RESUMEN
In the presence of 5 mol% Pd(OAc)2, 1 equiv. of norbornene, and K2CO3, the reaction of 4-iodo-2-quinolones with tertiary o-bromobenzylic alcohols produced the desired benzopyran-fused 2-quinolones in moderate to high yields. A Catellani-type mechanism involving vinylic C-H cleavage is proposed based on the results of control experiments and density functional theory calculations.
RESUMEN
High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled. Patients who achieved complete remission (CR) were randomly assigned to receive therapy containing Hd-MTX (3 g/m2) or Id-MTX (0.5 g/m2). A total of 360 patients were enrolled. The CR rate was 86%. A total of 115 and 114 patients were assigned to the Hd-MTX and Id-MTX groups, respectively. The estimated 5-year disease-free survival rate of the Hd-MTX group was 58%, which was significantly better than that of the Id-MTX group at 32% (P=0.0218). The frequencies of severe adverse events were not significantly different. We herein demonstrated the effectiveness and safety of Hd-MTX therapy for adult Ph-negative ALL. Our results provide a strong rationale for protocols containing Hd-MTX therapy being applied to the treatment of adult ALL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Esquema de Medicación , Femenino , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.
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Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Recurrencia Local de Neoplasia/patología , Células Madre Neoplásicas/patología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinogénesis , Femenino , Humanos , Proteína 1 Inhibidora de la Diferenciación/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Ratones , Ratones Desnudos , FN-kappa B/genética , FN-kappa B/metabolismo , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Células Madre Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinasa/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Pronóstico , Transducción de Señal , Esferoides Celulares , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: The aim of this study is to investigate ipragliflozin as an initial type 2 diabetes (T2DM) drug. METHODS: Ipragliflozin 25-50 mg/day monotherapy was performed with drug naïve subjects with T2DM (n=31). As a comparator, 12.5-25 mg/day alogliptin monotherapy was undertaken (n=32). At 3 months, levels of metabolic parameters were compared with those at baseline. FINDINGS: 4 subjects discontinued ipragliflozin due to intolerance or adverse events, while none dropped out with alogliptin. At 3 months, similar decreases of HbA1c levels were observed with these 2 drugs (10.21-8.31%, p<0.00001, with ipragliflozin, and 10.08-8.25%, p<0.00001, with alogliptin), however fasting blood glucose (FBG) levels decreased with significant inter-group differences (- 23.5% with iprgliflozin and - 10.8% with alogliptin). While similar increases of homeostasis model assessment (HOMA)-B levels were observed with these 2 drugs, HOMA-R levels significantly decreased only with ipragliflozin (-19.4%, p<0.02). Un-correlative link between HOMA-R and HOMA-B levels at baseline became significantly correlative (R=0.6017, p<0.001) only with ipragliflozin. Significant reductions of body mass index (BMI, -2.6%, P<0.05) were observed with ipragliflozin, however, no correlations between the changes of BMI and those of HbA1c or FBG were noted. CONCLUSIONS: These results suggest that ipragliflozin has good glycemic efficacy as an initial therapy in subjects with T2DM, although certain adverse events or tolerability issues are concerned. It improves insulin sensitivity and may restore the impaired beta-cell function. However body weight reduction with ipragliflozin is not associated with its glycemic efficacy.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Tiofenos/uso terapéutico , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Femenino , Glucósidos/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Piperidinas/uso terapéutico , Estudios Prospectivos , Tiofenos/efectos adversos , Uracilo/análogos & derivados , Uracilo/uso terapéuticoAsunto(s)
