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Protein-losing enteropathy (PLE) is a rare syndrome characterized by hypoproteinemia due to gastrointestinal (GI) protein loss. Primary intestinal follicular lymphoma (PIFL), a specific variant of follicular lymphoma with essential only GI involvement, has not been reported as an etiology of PLE. We herein report a case of PLE complicated with PIFL that was successfully treated with rituximab, resulting in rapid improvement of PLE and a complete response of PIFL. Macroscopic findings of ulcerative lesions with diffuse involvement, which were precisely described by capsule and double-balloon enteroscopy at the diagnosis, also improved following the treatment. This case provides a clue suggesting factors that promote PLE in PIFL.

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

Several region-specific vegetable varieties in Japan have an extensive cultivation history. Distinct tastes and aromas make them suitable for use in spices and pickles, and varieties with a high co...

Significance Neonicotinoids acting on insect nicotinic acetylcholine receptors (nAChRs) are deployed for crop protection, but growing evidence for adverse effects on insect pollinators has led to restricted use of some neonicotinoids in the EU. It is therefore vital to understand the target site actions of neonicotinoids in pollinators, but to date the difficulties of heterologous expression of insect nAChRs have hampered progress. We have found that a thioredoxin (TMX3) enables robust functional expression of honeybee, bumblebee, and fruit fly nAChRs in Xenopus laevis oocytes. With this advance, we show that expressed bee nAChRs are more neonicotinoid-sensitive than those of fruit fly, and clothianidin can modulate both honeybee and bumblebee nAChRs at a concentration below that commonly observed in agricultural fields., 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.

We previously reported a novel diagnostic method using follicle-sinus complexes (FSCs) in the muzzle skin for postmortem diagnosis of rabies in dogs. However, whether this method works in other animal species remains unclear. Here, FSCs were collected from a wolf, a red fox, 2 bats, and a cat, and examined for the presence of viral antigen, viral mRNA, and viral particles. Viral antigen and viral mRNA were confirmed in Merkel cells (MCs) in FSCs of all species. Electron microscopy performed using only samples from wolf and cat confirmed viral particles in MCs of FSCs. These results suggested that this novel diagnostic method using FSCs might be useful for detection of rabies not only in domestic but also wild animals.

Rabies is a highly neurotropic disease caused by rabies lyssavirus (RABV). Human rabies vaccines exist for pre- and postexposure prophylaxis; however, after clinical symptoms appear, the disease has an ∼100% mortality rate with no effective treatments available. In our previous study, mouse neuroblastoma cells transfected with a plasmid coding one clone of a single-chain variable fragment (scFv), scFv-P19, against RABV phosphoprotein (RABV-P) derived from an scFv phage-display library, before infection, exhibited reduced viral propagation after infection with the RABV-fixed strain, CVS11. In this study, we conducted epitope mapping of scFv-P19 through indirect fluorescent assay and Western blotting analysis against full-length and N- or C-terminal truncated RABV-P. Our results suggest that scFv-P19 targets a portion containing amino acids 47-52 at the N-terminus, which partially overlaps with the N-terminal nuclear export sequences. This provides insights into the underlying mechanism associated with inhibition of RABV by scFv-P19, while allowing for the design of additional scFv-based therapeutic studies for RABV by integrating appropriate delivery and application systems. Furthermore, the results of this study suggest that scFv-P19 may serve as an effective tool for investigating nuclear trafficking of RABV-P to explore the roles of RABV-P isoforms in rabies pathogenesis.

