RESUMEN
Irritation fibromas are recognized as fibrous lesions, usually reactive hyperplasias; however, the mechanism of enlargement is unclear. This paper reports on an abnormally large irritation fibroma of extremely gradual growth. The immunohistochemical features (CD34, α-SMA, vimentin, Ki-67, and TGF-α) of this irritation fibroma are presented to distinguish reactive hyperplasia from other true fibrous neoplasm diseases. In the only previous study, it was reported that the expression of TGF-α might be associated with the development of oral fibromas. Therefore, we investigated the relationship between this exceptionally-large fibrous lesion of extremely slow growth and the immunohistochemical reactivity of TGF-α, finding that, in contrast to the previous study, TGF-α was not expressed. This is the first study to evaluate the enlargement mechanism of such a large irritation fibroma using the approach of immunohistochemical analysis, and it indicates that such analysis can help elucidate the diverse causes and enlargement mechanisms of irritation fibromas.
RESUMEN
OBJECTIVE: Only a few benign tumours of the middle ear have been reported to lead to the development of facial palsy. Here, we describe a patient with middle-ear cavernous lymphangioma and facial palsy. STUDY DESIGN: Single case study. PATIENT: A 61-year-old man presented with left-sided hearing impairment and incomplete left facial palsy. A tumour was confirmed to be occupying the epi- to mesotympanum and to be joined to the facial nerve. The tumour was removed along with facial nerve tissue, which was resected at its horizontal portion, and the remaining facial nerve was fixed by end-to-end anastomosis. Complete facial paralysis occurred after the operation, but the patient's House-Brackmann grade gradually improved to grade III. Post-operative histopathological examination revealed infiltration of the lymphangioma into the facial nerve tissue, together with mild neural atrophy of the facial nerve. CONCLUSION: These findings suggested that tumour invasion was the cause of facial palsy in this patient.
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Neoplasias del Oído/complicaciones , Oído Medio , Parálisis Facial/etiología , Linfangioma/complicaciones , Neoplasias del Oído/diagnóstico , Neoplasias del Oído/cirugía , Nervio Facial/patología , Humanos , Linfangioma/diagnóstico , Linfangioma/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Tomografía Computarizada por Rayos XRESUMEN
The mechanisms for the establishment and maintenance of cell polarity in neurons are not well understood. Axon regeneration from dendrites has been reported after axotomy near the cell body in vivo. We report here in vitro a reversal of neuronal polarity characterized by the conversion of dendrites into axons. We isolated neurons from the neonatal rat cerebral cortex. Neurons that exhibited an apical dendrite with a length of >100 microm were monitored for 3 days in culture. In 66% of neurons examined, a new axon, as identified by reactivity with an antibody to dephosphorylated tau or by lack of reactivity with an antibody to the a and b isoforms of microtubule-associated protein 2, appeared to form from the tip of the original dendrite. Further analysis of such neurons revealed that the distal half of the original dendrite became positive for dephosphorylated tau or negative for microtubule-associated protein 2. Time-lapse video microscopy demonstrated the conversion of the original dendrite into an axon without dendritic retraction. Axon regeneration from dendritic tips required a significantly longer time than axon regeneration from minor processes. Our observations thus demonstrate in vitro a time-consuming reversal of neuronal polarity and the conversion of a dendritic cytoskeleton into an axonal one.
