RESUMEN
Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide. Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death. In order to develop effective therapeutic strategies, it is urgent to study the molecular basis of liver cancer metastasis. Methods: Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC. Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion. Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification). Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3). The expression of STAT3, p-STAT3, matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method. Statistical analysis was performed using the t-test. Results: Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues. iTRAQ, Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3. Western blot analysis showed that the expression of p-STAT3, MMP-2 and MMP-9 decreased after FASN knockdown. Conclusion: FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.
Asunto(s)
Carcinoma Hepatocelular/patología , Acido Graso Sintasa Tipo I/metabolismo , Neoplasias Hepáticas/patología , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Movimiento Celular , Ácido Graso Sintasas , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismoRESUMEN
BACKGROUND: Under 'cocktail party' listening conditions, healthy listeners and listeners with schizophrenia can use temporally pre-presented auditory speech-priming (ASP) stimuli to improve target-speech recognition, even though listeners with schizophrenia are more vulnerable to informational speech masking. METHOD: Using functional magnetic resonance imaging, this study searched for both brain substrates underlying the unmasking effect of ASP in 16 healthy controls and 22 patients with schizophrenia, and brain substrates underlying schizophrenia-related speech-recognition deficits under speech-masking conditions. RESULTS: In both controls and patients, introducing the ASP condition (against the auditory non-speech-priming condition) not only activated the left superior temporal gyrus (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced functional connectivity of the left STG/pMTG with the left caudate. It also enhanced functional connectivity of the left STG/pMTG with the left pars triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the left Rolandic operculum in patients. The strength of functional connectivity between the left STG and left TriIFG was correlated with target-speech recognition under the speech-masking condition in both controls and patients, but reduced in patients. CONCLUSIONS: The left STG/pMTG and their ASP-related functional connectivity with both the left caudate and some frontal regions (the left TriIFG in healthy listeners and the left Rolandic operculum in listeners with schizophrenia) are involved in the unmasking effect of ASP, possibly through facilitating the following processes: masker-signal inhibition, target-speech encoding, and speech production. The schizophrenia-related reduction of functional connectivity between the left STG and left TriIFG augments the vulnerability of speech recognition to speech masking.
Asunto(s)
Área de Broca/fisiología , Núcleo Caudado/fisiología , Conectoma/métodos , Memoria Implícita/fisiología , Esquizofrenia/fisiopatología , Percepción del Habla/fisiología , Lóbulo Temporal/fisiología , Adulto , Área de Broca/diagnóstico por imagen , Área de Broca/fisiopatología , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatologíaRESUMEN
BACKGROUND: People with schizophrenia recognize speech poorly under multiple-people-talking (informational masking) conditions. In reverberant environments, direct-wave signals from a speech source are perceptually integrated with the source reflections (the precedence effect), forming perceived spatial separation (PSS) between different sources and consequently improving target-speech recognition against informational masking. However, the brain substrates underlying the schizophrenia-related vulnerability to informational masking and whether schizophrenia affects the unmasking effect of PSS are largely unknown. METHOD: Using psychoacoustic testing and functional magnetic resonance imaging, respectively, the speech recognition under either the PSS or perceived spatial co-location (PSC) condition and the underlying brain substrates were examined in 20 patients with schizophrenia and 16 healthy controls. RESULTS: Speech recognition was worse in patients than controls. Under the PSS (but not PSC) condition, speech recognition was correlated with activation of the superior parietal lobule (SPL), and target speech-induced activation of the SPL, precuneus, middle cingulate cortex and caudate significantly declined in patients. Moreover, the separation (PSS)-against-co-location (PSC) contrast revealed (1) activation of the SPL, precuneus and anterior cingulate cortex in controls, (2) suppression of the SPL and precuneus in patients, (3) activation of the pars triangularis of the inferior frontal gyrus and middle frontal gyrus in both controls and patients, (4) activation of the medial superior frontal gyrus in patients, and (5) impaired functional connectivity of the SPL in patients. CONCLUSIONS: Introducing the PSS listening condition efficiently reveals both the brain substrates underlying schizophrenia-related speech-recognition deficits against informational masking and the schizophrenia-related neural compensatory strategy for impaired SPL functions.
