RESUMO
BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.
Assuntos
Adenocarcinoma Mucinoso/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Neoplasias Peritoneais/metabolismo , Receptor 4 Toll-Like/metabolismo , Adenocarcinoma Mucinoso/secundário , Idoso , Biomarcadores Tumorais/metabolismo , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/secundário , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/secundário , Prognóstico , Reto/metabolismo , Reto/patologia , Taxa de SobrevidaRESUMO
AIMS: Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. METHODS: By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. RESULTS: We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. CONCLUSIONS: Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.
Assuntos
Povo Asiático/genética , Proteínas de Ciclo Celular/análise , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Insulina/metabolismo , Proteínas Repressoras/análise , Adulto , Análise de Variância , Proteínas Reguladoras de Apoptose , Proteínas de Ciclo Celular/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Secreção de Insulina , Japão/etnologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Proteínas Repressoras/genéticaRESUMO
BACKGROUND: Although the serum adiponectin level is inversely correlated to body mass index and closely associated with obesity and related diseases, neither the impact of weight loss on the adiponectin level nor other factors that might influence the adiponectin level during weight loss intervention are well documented. OBJECTIVE: The objective of the study is to assess the change in the serum adiponectin level during weight loss intervention and to determine if sleep parameters affect the serum adiponectin level. METHODS: Ninety women with overweight or obesity aged 25 to 65 years completed a 7-month cognitive behavioural therapy based weight loss intervention that included dieting, exercise and stress management. Serum adiponectin level, body fat percent, symptoms of depression and anxiety and objective sleep parameters, assessed by actigraphy, were measured at baseline and at the end of the intervention. RESULTS: The serum adiponectin level was significantly increased after the weight loss intervention (P < 0.001). In a multiple regression analysis, the change of the adiponectin level was positively associated with the magnitude of body fat loss (ß = -0.317, P < 0.001) and an increase of sleep minutes (ß = 0.210, P = 0.043). CONCLUSION: An increase in objective sleep duration was related to a significantly increased serum adiponectin level independently of the change of body fat during the weight loss intervention.
RESUMO
We identified a protein with a molecular weight of about 44 kDa in an extract of rat regenerating liver. This protein was undetectable in normal, sham-operated, and completely regenerated liver. We also purified this 44-kDa protein from an extract of rat liver remnant after partial hepatectomy. The partial amino acid sequences of the purified protein were identical to those of gamma-actin in non-muscle cells. In addition, anti-pan actin antibody recognized the purified 44-kDa protein, whereas anti-muscle actin and anti-beta-actin antibodies did not. Thus, we concluded that the 44-kDa protein was non-muscle gamma-actin. An immunohistochemical study revealed that the non-muscle gamma-actin accumulated next to the plasma membrane of liver parenchymal cells during regeneration. Moreover, the gamma-actin level was augmented in primary cultured rat hepatocytes prior to DNA synthesis. Intracellular gamma-actin in cultured hepatocytes was distributed across the entire basal plane after stimulation with hepatocyte mitogens. This change in the distribution of gamma-actin correlated with the cell spreading that occurred during the G1/S phase transition. These findings indicated that gamma-actin plays specific roles in the growth of liver parenchymal cells during liver regeneration.
Assuntos
Actinas/metabolismo , Regeneração Hepática , Fígado/metabolismo , Actinas/imunologia , Actinas/isolamento & purificação , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Western Blotting , Membrana Celular/metabolismo , Células Cultivadas , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Feminino , Fígado/citologia , Fígado/fisiologia , Dados de Sequência Molecular , Ratos , Ratos WistarRESUMO
Most single fibers of the cochlear nerve (CN) in 22 cats exhibited effects of mechanical interaction in one cochlea between two sounds applied binaurally, similarly to results in two cats in which the contralateral CN was transected. In 11 of 189 fibers, the spontaneous and/or the sound-evoked activity was suppressed by a contralateral intense best-frequency sound; this indicates an interaural neural inhibition, probably through the olivocochlear bundle (OCB). The inhibited fiber population was small, and the intensity differences between the binaural sounds were exceptionally large, so that a simple negative feed-back function via the OCB is not likely.
