Search

Autoimmune diseases including inflammatory bowel disease (IBD) occur in association with myelodysplastic syndrome (MDS). MDS-associated IBD frequently demonstrates a complicated course. We herein report the first case with MDS-associated IBD that was successfully treated with ustekinumab (UST), an anti-interleukin (IL) 12/23p40 monoclonal antibody. A 63-year-old man with a 7-year history of MDS was referred for examination of diarrhea, abdominal pain and fever. A blood examination revealed a marked elevation of C-reactive protein. Colonoscopy showed multiple ulcers in the terminal ileum. He was resistant to anti-tumor necrosis factor (TNF)-α antibody and azacitidine. Subsequently, UST treatment reduced colonic IL-17 and IL-6 expression and the patient currently maintains a state of remission.

Lymphomatoid granulomatosis (LYG) is an angiocentric, angiodestructive lymphoreticular proliferative disease that usually affects the lungs but it has been speculated to also effect the central nervous system (CNS). However, unique primary LYG of the CNS has rarely been reported in the literature. Herein, we describe a clinical case of a 37-year-old female patient with grade 1 primary CNS-LYG having a good prognosis owing to corticosteroid treatment. The aforesaid patient, presented with a headache and left leg weakness with no evidence of a systemic disease. MRI revealed multiple small enhancing nodules in the right hemisphere with diffuse high-intensity lesions on T

A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.

The patient was a 20-year-old male in whom a hepatic hypervascular mass accompanied by intratumoral hemorrhage was detected on examination for epigastric pain. Based on the enlargement of the mass and diagnostic imaging, hepatocellular adenoma (HCA) was suspected and hepatectomy was performed. The lesion was diagnosed as malignant transformation of β-catenin-activated HCA. There are only few reports of cases with malignant transformation of HCA in Japan; it is necessary to accumulate cases to investigate it.

Cases of research misconduct (fabrication, falsification, and plagiarism) have been increasing worldwide, including in Japan. In particular, since 2006, many cases of research misconduct have been reported in Japan, and these cases have also been covered by the media. The 2014 case of the withdrawal of articles on STAP cells followed a rare course in which research misconduct became a full-blown social phenomenon. In recent years, even the University of Tokyo has experienced reported cases of research misconduct. In this report, I would like to introduce some representative cases of research misconduct in the field of life sciences over the past decade. These examples include studies conducted at Osaka University Graduate School of Medicine (2006), Osaka University Graduate School of Frontier Bioscience (2006), Ryukyu University School of Medicine (2010), Toho University School of Medicine (2012), The University of Tokyo Institute of Molecular and Cellular Biosciences (2013), and several cases outside of Japan. I will discuss what researchers should do to reduce the incidence of research misconduct. In addition, I will discuss how these cases were covered by the media, because the public's impression of research misconduct is formed by media coverage.

OBJECTIVES: To report MR imaging features of mammary analogue secretory carcinoma (MASC) and acinic cell carcinoma (AciCC) of the salivary gland based on the latest version of the World Health Organization (WHO) 2017 classification of head and neck tumours. METHODS: MR images in 4 patients with MASC and 4 with AciCC were reviewed for margin characteristics, the presence of pathological cervical nodes, the presence of a cystic component and interface between cystic and solid component, signal intensity of the cystic components on T(1) weighted images, and signal intensity of the solid component on T(1) and T(2) weighted images. RESULTS: All the MASCs and AciCCs had well-defined boundaries, and 1 AciCC had pathological nodes. All 4 MASCs presented as predominantly cystic tumours with papillary projection of the solid component. All 4 AciCCs presented as solid tumours. The signal intensity of the cystic components on T(1) weighted images was entirely hyperintense in 2, and partly hyperintense demonstrating fluid–fluid level in 2. In all the MASCs, the signal intensity of the solid components on T(1) weighted images was intermediate. In the AciCCs, the signal intensity of the solid components on T(1) weighted images was high in 2 tumours and intermediate in 2. The signal intensity of the solid components on T(2) weighted images varied from low to high in both MSACs and AciCCs. CONCLUSIONS: All 4 MASCs had a large cystic component, including areas of high signal intensity on T(1) weighted images. The solid component appeared as a papillary projection into the cystic component. All 4 AciCCs presented as solid tumours, 2 of which showed high signal intensity on T(1) weighted images.

