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Abstract Lymphoid follicular hyperplasia (LFH) is a benign lymphoproliferative disease. Although it can occur within the thoracic cavity, LFH originating from the chest wall has not been reported. A 79‐year‐old woman was incidentally found to have a well‐defined mass on the left posterior chest wall during a preoperative examination for aortic valve replacement. The mass had slowly grown over 6 years. Thoracoscopic surgical resection was performed without complications. Pathological examination ruled out lymphoproliferative diseases, such as Castleman disease or malignant lymphoma, and a diagnosis of LFH was made. Although LFH generally has a good prognosis, surgical resection is recommended for diagnostic and therapeutic purposes owing to the possibility of malignancy masquerading as a reactive lesion. This is the first report of an LFH arising from the chest wall with imaging findings similar to other benign tumours. Its potential as a differential diagnosis for tumours with similar imaging findings is highlighted.

An 80-year-old Japanese man presented to our hospital with intra-abdominal hemorrhage due to a ruptured liver tumor. Transcatheter arterial embolization (TAE) temporarily achieved hemostasis, but he died following re-rupture 4 days later. Based on autopsy findings, the liver tumor was diagnosed as hepatic angiosarcoma. Embolic agents used during embolization were identified within the hepatic small interlobular arteries. However, there were no findings of tumor cell necrosis or ischemic change in the angiosarcoma. In the present case, TAE alone did not induce ischemia-induced tumor necrosis, suggesting that TAE might be unsuitable to treat hepatic angiosarcoma. Treatment optimization for ruptured hepatic angiosarcoma is desired.

DNA immunization has been used to study vaccination methods and for production of specific antibodies. The present study aimed to apply DNA immunization to prepare specific IgYs, which react against rabies virus N protein (RV-N) and can be used to research and diagnose rabies virus. The DNA sequence of RV-N was ligated into a pcDNA 3.1 plasmid for constructing pcDNA-N. Eight hens were divided into four groups. Group 1 comprised the control group (non-immunized). In Groups 2, 3, and 4, hens were injected intramuscularly with pcDNA-N (400 μg/hen). Eight injections were administered every other week. From the 4th week, an adjuvant was injected in addition to pcDNA-N. Freund’s complete adjuvant (FCA) and λ-carrageenan were administered to Groups 3 and 4, respectively. Eggs were collected daily, and the specific antibody activities of egg yolks were measured by ELISA. IgYs were purified from pooled egg yolks at 16-19 weeks post-administration in each group. The detection sensitivities of the RV-N were compared using purified IgY as the primary antibody for ELISA, dot blotting, and western blotting. Egg yolks from one of the two hens in Group 2 (pcDNA-N alone) and all hens in Groups 3 (pcDNA-N + FCA) and 4 (pcDNA-N + λCarra) had increased ELISA values. The combined use of λ-carrageen in DNA immunization resulted in an adjuvant effect comparable to that of FCA. Each purified specific IgY detected RV-N in the ELISA, western blotting, and dot blotting; however, the detection sensitivity differed. Higher detection sensitivity of the +λCarra IgY was observed by ELISA, whereas there was higher detection sensitivity of +FCA IgY in western blotting and dot blotting. In summary, anti-rabies virus N protein IgY was prepared through DNA immunization of hens using FCA or λ-carrageenan as adjuvants and can be used as a primary antibody to detect rabies viruses.

Small cell neuroendocrine carcinoma is rare among urinary bladder cancer types, and to date, there are no case reports of concurrent antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis. We describe the case of a 69-year-old Japanese man who presented with elevated creatine kinase levels and haematuria on medical examination. Approximately one month later, he developed dysphagia. Laryngoscopy confirmed laryngeal dysfunction. He also presented with muscle weakness and a skin rash. Magnetic resonance imaging of the upper extremities suggested bilateral brachial muscle myositis. He was diagnosed as having dermatomyositis and was later found to be positive for antitranscriptional intermediary factor 1-γ antibody. Computed tomography revealed an intravesical space-occupying lesion and right iliac lymphadenopathy, suggesting urinary bladder cancer. The patient was admitted to our hospital for treatment. Urinary bladder biopsy confirmed small cell neuroendocrine carcinoma because tumour cells were positive for synaptophysin, CD56, and chromogranin A. Thus, the patient was diagnosed as having an antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis concomitant with urinary bladder small cell neuroendocrine carcinoma. The patient was treated with glucocorticoid and intravenous immune globulin therapy for dermatomyositis. Radiotherapy was selected for the carcinoma. Although muscle weakness and skin symptoms improved with treatment, dysphagia persisted. Furthermore, expression of the transcriptional intermediary factor 1-γ protein in tumour cells was also confirmed by immunohistochemistry, but the significance is unknown. It should be noted that antitranscriptional intermediary factor 1-γantibody-positive dermatomyositis can occur concomitantly with such a rare malignancy.