Assuntos
Nervo Coclear/fisiologia , Neurônios/fisiologia , Estimulação Acústica , Animais , Gatos , Cóclea/fisiologia , Lateralidade FuncionalRESUMO
From the cultures of the spore-derived mycobionts of the lichen Lecanora cinereocarnea, five dibenzofurans, 3,7-dihydroxy-1,9-dimethyldibenzofuran, 2-chloro-3,7-dihydroxy-1,9-dimethyldibenzofuran, 2,8-dichloro-3,7-dihydroxy-1,9-dimethyldibenzofuran, 3-hydroxy-7-methoxy-1,9-dimethyldibenzofuran, and 2-chloro-7-hydroxy-3-methoxy-1,9-dimethyldibenzofuran, were isolated. Their structures were determined by spectroscopic methods.
Assuntos
Benzofuranos/isolamento & purificação , Líquens/química , Benzofuranos/química , Estrutura Molecular , Análise EspectralRESUMO
From the dried roots of Cephaelis acuminata, five ipecac alkaloids, neocephaeline, 7'-O-demethylcephaeline, 10-O-demethylcephaeline, 2'-N-(1"-deoxy-1"-beta-D-fructopyranosyl)cephaeline and 2'-N-(1"-deoxy-1"-beta-D-fructopyranosyl)neocephaeline, were isolated, along with emetine, cephaeline, psychotrine, protoemetine, 9-demethylprotoemetinol and isocephaeline. Structures were determined by spectroscopic and chemical means.
Assuntos
Ipeca/química , Ipeca/isolamento & purificação , Rubiaceae/química , Espectrometria de Massas , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Investigation of the leaves of Fraxinus americana led to the isolation of five secoiridoid glucosides, demethylligstroside, (2"R)- and (2"S)-2"-hydroxyoleuropeins, fraxamoside and frameroside, together with 18 known compounds. Their structures were determined on the basis of spectroscopic studies and chemical evidence.
Assuntos
Glucosídeos/isolamento & purificação , Magnoliopsida/química , Piranos/isolamento & purificação , Glucosídeos/química , Iridoides , Espectroscopia de Ressonância Magnética , Conformação Molecular , Folhas de Planta/química , Piranos/químicaRESUMO
From the water soluble fraction of the dried fruits of Alangium lamrckii, four tetrahydroisoquinoline-monoterpene glycosides, 6-O-methyl-N-deacetylisoipecosidic acid, 7-O-methyl-N-deacetylisoipecosidic acid, 6,7-di-O-methyl-N-deacetylisoipecosidic acid and 6"-O-alpha-D-glucopyranosyl-6-O-methyl-N-deacetylisoipecosidic acid, and an iridoid glycoside, 6'-O-alpha-D-glucopyranosylloganic acid, were isolated, together with six known compounds. The structures of the previously unknown compounds were determined by spectroscopic and chemical means. The significance of these glucosides in the biogenesis of Alangium alkaloids is discussed; 6-O-methyl-N-deacetylisoipecosidic acid was also chemically converted into 10-O-demethylprotoemetine and dihydroisoalangine.
Assuntos
Asteraceae/química , Glicosídeos/química , Isoquinolinas/química , Plantas Medicinais/química , Piranos/química , Terpenos/química , Glicosídeos/isolamento & purificação , Isoquinolinas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Estrutura Molecular , Fitoterapia , Piranos/isolamento & purificação , Terpenos/isolamento & purificaçãoRESUMO
A rare case of endoscopic and histological regression of a gastric lymphoid mucosal lesion after eradication of Helicobacter pylori is reported. A 72-year-old man was suspected of having a low-grade B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma by endoscopic and histological findings. Histology of biopsy specimens showed massive infiltration of atypical lymphocytes and lymphoepithelial lesions. Immunohistochemical staining revealed kappa light chain expression in the infiltrated atypical lymphocytes to be twofold that of lambda light chain. The above diagnosis was thus highly suspected but not confirmed. Antibiotic therapy was given on the basis of evidence of H. pylori infection. Successful eradication of H. pylori resulted in remarkable improvement of endoscopic and histological findings. Follow-up studies were carried out 8 months after eradication, with no evidence of relapse. The eradication of H. pylori appears to be an effective alternative therapy for B-cell lymphoproliferative disease, although longer follow-up and further studies are needed before this treatment can be established.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Linfócitos do Interstício Tumoral/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Gástricas/patologia , Idoso , Antibacterianos , Biópsia , Quimioterapia Combinada/uso terapêutico , Endoscopia , Infecções por Helicobacter/diagnóstico , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Cadeias kappa de Imunoglobulina/análise , Imuno-Histoquímica , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Masculino , Neoplasias Gástricas/química , Neoplasias Gástricas/tratamento farmacológicoRESUMO
It was shown possible to assess macroscopically countries' receptivity to cholera through the use of two commonly available socio-economic indicators. The indicators used were per capita GNP and population density per km2 of inhabitable area. These are related respectively to two major determinants of cholera receptivity: standard of living and population congestion. The global assessment of cholera receptivity indicated the seriousness of cholera as a public health problem in Africa and Asia. It also showed that cholera epidemics are a potential danger to a majority of the population of Latin America.