Myelodysplastic syndrome [MDS] is a clonal disorder of bone marrow [BM] cells, caused by acquired chromosomal abnormalities and gene mutations. Pro-inflammatory antigen-presenting cells [APCs] originating from BM cells bearing chromosomal abnormalities and gene mutations can cause immune-mediated disorders including inflammatory bowel disease [IBD]. Here, we report the first case with MDS-associated IBD that was successfully treated with the DNA methyltransferase inhibitor, azacitidine [AZA]. A 75-year-old man with a 5-year history of MDS was admitted for examination of diarrhoea and high fever. Blood examination revealed pancytopenia and a marked elevation of C-reactive protein. Colonoscopy revealed multiple round ulcers from the terminal ileum to the sigmoid colon. Pathological examination of the endoscopic biopsy specimens showed destruction of crypt architecture and infiltration of CD3+ T cells and CD68+ macrophages. Surprisingly, administration of AZA, which has been approved for the treatment of high-risk MDS, improved the symptoms, and the multiple round ulcers disappeared. AZA treatment markedly decreased the expressions of tumour necrosis factor-α, interleukin-12 (IL-12)/23p40 and IL-17 in colonic biopsy samples, as assessed by quantitative reverse transcription polymerase chain reaction. In contrast, AZA treatment did not change the expression of forkhead box P3, a master regulator of regulatory T cells. These data suggest that AZA treatment led to complete remission in MDS-associated IBD through suppression of pro-inflammatory cytokine responses.

Chronic sclerosing sialadenitis is a benign inflammatory condition that most commonly affects the submandibular gland in elderly individuals. It is currently known to belong to the spectrum of IgG4-related systemic diseases, which is reflected by systemic involvement on F-FDG PET/CT images. We presented a case of a 73-year-old man with histologically proven IgG4-related chronic sclerosing sialadenitis, unilateral localized form, on whole-body F-FDG PET/CT images that mimicked submandibular carcinoma with lymph node metastasis.

Objectives:To report MRI findings of spontaneous infarction in parotid tumours.Methods:14 patients (13 male, 1 female; mean age 73 years) with spontaneously infarcted parotid tumours were reviewed retrospectively. MR images were assessed for the location, the presence of synchronous parotid masses, margin characteristics, signal intensity on T1and T2weighted images, and internal architecture according to the distribution of T2signal hyperintensity.Results:12 tumours were located in the parotid tail and 2 in the superficial lobe. Synchronous parotid masses were seen in four tumours, three of which were located in the ipsilateral parotid tail and one in the contralateral parotid tail. Seven tumours had well-defined margins and seven had ill-defined margins. The signal intensities on T1weighted images were a mixture of high and intermediate in all cases; in 11 tumours, hyperintense areas were dominant. On T2weighted images, all tumours also showed a mixture of high and intermediate signal intensities. Internal architectures on T2weighted images were mosaic hyperintensity in three tumours, central hyperintensity in five, and multiseparated hyperintensity in six.Conclusions:Spontaneously infarcted parotid tumours were mostly located in the parotid tail and showed mixed signal intensities with predominant hyperintensity on T1weighted images. Half of the tumours had ill-defined margins, and the internal architectures varied.

Hyphae are usually the only fungal elements found in tissue of mucormycosis, and other fungal elements are quite rarely encountered. We found chlamydospores in bronchial lumina in autopsied tissue of pulmonary mucormycosis of a diabetic patient. Chlamydospores are thick-walled, asexually produced spores arising from the modification of a hyphal segment. This is the first histologic demonstration of chlamydospores in mucormycosis in which the causative fungus is culturally identified to species level. Rhizopus microsporus var. rhizopodiformis was isolated from the present autopsied pulmonary tissue. A literature review of human infection by this fungus found 27 cases with histopathologic evidence.

