Blockade of brain melanin-concentrating hormone 1 receptor (MCH1R) significantly ameliorates fatty liver as well as obesity. However, the mode of action of this effect is unknown. This study examined the effect of a MCH1R antagonist in murine steatohepatitis models with and without obesity and clarified whether these pharmacological effects were attributed to anti-obesity effects. Steatohepatitis with concomitant obese phenotypes was developed after 52-week exposure to a high-fat diet, and steatohepatitis with reduced body weight was developed by exposure to a methionine- and choline-deficient diet for 10 days. Chronic intracerebroventricular infusion of a peptidic MCH1R antagonist reduced hepatic triglyceride contents and ameliorated steatohepatitis on histological observations in both mice models. Improvement of steatohepatitis was concomitant with amelioration of obese phenotypes such as hyperinsulinemia and hyperleptinemia in the case of the obese model, whereas body weight reduction was not associated with amelioration of steatohepatitis by the antagonist in the lean model. Reduction of hepatic gene expressions encoding cytochromes P450 4A was identified by treatment with the antagonist in both the obese and lean models. These results suggest that brain blockade of MCH1R could alleviate steatohepatitis independently from anti-obesity effects. In conclusion, MCH1R antagonist could have a new therapeutic potential for the treatment of human nonalcoholic steatohepatitis. 相似文献
A microsurgical technique was used in performing anterior hepatic segmentectomy and pancreatoduodenectomy with reconstruction of the posterior hepatic artery in a 64-year-old man with widespread bile duct cancer from the intrapancreatic bile duct over the hepatic hilus. The anterior hepatic artery was obviously involved and the posterior hepatic artery just behind common hepatic duct was very close to the cancer. Microsurgical anastomosis between the remnant gastroduodenal artery and the posterior hepatic artery at the hepatic hilus made it possible to preserve the posterior segment of the liver and to perform a curative resection of the cancer. The patient had pyrexia because of suprahepatic abscess after the operation, but the abscess drained spontaneously. Postoperative arteriogram showed neither obstruction nor kinking of the reconstructed artery. He was discharged 2 months after surgery and has been enjoying a normal quality of life for 10 months since, with no signs of recurrence. It is suggested that a microsurgical technique is useful for performing an accurate anastomosis with good patency that allows not only a safe but also a highly curative operation for advanced bile duct cancer. 相似文献
PTEN is a tumor suppressor gene but whether cancer can develop in all PTEN-deficient cells is not known. In T cell-specific PTEN-deficient (tPTEN−/−) mice, which suffer from mature T cell lymphomas, we found that premalignancy, as defined by elevated AKT and senescence pathways, starts in immature T cell precursors and surprisingly not in mature T cells. Premalignancy only starts in 6-week-old mice and becomes much stronger in 9-week-old mice although PTEN is lost since birth. tPTEN−/− immature T cells do not become tumors, and senescence has no role in this model because these cells exist in a novel cell cycle state, expressing proliferating proteins but not proliferating to any significant degree. Instead, the levels of p27kip1, which is lower in tPTEN−/− immature T cells and almost nonexistent in tPTEN−/− mature T cells, correlate with the proliferation capability of these cells. Interestingly, transient reduction of these cancer precursor cells in adult tPTEN−/− mice within a crucial time window significantly delayed lymphomas and mouse lethality. Thus, loss of PTEN alone is not sufficient for cells to become cancerous, therefore other developmental events are necessary for tumor formation. 相似文献
Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB activity. These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB activation. 相似文献
To investigate the roles of c-myc during hematopoietic proliferation induced by growth factors, we used factor-dependent human leukemic cell lines (MO7e and F36P) in which proliferation, cell cycle progression, and c-Myc expression were strictly regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). In these cell lines, both c-myc mRNA and c-Myc protein stability were not affected by GM-CSF and IL-3, suggesting a regulation of c-Myc protein at the translational level. However, rapamycin, an inhibitor of cap-dependent translation, did not block c-myc induction by GM-CSF and IL-3. Thus, we studied the cap-independent translation, the internal ribosome entry site (IRES), during c-Myc protein synthesis using dicistronic reporter gene plasmids and found that GM-CSF and IL-3 activated c-myc IRES to initiate translation. c-myc IRES activation, c-Myc protein expression, and cell cycle progression were all blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In another factor-dependent cell line, UT7, we observed the cell cycle progression and up-regulation of c-Myc protein, c-myc mRNA, and c-myc IRES simultaneously, which were all inhibited by LY294002. Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor-dependent leukemic cells. 相似文献
