RESUMEN
Little information on the effect of plasma on hepatocyte cytochrome P450 (CYP) activities is currently available. We characterized the effect of plasma on CYPs of hepatocyte-mesenchymal cell co-cultures, which exhibit stable liver specific functions and may be potentially useful for bioartificial liver design. Rat hepatocyte-mouse 3T3-J2 cell co-cultures were maintained for 6 days in medium, and then switched to heparinized human plasma containing 3-methylcholanthrene (3MC; 2 microM), phenobarbital (PB; 1 mM), or no inducer for up to 7 days. CYP activities were measured in situ based on the o-dealkylation of ethoxy- (EROD), methoxy- (MROD), pentoxy- (PROD), or benzyloxy- (BROD) resorufin. Plasma alone increased PROD/BROD but not EROD/MROD. The endogenous inducer was in the high molecular weight fraction (>5 kD) of plasma and inhibited by >5 nM okadaic acid and >10 microM dibutyryl cyclic AMP, two inhibitors of PB-inducible CYPs. Furthermore, plasma increased CYP1A1 and CYP2B1/2 mRNA levels. In plasma, 3MC induced EROD/MROD to about 60% of the level induced in culture medium while PB induced PROD/BROD that were three- to 10-fold above levels induced in medium. CYP activities decreased between days 2 and 7 of plasma exposure, but were enhanced by plasma supplementation with amino acids, insulin, glucagon, and hydrocortisone.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Fibroblastos/enzimología , Hepatocitos/enzimología , Células 3T3 , Animales , Técnicas de Cocultivo/métodos , Medios de Cultivo , Sistema Enzimático del Citocromo P-450/análisis , Fibroblastos/citología , Heparina , Hepatocitos/citología , Humanos , Metilcolantreno , Ratones , Fenobarbital , RatasRESUMEN
Spindle cell carcinoma is a rare tumor that generally occurs in the upper digestive tract. We report an 81-year-old man with spindle cell carcinoma located in the extrahepatic bile ducts, resulting in obstructive jaundice. The patient died 10 months after operation due to local recurrence. The literature on this rare disease is reviewed and discussed.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Conductos Biliares Extrahepáticos , Carcinoma/patología , Anciano , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
We recently reported that the number of gamma delta T cells was increased after infection with Escherichia coli in C3H/HeN mice. We here showed that an i.p. injection with native lipid A derived from E. coli induced an increase of gamma delta T cells in the peritoneal cavity of LPS-responsive C3H/HeN mice and, albeit to a lesser degree, also in LPS-hyporesponsive C3H/HeJ mice. The purified gamma delta T cells from C3H/HeN and C3H/HeJ mice expressed a canonical TCR repertoire encoded by V gamma 6-J gamma 1/V delta 1-D delta 2-J delta 2 gene segments and proliferated in response to the native lipid A derived from E. coli in a TCR-independent manner. The lipid A-reactive gamma delta T cells bearing canonical V gamma 6/V delta 1 expressed Toll-like receptor (TLR) 2 mRNA, while TLR4 mRNA was undetectable. Treatment with a TLR2 anti-sense oligonucleotide resulted in hyporesponsiveness of the gamma delta T cells to the native lipid A. TLR2-deficient mice showed an impaired increase of the gamma delta T cells following injection of native lipid A. These results suggest that TLR2 is involved in the activation of canonical V gamma 6/V delta 1 T cells by native E. coli lipid A.
Asunto(s)
Proteínas de Drosophila , Infecciones por Escherichia coli/inmunología , Glicoproteínas de Membrana/biosíntesis , Receptores de Antígenos de Linfocitos T gamma-delta/biosíntesis , Receptores de Superficie Celular/biosíntesis , Subgrupos de Linfocitos T/metabolismo , Animales , Líquido Ascítico/inmunología , Líquido Ascítico/metabolismo , Línea Celular , Citocinas/biosíntesis , Infecciones por Escherichia coli/metabolismo , Femenino , Regulación de la Expresión Génica/inmunología , Genes Codificadores de la Cadena delta de los Receptores de Linfocito T , Genes Codificadores de la Cadena gamma de los Receptores de Linfocito T , Inyecciones Intraperitoneales , Lípido A/administración & dosificación , Lípido A/fisiología , Receptores de Lipopolisacáridos/biosíntesis , Receptores de Lipopolisacáridos/metabolismo , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Activación de Linfocitos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/fisiología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Noqueados , Cavidad Peritoneal/citología , ARN Mensajero/biosíntesis , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/fisiología , Receptor Toll-Like 2 , Receptor Toll-Like 4 , Receptores Toll-LikeRESUMEN
Prostaglandin E series (PGEs) are known to protect against lipopolysaccharide (LPS)-induced liver injury by down-regulating the production of inflammatory cytokines. We show here a novel mechanism whereby prostaglandin E(1) protects mice against liver injury after Escherichia coli infection. Prostaglandin E(1) administration suppressed circulating interleukin 12 (IL-12) levels but increased the IL-10 production after E. coli challenge. Furthermore, prostaglandin E(1)-alpha-cyclodextrin (PGE(1)) shifted the Th1/Th2 balance of CD3(intermediate) IL-2Rbeta(+) T cells in the liver to a dominant Th2-like response. Neutralization of endogenous IL-4 by administration of anti-IL-4 monoclonal antibody (mAb) diminished the inhibitory effect of prostaglandin E(1) on liver injury after E. coli challenge. These results suggested that the Th2-like response of liver T cells may be at least partly involved in the mechanism whereby prostaglandin E(1) protects against E. coli-induced liver injury.
