Novel drugs possessing a mechanism of action specific to pathogenic mycobacteria, including Mycobacterium tuberculosis, are needed. In 2010, we discovered that the biosynthetic pathway of phosphatidylinositol, which is a membrane phospholipid, differs between humans and mycobacteria. The key enzyme responsible for this difference is phosphatidylinositol phosphate (PIP) synthase, which is present only in a few bacteria belonging to the phylum Actinobacteria. Discovering compounds that inhibit the activity of this enzyme will lead to the development of new drugs specific to pathogenic mycobacteria. Measuring PIP synthase activity requires the isotope-labeled substrate 1l-myo-inositol 1-phosphate (1l-Ino-1P). Because this substrate is not commercially available, we synthesized it from [14C] glucose 6-phosphate ([14C] Glc-6P), using a crude enzyme solution isolated from the methanoarchaeon 1l-Ino-1P synthase. The activity of 1l-Ino-1P synthase in the crude enzyme mixture was low, and quantitative analysis of the synthesized 1l-Ino-1P was inaccurate due to impurities present in the crude enzyme mixture. In the present study, we describe a method for synthesizing 1l-Ino-1P using a solution containing recombinant 1l-Ino-1P synthase derived from the hyperthermophilic archaeon Aeropyrum pernix. In addition, we elucidate the conditions leading to the almost complete conversion of Glc-6P into 1l-Ino-1P using this enzyme. Quantitation of the synthesized 1l -Ino-1P was performed by colorimetry and gas liquid chromatography. Further, we confirmed that isotope-labeled 1l-Ino-1P, which is difficult to quantitate by gas liquid chromatography, can be accurately quantified by colorimetry. We also confirmed that 1d-inositol 1-phosphate cannot be a substrate for PIP synthase.
There has been a growing interest in presenteeism in recent years in both the occupational health and management fields. However, the term “presenteeism” was introduced in Japan relatively recently, and only limited knowledge on the subject has since been accumulated. This review will outline the current knowledge on presenteeism and discuss the significance of addressing presenteeism in occupational health in Japan. A common definition of presenteeism is the state that showing up at the office while having health problems, and some have added a decline in productivity. Several methods have been proposed to convert a degree of presenteeism into monetary value in terms of a health economics perspective, but there is no consistent method. A new approach is needed to evaluate and support workers who are experiencing presenteeism.
We report here a 13-year-old female with Graves’ disease, whose diagnostic clue was glycosuria, which was detected by a urine glucose screening program at school. She had had mild general malaise, and a physical examination revealed a slightly enlarged thyroid gland. Hyperthyroidism (thyroid-stimulating hormone (TSH) < 0.01 μU/ml, free triiodothyronine (fT3) 23.57 pg/ml, free thyroxine (fT4) 3.38 ng/dl) and anti-thyroid autoantibodies (TRAb 43.6%) were detected in laboratory tests, and her plasma glucose at 120 minutes was 142 mg/dl in a 75 g oral glucose tolerance test. She was diagnosed as having borderline diabetes. These findings revealed a diagnosis of Graves’ hyperthyroidism with associated impaired glucose tolerance. Although it is reported that many adults with hyperthyroidism develop disorders of glucose metabolism, pediatric patients rarely have complications of glucose intolerance or diabetes mellitus, and there are no previous reports of Graves’ disease diagnosed by a urine glucose screening program at school. This case suggests a possibility of abnormalities in glucose metabolism even in pediatric cases of Graves’ disease. To avoid overlooking the diagnosis of glucose intolerance associated with hyperthyroidism, a careful medical interview and examination should be performed even if the clinical features are mild.
Situs inversus totalis is a rare clinical condition that represents a complete mirror image of the normal arrangement of the thoracic and abdominal viscera. There are very few reported cases of lung cancer patients with situs inversus totalis, but this condition requires particular care during surgery. A 61-year-old woman presented to our hospital with an abnormal shadow on chest radiography. Computed tomography revealed a 25×12 mm solitary pulmonary nodule in the left upper lobe (S2) and a complete mirror image of the normal organ arrangement, which findings met the criteria of situs inversus totalis. Preoperative examination revealed left upper lobe lung cancer (c-T1bN0M0 Stage IA), and surgery was planned for diagnosis and treatment. Before the surgery, three-dimensional CT images were reconstructed for a precise evaluation of the pulmonary vessels and bronchi. The nodule was microscopically diagnosed as adenocarcinoma from a frozen section obtained by wedge resection. We performed a left upper lobectomy with lymph node dissection using video-assisted thoracic surgery. The aortic arch was absent from the left thoracic cavity and the left lung was well lobulated into three lobes. Although it revealed a mirror image of the usual arrangement, we could accomplished in the usual procedure and process. Careful preoperative anatomical evaluation and perioperative handling are essential for the prevention of intraoperative injuries and complications in patients with situs inversus totalis.