Asunto(s)
Diferenciación Celular/fisiología , Polaridad Celular/fisiología , Corteza Cerebral/crecimiento & desarrollo , Dendritas/ultraestructura , Conos de Crecimiento/ultraestructura , Regeneración Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Actinas/metabolismo , Animales , Animales Recién Nacidos , Carbocianinas , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Dendritas/metabolismo , Colorantes Fluorescentes , Aparato de Golgi/ultraestructura , Conos de Crecimiento/metabolismo , Microscopía por Video , Proteínas Asociadas a Microtúbulos/metabolismo , Células Piramidales/citología , Células Piramidales/metabolismo , Ratas , Proteínas tau/metabolismoRESUMEN
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is an important clinical problem and leads to the release of the proinflammatory cytokines, TNF-alpha and IL-1. These cytokines play important roles in the induction of polymorphonuclear neutrophil (PMN) activation and infiltration, and induce not only localized hepatic injury but also remote organ injury, especially pulmonary injury. Using a total hepatic ischemia model in rats, we tested our hypothesis that suppression of TNF-alpha and IL-1 by FR167653 ameliorates I/R injury in the liver and lung. METHODS: Male Wistar rats, weighing 240-280 g, were divided into 3 groups, an FR group, a control group and a sham group. In the FR group, FR167653 (1 mg/kg/h) was administered continuously to the animals for 30 min prior to the onset of ischemia and for 2 h after reperfusion. The control group received normal saline. A porto-systemic shunt was placed between the cecal branch of the portal vein and the jugular vein, and total hepatic ischemia was produced for 90 min. The sham group was treated with placement of the porto-systemic shunt only. The 1-week survival rate, liver enzyme activity, hepatic tissue blood flow (HTBF), cytokine mRNA expression, myeloperoxidase (MPO) activity and histological results were studied. RESULTS: The 1-week survival rate and HTBF were significantly higher in the FR group than in the control group. Serum AST, ALT, and LDH levels were significantly lower in the FR group at 30 min, 1 h and 3 h after reperfusion. MPO levels in liver and lung tissue were also significantly lower in the FR group. The expression of IL-1beta mRNA remarkably decreased up to 6 h after reperfusion in the FR group. CONCLUSIONS: We concluded that the inflammatory cytokines, IL-1beta, play important roles in hepatic I/R injury. FR167653 might ameliorate I/R injury and be useful in liver surgery with ischemia.
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Citocinas/antagonistas & inhibidores , Inmunosupresores/farmacología , Isquemia/patología , Circulación Hepática , Hígado/patología , Pulmón/patología , Pirazoles/farmacología , Piridinas/farmacología , Daño por Reperfusión/patología , Animales , Northern Blotting , Interleucina-1/genética , Isquemia/mortalidad , Hígado/enzimología , Masculino , Peroxidasa/metabolismo , ARN Mensajero/antagonistas & inhibidores , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/mortalidadRESUMEN
We report two identical male twins who suffered from superior mesenteric artery (SMA) syndrome. A 28-year-old man was admitted for investigation of postprandial nausea and vomiting. Upper gastrointestinal examination revealed a dilated proximal duodenum with an abrupt vertical cutoff of barium flow in the third portion of the duodenum, establishing the diagnosis of SMA syndrome. One year later, his twin brother also presented similar symptoms and was radiologically diagnosed as SMA syndrome. The twin brothers did not respond adequately to conservative therapy and underwent duodenojejunostomy. This is the first report of SMA syndrome in identical twins.
Asunto(s)
Enfermedades en Gemelos , Síndrome de la Arteria Mesentérica Superior , Adulto , Diagnóstico Diferencial , Duodenostomía , Humanos , Masculino , Síndrome de la Arteria Mesentérica Superior/diagnóstico , Síndrome de la Arteria Mesentérica Superior/cirugía , Tomografía Computarizada por Rayos XRESUMEN
It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.
Asunto(s)
Carcinoma Hepatocelular/genética , Aberraciones Cromosómicas/genética , Ciclina E/metabolismo , Neoplasias Hepáticas/genética , Anciano , Anciano de 80 o más Años , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Trastornos de los Cromosomas , Ciclina A/genética , Ciclina A/metabolismo , Ciclina D , Ciclina E/genética , Ciclinas/genética , Ciclinas/metabolismo , Reparación del ADN , ADN de Neoplasias/análisis , Femenino , Fase G1 , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana EdadRESUMEN
BACKGROUND: Disruption of the G1/S check point leads to uncontrolled cell growth, resulting in the development of cancers. MATERIALS AND METHODS: Cell cycle regulatory molecules were investigated in 33 surgically resected hepatocellular carcinoma (HCC) samples from 30 patients by Western blotting. RESULTS: Enhanced expressions of cyclin E and cyclin A were detected at frequencies of 18/33 and 26/33 in HCCs, respectively, as compared with their neighboring noncancerous tissues. The enhanced expression of cyclin E, but not that of cyclin A, correlated with hyperphosphorylation of pRb and high frequency of Ki-67-positive cells. Thus, the HCCs with enhanced cyclin E expression probably contain a relatively large number of proliferating cancer cells. CONCLUSIONS: The degree of cyclin E expression can be used as a prognostic parameter of HCC. In addition, cyclin E may become a molecular target in the treatment of HCCs.