Asunto(s)
Alprostadil/farmacología , Infecciones por Escherichia coli/patología , Interleucina-4/biosíntesis , Hepatopatías/patología , Hígado/patología , Células Th2/inmunología , alfa-Ciclodextrinas , Animales , Anticuerpos Monoclonales , Ciclodextrinas , Relación Dosis-Respuesta a Droga , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/inmunología , Femenino , Interferón gamma/sangre , Interferón gamma/genética , Interleucina-10/biosíntesis , Interleucina-10/sangre , Interleucina-10/inmunología , Interleucina-12/sangre , Interleucina-4/sangre , Interleucina-4/genética , Interleucina-4/inmunología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/microbiología , Hepatopatías/tratamiento farmacológico , Hepatopatías/inmunología , Recuento de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C3H , ARN Mensajero/genética , ARN Mensajero/metabolismo , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Células Th2/efectos de los fármacos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
A resected case of metastatic liver carcinoid is presented. A 62 year-old woman, who had undergone removal of a typical bronchial carcinoid 19 years before, was found to have a well-defined, oval hepatic tumor on ultrasonography. The resected specimen was a hard and solid tumor, which was microscopically diagnosed as a carcinoid. Histological review of the previously resected lung tumor revealed that the liver tumor was a metastasis from the primary bronchial carcinoid. The patient is alive without recurrence 42 months after hepatectomy. This case suggests that typical bronchial carcinoid, a slowly growing tumor, may metastasize to distant sites after many years, and that re-excision of metastatic lesions may prolong survival time.
Asunto(s)
Tumor Carcinoide/secundario , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/cirugía , Tumor Carcinoide/patología , Tumor Carcinoide/cirugía , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Neumonectomía , ReoperaciónRESUMEN
cAMP-increasing agents such as prostaglandin E2 (PGE2) are known to protect against LPS-induced liver injury by downregulating the production of inflammatory cytokines such as TNF-alpha. However, the effects of such reagents on host defense against bacterial infection remain unknown. We show here that in vivo administration of PGE2 significantly protected mice against liver injury after Escherichia coli infection but hampered the resolution of the infection. PGE2 significantly suppressed circulating TNF-alpha and IL-12 levels but increased the IL-10 production after E. coli challenge. PGE2 inhibited the emergence of gammadelta T cells in the peritoneal cavity, which are important for host defense against E. coli, and deteriorated bacterial exclusion in the peritoneal cavity after E. coli challenge. These results suggested that PGE2 affects host defense mechanisms against E. coli infection through modulation of cytokine production and gammadelta T cell accumulation.
Asunto(s)
Dinoprostona/farmacología , Infecciones por Escherichia coli/prevención & control , Hepatopatías/prevención & control , Hígado/patología , Animales , Movimiento Celular/inmunología , Escherichia coli/crecimiento & desarrollo , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/patología , Femenino , Inyecciones Intraperitoneales , Interleucina-10/sangre , Interleucina-12/sangre , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Hígado/microbiología , Hepatopatías/inmunología , Hepatopatías/patología , Ratones , Ratones Endogámicos C3H , Cavidad Peritoneal/microbiología , Receptores de Antígenos de Linfocitos T gamma-delta/biosíntesis , Subgrupos de Linfocitos T/patología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Liver injury accompanied by apoptosis of hepatocytes was provoked in mice by an intravenous injection of recombinant tumor necrosis factor-alpha (rTNF-alpha) (1.0 microg/kg) together with an intraperitoneal injection of D-galactosamine (D-gal) (500 mg/kg). Injection of various doses of dibutyryl cAMP (DBcAMP) protected mice from TNF-alpha/D-gal-induced liver injury as assessed by serum alanine aminotransferase (ALT) levels, histological examination and DNA fragmentation. DBcAMP significantly enhanced the Hsp70 expression in the hepatocytes of D-gal/TNF-alpha-injected mice in close correlation with suppression of liver injury. DBcAMP induced Hsp70 expression in the hepatocyte in vitro. These results suggest that increase in Hsp70 expression by DBcAMP is involved in protective mechanisms by DBcAMP against TNF-alpha-induced liver injury in D-gal-sensitized mice.