Assuntos
Cólera/epidemiologia , Métodos Epidemiológicos , Humanos , Renda , Modelos Teóricos , Densidade DemográficaRESUMO
The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine, both of which activate the polyphosphoinositide system and consequently both the diacylglycerol-protein kinase C system and the Ca2+-Ca2+ receptor system, stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for phenylephrine-induced ANP release differs from that for stretch-induced ANP release.
Assuntos
Fator Natriurético Atrial/metabolismo , Calmodulina/antagonistas & inibidores , Coração/fisiologia , Isoquinolinas/farmacologia , Piperazinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Sulfonamidas/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Animais , Arginina Vasopressina/farmacologia , Função Atrial , Bucladesina/farmacologia , Dibutiril GMP Cíclico/farmacologia , Coração/efeitos dos fármacos , Átrios do Coração/efeitos dos fármacos , Masculino , Fenilefrina/farmacologia , Estimulação Física , Ratos , Ratos EndogâmicosRESUMO
In a case of hypervascular metastatic liver tumor, the vascularity of primary focus, pancreatic carcinoma was hypovascular. Based on the imaging findings, we thought before the operation that the two lesions were double cancers. Histological examination showed that the stromal volume of metastatic tumorous tissue was richer than that of the primary focus. It was suggested that the difference in the stromal volume was related to the difference of the vascularity. Some foctors originating in stromal cells might be involved in angiogenesis.
Assuntos
Carcinoma Ductal Pancreático/patologia , Neoplasias Hepáticas/secundário , Fígado/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/irrigação sanguínea , Carcinoma Ductal Pancreático/diagnóstico , Humanos , Fígado/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pâncreas/irrigação sanguínea , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
A 51-year-old woman with overt congestive heart failure with pleural and pericardial effusion was treated with furosemide and nifedipine, leading to improvement in her condition and a decrease in effusions. An echocardiography demonstrated mitral and aortic regurgitation with mitral valve prolapse, which caused the congestive heart failure. Since leukocytopenia and lymphocytopenia with arthralgia could be observed, serological investigations were performed. She was diagnosed as having systemic lupus erythematosus (SLE) with antiphospholipid syndrome, and started on a treatment of prednisolone and aspirin. Based on the treatment, the pleural and pericardial effusion went into complete remission, indicating that the serositis related to SLE had overlapped the heart failure. Since there was no evidence of any other diseases that could be responsible for the valvular lesions, we concluded that they were due to antiphospholipid syndrome. The administration of prednisolone had no significant effect on valvular morphology or function as demonstrated by echocardiography. When patients with valvular disease are seen, a valvulopathy related to antiphospholipid syndrome should be considered as part of the differential diagnosis.
Assuntos
Síndrome Antifosfolipídica/complicações , Insuficiência da Valva Aórtica/etiologia , Insuficiência Cardíaca/etiologia , Lúpus Eritematoso Sistêmico/complicações , Insuficiência da Valva Mitral/etiologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
In view of comparatively-high incidence of papillary, well or moderately-well differentiated, transitional cell carcinomas in urology, and of frequent recurrence of carcinomas after appropriate procedures, we have undertaken the correlative study on urinary cytology with cystoscopy, pathology and the amount of fibrinogen and degradation products of fibrinogen and fibrin (FDP). Cytopathologically, 191 cases were confirmed histologically for cancers out of 442 cases studied cytologically; among these 442 classes IV and V were found in 136 cases, and 99 of 136 cases (72.8%) had cancers. Admittedly, we were unable to suspect tumors cytologically in 24.5% of the cases. As to histological gradings and cytology, 48.7% of classes I and II in well differentiated were found against 52.9% and 57.1% of classes IV and V in moderately-well and poorly differentiated carcinomas, respectively. Urinary FDP assay was quite promising; out of 19 cases with both positive cytology and FDP, 18 (94.7% had carcinomas histologically, whereas 12 of 56 cases (21.4%) with both negative cytology and FDP bore cancers. Subsequently, several proposals for improving the diagnostic accuracy were discussed. We concluded the importance of accumulating more cases by combining several diagnostic procedures, especially among well and moderately-well differentiated carcinomas.
