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.
Although chemotherapy with oral S-1and oxaliplatin (SOX) plus bevacizumab (bev) is safe andfeasible for patients with advanced or recurrent colorectal cancer, it is difficult to achieve a completeresponse (CR) using only chemotherapy. A 67-year-old man underwent endoscopic mucosal resectionand additional sigmoidectomy (D2 dissection) for submucosal invasive sigmoid colon cancer. Multipleliver 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. Livermetastases could not be identified using CT after the end of the sixth course. Grade 1peripheralneuropathy was the only side effect of this regimen. Subsequently, the chemotherapy regimen waschanged to oral S-1. CT evaluation revealed that there was no recurrence at 6 months after theregimen change.
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.
A 38-year-old man diagnosed with craniopharyngioma at 8 years old underwent repeated surgeryand radiation therapy. Complications included panhypopituitarism including growth hormonedeficiency and hypogonadism at 13 years old. At 26 years of age, a slight fatty liver was found, whichfinally developed into liver cirrhosis (LC) at 35 years old. Viral infection or other etiologies causing LCwere negative on serum examinations. Liver biopsy suggested a possibility of burn-out non-alcoholicsteatohepatitis. This case indicates that a long-standing growth hormone deficiency and hypogonadismmay lead to LC as a type of burn-out non-alcoholic steatohepatitis.
Esophageal motility disorders (EMD) is characterized by impaired coordinated esophageal motilityfunction with symptoms including dysphasia, heartburn or noncardiac chest pain. Since EMDs isfunctional disorders, it is usually difficult to make a diagnosis by conventional examinations includingendoscopy and esophagography. Recently developed high-resolution manometry allows us to evaluateesophageal motility function precisely and to make a differential diagnosis of EMDs, together withChicago Classification (CC) version 3.0 (CC ver3.0). In this article, we reviewed diagnosis of EMDsbased on CC ver3.0 and current treatment strategy for EMDs.
BackgroundAlthough portal vein thrombosis in cirrhotic patients is frequently observed, thedetailed process remains to be clarified, and the role of anticardiolipin antibody in the development ofportal vein thrombosis has been controversial.Case ReportA 52-year-old man, who had been diagnosed with alcoholic cirrhosis of the liver, wasadmitted to our hospital suffering from dyspnea and ascites. Just after being diagnosed as havingantiphospholipid antibody syndrome with lung thrombosis and delivering a positive result for the β2-glycoprotein I-dependent anticardiolipin antibody, he sustained rupture of the esophageal variceswith rapid development of portal vein thrombosis, which resolved under anticoagulant therapy. Twoyears later, he was admitted again on suspicion of thrombosis because of an elevation in the serumD-dimer level, and computed tomography showed portal and upper mesenteric vein thrombosis.Although immediate anticoagulant therapy resulted in complete recanalization, he suffered the sameepisode 2 months later, which occurred with re-elevation of the serum D-dimer level.ConclusionA positive finding of an anticardiolipin antibody in cirrhotic patients has been consideredto 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-dependentanticardiolipin antibody should be regarded as being at high risk for portal vein thrombosis. Monitoringwith the serum D-dimer was useful in detecting portal vein thrombosis in its early stage.
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.
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. Classicallythe pattern formation process falls into three categories-vasculogenesis, angiogenesis and remodeling.Mathematical modeling study of these phenomena has been done byrelatively independent ofexperimental works by applied mathematicians, and not well understood by experimental biologists. Inthis review I provide intuitive explanations of proposed theoretical models and recent advance inmodelling study of vascular development.
We experienced a case of the cardiopulmonary arrest due to subglottic stenosis developed on thesecond day after lung cancer surgery. Case : A 73-year-old female who was diagnosed with primarylung cancer was referred to our department for surgery. The second day after left lungsegmentectomy, she showed respiratory discomfort symptoms and exhibited hoarseness and stridor,which were revealed as the subglottic stenosis by bronchoscopy. During the emergency airwaymanagement, she went into cardiopulmonary arrest. We performed cardiopulmonary resuscitationand simultaneous urgent tracheotomy.
The causative agent of hepatic encephalopathy (HE) has not been identified with certainty. Therecovery of consciousness in patients with acute liver failure (ALF) who underwent livertransplantation (LT) is sometimes drastic ; therefore, we thought that the causative agents of HEwould change markedly peri-operatively in these patients. We examined the biomarkers includingnew 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 usedthree chips made by the Biomek2000 robot. All duplicated samples were assayed and analyzed usingthe CiphergenExpressTM data manager. We divided the peri-operative changes in the intensity ofidentified peaks into seven patterns. The number of peaks whose intensity shows significant changesperi-operatively reached 755. Of course, it is difficult to determine each structure in all 755 peaks ; therefore, we should narrowdown the candidates for causative agents of HE in further studies. Our own results suggest that manydifficulties lie ahead in determining the causative agent of HE.
We here describe a case of solitary basaloid follicular hamartoma (BFH) : the case developing incompany with senile lentigo on the nose. BFH is a relatively rare benign follicular neoplasm ofundetermined etiology. Histologically, the specimen consisted of small-sized squamoid or basaloid cellsand 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 ofsquamoid or basaloid cells in company with infundibular cysts, tumor of follicular infundibulum ortrichoepithelioma. We analyzed the immunohistochemical findings of the case in comparison withthose of BCC and trichoepithelioma. An immunohistochemical examination revealed 1) that Bcl-2 andCD10 was preferentially expressed in the outermost cells in the tumor nests consisting of folliculargerm-like cells, 2) that most of the tumor cells, especially germ-like cells, were strongly positive forBer-EP4, and 3) that peritumoral stroma was positive for CD34. The immunohistochemical findings ofour cases supported that BFH should be differentiated from BCC, a common malignant neoplasm.
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.
Surgical treatment for heart failure includes coronary artery bypass grafting to ischemic heartdisease, valvular disease surgery such as mitral valvuloplasty, left ventricular restoration, ventricularassist device (VAD), and heart transplantation. In addition, HeartSheet which is regenerative medicineusing autologous skeletal myoblast sheets has been started from the spring of 2016. Formal insurancereimbursement of implantable LVAD was obtained in April 2011, and the life prognosis of patientswith severe heart failure improved markedly. However, the indication for implantable LVAD is limitedto bridge use for heart transplantation. Implantable LVAD cannot be implanted in patients over 65years old under health insurance because the adaptive age of heart transplantation in Japan is under 65years old. It is a problem that the indication of implantable LVAD is identical to that of hearttransplantation. Clinical trial of destination therapy is in progress for the purpose of optimizing theimplantable 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 generaltreatment.
