COMPLEX SYSTEMS AND MATHEMATICAL MODELS

Joint Research on Environmental Science and Technology for the Eart

Transforming Growth Factor-β1 as a Common Target Molecule for Development of Cardiovascular Diseases, Renal Insufficiency and Metabolic Syndrome

Transforming growth factor-β1 (TGF-β1) is a polypeptide member of the transforming growth factor β superfamily of cytokines. It is a secreted protein that performs many cellular functions including control of cell growth, cell proliferation, cell differentiation and apoptosis. In the cardiovascular system, TGF-β1 plays pivotal roles in the pathogenesis of hypertension, restenosis after percutaneous coronary intervention, atherosclerosis, cardiac hypertrophy and heart failure. In addition, TGF-β1 has been shown to be increased in adipose tissue of obese subjects with insulin resistance. Furthermore, TGF-β1 is a potent initiator of proliferation of renal mesangial cells leading to chronic kidney disease. Some currently available agents can manipulate TGF-β1 expression leading to amelioration of cardiovascular diseases. Thus, an understanding of interactions between chronic kidney disease and metabolic syndrome and the development of cardiovascular diseases is an important issue, and attention should be given to TGF-β1 as a crucial factor for regulation and modulation of those pathological conditions

A higher intramuscular fat in vastus medialis is associated with functional disabilities and symptoms in early stage of knee osteoarthritis: a case-control study

[Background] The characteristics of muscle degeneration in individual quadriceps in early knee osteoarthritis (OA) and the association of muscle quantity and quality on knee dysfunction remain unclear. This study aimed to clarify the characteristics of muscle degeneration in individual quadriceps muscles in early knee OA and elucidate the association of muscle volume and intramuscular adipose tissue (intraMAT) with knee dysfunction, including functional disabilities, symptoms, and joint morphology. [Methods] Fifty participants were categorized into early knee OA and healthy control groups. 3.0 T magnetic resonance imaging (MRI) using T1-weighted and Dixon methods and 3D SPACE in the thigh muscle and knee joint regions was performed. Quadriceps muscle volume, intraMAT, and whole-organ MRI score (WORMS) were assessed. The Knee Society Score (KSS) was used to evaluate functional disabilities and knee symptoms. Univariate analysis of variance was conducted with covariates to clarify the differences in muscle volume and intraMAT between the two groups. Multiple linear regression analyses were performed using the KSS function and symptom subcategories and WORMS as dependent variables and muscle volume, intraMAT, and the presence of early knee OA as independent variables, such as potential confounders. [Results] The quadriceps intraMAT, especially in the vastus medialis (VM), was significantly higher in patients with early knee OA than in healthy controls. The VM intraMAT, not muscle volume, was significantly associated with KSS function [B =  − 3.47; 95% confidence interval [CI],  − 5.24 to − 1.71; p < 0.001] and symptom scores [B =  − 0.63; 95% CI,  − 1.09 to − 0.17; p = 0.008], but not with WORMS. [Conclusion] These findings suggest that higher VM intraMAT is characteristic of quadriceps muscle degeneration in early knee OA and its increase is associated with functional disabilities and symptoms

Living Donor Liver Transplantation to a Survivor of LiverResection for Hepatocellular Carcinoma with Major Portal Vein Invasion

We present a case of living donor liver transplantation to a 3-year disease-free survivor of liver resection for hepatocellular carcinoma (HCC) with major portal vein invasion. A 48-year-old man had HCC in the right lobe with a portal venous tumor thrombus extending into the left portal vein. An extended right lobectomy with thrombectomy was performed to remove the thrombus. Three years after liver resection, the patient experienced liver failure, with massive ascites and jaundice due to the formation of a thrombus in the main and left portal veins. During the 3 years after liver resection, no metastasis or recurrence of HCC had been detected, and tumor markers had been within normal ranges. The portal venous thrombus did not show any arterial enhancement under contrast-enhanced computed tomography, suggesting that the co-existence of any HCC component in the portal venous thrombus may have been negative. Based on these findings, living donor liver transplantation was performed using a right lobe graft from the patientʼs son. The patient is alive at 87 months after the transplantation, with no evidence of HCC recurrence

Resection of Metachronous Lymph Node Metastases from Hepatocellular Carcinoma after Hepatectomy: Report of Four Cases

We report 4 cases of surgical resection of metachronous lymph node (LN) metastases from hepatocellular carcinoma (HCC) following hepatectomy. Clinicopathological features and results of LN dissection were investigated in the 4 patients. One patient was found to have a single metastasis in the mediastinal LNs, another had multiple metastases in the mediastinal and abdominal LNs, and the other 2 had single metastases in the abdominal LN. The locations of the abdominal LN metastases were behind the pancreas head in 2 patients and around the abdominal aorta in 1 patient. They all underwent surgical resection of metastatic LNs and had no postoperative complications. The 3 patients whose LN metastases were solitary have been alive for more than 2 years after LN resection, and one of them is free from recurrence. The patient with multiple LN metastases died 13 months after LN resection due to carcinomatosis. With the expectation of long-term survival, a single metachronous LN metastasis from HCC after hepatectomy should be resected in patients without uncontrollable intrahepatic or extrahepatic tumors