Asunto(s)
Percepción Auditiva/fisiología , Enmascaramiento Perceptual/fisiología , Esquizofrenia/fisiopatología , Percepción del Habla/fisiología , Adolescente , Adulto , Atención/fisiología , Mapeo Encefálico , Estudios de Casos y Controles , China , Femenino , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Parietal/fisiopatología , Adulto JovenRESUMEN
We randomly allocated 80 patients to intravenous dexmedetomidine (0.25, 0.5, or 1 µg.kg(-1) ) or placebo 15 min before anaesthetic induction. Dexmedetomidine 0.5 and 1.0 µg.kg(-1) significantly reduced the mean (95% CI) propofol effect-site concentrations by 0.83 (0.63-1.03) µg.ml(-1) , p = 0.001 and 1.29 (1.12-1.46) µg.ml(-1) , p = 0.0003 at intubation, by 1.05 (0.85-1.25 µg.ml(-1) , p = 0.0006 and 1.33 (1.15-1.51) µg.ml(-1) , p = 0.0002 when surgery started, and by 0.59 (0.39-0.79) µg.ml(-1) , p = 0.030 and 0.72 (0.57-0.87) µg.ml(-1) , p = 0.004 on completion of surgery, respectively. Patients' tracheas were extubated sooner after 0.5 and 1.0 µg.kg(-1) dexmedetomidine, by 5.36 (2.39-8.32) min, p = 0.009 and 7.37 (3.24-11.51) min p = 0.003, respectively. Tachycardic responses to intubation were present in five placebo patients and no dexmedetomidine patients. Bradycardia was treated after dexmedetomidine in six patients: five after 1.0 µg.kg(-1) ; and one after 0.25 µg.kg(-1) . Single-dose dexmedetomidine can reduce anaesthetic requirements, with both desirable and undesirable haemodynamic effects.
Asunto(s)
Anestesia General , Dexmedetomidina , Hipnóticos y Sedantes , Laringoscopía/métodos , Adulto , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestesia , Anestesia Intravenosa , Bradicardia/epidemiología , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Hemodinámica/efectos de los fármacos , Hemodinámica/fisiología , Humanos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Infusiones Intravenosas , Laringoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , Bloqueo Nervioso , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Propofol , Remifentanilo , Tamaño de la Muestra , Taquicardia/epidemiología , Adulto JovenRESUMEN
An association between idiopathic pulmonary fibrosis (IPF) and productive Epstein-Barr virus (EBV) infection has been found previously. Productive EBV replication can be associated with a rearrangement in EBV genomes termed WZhet. We hypothesized that WZhet genomes might be present in patients with IPF. Thirty-nine patients with IPF, 26 lung transplant recipients, and 24 normal subjects were studied. When EBV DNA-positive lung tissue biopsies from IPF patients were analyzed, 11 of 18 (61%) were positive for WZhet. Buffy coat DNA analysis showed that 75-85% were EBV DNA-positive in both IPF and control groups. Buffy coat analysis for WZhet was positive in 16 of 27 (59%) IPF patients, compared with none of 32 lung transplant recipients and 1 of 24 (4%) normal blood donors (p < or = 0.001). There was thus a good correlation between the presence of WZhet in lung tissue and peripheral blood. However, there was no significant association between the presence of WZhet and immunosuppressive therapy. These data further confirm the association between active EBV infection and IPF and provide a potential marker in the peripheral blood for the tracking of EBV in this disease.
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ADN Viral/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Reordenamiento Génico/genética , Herpesvirus Humano 4/genética , Fibrosis Pulmonar/virología , Recombinación Genética/genética , Proteínas Virales , Southern Blotting , Estudios de Casos y Controles , Mapeo Cromosómico , Proteínas de Unión al ADN/genética , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/patología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Fibrosis Pulmonar/terapia , Transactivadores/genética , Replicación Viral/genéticaRESUMEN
A series of amidine substituted phenyl-, benzyl-, and phenethylimidazoles based on the known H3 agonist SK&F 91606 (4) has been synthesized and tested as ligands for the histamine H3 receptor. Insertion of a phenyl ring between the imidazole ring and the amidine moiety produces antagonists. The benzyl series was found to be the most potent and was further investigated. Compounds 9c and 18 (entries 5 and 12, Table 1) are potent ligands for the H3 receptor with K(i) values of 16 nM and 7.2 nM respectively. In vivo, both compounds were shown to be equipotent to thioperamide (2), the standard H3 antagonist.