In light of the cartographic Complementizer Phrase (CP) analysis, in which two computationally requisite functional projections (i.e., Force Phrase: ForceP and Finite Phrase: FinP) sandwich two optional discourse-related projections (i.e., Topic Phrase: TopP and Focus Phrase: FocP) in the clause-peripheral domain, it is theoretically reasonable to postulate the former as phase, a basic computational unit assumed in recent minimalist syntactic theory. We call this hybrid-type of syntactic analysis Phase-based CP Cartographic Analysis. Using this, we investigate multiple discourse-related movement (MDM) phenomena in English, including Topicalization, Focalization and Wh-movement at the clausal periphery. Our approach can appropriately capture the grammaticality regarding word order, which is derived from the combination of these clause-peripheral movements.
Growth hormone (GH) therapy for short children born small for gestational age (SGA) has been approved in Japan. It is important to evaluate GH secretion ability before the initiation of GH therapy because there are some differences in dose and medical expenses between short children born SGA and GH deficiency (GHD). This study was designed to elucidate the incidence of GHD and to find a useful marker for detecting it in short SGA children. We retrospectively reviewed medical records to analyze the clinical features of short children born SGA and with GHD who had started GH therapy before the age of 6 in the University Hospital of Occupational and Environmental Health and Kyushu Rousai Hospital. Nine of 22 SGA subjects (41%) had GHD. There were no significant differences between two groups of short SGA children (GHD, non-GHD) in the median of height and serum insulin-like growth factors (IGF)-1 levels at birth or at the start of GH therapy. The probability of GHD was higher if the height standard deviation scores (SD) of the SGA children were lower than −3.2 (odds ratio, 11.6; 95% confidence interval, 1.52 − 89.1, P = 0.013). This study showed that there is an approximately 40% incidence of GHD in short SGA children needing GH treatment. We should do GH stimulation tests for short SGA children whose height SD is lower than -3 to determine the appropriate GH therapy.
The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and heterogeneous internal echo level with calcification and an irregular margin. The tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph node swelling was detected in a computer tomography (CT) image, but no metastatic lesion was found by positron emission tomography (PET)-CT. In a fine needle aspiration cytology of the tumor, papillary thyroid carcinoma was suggested because of the atypical epithelial cells having some changes other than intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph node dissection were performed. The excised tumor was histologically composed of irregular nests or sheets of atypical squamoid epithelial cells with some ductal structures that leached to the sternothyroid muscle and involved the right lower parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was diagnosed histopathologically and immunohistochemically with the following immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117)) (+), thyroglobulin (−), and thyroid transcription factor-1 (TTF-1) (−). CASTLE is a rare carcinoma of the thyroid that architecturally resembles thymic epithelial tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma of the thyroid. Immunohistochemical examination, including CD5 played an important role in the final diagnosis of CASTLE, although the distinction from diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin-Eosin staining was challenging in our case. Nodal metastasis and perithyroidal tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful follow-up studies are mandatory in cases of CASTLE.
Enabling students to acquire practical skills that can be utilized after graduation has become an agenda for basic nursing education since the start of Japan’s “super-aging society” and the sophistication of modern medical treatment. Nursing schools are attempting to introduce the Objective Structured Clinical Examination (OSCE) in an attempt to integrate this important agenda. OSCE has been implemented at our school of nursing since 2014 in the first semester for third year students as a part of the integrated course for clinical training. E-learning has been utilized to help students study for the examination, and, according to students’ subjective evaluations, a certain level of effect has been confirmed. However, as we have new agendas for each school year, adjustments need to be made every year. We have made 3 adjustments so far since 2017. In this paper we report on our implementation of the OSCE in the year 2014, evaluations and adjustments to the OSCE in 2014 from the perspectives of 1) learning support, 2) evaluation methods, and 3) the application of the OSCE.