Exercise is a key intervention for improving older adults’ physical function and life expectancy. Here, we investigated a short-term intervention program designed to improve the physical functioning of elderly adults in a community-dwelling setting. We examined the effect of a 5-week combined exercise and education program on the physical function, social engagement, mobility performance, and fear of falling in 42 subjects older than 65 years. Eleven subjects dropped out. There was significant improvement in the 30-second chair stand test ( p

Pancreatic cancer is a malignant neoplasm with high invasiveness and poor prognosis. In a previous study, a highly invasive pancreatic cancer cell line was established and found to feature enhanced interleukin-32 (IL-32) expression. However, whether IL-32 promotes the invasiveness by enhancing or suppressing the expression of IL-32 through regulating downstream molecules was unclear. To investigate the effect of IL-32, cells were established with high levels of expression or downregulated IL-32; their invasive ability was measured using a real-time measurement system and the expression of some candidate downstream molecules involved in invasion was evaluated in the two cell types. The morphological changes in both cell types and the localization of IL-32 expression in pancreatic cancer tissues were studied using immunohistochemistry. Among the several splice variants of IL-32, cells transfected with the ε isoform had increased invasiveness, whereas the IL-32-suppressed cells had reduced invasiveness. Several downstream molecules, whose expression was changed in the two cell types, were monitored. Notably, changes of E-cadherin, CLDN1, CD44, CTGF and Wnt were documented. The morphologies of the two cell types differed from the original cell line. Immunohistochemically, the expression of IL-32 was observed only in tumor cells and not in normal pancreatic cells. In conclusion, IL-32 was found to promote the invasiveness of pancreatic cancer cells by regulating downstream molecules.

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., This report describes the clinical and histologic features of this extremely rare case of central mucoepidermoid carcinoma admixed with a calcifying odontogenic cyst.

A 32-year-old man, who visited Japan from the Philippines in 2020, was diagnosed with rabies, the first reported case in Japan since 2006. This is the fourth imported case of rabies since 1957; one case in 1970 was imported from Nepal and two in 2006 were imported from the Philippines.

BackgroundOvarian tumors are predominantly of epithelial origin and are currently divided into three groups: Adenoma, borderline tumor, and adenocarcinoma by the presence or absence of invasion and cellular atypia. However, it is difficult to assess invasion, so a more objective biomarker would be desirable. Laminin-5 (Lam5) is a protein that constitutes the extracellular matrix of the basement membrane, and it is composed of three short-chain subunits. One of them, the Lam5γ2 chain (Lam5γ2), has been reported to be expressed in some malignant tumors and is suggested to be related to tumor cell invasion. Against this background, we investigated immunohistologically whether the Lam5γ2 would be useful as a marker to predict invasion in ovarian serous and mucinous tumors.MethodsImmunohistochemistry for Lam5γ2 was performed on a total of 80 cases of serous and mucinous tumor adenomas, borderline tumors, and adenocarcinomas, and the differences in the localization of Lam5γ2 expression were observed.ResultsThe basement membrane expression of Lam5γ2 tended to be preserved or had disappeared in half of the adenomas and borderline serous tumors. In all cases of adenocarcinoma, the expression on the basement membrane had disappeared. The frequency of expression in tumor cells increased in the order of adenoma, borderline tumor, adenocarcinoma. In particular, in most adenocarcinoma cases a cytoplasmic expression was observed. The same tendency was noted in mucinous tumors, and the basement membrane expression tended to disappear in the order of adenoma, borderline tumor and adenocarcinoma. Many cases of adenocarcinoma were observed among the tumor cells. In adenocarcinoma cases of both types of tumor, many tumor cells showed prominent cytoplasmic expression particularly in the microinvasive foci and in the invasive front.ConclusionsThe disappearance of Lam5γ2 from the basement membrane and its aberrant expression in serous and mucinous tumor cells may serve as a phenotype for invasiveness.

AIMS This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD), or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of HGD area with crypt differentiation, HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends on the presence or absence of crypt differentiation.

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.

A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.