Proteínas de Fusión bcr-abl/genética , Células Madre Hematopoyéticas/metabolismo , Hemoglobinuria Paroxística/genética , Proteínas de la Membrana/genética , Adulto , Femenino , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Humanos , Inmunofenotipificación , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Transient receptor potential channel melastatin 8 (TRPM8) is activated by cold temperatures and cooling agents (menthol and icilin). Recent studies showed TRPM8 is expressed in visceral organs and peripheral sensory pathways. However, the role of TRPM8 in visceral hyperalgesia is poorly understood in pathological states such as inflammatory bowel disease. Hence, we investigated the distribution of TRPM8 and its involvement in visceral hyperalgesia in experimental colitis mice. METHODS: TRPM8 immunoreactivity was detected using immunohistochemical staining with fluorescein-conjugated tyramide amplification. Visceral hyperalgesia was measured by the intracolonic administration of TRPM8 agonist, WS-12, in control and dextran sodium sulfate (DSS)-induced colitis mice. KEY RESULTS: TRPM8 immunoreactivity in the distal colon was much higher than in the transverse and proximal colon under physiological conditions. TRPM8 immunoreactivity markedly increased in the distal colon mucosa of DSS-induced colitis mice compared with control mice. The number of TRPM8 nerve fibers in mucosa of DSS- or 2,4,6-trinitrobenzene sulfonic acid-induced colitis model mice drastically increased compared with control mice. TRPM8 immunoreactivities colocalized with the calcitonin gene-related peptide- and substance P-immunoreactive nerve fibers in the mucosa. Intracolonic administration of WS-12 induced behavioral visceral pain-like responses. The numbers of these responses in the colitis model mice were 3 times higher than in control mice, and were decreased by pretreatment with the TRPM8 channel blocker AMTB. CONCLUSIONS & INFERENCES: Increased expression of TRPM8 may contribute to the visceral hyperalgesia of experimental colitis.
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Colitis/complicaciones , Colon/metabolismo , Hiperalgesia/metabolismo , Canales Catiónicos TRPM/metabolismo , Anilidas/farmacología , Animales , Colitis/inducido químicamente , Sulfato de Dextran , Modelos Animales de Enfermedad , Hiperalgesia/etiología , Hiperalgesia/psicología , Masculino , Mentol/análogos & derivados , Mentol/farmacología , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Fibras Nerviosas/metabolismo , Canales Catiónicos TRPM/agonistasRESUMEN
The methionine sulphoxide reductase A (msrA) gene and its adjacent genetic loci from urease-negative (UN) Campylobacter lari RM2100 and urease-positive thermophilic Campylobacter (UPTC)CF89-12 strains appear to be composed of a msrA structure gene (507 base pairs [bp]) and another five-gene cluster (approximately 6300 bp) in the same strand and direction. A primer pair (F1/R4-msrA) for polymerase chain reaction (PCR) amplification was designed to generate a product of approximately 900 bp of the msrA gene, including its adjacent genetic loci for the thermophilic Campylobacter organisms and generate an amplicon with 16 C. lari isolates (n = 4 for UN C. lari; n = 12 for UPTC). Following direct nucleotide sequencing, sequence analysis and nucleotide sequence alignment analysis, the putative full-length msrA gene from the 16 C. lari isolates showed high nucleotide sequence similarities (91.8-100%) to each other and relatively low similarity (69.3-71.8%) to three reference C. jejuni and C. coli strains. In addition, the msrA gene was transcribed in both the UPTC CF89-12 and NCTC12893 cells using reverse transcription PCR. An immunoreactively positive signal was identified in the UPTC CF89-12 and NCTC12893 cells with anti-UPTC MsrA synthetic peptide antibodies.