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Carcinoma Hepatocelular/química , Proteínas de Ciclo Celular , Ciclina A/análisis , Ciclina E/análisis , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/química , Proteínas de Neoplasias/análisis , Proteínas Supresoras de Tumor , Anciano , Anciano de 80 o más Años , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclina A/biosíntesis , Ciclina A/genética , Ciclina E/biosíntesis , Ciclina E/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Ciclinas/análisis , Femenino , Fase G1 , Genes p53 , Humanos , Antígeno Ki-67/análisis , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Proteínas Asociadas a Microtúbulos/análisis , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Fosforilación , Procesamiento Proteico-Postraduccional , Proteína de Retinoblastoma/químicaRESUMEN
BACKGROUND: The efficacy of combination therapy adding multiple doses of anticholinergics to beta(2)-agonists to improve outcome has not been established in adults with acute severe asthma. OBJECTIVE: This study was undertaken to compare the outcome of adults with acute severe asthma treated with 4 puffs of salbutamol (100 microg/actuation) every 20 minutes for 3 doses plus 4 puffs of oxitropium bromide (100 microg/actuation) with each of the 3 salbutamol doses versus salbutamol alone administered by means of a metered-dose inhaler with a spacer device. METHODS: A randomized, single-blind, placebo-controlled study was performed in 74 patients between 18 and 55 years old presenting to the emergency department (ED) for treatment of acute asthma with a peak expiratory flow (PEF) of 50% or less than the normal predicted value. The primary endpoint was improvement in PEF over the course. The secondary endpoint was the need for additional ED treatment at 120 minutes. RESULTS: The increase in PEF over the course was significantly greater in the oxitropium plus salbutamol treatment group (P <.0001). The mean absolute difference in PEF at 120 minutes for combination therapy compared with salbutamol alone was 37.8 L/min (P =.001). In addition, the proportion of need for additional ED treatment was less in the combination group than the group receiving salbutamol alone (odds ratio, 0.32; 95% confidence interval, 0.11-0.90). CONCLUSION: Adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device for acute severe asthma produces a significant improvement in lung function and reduces the need for additional ED treatment.
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Albuterol/administración & dosificación , Albuterol/farmacocinética , Asma/tratamiento farmacológico , Derivados de Escopolamina/administración & dosificación , Derivados de Escopolamina/farmacocinética , Enfermedad Aguda , Administración por Inhalación , Adolescente , Adulto , Sistemas de Liberación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Equivalencia TerapéuticaRESUMEN
Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.
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Factor de Crecimiento de Hepatocito/metabolismo , Hígado/metabolismo , Vena Porta/metabolismo , Animales , Northern Blotting , Hepatectomía , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Isquemia/metabolismo , Ligadura , Hígado/anatomía & histología , Hígado/irrigación sanguínea , Masculino , Tamaño de los Órganos , ARN Mensajero/análisis , Ratas , Ratas Wistar , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2EI cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1.