Abstract Background The complete genome sequences of 44 Bacillus cereus group isolates collected from diverse sources in Japan were analyzed to determine their genetic backgrounds and diversity levels in Japan. Multilocus sequence typing (MLST) and core-genome single-nucleotide polymorphism (SNP) typing data from whole-genome sequences were analyzed to determine genetic diversity levels. Virulence-associated gene profiles were also used to evaluate the genetic backgrounds and relationships among the isolates. Results The 44 B. cereus group isolates, including soil- and animal-derived isolates and isolates recovered from hospitalized patients and food poisoning cases, were genotyped by MLST and core-genome SNP typing. Genetic variation among the isolates was identified by the MLST and core-genome SNP phylogeny comparison against reference strains from countries outside of Japan. Exploratory principal component analysis and nonmetric multidimensional scaling (NMDS) analyses were used to assess the genetic similarities among the isolates using gene presence and absence information and isolate origins as the metadata. A significant correlation was seen between the principal components and the presence of genes encoding hemolysin BL and emetic genetic determinants in B. cereus, and the capsule proteins in B. anthracis. NMDS showed that the cluster of soil isolates overlapped with the cluster comprising animal-derived and clinical isolates. Conclusions Molecular and epidemiological analyses of B. cereus group isolates in Japan suggest that the soil- and animal-derived bacteria from our study are not a significant risk to human health. However, because several of the clinical isolates share close genetic relationships with the environmental isolates, both molecular and epidemiological surveillance studies could be used effectively to estimate virulence in these important pathogens.

Abstract Intraosseous mucoepidermoid carcinoma of the jaw is a rare lesion that has been suggested to originate from the odontogenic epithelium. We report an unusual case of central mucoepidermoid carcinoma in an 18‐year‐old Japanese man with an odontogenic cyst.

Background: Melanotic oncocytic metaplasia is a rare non-neoplastic lesion. It has been described as a phenomenon in which cells change their morphology to adapt to various stimuli. The incidence of melanotic oncocytic metaplasia is higher in middle-aged Asian males and smokers. The nasopharynx is the most common site of occurrence. Clinically, it is necessary to distinguish this lesion from malignant melanoma. Case: The patient was a man in his sixties and a heavy smoker. Brownish lesions were observed at bilateral pharyngeal openings of the eustachian tube through nasopharyngoscopy. Histopathologically, oncocytic cells without atypia having abundant granular cytoplasm and brownish pigmented granules were observed in the biopsy specimen obtained from the lesion. Immunohistochemically, most of these cells showed positive reaction for anti-mitochondria, S100, and Melan A, but not for HMB45. Discussion: The characteristic histological finding of this lesion was the presence of abundant mitochondria and melanin pigments in the cytoplasm. The former may be the result of a mitochondrial response to various stimuli, while the latter may be transported from dendritic cells mixed in the surrounding mucosal epithelium. Conclusion: It is important that otolaryngologists understand the features of this lesion, perform thorough observations, and reach a diagnosis through biopsy.

Ayu-narezushi, a traditional Japanese fermented food, comprises abundant levels of lactic acid bacteria (LAB) and free amino acids. This study aimed to examine the potential beneficial effects of ayu-narezushi and investigated whether ayu-narezushi led to improvements in the Tsumura Suzuki obese diabetes (TSOD) mice model of spontaneous metabolic syndrome because useful LAB are known as probiotics that regulate intestinal function. In the present study, the increased body weight of the TSOD mice was attenuated in those fed the ayu-narezushi-comprised chow (ayu-narezushi group) compared with those fed the normal rodent chow (control group). Serum triglyceride and cholesterol levels were significantly lower in the Ayu-narezushi group than in the control group at 24 weeks of age. Furthermore, hepatic mRNA levels of carnitine-palmitoyl transferase 1 and acyl-CoA oxidase, which related to fatty acid oxidation, were significantly increased in the ayu-narezushi group than in the control group at 24 weeks of age. In conclusion, these results suggested that continuous feeding with ayu-narezushi improved obesity and dyslipidemia in the TSOD mice and that the activation of fatty acid oxidation in the liver might contribute to these improvements.