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Proteínas Bacterianas/genética , Campylobacter lari/genética , Metionina Sulfóxido Reductasas/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Secuencia de Bases , Southern Blotting , Campylobacter lari/enzimología , Clonación Molecular , Cartilla de ADN , Biblioteca de Genes , Metionina Sulfóxido Reductasas/química , Datos de Secuencia Molecular , Familia de Multigenes , Estrés Oxidativo , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Leucemia/patología , Recurrencia Local de Neoplasia/patología , Aminoglicósidos/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Azacitidina/administración & dosificación , Azacitidina/análogos & derivados , Decitabina , Relación Dosis-Respuesta a Droga , Gemtuzumab , Humanos , Leucemia/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Células Tumorales CultivadasRESUMEN
BACKGROUND: Pasteurella species, widely known as indigenous organisms in the oral and gastrointestinal floras of many wild and domestic animals, are important pathogens in both animals and humans. Human infections due to Pasteurella species are in most cases associated with infected injuries following animal bites. We encountered a rare case of dual infections caused by different two Pasteurella species occurred in a previously healthy 25-year-old female sustaining injury by a dog-bite. METHODOLOGY: Exudates from the open wound of her dog-bite site, together with the saliva of the dog were submitted for bacteriological examination. Predominantly appearing grayish-white smooth colonies with almost the same colonial properties but slightly different glistening grown on chocolate and sheep blood agar plates were characterized morphologically by Gram's stain, biochemically by automated instrument using Vitek 2 system using GN cards together with commercially available kit system, ID-Test HN-20 rapid panels, and genetically by sequencing the 16S rRNA genes of the organism using a Taq DyeDeoxy Terminator Cycle Sequencing and a model 3100 DNA sequencer instrument. RESULTS: The causative isolates from the dog-bite site were finally identified as P. canis and P. dagmatis from the findings of the morphological, cultural, and biochemical properties together with the comparative sequences of the 16S rRNA genes. Both the isolates were highly susceptible to many antibiotics and the patient was successfully treated with the administration of so-called the first generation cephalosporin, cefazolin followed by so-called the third generation cephalosporin, cefcapene pivoxil. The isolate from the dog was subsequently identified as P. canis, the same species as the isolate from the patient. CONCLUSIONS: To the best of our knowledge, this was the second report of a dual infection with Pasteurella species consisting of P. dagmatis and P. canis resulting from a dog-bite, followed by the first report of dual infections due to P. dagmatis and P. multocida in 1988. Our isolate finally identified as P. dagmatis was misidentified as P. pneumotripica by means of the Vitek 2 system. The species name "P. dagmatis" was not included in the database of the system. It is also important for routine clinical microbiology laboratories to know the limitation of the automated Vitek 2 system for the accurate identification of Pasteurella species especially P. dagmatis. It should be emphasized that there still exists much room for improvement in Vitek 2 system. Significant improvement of Vitek 2 system especially in the identification of Pasteurella species is urgently desired.
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Técnicas de Tipificación Bacteriana/métodos , Mordeduras y Picaduras/microbiología , Infecciones por Pasteurella/microbiología , Pasteurella/aislamiento & purificación , Infección de Heridas/microbiología , Adulto , Animales , Antibacterianos/uso terapéutico , Mordeduras y Picaduras/complicaciones , Cefazolina/uso terapéutico , Cefalosporinas/uso terapéutico , Perros , Femenino , Humanos , Pasteurella/clasificación , Infecciones por Pasteurella/tratamiento farmacológico , Infecciones por Pasteurella/etiología , Infección de Heridas/etiologíaRESUMEN
In the gut, transient receptor potential vanilloid (TRPV) 1 activation leads to release of neurotransmitters such as neuropeptides and nitric oxide. However, the distribution of TRPV1 nerve fibers and neurotransmitters released form sensory nerve endings in the enteric nervous system are currently not well understood. The present study investigated the immunohistochemical distribution of TRPV1 channels, sensory neuropeptides, and nitric oxide and their co-localization in mouse large intestine. Numerous TRPV1 and calcitonin gene-related peptide (CGRP) immunoreactivities were detected, mainly in the mucosa, submucosal layer, and myenteric plexus. Abundant substance P (SP), neurokinin A (NKA), and neuronal nitric oxide synthase (nNOS)-immunoreactivity were revealed in muscle layers. Motor function studies of circular and longitudinal muscles found that contractile responses to capsaicin in the rectum were most sensitive among the rectum, and distal, transverse, and proximal colon. Double labeling studies were carried out in horizontal sections of mouse rectum. TRPV1/protein gene product (PGP)9.5 double labeled axons were observed, but PGP9.5 and neuronal nuclear protein immunopositive cell bodies did not express TRPV1 immunoreactivity in the myenteric plexus. In the mucosa, submucosal layer, deep muscular plexus, circular muscle, myenteric plexus and longitudinal muscle layer, TRPV1 nerve fibers were found to contain CGRP, SP and nNOS. SP and NKA were almost entirely colocalized at the axons and cell bodies in all layers. Double labeling with c-Kit revealed that TRPV1 nerve fibers localized adjacent to the interstitial cells of Cajal (ICC). These results suggest that the TRPV1-expressing nerve and its neurotransmitters regulate various functions of the large intestine.
