Surgical treatment for heart failure includes coronary artery bypass grafting to ischemic heart disease, valvular disease surgery such as mitral valvuloplasty, left ventricular restoration, ventricular assist device (VAD...Surgical treatment for heart failure includes coronary artery bypass grafting to ischemic heart disease, valvular disease surgery such as mitral valvuloplasty, left ventricular restoration, ventricular assist device (VAD), and heart transplantation. In addition, HeartSheet which is regenerative medicine using autologous skeletal myoblast sheets has been started from the spring of 2016. Formal insurance reimbursement of implantable LVAD was obtained in April 2011, and the life prognosis of patients with severe heart failure improved markedly. However, the indication for implantable LVAD is limited to bridge use for heart transplantation. Implantable LVAD cannot be implanted in patients over 65 years old under health insurance because the adaptive age of heart transplantation in Japan is under 65 years old. It is a problem that the indication of implantable LVAD is identical to that of heart transplantation. Clinical trial of destination therapy is in progress for the purpose of optimizing the implantable LVAD indication. I strongly pray that VAD treatment including destination therapy (DT) and transplant medical treatment based on good intentions will be accepted socially as general treatment.
We have focused on the role of innate immunity during the formation oföchoroidal neovascularization (CNV) -related diseasesù. Inflammation affects the formation and the progression of various vitreoretinal diseases. We p...We have focused on the role of innate immunity during the formation oföchoroidal neovascularization (CNV) -related diseasesù. Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids with diabetic macular edema, proliferative diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion and rhegmatogenous retinal detachment. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors : interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases compared with control group. According to the correlation analysis in the individual patientʼs level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. We also elucidated the role of natural killer (NK)T cells, which restricted CD1 molecule and participate in the innate immune response, in laser-induced experimental CNV. We examined CNV formation in independent two NKT cell-deficient mice, either CD1 knockout (KO) mice or Ja18 KO mice, and found that both KO mice showed significant reduction of experimental CNV. During the clinical process of CNV-related diseases, not only CNV formation, subretinal scaring is thought to be another important step. We thus established the experimental model of subretinal scaring by injecting peritoneal exudating macrophages into subretinal space. Subretinal fibrous tissue was observed by fundus scope in PEC-inoculated mice after seven days. The tissue was consisted of monotonous and low cell-density area, which expressed a-SMA with collagen synthesis. Because PEC-inoculated MCP-1 KO mice showed less amount of glial residual, not only exogenous macrophages, but also intrinsic macrophages are critical. Activated macrophages directly induced myofibrotic changes in RPE cells in vitro.
Furue M, Takemura M, Nishio K
… +8 more, Sato Y, Nagata S, Kan N, Suenaga A, Furue K, Yoshida M, Konishi S, Tsuji G
Fukuoka Igaku Zasshi
· 2016 Nov · PMID 29227070
The immunohistological localization of peroxisome proliferator-activated receptor a (PPARa) and PPAR g was examined in 28 pilosebaceous units in 10 paraffin-embedded normal human skin specimens. Rabbit polyclonal antibod...The immunohistological localization of peroxisome proliferator-activated receptor a (PPARa) and PPAR g was examined in 28 pilosebaceous units in 10 paraffin-embedded normal human skin specimens. Rabbit polyclonal antibody against human PPARa and monoclonal antibody against human PPARg were used as specific primary antibodies. The nuclear and cytoplasmic expression of PPARa was detected in basal to differentiated sebocytes. In contrast, the expression of PPARg was confined to nuclei of suprabasal to early-differentiated sebocytes. The nuclear PPARg expression was present only occasionally in the basal sebocytes. These results suggest that PPARa and PPARg are integral parts of sebocyte differentiation in human sebaceous glands.