Asunto(s)
Benzamidinas/síntesis química , Antagonistas de los Receptores Histamínicos/síntesis química , Imidazoles/síntesis química , Receptores Histamínicos H3/fisiología , Animales , Benzamidinas/química , Benzamidinas/farmacología , Diseño de Fármacos , Cobayas , Antagonistas de los Receptores Histamínicos/química , Antagonistas de los Receptores Histamínicos/farmacología , Imidazoles/química , Imidazoles/farmacología , Técnicas In Vitro , Indicadores y Reactivos , Cinética , Ligandos , Conformación Molecular , Estructura Molecular , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Receptores Histamínicos H3/efectos de los fármacosRESUMEN
Injection of an antigen into the anterior chamber induces an immune response in which antibody production is normal while delayed hypersensitivity reactivity is depressed. Several antigens have been used to induce this response which has been termed anterior chamber associated immune deviation. We have demonstrated that allogeneic lymphocytes injected into the anterior chamber of Lewis rats increase the success rate of subsequent corneal grafts derived from the lymphocyte donor strain. To begin understanding the antigenic requirements of this phenomenon, Wistar/Furth lymphocytes were partially purified into B- and T-cell populations by panning on anti-immunoglobulin coated petri-dishes. These enriched populations were injected separately into the anterior chamber of Lewis rats. Two weeks later these Lewis rats received a full-thickness corneal graft derived from Wistar/Furth donors. Grafts were scored for opacity and neovascularization over the subsequent 8-10 weeks. In control animals injected with balanced salt solution, 20% of the grafts cleared sufficiently to be judged successful. Grafts placed on rats injected with unseparated splenic lymphocytes were judged successful in 75% of the cases. Comparable percentages for grafts on animals injected with B-cell enriched and T-cell enriched populations were 85 and 50 respectively. These results suggest that B cells, which express both class I and class II major histocompatibility antigens are more efficient at inducing anterior chamber associated immune deviation than are T cells, the majority of which express only class I major histocompatibility antigens.
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Linfocitos B/inmunología , Supervivencia de Injerto/inmunología , Isoantígenos/inmunología , Queratoplastia Penetrante/inmunología , Linfocitos T/inmunología , Animales , Cámara Anterior/inmunología , Córnea/patología , Femenino , Antígenos de Histocompatibilidad/inmunología , Inmunoterapia , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Trasplante HomólogoRESUMEN
In an attempt to overcome the lack of well characterized, inbred, and congenic strains, as well as a paucity of immunological reagents, in rabbit and rat models, we have developed a procedure for performing full-thickness, penetrating keratoplasty in the mouse. One hundred percent of isografts (BALB/c onto BALB/c) were successful, while 83.3% of allografts (C3H onto BALB/c) failed. The use of a mouse model to study corneal graft failure will allow a critical evaluation of the role of a variety of immunological mediators in causing graft failure.
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Queratoplastia Penetrante/métodos , Animales , Córnea/irrigación sanguínea , Córnea/patología , Opacidad de la Córnea/etiología , Opacidad de la Córnea/patología , Femenino , Rechazo de Injerto , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Complicaciones Posoperatorias , Trasplante Homólogo , Trasplante IsogénicoRESUMEN
Failure of corneal grafts is thought to involve the development and activation of specifically sensitized T-cells. One method which might be used to circumvent the development of such cells is the phenomenon of anterior chamber-associated immune deviation (ACAID). Injection of antigen into the anterior chamber of the eye leads to an immune response characterized by normal antibody response coupled with depressed T-cell reactivity especially as measured by delayed-type hypersensitivity. To determine if this phenomenon could be used to alter the course of graft failure, potential recipients (Lewis rats) were injected intracamerally (IC) with allogeneic lymphoid cells (Wistar-Furth). Orthotopic, full-thickness, penetrating keratoplasty was done 0-30 days later, and the recipients were observed for at least 60 days. Approximately 75% of Wistar-Furth corneal grafts placed on uninjected Lewis rats failed as evidenced by continued opacity, edema, and infiltration of mononuclear cells into the grafts. The IC injection of Wistar-Furth lymphocytes decreased this failure rate to 25% and 50% when grafting was done 14 and 7 days after injection, respectively. Grafts of cornea from a third strain onto IC injected animals failed at an intermediate rate which demonstrated some immunologic protection. The results of these studies indicate that IC injection of allogeneic lymphocytes results in prolonged acceptance of corneal grafts syngeneic with the injected lymphocytes.
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Cámara Anterior/inmunología , Antígenos/inmunología , Trasplante de Córnea , Supervivencia de Injerto , Transfusión de Linfocitos , Animales , Ojo , Femenino , Inyecciones , Linfocitos/inmunología , Linfocitos/fisiología , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
A simple and accurate perturbation method for the analysis of attenuation of guided modes in metal-clad waveguides and weakly absorptive waveguides is presented. The imaginary part N'' of the complex modal index N = N' + iN'' is obtained by solving the corresponding real eigenvalue equation and is given by partial differentialN'/ partial differentialepsilon' times epsilon'', where epsilon = epsilon' + iepsilon'' is the complex dielectric constant of the absorptive layer and partial differentialN'/ partial differentialepsilon' is obtained by numerical differentiation. The method is straightforward, and a cumbersome solution of complex transcendental equations is completely eliminated. Results for simple structures are in good agreement with those obtained by exact analysis.