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Citocromo P-450 CYP2E1/metabolismo , Neoplasias Hepáticas/patología , Células Tumorales Cultivadas , Acetaminofén/farmacología , Butionina Sulfoximina/farmacología , Carcinoma Hepatocelular , División Celular , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Citocromo P-450 CYP2E1/genética , Etanol/farmacología , Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismoRESUMEN
Drebrin is an actin-binding protein which is expressed at highly levels in neurons. When introduced into fibroblasts, it has been known to bind to F-actin and to cause remodeling of F-actin. Here, we performed a domain analysis of the actin-binding and actin-remodeling activities of drebrin. Various fragments of drebrin cDNA were fused with green fluorescent protein cDNA and introduced into Chinese hamster ovary cells. Association of the fusion protein with F-actin and remodeling of the F-actin were examined. We found that the central 85-amino-acid sequence (residues 233-317) was sufficient for the binding to and remodeling of F-actin. The binding activity of this fragment was relatively low compared with that of full-length drebrin, but all the types of abnormalities of F-actin that are observed with full-length drebrin were also observed with this fragment. When this sequence was further fragmented, the actin-binding activity was greatly reduced and the actin-remodeling activity disappeared. The actin-binding activity of the central region of drebrin was confirmed by a cosedimentation assay of chymotryptic fragments of drebrin with purified actin. These data indicate that the actin-binding domain and actin-remodeling domain are identical and that this domain is located at the central region of drebrin.
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Actinas/metabolismo , Proteínas de Microfilamentos/química , Proteínas de Microfilamentos/metabolismo , Neuropéptidos/química , Neuropéptidos/metabolismo , Animales , Western Blotting , Células CHO , Quimotripsina , Cricetinae , ADN Complementario , Genes Reporteros , Proteínas Fluorescentes Verdes , Indicadores y Reactivos/metabolismo , Proteínas Luminiscentes/genética , Proteínas de Microfilamentos/genética , Mutagénesis Insercional/fisiología , Neuropéptidos/genética , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Fosforilación , Unión Proteica/fisiología , Proteínas Recombinantes de Fusión/análisis , Estrés MecánicoRESUMEN
This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6). Saline water was administered in the same way in the control group (n = 6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function after warm ischemia of porcine liver.
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Guanosina Monofosfato/administración & dosificación , Circulación Hepática/efectos de los fármacos , Daño por Reperfusión/prevención & control , Análisis de Varianza , Animales , GMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Inyecciones Intravenosas , Pruebas de Función Hepática , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Vena Porta , Valores de Referencia , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , PorcinosRESUMEN
Sequencing of HFE exons 2, 3, 4, and 5, and of portions of introns 2, 4, and 5 revealed novel mutations in four of twenty hemochromatosis probands who lacked C282Y homozygosity, C282Y/H63D compound heterozygosity, or H63D homozygosity. Probands 1 and 2 were heterozygous for previously undescribed mutations: exon 2, nt 314T-->C (314C; I105T), and exon 2, nt 277G-->(277C; G93R), respectively; these probands were also heterozygous for H63D and C282Y, respectively. Probands 3 and 4 were heterozygous for a previously described but uncommon HFE mutation: exon 2, nt 193A-->T (193T; S65C). Proband 3 was also heterozygous for C282Y and had porphyria cutanea tarda, and Proband 4 had hereditary stomatocytosis. Each of these four probands had iron overload. In each proband with an uncommon HFE coding region mutation, I105T, G93R, and S65C occurred on separate chromosomes from those with the C282Y or H63D mutations. Neither I105T, G93R, nor S65C occurred as spontaneous mutations in our probands. The I105T and G93R mutations were linked to haplotypes bearing HLA-A3,-B7 and HLA-A2,-B62, respectively. The S65C mutation was linked to a haplotype characterized by HLA-32. Sixteen other probands did not have an uncommon HFE exon mutation. In 176 normal control subjects, two were heterozygous for S65C, but I105T and G93R were not detected. Nine of twenty probands were heterozygous and two probands were homozygous for a previously described base-pair change at intron 2, nt 3671T-->C. One proband without a detectable missense mutation had a previously described intron 5 allele (nt 6700G-->A). Heterozygosity for a previously described base-pair change in intron 4 (nt 5636T-->C) was detected in all persons we studied who also had the S65C mutation. One proband was heterozygous for a previously undescribed base-pair change at intron 5 (nt 5807A-->G). We conclude that uncommon HFE exon and intron mutations may be discovered among hemochromatosis patients who have "atypical" HFE genotypes.