The integration of multiple sensory modalities allows us to adapt to the environment of the outside world. It is widely known that visual stimuli interfere with the processing of auditory information, which is involved in the ability to pay attention. Additionally, visuospatial attention has the characteristic of laterality. It is unclear whether this laterality of visuospatial attention affects the processing of auditory stimuli. The sensorimotor gating system is a neurological process, which filters out unnecessary stimuli from environmental stimuli in the brain. Prepulse inhibition (PPI) is an operational measure of the sensorimotor gating system, which a weaker prestimulus (prepulse), such as a visual stimulus, inhibits the startle reflex elicited by a subsequent robust startling stimulus (pulse) such as a tone. Therefore, we investigated whether the visual stimulus from the left or right visual space affects the sensorimotor gating system in a “rest” task (low attentional condition) and a “selective attention” task (high attentional condition). In the selective attention task, we found that the target prepulse presented in the left and bilateral visual fields suppressed the startle reflex more than that presented in the right visual field. By contrast, there was no laterality of PPI in the no-target prepulse condition, and there was no laterality of PPI in the rest task. These results suggest that the laterality of visuospatial attention affects the sensorimotor gating system depending on the attentional condition. Moreover, the process of visual information processing may differ between the left and right brain.

BACKGROUND: Rabies continues to be a major public health problem in the Philippines, where 200-300 human cases were reported annually between 2001 and 2011. Understanding the phylogeography of rabies viruses is important for establishing a more effective and feasible control strategy. METHODS: We performed a molecular analysis of rabies viruses in the Philippines using rabied animal brain samples. The samples were collected from 11 of 17 regions, which covered three island groups (Luzon, Visayas, and Mindanao). Partial nucleoprotein (N) gene sequencing was performed on 57 samples and complete glycoprotein (G) gene sequencing was performed on 235 samples collected between 2004 and 2010. RESULTS: The Philippine strains of rabies viruses were included in a distinct phylogenetic cluster, previously named Asian 2b, which appeared to have diverged from the Chinese strain named Asian 2a. The Philippine strains were further divided into three major clades, which were found exclusively in different island groups: clades L, V, and M in Luzon, Visayas, and Mindanao, respectively. Clade L was subdivided into nine subclades (L1-L9) and clade V was subdivided into two subclades (V1 and V2). With a few exceptions, most strains in each subclade were distributed in specific geographic areas. There were also four strains that were divided into two genogroups but were not classified into any of the three major clades, and all four strains were found in the island group of Luzon. CONCLUSION: We detected three major clades and two distinct genogroups of rabies viruses in the Philippines. Our data suggest that viruses of each clade and subclade evolved independently in each area without frequent introduction into other areas. An important implication of these data is that geographically targeted dog vaccination using the island group approach may effectively control rabies in the Philippines.