RESUMEN
An outbreak of 18 acute infant diarrhoea cases caused by enteroinvasive E. coli O152:K? and O112ac: K66 were reported in a nursery in the obstetrics department of a hospital in Huangshi city in 1987. Among them 2 cases died. Epidemic state, etiology biochemical and serological tests, clinical feature and resistance to drugs were discussed. The importance of the management of nurseries and stool examination for the pathogens in intestinal tract in puerpera were emphasized.
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Diarrea Infantil/epidemiología , Brotes de Enfermedades , Infecciones por Escherichia coli , China/epidemiología , Humanos , Incidencia , Recién Nacido , Salas Cuna en HospitalRESUMEN
The fate of orthotopic, allogeneic corneal grafts was followed in inbred rats following three different grafting procedures. Corneas were grafted to recipient rats either in an intralamellar pocket, on a deep stromal bed or by penetrating keratoplasty. In all cases the donor cornea consisted of all three tissue layers (epithelium, stromal and endothelium). Recipient corneas were pretreated with lipopolysaccharide to induce neovascularization. In all three experimental groups, allogeneic grafts went through a phase which clinically resembled a rejection. This phase was characterized by the development of vessels into the transplanted cornea, and opacification. This phase peaked at between 2 and 3 weeks after which some of the grafts cleared and the vascularization receded. Approximately 65% of grafts placed on a deep stroma bed cleared and were considered successful while only 30-35% of the grafts placed in intralamellar pockets or in full-thickness defects were deemed successful. Histological observations paralleled these clinical impressions.
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Trasplante de Córnea/efectos adversos , Rechazo de Injerto , Trasplante/métodos , Animales , Opacidad de la Córnea/complicaciones , Femenino , Lipopolisacáridos/metabolismo , Neovascularización Patológica , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas WF , Factores de TiempoRESUMEN
Cytarabine has been demonstrated to be a more potent inhibitor of fibroblast proliferation than fluorouracil. It is, however, more toxic to the retina. We evaluated the ocular toxicity of liposome-encapsulated cytarabine in vitrectomized and nonvitrectomized rabbit eyes by ophthalmic and histopathologic examination. In the vitrectomized group, doses of up to 26 micrograms were nontoxic to the retina. In nonvitrectomized eyes, doses of up to 55 micrograms were nontoxic. Doses of 85 micrograms resulted in loss of ganglion cells and disorganization of photoreceptor cells. The results obtained in this study demonstrated a substantial reduction in ocular toxicity of liposome-encapsulated cytarabine, as compared with a previous study which employed free drug. By virtue of its reduced toxicity, cytarabine in a liposomal vehicle may be of value in the treatment of ocular proliferative disorders.
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Citarabina/toxicidad , Retina/efectos de los fármacos , Animales , Afaquia/cirugía , Citarabina/administración & dosificación , Portadores de Fármacos , Fibroblastos/citología , Inyecciones , Liposomas , Células Fotorreceptoras/efectos de los fármacos , Células Fotorreceptoras/patología , Conejos , Retina/patología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Vitrectomía , Cuerpo VítreoRESUMEN
Foscarnet (sodium phosphonoformate) is an antiviral with a high degree of efficacy against members of the herpes simplex virus family. We studied the toxicity of single doses of intravitreally administered foscarnet in the albino rabbit. Eyes were evaluated clinically and by light microscopy. Data demonstrated that doses ranging from 20 to 1000 micrograms per 0.1 milliliter are nontoxic to the retina, suggesting that foscarnet may be useful in the treatment of acute retinal necrosis and cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.
Asunto(s)
Compuestos Organofosforados/toxicidad , Ácido Fosfonoacético/toxicidad , Cuerpo Vítreo/efectos de los fármacos , Animales , Foscarnet , Inyecciones , Presión Intraocular , Oftalmoscopía , Ácido Fosfonoacético/análogos & derivados , Conejos , Retina/patologíaRESUMEN
Between March and August 1986 in Huangshi City, serum samples were collected from 316 apparently healthy barbers as a study group, as well as from 361 healthy employees of department stores as a control group. They were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) by enzyme-linked immunoadsorbent assays. Barbers showed a prevalence higher than that in controls for HBsAg (16.8 vs. 9.2%, P less than 0.01), anti-HBs (67.1 vs. 45.9%, P less than 0.001), and anti-HBc (39.2 vs. 21.2%, P less than 0.001). The prevalence of at least one marker of hepatitis B virus (HBV) infection was significantly higher in barbers than in controls (86.1 vs. 61.7%, P less than 0.001). Although the socioeconomic status and education level did not correlate with the frequency of HBV markers, the prevalence of HBsAg increased in parallel with the duration of practice. Because of their high risk for HBV infection, barbers need to be screened for markers of HBV infection on a routine basis, and are prime candidates for immunoprophylaxis with hepatitis B vaccine.