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Genes MHC Clase I/genética , Antígenos HLA/genética , Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana , Adulto , Alabama/epidemiología , Alelos , Exones/genética , Salud de la Familia , Femenino , Frecuencia de los Genes , Genotipo , Antígenos HLA/inmunología , Hemocromatosis/epidemiología , Proteína de la Hemocromatosis , Humanos , Inmunofenotipificación , Intrones/genética , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Mutación Puntual , Análisis de Secuencia de ADNAsunto(s)
Anticoagulantes/efectos adversos , Ácido Edético/efectos adversos , Complicaciones Hematológicas del Embarazo , Trombocitopenia/etiología , Adulto , Autoanticuerpos/metabolismo , Plaquetas/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Recién Nacido , Masculino , Intercambio Materno-Fetal , Embarazo , Remisión Espontánea , Trombocitopenia/sangre , Trombocitopenia/diagnósticoAsunto(s)
Adenocarcinoma/secundario , Neoplasias de la Vesícula Biliar/irrigación sanguínea , Neoplasias de la Vesícula Biliar/patología , Neoplasias Hepáticas/secundario , Células Neoplásicas Circulantes , Adenocarcinoma/diagnóstico por imagen , Anciano , Femenino , Vesícula Biliar/irrigación sanguínea , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Radiografía , Venas/anatomía & histologíaRESUMEN
This study was conducted to clarify the role of endothelin-1 in the portal vein after hepatic ischemia/ reperfusion and to ascertain whether it is related to hepatic microcirculation disturbance. Using a canine ischemic liver model, the portal and systemic endothelin-1 levels were measured before ischemia, then after 1 h and 2 h of reperfusion, and comparatively evaluated with the serum levels of GOT and lactic dehydrogenase (LDH). As an indicator of liver tissue microcirculation, tissue blood flow volume (TBF) was also measured in the site subjected to ischemia. The animals were divided into: group 1, which received ischemia for 30 min; group 2, which received ischemia for 60 min; and group 3, which received a sequence repeated four times of 15 min ischemia and 10 min reperfusion. The portal endothelin-1 level became significantly elevated after reperfusion compared to that before ischemia in all groups, being significantly higher in group 2 than in the other groups. The systemic endothelin-1 level also increased after reperfusion; significantly in group 2. The portal endothelin-1 level was generally higher than the systemic level, which again was statistically significant in group 2. After 2 h of reperfusion, a significant positive correlation was found between the portal endothelin-I level and serum LDH, whereas a significant negative correlation was found between the portal endothelin-1 level and TBF. The finding that the portal endothelin-1 level became elevated after hepatic ischemia/reperfusion suggests that it probably plays an essential role in hepatic ischemia/ reperfusion injury by adversely influencing tissue microcirculation.
Asunto(s)
Endotelina-1/sangre , Circulación Hepática , Daño por Reperfusión/sangre , Animales , Aspartato Aminotransferasas/sangre , Presión Sanguínea , Volumen Sanguíneo , Perros , L-Lactato Deshidrogenasa/sangre , Microcirculación , Presión Portal , Vena PortaRESUMEN
We evaluated Alabama hemochromatosis probands (n = 74) and normal control subjects (n = 142) for expression of the hemochromatosis-associated mutations nt 845G-->A (845A; Cys282Tyr) and nt 187C-->G (His63Asp) in a gene linked to the major histocompatibility complex (MHC). We also tabulated parameters of iron metabolism and iron overload in probands and in obligate heterozygote family members of homozygous Cys282Tyr probands. Among probands, 59.4% were Cys282Tyr homozygotes and 20.3% were heterozygotes; 20.3% did not express this mutation. In normal control subjects, 14.7% were heterozygous for the Cys282Tyr mutation; one normal control subject was homozygous for the Cys282Tyr mutation. None (0 of 44) of our Cys282Tyr-homozygous hemochromatosis probands had the His63Asp mutation. Of the Cys282Tyr-heterozygous and -negative probands, the His63Asp mutation occurred in 26.7% (4/15) and 53.3% (8/15), respectively. In normal control subjects, 23.2% were heterozygous for the His63Asp mutation; 2.8% were homozygous. Induction phlebotomy requirements and other manifestations of iron overload were significantly greater in Cys282Tyr homozygotes than among other probands. Cys282Tyr-heterozygous probands had significantly higher values of serum iron parameters than did obligate Cys282Tyr heterozygotes whose values were, on the average, normal. Co-expression of HLA-A3, HLA-B7, and D6S105(8) was significantly more frequent in all subgroups of probands stratified by Cys282Tyr expression than in normal control subjects. These results demonstrate that the severity of iron overload in hemochromatosis is affected significantly by genetic factors. Further, our findings support the hypothesis that one or more MHC-linked genes other than that corresponding to the Cys282Tyr and His63Asp mutations contributes to increased iron absorption and iron overload in hemochromatosis probands.