Energy homeostasis is maintained locally through parenchymal-stromal cell interaction and systemically through metabolic organ network. In obese adipose tissue, saturated fatty acids, which are released as a danger signa...Energy homeostasis is maintained locally through parenchymal-stromal cell interaction and systemically through metabolic organ network. In obese adipose tissue, saturated fatty acids, which are released as a danger signal from hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating macrophages, thus establishing a vicious cycle between adipocytes and macrophages to stimulate adipose tissue inflammation. Histologically, macrophages aggregate to constitute crown-like structures (CLS), where they are thought to scavenge the residual lipid droplets of dead adipocytes. Free fatty acids, when released from obese visceral fat depots, are transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thus developing non-alcoholic fatty liver disease (NAFLD). There is a unique histological feature termed÷hepatic CLS (hCLS)øin the non-alcoholic steatohepatitis (NASH) liver, where macrophages aggregate to surround dead hepatocytes with large lipid droplets. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. Our data suggest that hCLS serves as an origin of hepatic inflammation and fibrosis during the progression from simple steatosis to NASH. Sodium glucose cotransporter 2 (SGLT2) inhibitors, an oral antidiabetic drug, promotes the urinaryexcretion of glucose by blocking its reabsorption in renal proximal tubules. Inhibition of SGLT2 lowers is expected to reduce body weight because of urinary calorie loss. Interestingly, SGLT2 inhibition improves hepatic steatosis in obese mice irrespective of body weight reduction. There is an inverse correlation between liver weight and adipose tissue weight in obese mice with SGLT2 inhibition, suggesting that SGLT2 inhibition induces the÷healthyøadipose tissue expansion and prevents ectopic fat accumulation in the liver. Our data suggest that seeing both the wood and trees is Required to understand the molecular mechanism of lifestyle-related diseases.
Kabashima A, Kimura K, Sanefuji K
… +1 more, Maekawa S
Fukuoka Igaku Zasshi
· 2017 Jan · PMID 29226661
Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev) is safe and feasible for patients with advanced or recurrent colorectal cancer, it is difficult to achieve a complete response (CR) using on...Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev) is safe and feasible for patients with advanced or recurrent colorectal cancer, it is difficult to achieve a complete response (CR) using only chemotherapy. A 67-year-old man underwent endoscopic mucosal resection and additional sigmoidectomy (D2 dissection) for submucosal invasive sigmoid colon cancer. Multiple liver metastases were diagnosed 1.5 years later, and chemotherapy with SOX + bev was initiated. Computed tomography (CT) after the end of the third course revealed reduced liver recurrence. Liver metastases could not be identified using CT after the end of the sixth course. Grade 1peripheral neuropathy was the only side effect of this regimen. Subsequently, the chemotherapy regimen was changed to oral S-1. CT evaluation revealed that there was no recurrence at 6 months after the regimen change.
Nakashima Y, Okazak K, Nakayama K
… +2 more, Okada S, Mizu-uchi H
Fukuoka Igaku Zasshi
· 2017 Jan · PMID 29226660
With the increase of elderly population, orthopaedic surgeons need to deal with the diseases related to aging, such as joint disorders and fragility fractures. The number of total joint replacements, for example, is two...With the increase of elderly population, orthopaedic surgeons need to deal with the diseases related to aging, such as joint disorders and fragility fractures. The number of total joint replacements, for example, is two times more than it was 10 years ago. With these backgrounds, the Japanese Orthopaedic Association (JOA) has proposed the concept of locomotive syndrome; conditions under which the elderly have been receiving care services due to problems of the locomotive organs. To prevent geriatric or disuse syndrome, JOA is currently providing the care‒prevention programs such as the loco-check and loco-training. Recent advances in the orthopaedic fields were cited in this review article, including the topics of new biomaterials, regenerative medicine of cartilage, spinal cord injury and computer assisted orthopaedic surgery. These new technologies and knowledge are changing or have potential to change the future orthopedic medical care.
Ohe M, Mutsuki T, Goya T
… +4 more, Yamashita S, Satoh T, Kohjima M, Kato M
Fukuoka Igaku Zasshi
· 2016 Oct · PMID 29227068
BACKGROUND: Although portal vein thrombosis in cirrhotic patients is frequently observed, the detailed process remains to be clarified, and the role of anticardiolipin antibody in the development of portal vein thrombosi...BACKGROUND: Although portal vein thrombosis in cirrhotic patients is frequently observed, the detailed process remains to be clarified, and the role of anticardiolipin antibody in the development of portal vein thrombosis has been controversial. CASE REPORT: A 52-year-old man, who had been diagnosed with alcoholic cirrhosis of the liver, was admitted to our hospital suffering from dyspnea and ascites. Just after being diagnosed as having antiphospholipid antibody syndrome with lung thrombosis and delivering a positive result for the β 2-glycoprotein I-dependent anticardiolipin antibody, he sustained rupture of the esophageal varices with rapid development of portal vein thrombosis, which resolved under anticoagulant therapy. Two years later, he was admitted again on suspicion of thrombosis because of an elevation in the serum D-dimer level, and computed tomography showed portal and upper mesenteric vein thrombosis. Although immediate anticoagulant therapy resulted in complete recanalization, he suffered the same episode 2 months later, which occurred with re-elevation of the serum D-dimer level. CONCLUSION: A positive finding of an anticardiolipin antibody in cirrhotic patients has been considered to be nonspecific and not related to the development of thrombus in the portal vein. This case, however, seems to indicate that cirrhotic patients with the β2-glycoprotein I-dependent anticardiolipin antibody should be regarded as being at high risk for portal vein thrombosis. Monitoring with the serum D-dimer was useful in detecting portal vein thrombosis in its early stage.
Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce i...Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling. We thus examined whether the activation of iNKT cells might affect the development of LV remodeling and failure. After creation of MI, mice received the injection of either a-galactosylceramide (aGC), the activator of iNKT cells, or phosphate-buffered saline 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI +aGC than MI + PBS. LV cavity dilatation and dysfunction were significantly attenuated inMI +aGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in noninfarcted LV from MI and aGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntiIL-10 receptor antibody abrogated these protective effects of aGC on MI remodeling. The administration of aGC into iNKT cell-deficient Ja18(-/-) mice had no such effects, suggesting that aGC was a specific activator of iNKT cells. iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.
Pattern formation of vascular structure has been extensively studied in vascular biology. Classically the pattern formation process falls into three categories-vasculogenesis, angiogenesis and remodeling. Mathematical mo...Pattern formation of vascular structure has been extensively studied in vascular biology. Classically the pattern formation process falls into three categories-vasculogenesis, angiogenesis and remodeling. Mathematical modeling study of these phenomena has been done byrelatively independent of experimental works by applied mathematicians, and not well understood by experimental biologists. In this review I provide intuitive explanations of proposed theoretical models and recent advance in modelling study of vascular development.
Usagawa Y, Mitoma C, Ito T
… +4 more, Ito S, Kiryu H, Uchi H, Furue M
Fukuoka Igaku Zasshi
· 2016 Aug · PMID 29227064
We here describe a case of solitary basaloid follicular hamartoma (BFH) : the case developing in company with senile lentigo on the nose. BFH is a relatively rare benign follicular neoplasm of undetermined etiology. Hist...We here describe a case of solitary basaloid follicular hamartoma (BFH) : the case developing in company with senile lentigo on the nose. BFH is a relatively rare benign follicular neoplasm of undetermined etiology. Histologically, the specimen consisted of small-sized squamoid or basaloid cells and follicular germ-like cells in the periphery of the tumor nests. There were no infundibular cysts. BFH should be differentiated from infundibulocystic basal cell carcinoma (BCC), which consists of squamoid or basaloid cells in company with infundibular cysts, tumor of follicular infundibulum or trichoepithelioma. We analyzed the immunohistochemical findings of the case in comparison with those of BCC and trichoepithelioma. An immunohistochemical examination revealed 1) that Bcl-2 and CD10 was preferentially expressed in the outermost cells in the tumor nests consisting of follicular germ-like cells, 2) that most of the tumor cells, especially germ-like cells, were strongly positive for Ber-EP4, and 3) that peritumoral stroma was positive for CD34. The immunohistochemical findings of our cases supported that BFH should be differentiated from BCC, a common malignant neoplasm.
Recent advances reveal that mitochondria are not limited to functioning only as the cellular powerhouse and in apoptosis, but that they act as central hubs for multiple signal transductions. Studies over the last decade...Recent advances reveal that mitochondria are not limited to functioning only as the cellular powerhouse and in apoptosis, but that they act as central hubs for multiple signal transductions. Studies over the last decade indicate that mitochondria in vertebrates are involved in the front line of host defense, especially against RNA viruses. Mitochondrial-mediated antiviral innate immunity depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors signal transduction pathway, and the mitochondrial surface acts as a platform for the assembly of signaling molecules, including mitochondrial antiviral signaling (MAVS) during the process. Some viral encoded proteins target to the mitochondria post-infection, however, thereby evading the cellular immune response. Here we review specific interactions between mitochondria and viral proteins and discuss their physiologic effects on the host cells.