Background/Aim: Immune checkpoint inhibitors can induce immune-related adverse events in various organs, thus careful observation is required. Case Report: A 69-yearold man was diagnosed with advanced lung adenocarcinoma and treated with combined therapy of carboplatin plus pemetrexed plus pembrolizumab. After two cycles of treatment, anemia was noted. Myelosuppression due to cytotoxic anticancer agents was suspected and the cytotoxic agents were discontinued, followed by three courses of pembrolizumab monotherapy. However, the anemia persisted, requiring red blood cell transfusions. A bone marrow biopsy revealed erythroblast hypoplasia and chromosomal abnormalities, resulting in a diagnosis of pure red cell aplasia. These adverse events were considered immunerelated because of the treatment history with an immune checkpoint inhibitor, and 60 mg/day (1 mg/kg/day) of prednisolone was initiated. Anemia improved, and it did not recur during the tapering of prednisolone. Conclusion: Immune-related pure red cell aplasia should be considered for patients presenting anemia during treatment with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum (HC), which can occasionally be aggressive resulting in the formation of granulomatous lesions. These are usually located in the lungs; however, immunocom‑ promised patients may occasionally develop disseminated lesions in other organs as well. Human immunodeficiency virus (HIV) primarily infects cells of the immune system expressing CD4 molecules. Not only does HIV multiply within these cells, but it can also kill them or otherwise cause loss of cellular function, leading to an immunocompromised state. As a result, in an immunocompromised patient, infection with HC can have serious implications, often the development of visceral histoplasmosis in different organs. Although several types of lesions are formed in HC‑infected organs, it may be difficult to distinguish the causative organism from other pathogens based on morphology alone. The present case report describes the case of a 57‑year‑old woman, from South America, who may have been infected with HC >20 years previously, remaining asymptomatic over the years. She later developed a lesion in the duodenum associated with immunodeficiency caused by HIV infection. The differential diagnosis of this case was made on the basis of several specific morphological findings using histopathological analysis and molecular pathological techniques. The pathogenesis of characteristic lesions caused by HC in the presence of HIV infection was also reviewed. [ABSTRACT FROM AUTHOR]

Extramammary Paget's disease (EMPD) is a rare malignant skin neoplasm characterized by intraepidermal proliferation of tumor cells. The tumor cells of EMPD may sometimes invade into the dermis or metastasize into the regional lymph nodes. Several studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicating invasiveness have yet to be well characterized. Laminin-5 (Lam-5), a heterotrimer composed of three chains (a3, b3, and c2), is a major component of the basement membrane in many tissues. One of the chains, Lam-5 c2, is a marker of invasion, because it often develops as a monomer in malignant neoplasms. We investigated the expression of Lam-5 c2 and its role for the invasiveness in EMPD. Paraffin-embedded specimens of EMPD obtained from 36 patients were examined immunohistochemically for Lam-5 c2. The cases adopted into this study comprised 16 cases of intraepidermal lesions and 20 cases with dermal invasion. The basement membrane seen in normal skin disappeared in one-third of non-invasive cases and in most invasive cases. The disappearance of Lam-5 c2 in the basement membrane and its cytoplasmic expression was more observed in the invasive cases than non-invasive cases. Expression of Lam-5 c2 may be a biological marker to predict invasiveness of EMPD. [ABSTRACT FROM AUTHOR]

The difficulty of achieving robust functional expression of insect nicotinic acetylcholine receptors (nAChRs) has hampered our understanding of these important molecular targets of globally deployed neonicotinoid insecticides at a time when concerns have grown regarding the toxicity of this chemotype to insect pollinators. We show that thioredoxin-related transmembrane protein 3 (TMX3) is essential to enable robust expression in Xenopus laevis oocytes of honeybee (Apis mellifera) and bumblebee (Bombus terrestris) as well as fruit fly (Drosophila melanogaster) nAChR heteromers targeted by neonicotinoids and not hitherto robustly expressed. This has enabled the characterization of picomolar target site actions of neonicotinoids, findings important in understanding their toxicity. [ABSTRACT FROM AUTHOR]

Recently, we reported that follicle-sinus complexes (FSCs) in the muzzle skin are useful for postmortem diagnosis of rabid dogs. Here, we compared the sensitivity and specificity of detecting the viral antigen in the brain and FSCs of 226 suspected rabid dogs, and assessed whether the FSC harbored the virus genome and particles. The viral antigen was detected in 211 of 226 samples with 100% sensitivity and specificity. Viral RNA and particles were observed in the cytoplasm of Merkel cells (MCs). These results suggest that MCs are targets of virus infection and FSCs are useful material for diagnosing rabies. [ABSTRACT FROM AUTHOR]

Two Melaleuca species, M. cajuputi and M. bracteata, were compared to identify the factors determining their distinct aluminum (Al) resistance levels. The presence of Al in a liquid culture medium (maximum tested concentration, 2 mM) did not affect the growth of M. cajuputi, but severely inhibited the growth of M. bracteata. The Al content in the roots was 50% higher in Al-sensitive M. bracteata than in Al-resistant M. cajuputi. Al penetration and tissue damage were obvious in the roots of M. bracteata, but only mild in the roots of M. cajuputi. Relatively high levels of fumarate were released by the roots of M. cajuputi, but not by those of M. bracteata. Supplementation of Al-containing liquid media with fumarate resulted in a reduction of Al toxicity on M. bracteata. These results suggest that Al-resistant M. cajuputi releases fumarate from its roots, thereby detoxifying Al. [ABSTRACT FROM AUTHOR]