Asunto(s)
Genes MHC Clase I , Ligamiento Genético , Hemocromatosis/genética , Heterocigoto , Mutación , Adulto , Alelos , Ácido Aspártico/genética , Cromosomas Humanos Par 6 , Cisteína/genética , Femenino , Frecuencia de los Genes , Antígenos HLA/genética , Histidina/genética , Prueba de Histocompatibilidad , Homocigoto , Humanos , Hierro/metabolismo , Masculino , Persona de Mediana Edad , Tirosina/genética , Población Blanca/genéticaRESUMEN
An experiment was conducted to determine whether the oxygen and carbon dioxide gas tensions in liver tissue (PtO2 and PtCO2, respectively) reflect the state of microcirculation and/or metabolism in the ischemic liver. Subjects were divided into three groups: group 1, 30 min ischemia; group 2, 60 min ischemia; group 3, four times of intermittent 15 min ischemia after every 10 min of reperfusion. PtO2, PtCO2 and tissue blood flow (TBF) were measured by mass spectrometry, comparatively studied with the serum GOT level as an indicator of liver tissue damage. Furthermore, the time point at which the PtCO2 increase for 1 min initially became less than 1/2 of the maximum value was located on the transit curve of PtCO2, referred to as the critically anaerobic (CA) point, with which new indices of critically anaerobic score (CAS) and time (CAT) (see details in text) were developed. The profiles of PtO2 and PtCO2 during ischemia and reperfusion were clearly demonstrated, and the CA point was observed 12.7 +/- 2.9 min after induction of ischemia. PtO2 was positively correlated with TBF and negatively with the serum GOT level. Furthermore, not only CAS but also CAT were significantly correlated with PtO2, TBF, and the serum GOT level. It was concluded that PtCO2 reflects the state of anaerobic tissue metabolism during ischemia and PtO2 reflects the magnitude of microcirculatory disturbance and tissue injury caused by ischemia/reperfusion. Therefore, continuous monitoring of not only PtO2 but also PtCO2 is beneficial for patients undergoing hepatic surgery with ischemia.
Asunto(s)
Dióxido de Carbono/metabolismo , Hígado/metabolismo , Oxígeno/metabolismo , Daño por Reperfusión/fisiopatología , Animales , Presión Sanguínea , Perros , Circulación Hepática , Espectrometría de Masas , Microcirculación , Presión ParcialRESUMEN
In the signal transduction of transforming growth factor-beta (TGF-beta), the TGF-beta type II receptor (betaR-II) binds TGF-beta, presents the ligand to type I receptor, and forms a heterodimeric receptor complex that functions as an active signaling receptor. We isolated cDNA clones encoding an isoform of human betaR-II from vascular endothelial cells by RT-PCR. The deduced structure of the isoform designated as betaR-IIb contained a 25-amino-acid residue inserted at the extracellular region. The insert exhibited 73% homology to a similar insertion found in a mouse betaR-II variant. BetaR-IIb mRNA was ubiquitously expressed in all human cell lines examined. BetaR-IIb as well as betaR-II stably expressed in betaR-II deficient DR26 cells acted as a functional receptor transducing signals from TGF-beta for growth inhibition and the transcriptional activation of the plasminogen activator inhibitor-1 promoter. These results indicated that the betaR-IIb expressed in mammalian cells functions indistinguishably from in betaR-II. The potential function of betaR-IIb is discussed.