Shimagaki T, Okamoto T, Morodomi Y
… +11 more, Shoji F, Akamine T, Takamori S, Katsura M, Takada K, Suzuki Y, Fujishita T, Hayamizu K, Tokuda K, Yasuda M, Maehara Y
Fukuoka Igaku Zasshi
· 2016 Jul · PMID 29226664
We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on the second day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primary lung cancer was referred to...We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on the second day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primary lung cancer was referred to our department for surgery. The second day after left lung segmentectomy, she showed respiratory discomfort symptoms and exhibited hoarseness and stridor, which were revealed as the subglottic stenosis by bronchoscopy. During the emergency airway management, she went into cardiopulmonary arrest. We performed cardiopulmonary resuscitation and simultaneous urgent tracheotomy.
Yamashita YI, Yoshizumi T, Ikegami T
… +8 more, Uchiyama H, Tsujita E, Itoh S, Harimoto N, Soejima Y, Taketomi A, Baba H, Maehara Y
Fukuoka Igaku Zasshi
· 2016 Jul · PMID 29226663
The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. The recovery of consciousness in patients with acute liver failure (ALF) who underwent liver transplantation (LT) is sometimes dr...The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. The recovery of consciousness in patients with acute liver failure (ALF) who underwent liver transplantation (LT) is sometimes drastic ; therefore, we thought that the causative agents of HE would change markedly peri-operatively in these patients. We examined the biomarkers including new agents in the serum of patients using the ProteinChip® System 4000 (Ciphergen Biosystems, Yokohama, JAPAN). Sixteen samples were obtained from four patients with ALF who underwent living donor LT (LDLT) at four time points ; pre-operative, one post-operative day (1POD), 3POD, and 7POD. We used three chips made by the Biomek2000 robot. All duplicated samples were assayed and analyzed using the CiphergenExpressTM data manager. We divided the peri-operative changes in the intensity of identified peaks into seven patterns. The number of peaks whose intensity shows significant changes peri-operatively reached 755. Of course, it is difficult to determine each structure in all 755 peaks ; therefore, we should narrow down the candidates for causative agents of HE in further studies. Our own results suggest that many difficulties lie ahead in determining the causative agent of HE.
Ihara E, Muta K, Fukaura K
… +5 more, Tanaka Y, Bai X, Aso A, Iwasa T, Nakamura K
Fukuoka Igaku Zasshi
· 2016 Jul · PMID 29226662
Esophageal motility disorders (EMD) is characterized by impaired coordinated esophageal motility function with symptoms including dysphasia, heartburn or noncardiac chest pain. Since EMDs is functional disorders, it is u...Esophageal motility disorders (EMD) is characterized by impaired coordinated esophageal motility function with symptoms including dysphasia, heartburn or noncardiac chest pain. Since EMDs is functional disorders, it is usually difficult to make a diagnosis by conventional examinations including endoscopy and esophagography. Recently developed high-resolution manometry allows us to evaluate esophageal motility function precisely and to make a differential diagnosis of EMDs, together with Chicago Classification (CC) version 3.0 (CC ver3.0). In this article, we reviewed diagnosis of EMDs based on CC ver3.0 and current treatment strategy for EMDs.
Tsujita J, Doi K, Nakahara M
… +10 more, Nakahara T, Kaku Y, Nishio K, Kan N, Sato Y, Nagata S, Nakao A, Yoshida M, Uchi H, Furue M
Fukuoka Igaku Zasshi
· 2016 Jan · PMID 27333655
The expression of p16(INK4a) has been reported to induce cell-cycle arrest and cellular senescence. The p16(INK4a) expression has never been examined in human mast cells and mastocytosis. We immunohistologically examined...The expression of p16(INK4a) has been reported to induce cell-cycle arrest and cellular senescence. The p16(INK4a) expression has never been examined in human mast cells and mastocytosis. We immunohistologically examined the expression of p16(INK4a) and tryptase in 5 normal human skin and 4 mastocytosis. In normal mast cells, only 5.9 ± 3.4 (mean ± standard deviation) % of tryptase-positive mast cells coexpressed p16(INK4a). However, significantly higher percentage (86.0 ± 14.1%) of tryptase-positive tumor cells was immunoreactive to p16(INK4a) in all of 4 mastocytosis. The p16(INK4a) overexpression may induce the senescence of neoplastic mast cells to undergo spontaneous regression of mastocytosis.