This study showed that we need to bear in mind the possibility of gastric adenocarcinoma of the fundic gland type upon encounter with such elevated lesions originating from Helicobacter pylori (H. pylori)-negative gastric mucosa. We believe that our study makes a significant contribution to the literature because small invasive gastric adenocarcinoma of the fundic gland type is a rare disease entity, which exhibits a submucosal tumor-like or superficial flat-type elevated lesion on H. pylori-negative gastric mucosa in the endoscopic examinations.

症例は53歳，男性．神経線維腫症1型と診断されている．今回，血便を自覚し，他院にて直腸カルチノイドと診断された．精査加療目的で当院に紹介され，入院となった．下部消化管内視鏡検査で，歯状線より約3cmの部位に11mm大の粘膜下腫瘍形態の腫瘤を認めた．腹部CT検査では，直腸前壁に壁肥厚を認めたが，明らかな遠隔転移は認めなかった．直腸カルチノイドの診断で，腹腔鏡補助下直腸低位前方切除術を施行した．病理組織学的には粘膜下層に浸潤した直腸カルチノイドで，リンパ節転移は認めなかった．神経線維腫症1型には，一般的にカルチノイドは併発しやすいとされているが，十二指腸乳頭部領域に多く，直腸カルチノイドの合併は極めて稀である．今回，神経線維腫症1型に伴う直腸カルチノイドに対し，腹腔鏡補助下直腸低位前方切除術を施行した症例を経験したので，若干の文献的考察を加えて報告する．

We present an autopsy case of intrauterine pneumonia in a term newborn in whom Ureaplasma parvum was confirmed by PCR examinations, including a novel diagnostic tool for detecting pathogens that caused neonatal infections using multiplex PCR. This is the first report of U. parvum being implicated in the pathogenesis of congenital pneumonia with sepsis in a term newborn.

Background Lung alveolar epithelial cell (AEC) apoptosis has attracted attention as an early pathogenic event in the development of idiopathic interstitial pneumonia (IIP); however, the causative mechanism remains unclear. Cell adhesion molecule 1 (CADM1) is an AEC adhesion molecule in the immunoglobulin superfamily. It generates a membrane-associated C-terminal fragment, αCTF, through protease-mediated ectodomain shedding, termed α-shedding. Increased CADM1 α-shedding contributes to AEC apoptosis in emphysematous lungs. Methods Formalin-fixed, paraffin-embedded lung lobes (n = 39) from 36 autopsied patients with IIP were classified as acute IIP (n = 10), fibrosing-type nonspecific IIP (f-NSIP, n = 10), cryptogenic organizing IIP (n = 9), and usual IIP (n = 10). CADM1 expression in the lung sections was examined by western blotting and compared with control lungs (n = 10). The rate of CADM1 α-shedding was calculated as the relative amount of αCTF to full-length CADM1, and the full-length CADM1 level was estimated per epithelial cell by normalization to cytokeratin 7, a lung epithelial marker. Apoptotic AECs were detected by immunohistochemistry for single-stranded DNA (ssDNA). NCI-H441 and A549 human lung epithelial cells were transfected with small interfering RNA (siRNA) to silence CADM1 expression and analyzed by terminal nucleotide nick end labeling assays. Results The rate of CADM1 α-shedding was higher in all IIP subtypes than in the control (P ≤ 0.019), and the full-length CADM1 level was lower in f-NSIP (P = 0.007). The α-shedding rate and full-length CADM1 level were correlated with each other (P = 0.015) and with the proportion of ssDNA-positive AECs (P ≤ 0.024). NCI-H441 cells transfected with siRNA exhibited a 61 % lower rate of expression of full-length CADM1 and a 17-fold increased proportion of apoptotic cells. Similar results were obtained with A549 cells. Conclusions CADM1 α-shedding appeared to be increased in all four IIP subtypes and consequently contributed to AEC apoptosis by decreasing the full-length CADM1 level. This mechanism particularly impacted f-NSIP. The molecular mechanism causing AEC apoptosis may be similar between IIP and emphysema. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0255-x) contains supplementary material, which is available to authorized users.

