. CONCLUSIONS: Pancreatic duct obstruction is an aggravating factor in chronic alcoholic pancreatitis.
Asunto(s)
Conductos Pancreáticos/fisiopatología , Pancreatitis Alcohólica/fisiopatología , Enfermedad Aguda , Animales , Cálculos/patología , Enfermedad Crónica , Perros , Ligadura , Páncreas/diagnóstico por imagen , Páncreas/patología , Páncreas/fisiopatología , Enfermedades Pancreáticas/patología , Pruebas de Función Pancreática , Jugo Pancreático/química , Pancreatitis Alcohólica/patología , Radiografía , SecretinaRESUMEN
Poly-glutamic acid, a polyanion, has been shown to induce the all-or-none collapse transition in individual duplex DNAs from an elongated coil into a collapsed compact state, through the observation of single chains by fluorescence microscopy. This experimental finding is discussed in relation to the change in the higher-order structure of DNAs in the cytoplasmic space induced by a change in the concentration of polyanions, such as mRNA, as a possible route for feedback in gene expression.
Asunto(s)
ADN/metabolismo , Conformación de Ácido Nucleico , Polímeros/farmacología , Bacteriófago T4/química , ADN/ultraestructura , ADN Viral/química , ADN Viral/metabolismo , Regulación de la Expresión Génica/genética , Procesamiento de Imagen Asistido por Computador , Microscopía Fluorescente , Tamaño de la Partícula , Polielectrolitos , Polietilenglicoles/metabolismo , Ácido Poliglutámico/metabolismo , ARN Mensajero/farmacologíaRESUMEN
UNLABELLED: Histopathological findings were examined in the models of chronic pancreatitis. Using mongrel dogs, we prepared a control group (group C), a chronic ischemic group (group I), an alcohol administration group (group A), a duct obstruction group (group O), and an alcohol + obstruction group (group AO). Group I showed severe inflammatory cell infiltration, fibrosis, fat replacement and loss of acinar cells. Group A showed no change. In group O, mild periductal fibrosis was recognized. Group AO showed moderate inter-lobular fibrosis and inflammatory cell infiltration, resembling those of human chronic alcoholic pancreatitis. CONCLUSION: 1) Histological findings of chronic ischemic group is severer than that of group O and AO. 2) The model of alcohol administration with incomplete duct obstruction is a useful model of human chronic alcoholic pancreatitis.
Asunto(s)
Pancreatitis/patología , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Perros , Fibrosis , Páncreas/patología , Pancreatitis/etiologíaRESUMEN
PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene, which encodes a pituitary specific transcription factor Pit-1/GHF-1.PIT1 abnormality has been reported in several patients displaying either complete or incomplete deficiency of thyrotropin (TSH), growth hormone (GH), and prolactin (PRL) in either familial or sporadic cases. To see if there are abnormalities in the PIT1 gene in patients with incomplete TSH, GH, and PRL deficiency, we utilized a PCR direct sequencing method to determine the Pit-1/GHF-1 coding sequence. A total of 15 patients, 1 patient from a family with TSH and GH deficiency, 3 patients with TSH, GH, and PRL deficiency, and 11 patients treated with both human GH (hGH) and thyroid hormone were studied. In one patient of combined pituitary hormone deficiency, the Arg-271-Trp mutation was detected. Since both of the parents did not harbor this mutation, it is a de novo germ line mutation. No mutation was detected in the other patients, showing that PIT1 abnormality is not a frequent cause of GH deficiency.
Asunto(s)
Proteínas Portadoras/genética , Proteínas de la Membrana , Mutación , Proteínas de Saccharomyces cerevisiae , Secuencia de Bases , Femenino , Mutación de Línea Germinal , Hormona del Crecimiento/deficiencia , Hormona del Crecimiento/uso terapéutico , Humanos , Masculino , Datos de Secuencia Molecular , Proteínas de Transferencia de Fosfolípidos , Hormonas Hipofisarias/deficiencia , Mutación Puntual , Reacción en Cadena de la Polimerasa , Prolactina/deficiencia , Hormonas Tiroideas/uso terapéutico , Tirotropina/deficienciaRESUMEN
An experimental model of chronic pancreatitis was produced by a chronic ischemia which was induced by ligation and separation of branches flowing into the left pancreatic lobe from the splenic artery. Macroscopic findings at 3 and 6 months after model preparation showed that the pancreas was hard, with severe inflammatory change. In the secretin-cerulein test at 3 and 6 months, the flow rate of pancreatic juice, amylase output and bicarbonate concentration were significantly reduced as compared with the controls. The histopathological findings consisted of a decrease in the pancreatic parenchyma, replacement of fat, severe inflammatory cell infiltration, extensive fibrosis and tubular complexes. As this model closely resembles human chronic pancreatitis, we conclude that ischemia is an etiological factor in chronic pancreatitis.