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Intestino Grueso/inervación , Fibras Nerviosas/fisiología , Neuropéptidos/fisiología , Óxido Nítrico/fisiología , Canales Catiónicos TRPV/fisiología , Animales , Péptido Relacionado con Gen de Calcitonina/fisiología , Colon/inervación , Colon/fisiología , Células Intersticiales de Cajal/citología , Células Intersticiales de Cajal/metabolismo , Células Intersticiales de Cajal/fisiología , Intestino Grueso/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas Nitrérgicas/citología , Neuronas Nitrérgicas/metabolismo , Recto/inervación , Recto/fisiologíaRESUMEN
BACKGROUND AND AIM: Oxidative stress may play an important role in the development of atherosclerosis. Some angiotensin II type 1 (AT(1)) receptor antagonists have the capacity of reducing oxidative stress in addition to the hemodynamic actions. Accordingly, we assessed the hypothesis that olmesartan, a novel AT(1) receptor antagonist, reduced the severity of atherosclerosis in apolipoprotein (apo) E-deficient mice associated with reducing oxidative stress. METHODS AND RESULTS: Atherosclerosis was induced in apo E-deficient mice fed a high fat diet. Mice were intraperitoneally treated with an injection of olmesartan (1mg/kg/day) daily over 8 weeks, and were compared with the untreated controls. Blood pressure was not changed significantly by the olmesartan treatment. Fatty streak plaque developed in apo E-deficient mice, and was suppressed in mice that received olmesartan. In addition, olmesartan reduced not only superoxide production but the overload of oxidative stress in aortic walls. There were no significant differences in serum lipid levels between olmesartan-treated and -untreated groups. In vitro study showed that both olmesartan and its active metabolite RNH-6270, an enantiomer of olmesartan, suppressed interferon-γ, macrophage inflammatory protein-2, and thioredoxin (a marker of oxidative stress) concentrations in cultured cells. CONCLUSION: Olmesartan may suppress atherosclerosis via reducing not only superoxide production but also the overload of oxidative stress in this animal model.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Apolipoproteínas E/deficiencia , Aterosclerosis/tratamiento farmacológico , Imidazoles/farmacología , Superóxidos/metabolismo , Tetrazoles/farmacología , Animales , Aorta/efectos de los fármacos , Biomarcadores/sangre , Células Cultivadas , Quimiocina CXCL2/antagonistas & inhibidores , Quimiocina CXCL2/sangre , Interferón gamma/antagonistas & inhibidores , Interferón gamma/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Tiorredoxinas/antagonistas & inhibidores , Tiorredoxinas/sangreRESUMEN
Ischemic reperfusion injury (IRI) enhances allograft immunogenicity, worsens transplantation outcome, and is the primary cause of activation of the recipient innate immune response, resulting in subsequent amplification of the alloimmune adaptive response. Here, we aimed at demonstrating that the link between innate injury and alloimmunity occurs predominantly through activation of allograft-derived dendritic cells (ADDC). Perfusion of MCI-186, a free radical scavenger, into donor cardiac allografts prior to transplantation resulted in prolongation of complete MHC-mismatched allograft survival in the absence of immunosuppression (MST of 8 vs. 26 days). This prolongation was associated with a reduction in trafficking of ADDC to recipient lymphoid tissue as well as a reduction in T cell priming. Depleting ADDC with diphtheria toxin (using DTR-GFP-DC mice as donors) 24 h prior to transplant resulted in abrogation of the prolongation observed with MCI-186 treatment, demonstrating that the beneficial effect of MCI-186 is mediated by ADDC. This donor-specific anti-ischemic regimen was also shown to reduce chronic rejection, which represents the primary obstacle to long-term allograft acceptance. These data for the first time establish a basis for donor anti-ischemic strategies, which in the ever-expanding marginal donor pools, can be instituted to promote engraftment.