Assuntos
Carcinoma de Células de Transição/diagnóstico , Cistoscopia , Produtos de Degradação da Fibrina e do Fibrinogênio/urina , Neoplasias da Bexiga Urinária/diagnóstico , Urina/citologia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/urina , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/urinaRESUMO
The effects of steroid sex hormones on the established cell lines derived from human urinary bladder cancer, T24, and from human transitional cell cancer of the urinary tract, 253J, were examined using the colony formation method. Of the seven kinds of steroid hormones tested, estradiol-17 beta was intensively cytotoxic for both cells. The cytotoxic effect was depended on the dose and time of treatment. The combined effect of Adriamycin and estradiol-17 beta on T24 cells could be recognized at low concentrations of Adriamycin (less than or equal to 10(-3) micrograms/ml) after exposure for 24 h.
Assuntos
Doxorrubicina/administração & dosagem , Estradiol/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Quimioterapia Combinada , Feminino , Hormônios Esteroides Gonadais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologiaRESUMO
Seventy-eight patients were treated with intravesical instillation of Thio-Tepa in an attempt to prevent postoperative recurrences of bladder tumors. Fifty-six patients who were given no preventive treatment against recurrences were taken as the control group. The patients in this series presented at the Okayama University Hospital between 1961 and 1976 and only the first recurrence after the primary operation was taken into consideration. There was no significant difference in the recurrence rates of the control and instillation groups.
Assuntos
Tiotepa/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tiotepa/uso terapêutico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
From the cultures of the spore-derived mycobionts of the lichen Pyrenula japonica, two new xanthones, 1,8-dihydroxy-3-hydroxymethyl-5-methoxyxanthone and 1,2,8-trihydroxy-5-methoxy-3-methylxanthone, were isolated along with 1,7-dihydroxy-3-methylxanthone, 1,5,8-trihydroxy-3-methylxanthone, 1,8-dihydroxy-5-methoxy-3-methylxanthone, emodin and sclerotiorin. Their structures were determined by spectroscopic methods. Sclerotiorin was isolated for the first time from lichen mycobionts. Radical scavenging activities of the isolated xanthones were also studied.
Assuntos
Ascomicetos/fisiologia , Benzopiranos/metabolismo , Emodina/metabolismo , Sequestradores de Radicais Livres/química , Líquens/fisiologia , Xantenos/metabolismo , Benzopiranos/química , Emodina/química , Cinética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Esporos Fúngicos , Relação Estrutura-Atividade , Xantenos/químicaRESUMO
The intraocular penetration of levofloxacin was studied in albino and pigmented rabbits after oral administration of 14C-levofloxacin at a dose of 20 mg/kg. The radioactivity of the eyeball of albino rabbits in the autoradiogram was much higher at 1 hr than at 2 or 6 hr after administration. On the other hand, the distribution of radioactivity in pigmented rabbits was similar at 1, 2, and 6 hr after administration. The radioactivity levels in melanin-containing tissues such as the iris-ciliary body and the choroid-retina were significantly higher in pigmented rabbits than in albino rabbits 2 hr after oral administration. The radioactivity levels in the ocular tissues without melanin except for the cornea were similar in albino and pigmented rabbits. These results indicate that the intraocular pharmacokinetics of levofloxacin are markedly affected by its affinity for melanin.
Assuntos
Olho/metabolismo , Levofloxacino , Ofloxacino/farmacocinética , Administração Oral , Albinismo Ocular/metabolismo , Animais , Autorradiografia , Melaninas/metabolismo , Ofloxacino/administração & dosagem , Coelhos , Distribuição TecidualRESUMO
Effects of intravitreal injection of levofloxacin (LVFX) on the electroretinogram (ERG), visual evoked potential (VEP), and retinal histology were studied in 23 albino and 23 pigmented rabbits to establish the non-toxic intravitreal dosage of LVFX. Doses of 200, 500, 1,000 or 2,000 micrograms of LVFX were injected intravitreally. The ERG and VEP were recorded before injection, and 3 hours, 2 days, 1 week, 2 weeks and 4 weeks after injection. The oscillatory potential transiently deteriorated with 1,000 and 2,000 micrograms doses of LVFX in albino and pigmented rabbits. No ERG changes were observed with 200 and 500 micrograms doses. No abnormal changes were observed in the VEP or retinal histology with any doses of LVFX. These results indicate that intravitreal injections of 200 and 500 micrograms of LVFX are nontoxic to the rabbit retina.