The autogenic lens tumors induced by the Simian vacuolating virus 40 (SV40) T antigen in α-crystallin/SV40 T antigen transgenic (TG) mice, provide a tool to screen anti-tumor reagents in vivo and to clarify the underlying mechanisms. Juzen-taiho-to, a Chinese medicine composed of 10 herbs, was frequently used as an alternative medicine for cancer patients by clinicians and occasionally it was demonstrated to have beneficial effects on the prognosis and general condition of cancer patients. However, it was not scientifically verified. In the present study, the anti-tumor effects and underlying mechanisms of Juzen-taiho-to in the TG mice model was examined using cDNA microarray analysis and the results were confirmed by real-time PCR. The TG mice demonstrated a higher cumulative survival rate after treatment with the drug compared with the control group (P<0.05). Gene chip profiles demonstrated that cell functions involving the membrane, glycoprotein, cell membrane, signal and ionic channel for the lens tumor, the cell cycle, DNA replication, homeobox, mitosis and cell division for the spleen and the acetylation, mitochondrion, ribosomal protein, ribonucleoprotein for the liver, were altered by the administration of Juzen-taiho-to. The important canonical pathways were those of the mitogen-activated protein kinase (MAPK), the cell cycle and the ribosome for the altered genes of the lens tumor, spleen and liver after drug administration, respectively. From real-time PCR, in the eyeball, epidermal growth factor receptor (Egfr), Rasgrf1 and heat shock protein 1B (Hspa1b) mRNAs were found to be significantly lower in treated lenses than in those not exposed to the drug, while Rps25 mRNA demonstrated the opposite association in the liver. It was suggested that Juzen-taiho-to may prolong the survival time of SV40 T antigen TG mice by improving their nutritional condition, inhibiting the MAPK pathway and strengthening the immune system without causing hepatic toxicity. [ABSTRACT FROM AUTHOR]

Background: In 2009, a novel influenza A/H1N1 virus (H1N1pdm) quickly spread worldwide and co-circulated with then-existing seasonal H1N1 virus (sH1N1). Distinguishing between these 2 viruses was necessary to better characterize the epidemiological properties of the emergent virus, including transmission patterns, pathogenesis, and anti-influenza drug resistance. This situation prompted us to develop a point-of-care virus differentiation system before entering the 2009-2010 influenza season. Aiming to establish H1N1pdm-specific detection tools rapidly, we employed phage display libraries to select H1N1pdm-specific single-chain variable fragments (scFvs). Findings: Human single-fold scFv libraries (Tomlinson I + J) underwent selection for the ability to bind H1N1pdm virus particles. Three rounds of panning brought 1152 phage-bound scFvs, of which 58 clones reacted with H1N1pdm specifically or preferentially over sH1N1 in an enzyme-linked immunosorbent assay (ELISA). After conversion of the scFvs to soluble form, 7 clones demonstrating high/stable expression were finally obtained. However, all the soluble scFvs except No. 29 were found to have lost their specificity/preference for H1N1pdm in ELISA. The specificity/preference of No. 29 was also confirmed by immunofluorescence assay and immunoprecipitation, and the viral nucleoprotein was identified by ELISA as its target protein. The change in specificity associated with scFv conversion from phage-bound to soluble form could be due to loss of phage scaffold pIII protein, which likely provides structural support for the scFv antigen-binding site. It is also possible that the similar antigenic properties of H1N1pdm and sH1N1 led to the observed alterations in scFv specificity. Discussion: Using a phage display library, we obtained 7 soluble scFv clones reactive against H1N1pdm; however, only 1 showed specificity/preference toward H1N1pdm. Our results confirmed that using phage display libraries was highly advantageous for the rapid development of molecules to detect target antigens. However, our results also indicated that this strategy might not have been effective for selecting H1N1pdm-specific antibodies during the 2009 pandemic, where the co-circulating sH1N1 virus shared similar antigenic properties. This suggests that it might be advisable to use a synthetic scFv phage display library by strategically considering the characteristics of target antigens and the potential situations. [ABSTRACT FROM AUTHOR]