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Antioxidantes/administración & dosificación , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Trasplante de Corazón/métodos , Donantes de Tejidos , Animales , Antipirina/administración & dosificación , Antipirina/análogos & derivados , Edaravona , Depuradores de Radicales Libres/administración & dosificación , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Trasplante de Corazón/inmunología , Trasplante de Corazón/patología , Tejido Linfoide/efectos de los fármacos , Tejido Linfoide/inmunología , Tejido Linfoide/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Estrés Oxidativo/inmunología , Factores de Tiempo , Trasplante HomólogoRESUMEN
The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2-4, P=0.003), involved lymph nodes (P=0.010), and tumour stage (I vs II-IV, P=0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (P<0.001,=0.035, and <0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P=0.037) and overall survival (OS, P=0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P=0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Proteínas Quinasas/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Proteína Oncogénica v-akt/metabolismo , Fosforilación , Pronóstico , Serina-Treonina Quinasas TOR , Distribución TisularRESUMEN
OBJECTIVE: To study the contribution of the CD14 gene to the pathogenesis of rheumatoid arthritis (RA) in Japanese patients. METHODS: CD14 genotyping was carried out at the -159C/T dimorphic site in 97 RA patients and 104 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) METHOD: HLA-DRB1 genotyping was performed by the PCR-SSCP (sequence specific conformational polymorphism) method. RESULTS: The -159C/T dimorphism is not associated with whole RA or with female RA, and the results were compatible with a previous report from Germany. The -159C/T dimorphism was not associated with rheumatoid factor (RF)-positive RA, although the -159T allele tended to be associated with RF in the German report. The -159C/T dimorphism showed no association even in RA patients with the RA-susceptibility HLA-DRB1*0405. The -159T allele was prevalent in Japanese controls. CONCLUSION: The CD14 gene is very unlikely to be genetically involved in the pathogenesis of Japanese RA.
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Artritis Reumatoide/etnología , Artritis Reumatoide/genética , Receptores de Lipopolisacáridos/genética , Anciano , Femenino , Predisposición Genética a la Enfermedad/etnología , Genotipo , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , Prevalencia , Regiones Promotoras Genéticas/genéticaRESUMEN
After bleeding from trauma or surgery, most of the hematomas undergo spontaneous reabsorption. But, in some rare cases, hematomas persist for long periods as slowly expanding masses for months or years. These hematomas were termed as chronic expanding hematomas. In this report, we describe a case of chronic expanding hematoma with a pseudoaneurysm that underwent surgical biopsy, which led to an increase in its expansion speed.
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Aneurisma Falso/patología , Hematoma/patología , Aneurisma Falso/complicaciones , Aneurisma Falso/cirugía , Axila , Biopsia/efectos adversos , Diagnóstico Diferencial , Progresión de la Enfermedad , Hematoma/complicaciones , Hematoma/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Antígenos de Diferenciación/genética , Artritis Reumatoide/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Antígenos CD , Artritis Reumatoide/epidemiología , Antígeno CTLA-4 , Exones , Genotipo , Humanos , Incidencia , Japón/epidemiología , Reacción en Cadena de la PolimerasaRESUMEN
Aging is associated with a decrease in growth hormone (GH) secretion, appetite and energy intake. As ghrelin stimulates both GH secretion and appetite, reductions in ghrelin levels may be involved in the reductions in GH secretion and appetite observed in the elderly. However, only preliminary studies have been performed on the role of ghrelin in elderly subjects. In this study, we sought to clarify the physiologic implications of the age-related alterations in ghrelin secretion by determining plasma ghrelin levels and other clinical parameters in healthy elderly subjects. Subjects were > or = 65 years old, corresponding to the SENIEUR protocol, had not had a resection of the upper gastrointestinal tract and had not been treated with hormones. One hundred and five volunteers (49 men and 56 women) were admitted to this study (73.4 +/- 6.3 years old). Plasma levels of acylated ghrelin in elderly female subjects positively correlated with serum IGF-I levels and bowel movement frequency and negatively with systolic blood pressure. In elderly men, desacyl ghrelin levels correlated only weakly with bowel movement frequency. These findings suggest that the plasma levels of the acylated form of ghrelin may influence the age-related alterations in GH/IGF-I regulation, blood pressure and bowel motility. These observational associations warrant further experimental studies to clarify the physiologic significance of these effects.