Asunto(s)
Isquemia/complicaciones , Páncreas/irrigación sanguínea , Pancreatitis/etiología , Amilasas/metabolismo , Animales , Bicarbonatos/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Perros , Fibrosis , Ligadura , Páncreas/metabolismo , Páncreas/patología , Jugo Pancreático/metabolismo , Pancreatitis/metabolismo , Pancreatitis/patología , Arteria EsplénicaRESUMEN
Maple syrup urine disease (MSUD) is an autosomal recessive disease caused by a deficiency in subunits of the branched-chain alpha-keto-acid dehydrogenase complex (BCKDH). To characterize the mutations present in five patients with MSUD (four classic and one intermediate), three-step analyses were established: (1), identification of the involved subunit by complementation analysis using three different cell lines derived from homozygotes having E1 alpha, E1 beta or the E2 mutant gene; (2), screening for a mutation site in cDNA of the corresponding subunit by RT-PCR-SSCP and (3), mutant analysis by sequencing the amplified cDNA fragment. Four single-base missense mutations, R115W, Q146K [corrected], A209T and I282T, were detected in the E1 alpha subunit. A single-base missense mutation H156R and three frame-shift mutations to generate stop codons downstream, including an 11-bp deletion of the tandem repeat in exon 1, a single-base (T) deletion and a single-base (G) insertion, were identified in the E1 beta subunit gene. All except one (11-bp deletion in E1 beta (Nobukuni, Y., Mitsubuchi, H., Akaboshi, I., Indo, Y., Endo, F., Yoshioka, A. and Matsuda, I. (1991) J. Clin. Invest. 87, 1862-1866)) were novel mutations. The sites of amino-acid substitution were all conserved in other species. Thus, mutations causing MSUD are heterogenous.
Asunto(s)
Cetona Oxidorreductasas/genética , Enfermedad de la Orina de Jarabe de Arce/genética , Complejos Multienzimáticos/genética , 3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida) , Secuencia de Bases , Fusión Celular , Línea Celular , ADN Complementario/genética , Prueba de Complementación Genética , Humanos , Recién Nacido , Cetona Oxidorreductasas/química , Enfermedad de la Orina de Jarabe de Arce/enzimología , Datos de Secuencia Molecular , Complejos Multienzimáticos/química , Mutación , FenotipoAsunto(s)
Conductos Biliares/patología , Quiste del Colédoco/patología , Conductos Pancreáticos/patología , Adenoma/complicaciones , Neoplasias de las Glándulas Suprarrenales/complicaciones , Adulto , Conductos Biliares/cirugía , Quiste del Colédoco/complicaciones , Quiste del Colédoco/cirugía , Femenino , Humanos , Hiperaldosteronismo/complicaciones , Conductos Pancreáticos/cirugíaRESUMEN
A young Japanese female demonstrated unusual features of Cushing's syndrome, cardiac myxomas and mucocutaneous lentigines. At the age of 12 years she presented with growth failure and obesity. The dexamethasone suppression test, the metyrapone test and low corticotropin concentrations indicated a primary adrenal disorder. At surgery, the adrenal glands were not enlarged (the right, 4.0 g; the left; 4.5 g) but had numerous small dark brown nodules. The pathological findings showed multiple small black cortical nodules containing large cells with eosinophilic cytoplasm and lipofuscin, and internodular cortical atrophy. These abnormalities were consistent with primary pigmented nodular adrenocortical disease. At age 22 years she complained of fatigue and palpitations associated with mid-chest pain. Four cardiac myxomas, suspected from the echocardiogram, were surgically removed. Because Cushing's syndrome and cardiac myxomas are life-threatening conditions, an awareness of the complex is important.
Asunto(s)
Enfermedades de la Corteza Suprarrenal/complicaciones , Síndrome de Cushing/etiología , Neoplasias Cardíacas/complicaciones , Lentigo/complicaciones , Mixoma/complicaciones , Adolescente , Enfermedades de la Corteza Suprarrenal/diagnóstico , Adulto , Niño , Síndrome de Cushing/diagnóstico , Femenino , Atrios Cardíacos , Neoplasias Cardíacas/diagnóstico , Humanos , Lentigo/diagnóstico , Mixoma/cirugía , SíndromeRESUMEN
A case of myxoid leiomyosarcoma of the stomach which developed in a 53-year-old man is reported. The tumor was localized mainly in the greater omentum and was directly connected to the muscle layer of the stomach. No direct invasion to adjacent organs, peritoneal disseminations or distant metastases were noted. Histologically, the tumor prominently comprised a myxomatous lesion with a cellular area portion. The tumor cells had a bipolar or multipolar shape with oval or elongated nuclei, and were scattered in the myxoid stroma which was rich in hyaluronic acid. The cellular area showed a fascicular tumor cell arrangement and also contained pleomorphic tumor cells with abundant mitoses. Immunohistochemically, the tumor cells were positive to vimentin and weakly positive to desmin. Ultrastructurally, pinocytotic vesicles and cytoplasmic microfilaments with focal densities were found in the tumor cells. It is considered important to differentiate between the diagnosis of myxoid leiomyosarcoma and that of any other myxoid malignant tumor.