Several topics on taeniasis and cysticercosis in Asia and the Pacific are overviewed. In Asia and the Pacific, three human taeniid species have been recognized: Taenia solium, Taenia saginata and Taenia asiatica. The first topic is on evolution of T. solium. Mitochondrial DNA polymorphisms of T. solium worldwide are discussed with emphasis of two specific genotypes: American-African and Asian. The second topic is recent major advances in sero- and molecular-diagnosis of T. solium cysticercosis in humans, pigs and dogs. The third is the present situation of T. solium taeniasis/cysticercosis in Papua (Irian Jaya), Indonesia. The forth is the present situation of T. solium cysticercosis and T. saginata taeniasis in Bali, Indonesia. The fifth is the present situation of T. asiatica taeniasis in Asia and the Pacific and in North Sumatra, Indonesia. The sixth is on the debate of the exact definition of T. asiatica. Because T. asiatica can not be differentiated from T. saginata morphologically, it is time to re-evaluate T. saginata in Asia and the Pacific. New and broad-based surveys across this region are necessary from epidemiological and public health perspectives, based on evidence. 相似文献
Conclusion: Longitudinal assessments of carnitine and fatigue in patients with head and neck squamous cell carcinoma suggest that cisplatin damages the carnitine system in patients undergoing chemoradiotherapy and that carnitine deficiency increases fatigue. Objectives: The purpose of this study was to monitor carnitine levels and fatigue in patients who received cisplatin-based CRT and, for comparison, in patients treated by surgery alone. Methods: To investigate the level of carnitine, mice were administered cisplatin. Next, a prospective analysis was performed to compare plasma carnitine levels before and after cisplatin-based chemoradiotherapy and to assess the relationship between carnitine levels and fatigue. Results: The plasma levels of total carnitine (TC), free carnitine (FC), and fatty acylcarnitine (AC) were significantly lower in mice receiving cisplatin compared with control mice. Mean total carnitine and free carnitine levels were significantly lower 2 weeks after chemoradiotherapy (total carnitine: Mean = 45.6, SD = 16.5, p = 0.01; free carnitine: Mean = 37.8, SD = 12.7, p = 0.02) than before chemoradiotherapy (total carnitine: Mean = 57.7, SD = 12.2; free carnitine: Mean = 48.1, SD = 11.6). There was a significant inverse correlation between carnitine levels and fatigue after chemoradiotherapy. 相似文献
We describe a case of malignant lymphoma which presented in the body cavities without identifiable tumor masses. Malignant lymphoma cells showed strong atypia with prominent nuclei and basophilic cytoplasm containing vacuoles. The chromosomes showed diploidy and complex abnormalities including translocations and deletions. We diagnosed this patient with primary effusion lymphoma (PEL), even though she tested negative for human herpes virus-8 (HHV-8) which has been suggested to be causally related to PEL. Interestingly, the patient also showed complicated protein-losing enteropathy, and PEL occurred after repeated chylous ascites and chylothorax. The possible pathogenesis of this rare disease is discussed here. 相似文献
Patients with aneurysmal subarachnoid hemorrhage (SAH) typically develop appetite loss. However, the mechanisms regulating appetite are not understood. Ghrelin and leptin, both of which signal nutritional status and energy storage levels to the hypothalamus, are essential elements of the appetite system. Thus, the goal of this study was to investigate the relationship between appetite and ghrelin and leptin concentrations in patients with SAH.
Methods
Blood plasma or serum profiles and appetite status were measured in 19 patients with SAH who underwent aneurysmal clipping within 48 hours of SAH onset. Appetite status was measured using dietary oral calorie intake. All outcome variables were measured at an early (day 3) and late (day 8) time point after SAH onset (day 0).
Results
Of the 19 patients studied, 6 (31.6%) showed lower dietary oral calorie intake at the late time point than at the early time point. In these patients with appetite loss, plasma hemoglobin (P < 0.02), albumin (P < 0.01), glucose (P < 0.01), plasma insulin (P < 0.04), and serum ghrelin (P < 0.03) concentrations were lower at the late time point than at the early time point. Serum leptin was higher at the late time point than at the early time point (P < 0.02).
Conclusion
In SAH patients, appetite loss may be induced by lower serum ghrelin and higher serum leptin concentrations resulting from high plasma glucose and insulin levels due to a catecholamine surge following SAH. 相似文献