Asunto(s)
Apoptosis/fisiología , Bucladesina/farmacología , Proteínas HSP70 de Choque Térmico/biosíntesis , Hígado/efectos de los fármacos , Factor de Necrosis Tumoral alfa/toxicidad , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Femenino , Galactosamina/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas HSP70 de Choque Térmico/genética , Inyecciones Intravenosas , Hígado/citología , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/antagonistas & inhibidores , Proteínas Recombinantes/toxicidad , Factor de Necrosis Tumoral alfa/administración & dosificación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
The number of gamma delta T cells in the peritoneal cavity was increased after an intraperitoneal (i.p.) infection with Escherichia coli in lipopolysaccharide (LPS)-responsive C3H/HeN mice but not in LPS-hyporesponsive C3H/HeJ mice. The gamma delta T cells preferentially expressed invariant Vgamma6 and Vdelta1 chains and proliferated to produce a large amount of gamma interferon in the presence of LPS. Mice depleted of gamma delta T cells by T-cell receptor delta gene mutation showed impaired resistance against E. coli as assessed by bacterial growth. Macrophages from C3H/HeN mice infected with E. coli expressed higher levels of interleukin-15 (IL-15) mRNA than those from the infected C3H/HeJ mice. Administration of anti-IL-15 monoclonal antibody inhibited, albeit partially, the appearance of gamma delta T cells in C3H/HeN mice after E. coli infection and diminished the host defense against the infection. These results suggest that LPS-stimulated gamma delta T cells play an important role in the host defense against E. coli infection and that IL-15 may be partly involved in the protection via an increase in the gamma delta T cells.
Asunto(s)
Infecciones por Escherichia coli/inmunología , Interleucina-15/fisiología , Receptores de Antígenos de Linfocitos T gamma-delta/fisiología , Linfocitos T/fisiología , Animales , Citocinas/biosíntesis , Escherichia coli/crecimiento & desarrollo , Femenino , Lipopolisacáridos/farmacología , Hígado/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Peritoneo/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/genéticaRESUMEN
Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal cells by neuropeptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6 production by rat BM-derived stromal cells at physiological concentrations ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate (IP3) in rat BM-derived stromal cells with similar 50% effective concentrations. The stimulatory potency of the three related peptides for the production of IL-6, cAMP, and IP3 was almost consistent, suggesting that the dual signaling transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP receptor (PVR3) was found to be abundantly expressed in both BM-derived stromal cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2 (PVR2) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in the BM. The results shown in this paper suggest that PACAP/VIP and their receptor play an important role in the IL-6 production and perhaps in the hematopoiesis in the BM.
Asunto(s)
Células de la Médula Ósea , Interleucina-6/biosíntesis , Neuropéptidos/farmacología , Receptores de la Hormona Hipofisaria/fisiología , Receptores de Péptido Intestinal Vasoactivo/fisiología , Péptido Intestinal Vasoactivo/farmacología , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Células Cultivadas , AMP Cíclico/metabolismo , Cartilla de ADN , Inositol 1,4,5-Trifosfato/metabolismo , Cinética , Masculino , Neurotransmisores/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Reacción en Cadena de la Polimerasa , ARN Mensajero/biosíntesis , Ratas , Ratas Endogámicas F344 , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria , Receptores de la Hormona Hipofisaria/clasificación , Receptores de Péptido Intestinal Vasoactivo/clasificación , Células del Estroma/efectos de los fármacos , Células del Estroma/inmunología , Transcripción Genética/efectos de los fármacosRESUMEN
Heavy ion microprobes (HIM) such as 3 MeV Si2+ and 3 MeV p2+ have been applied to the elemental analysis by PIXE (proton-induced X-ray emission). It was found that silicon and phosphorus microprobes have several times higher sensitivity for aluminum K alpha X-rays than 2 MeV proton microprobes, and detection limits were more favorable in a phosphorus microprobe. Using a 3 MeV P2+ microprobe, the liver of a rat, which had been injected with aluminum-lactate, was investigated and it was found that aluminum segregates in areas with a dimension of about 10 microns. These areas could hardly be observed with 2 MeV proton microprobes.
Asunto(s)
Aluminio/análisis , Microanálisis por Sonda Electrónica/métodos , Hígado/química , Espectrometría por Rayos X/métodos , Animales , Fósforo , Ratas , SilicioRESUMEN
A Pomeranian puppy which died from diarrhea and nasal discharge showed catarrhal pneumonia, acute enteritis and focal liver necrosis. Slender bacilli were detected within ileal enterocytes and hepatocytes. A double infection with a distemper virus and Tyzzer's organism at a cellular level was seen within the ileal enterocytes.