Needle-Tract Seeding on the Proximal Gastric Wall After EUS-Guided Fine-Needle Aspiration of a Pancreatic Mass

Aims An immunohistochemical screen for mouse embryos showed that cell adhesion molecule 1 (CADM1), which is an immunoglobulin superfamily member, was expressed in developing bones. Here, we determined the cell types expressing CADM1 and examined its usefulness in the differential diagnosis of osteosarcoma. Main methods Serial sections of murine developing mandibles were stained with anti-CADM1 antibody, by a coloring substrate reactive to alkaline phosphatase (ALP), a broad osteoblastic marker for preosteoblasts to osteoblasts, and by in situ hybridization for osteopontin (OPN), a marker for mature osteoblasts. CADM1 immunohistochemistry was also performed on human remodeling bones, osteosarcomas and other soft tissue tumors. Key findings CADM1 immunohistochemistry for the mandible revealed that morphologically identifiable osteoblasts expressed CADM1 on their plasma membranes, but neither osteocytes nor bone lining cells did. At the mandibular margin, not only OPN-positive cells but also OPN-negative, ALP-positive cells were CADM1-positive, whereas inside the mandible, OPN-positive cells were often CADM1-negative. Clear membranous staining was detected in the majority of osteosarcomas (46/57), whereas only 13% (6/46) of the other soft tissue tumors were CADM1-positive ( P Significance These results indicated that CADM1 was a novel osteoblastic adhesion molecule that is expressed transiently during osteoblastic maturation, and a useful diagnostic marker for osteosarcoma cells.

The metastasis of malignant tumors to the oral cavity remains a rare clinical entity. Most metastatic tumors have the propensity for involving the mandible rather than the oral soft tissues. Herein, we describe an unusual case of ovarian mucinous cystadenocarcinoma that metastasized to the mandibular gingiva as an initial manifestation. There is little information regarding metastatic ovarian cancer to the oral cavity. A patient was a 54-year-old woman who developed the paresthesia and swelling of the right mandible after tooth extraction. A pantomograph revealed an osteolytic lesion in the right mandible. A biopsy taken from the gingiva showed mucinous adenocarcinoma, indicating the gingival metastasis of undiscovered primary cancer. A positron emission tomography and computed tomography using 18F-fluorodeoxyglucose depicted an ovarian tumor with multiple pelvic and paraaortic lymph node swellings. A magnetic resonance imaging (MRI) clearly demonstrated the presence of an ovarian cancer. Based on the imaging studies, the diagnosis of the gingival metastasis of an ovarian cancer was suspected. Serum CEA levels were elevated at 125.6 ng/ml (normal range, 0 - 5 ng/ml). She underwent the right segmental mandiblectomy with functional neck dissection and left salpingo-oophorectomy. The histology of surgical specimen confirmed the gingival metastasis of ovarian mucinous adenocarcinoma. Neoplastic cells in the gingiva infiltrated to the mandibular bone. She has been treated with adjuvant chemotherapy consisting of paclitaxel and carboplatin. This case emphasizes that although rare, metastatic ovarian cancer to the gingiva should be included in the differential diagnosis of tumors in the oral cavity.

Antigen-induced aggregation of the high affinity IgE receptor (FcεRI) on mast cells induces degranulation to release chemical mediators, leading to acute allergic inflammation. We have demonstrated that the treatment of rat mast cells, RBL-2H3, with a phenoxazine derivative Phx-1 (2-amino-4,4α-dihydro-4α,7-dimethyl-3H-phenoxazine-3-one) suppresses the antigen-induced degranulation. Biochemical analysis reveals that the complementary signaling pathway through Gab2 and Akt is inhibited by this compound in mast cells. These findings suggest that phenoxazine derivatives may have a therapeutic potential for allergic diseases by inhibiting mast cell degranulation. Keywords:: phenoxazine derivative, mast cell, degranulation