Age- and sex-related differences of muscle cross-sectional area in iliocapsularis: a cross-sectional study

[Background] This study aimed to determine in how many individuals the iliocapsularis muscle (IC) could be identified on magnetic resonance imaging (MRI) and whether age and sex are associated with the cross-sectional area (CSA) of the IC. [Methods] Thirty-seven healthy younger adults and 40 healthy older adults were assigned to four groups: 1) 20 younger men; 2) 17 younger women; 3) 20 older men; and 4) 20 older women. The CSAs of the IC, IP, the rectus femoris (RF) and the quadriceps (QUAD) were quantified on an axial MRI. [Results] The number of individuals with the identified IC was n = 17 (85.0%) of 20 younger men, n = 15 (88.2%) of 17 younger women, n = 18 (90.0%) of 20 older men, and 19 (95.0%) of 20 older women. Our results showed the main effect of sex, but not age, in the CSA of the IC. The men-groups had larger CSA of the IC than the women-groups; however, no difference in CSA of the IC was found between the younger and older groups. Meanwhile, the main effects of age and sex were found for the IP, RF, and QUAD; thus, younger or men groups have larger CSAs of the three muscles than the older or women groups. The IC muscle can be discriminated in 85% – 95% of healthy individuals. [Conclusion] Although sex and age are associated with the CSA of lower-limb muscles other than the IC, only sex is associated with the CSA of the IC

CD14 upregulation as a distinct feature of non-alcoholic fatty liver disease after pancreatoduodenectomy

AIM: To investigate the pathogenesis of non-alcoholic fatty liver disease (NAFLD) after pancreatoduodenectomy (PD). METHODS: A cohort of 82 patients who underwent PD at Okayama University Hospital between 2003 and 2009 was enrolled and the clinicopathological features were compared between patients with and without NAFLD after PD. Computed tomography (CT) images were evaluated every 6 mo after PD for follow-up. Hepatic steatosis was diagnosed on CT when hepatic attenuation values were 40 Hounsfield units. Liver biopsy was performed for 4 of 30 patients with NAFLD after PD who consented to undergo biopsies. To compare NAFLD after PD with NAFLD associated with metabolic syndrome, liver samples were obtained from 10 patients with NAFLD associated with metabolic syndrome [fatty liver, n = 5; non-alcoholic steatohepatitis (NASH), n = 5] by percutaneous ultrasonography-guided liver biopsy. Double-fluorescence immunohistochemistry was applied to examine CD14 expression as a marker of lipopolysaccharide (LPS)-sensitized macrophage cells (Kupffer cells) in liver biopsy specimens. RESULTS: The incidence of postoperative NAFLD was 36.6% (30/82). Univariate analysis identified cancer of the pancreatic head, sex, diameter of the main pancreatic duct, and dissection of the nerve plexus as factors associated with the development of NAFLD after PD. Those patients who developed NAFLD after PD demonstrated significantly decreased levels of serum albumin, total protein, cholesterol and triglycerides compared to patients without NAFLD after PD, but no glucose intolerance or insulin resistance. Liver biopsy was performed in four patients with NAFLD after PD. All four patients showed moderate-to-severe steatosis and NASH was diagnosed in two. Numbers of cells positive for CD68 (a marker of Kupffer cells) and CD14 (a marker of LPS-sensitized Kupffer cells) were counted in all biopsy specimens. The number of CD68+ cells in specimens of NAFLD after PD was significantly increased from that in specimens of NAFLD associated with metabolic syndrome specimens, which indicated the presence of significantly more Kupffer cells in NAFLD after PD than in NAFLD associated with metabolic syndrome. Similarly, more CD14+ cells, namely, LPS-sensitized Kupffer cells, were observed in NAFLD after PD than in NAFLD associated with metabolic syndrome. Regarding NASH, more CD68+ cells and CD14+ cells were observed in NASH after PD specimens than in NASH associated with metabolic syndrome. This showed that more Kupffer cells and more LPS-sensitized Kupffer cells were present in NASH after PD than in NASH associated with metabolic syndrome. These observations suggest that after PD, Kupffer cells and LPS-sensitized Kupffer cells were significantly upregulated, not only in NASH, but also in simple fatty liver. CONCLUSION: NAFLD after PD is characterized by both malnutrition and the up-regulation of CD14 on Kupffer cells. Gut-derived endotoxin appears central to the development of NAFLD after PD