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Defecación/fisiología , Factor I del Crecimiento Similar a la Insulina/análisis , Hormonas Peptídicas/sangre , Acilación , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Glucemia/análisis , Presión Sanguínea/fisiología , Índice de Masa Corporal , Femenino , Ghrelina , Hormona de Crecimiento Humana/sangre , Humanos , Insulina/sangre , Leptina/sangre , MasculinoRESUMEN
The analysis of the adherence capacity of fungi to surfaces of both oral tissue and different tissues would be of interest in the fungal dissemination as an oral and systemic pathogen. We developed an in vitro adenosine triphosphate (ATP)-based assay technique to extract the cellular and fungal ATP separately, which allowed the quantitative evaluation of the adhesion of the yeast to monolayers of human gingival epithelial cells (GEC), gingival fibroblasts (GF) and pulmonary fibroblasts (PF). Seven oral isolates of Candida species (three of Candida albicans, three of Candida tropicalis and one of Candida glabrata) were used in the study. The adherent level of the Candida species varied depending on both the isolates and the cell origins, although all the Candida isolates had a significantly higher level of adherence to GEC than to GF except the single isolate of C. tropicalis. Whereas the adherent level of the five isolates to GEC was significantly higher than that to PF, the adherent level of the remaining two isolates of C. tropicalis to GEC was significantly lower than that to PF. These results suggest that candidal adherence to host tissue cells should be regulated in an isolate-dependent and cell-origin-dependent manner, and that the phenomena may be involved in the colonisation and/or dissemination of the fungi.
Asunto(s)
Candida/fisiología , Adhesión Celular , Células Cultivadas , Células Epiteliales/microbiología , Fibroblastos/microbiología , Encía/microbiología , Humanos , Pulmón/microbiología , Especificidad de la EspecieRESUMEN
OBJECTIVES: The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients. METHODS: The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method. RESULTS: The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese. CONCLUSION: TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.
Asunto(s)
Alelos , Artritis Reumatoide/genética , Predisposición Genética a la Enfermedad , Linfotoxina-alfa/genética , Repeticiones de Microsatélite , Factor de Necrosis Tumoral alfa/genética , Artritis Reumatoide/etnología , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Antígenos HLA-DR/análisis , Cadenas HLA-DRB1 , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo GenéticoRESUMEN
Compared to cadaveric liver transplantation, living-related liver transplantation (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes in the level of blood glucose and lactate usually occur during the anhepatic phase in LRLT. For pediatric patients, intraoperative infusions have the potential to maintain immature homeostasis during LRLT. In the present study, a complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which mimics the procedure of pediatric LRLT, was established using a heparin-coated tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas analysis, electrolytes, blood lactate, and glucose) changes were observed during the anhepatic phase. Although no major difference was observed in hemodynamic parameters, arterial blood gas data, or concentration of electrolytes among the three solution groups, significant progressive hyperlactatemia was observed in the LR group. Also, though severe hypoglycemia was found in the LR and AR groups, the AR-G group maintained blood glucose levels throughout the anhepatic phase. To conclude, using the simplified pig anhepatic model, we evaluated various solutions for pediatric LRLT.