Background: Cetuximab is a powerful anti-neoplastic agent that can inhibit cell growth in oral squamous cell carcinomas (OSCCs). Unfortunately, there are cases with unfavorable outcomes. Because few studies have focused on the combined effects of cetuximab and histone deacetylase (HDAC) inhibitors, we aimed to evaluate the antitumor effect of cetuximab in combination with HDAC inhibitors in human OSCC cell lines, and investigate the mechanism of apoptosis enhancing activity thereof.Methods: We used human OSCC cell lines treated with cetuximab (500 mg/ml) and several HDAC inhibitors. The WST assay and ApoToxGlo™ Triplex Assay determined cell survival. We employed the TdT-mediated dUTP-biotin nick end labeling method to detect apoptosis. We used western blotting to examine the histone acetylation status, ER stress markers, and epidermal growth factor receptor (EGFR) signaling pathways.Results: Cetuximab in combination with 4-phenyl butyric acid (4-PBA) remarkably decreases cell growth in vitro. In addition, the combined treatment resulted in increased EGFR mRNA expression, and it promoted the activation of ERK. The combination treatment induced apoptosis at a significantly higher frequency than did either agent alone.Conclusions: The combination of cetuximab and 4-PBA is more effective against human OSCC cells than either agent alone, suggesting a potential clinical applicability of combination treatment in OSCC therapies.

The area of Kanto-Koushinetsu occupies 16% (63,041 km2) of the land area of Japan. This region includes the Tokyo metropolis and the prefectures of Ibaraki, Tochigi, Gunma, Saitama, Chiba, Kanagawa, Yamanashi, Nagano, Niigata. Significant depletion in agricultural land has been progressed from 1972 to 2011 due to the population concentration in the urban area of Tokyo metropolis and the prefectures of Saitama, Chiba, Kanagawa. The area around the population concentration zone plays an important role in supplying vegetables, and the national share of items is 33.8% for vegetables and 25.6% for a flowering plant, and these values are the top of the Japan. In the Kanto region, the plain area occupies a large area, and agricultural activities are being developed under good water use and the existence of a populated area. The characteristics of geology, topography, climatic conditions and soil characteristics and the effects of volcanic ash soil in this area are described. The relationship between the recent agricultural production of Kanto-Koshinetsu area and the soil characteristics of each area was clarified. On the other hand, anthropogenic soils are increasing in Tokyo metropolis and problems in current soil classification system emerged from these soils has been pointed out. As a topic, an action on restoration of habitat for the reintroduction of the crested ibis in Sado Island (Sado City, Niigata Prefecture) for selected as Globally Important Agricultural Heritage System (GIAHS) was introduced. Furthermore, examples of agricultural production and soil environment conservation were introduced.

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, immunocompromised 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.

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 (α3, β3, and γ2), is a major component of the basement membrane in many tissues. One of the chains, Lam-5 γ2, is a marker of invasion, because it often develops as a monomer in malignant neoplasms. We investigated the expression of Lam-5 γ2 and its role for the invasiveness in EMPD. Paraffin-embedded specimens of EMPD obtained from 36 patients were examined immunohistochemically for Lam-5 γ2. 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 γ2 in the basement membrane and its cytoplasmic expression was more observed in the invasive cases than non-invasive cases. Expression of Lam-5 γ2 may be a biological marker to predict invasiveness of EMPD.

Compared to tumors of other organs, pancreatic cancer is highly aggressive; with one of its biological features being that, despite a prominent fibrotic stroma, there is remarkable infiltration of tumor cells. This characteristic is considered to be the main reason for the poor prognosis of patients with pancreatic cancer. Therefore, in order to elucidate the factors that contribute to this high invasiveness, a selective invasion method was used to establish four highly invasive subclones from six human pancreatic cancer cell lines. The results demonstrated that two cell lines did not exhibit enhanced invasiveness. Microarray analysis revealed that, in the highly invasive cell lines, several genes were expressed at high levels, compared with the original cell lines. These highly expressed genes were recognized only in highly invasive cells. Among them, IL-32 was most strongly upregulated in the highly invasive cells, compared with cells with a low invasive potential, as well as the original cells. RT-qPCR and western blot analysis confirmed the high levels of expression of IL-32 in highly invasive cells at the RNA and protein levels. In addition, immunohistochemical analysis of resected surgical materials revealed that the tumor cells expressed IL-32 and, in particular, many IL-32 positive cells were seen at the invasive front of the tumor tissue. IL-32 is a cytokine that is widely involved in the development of cancer and has recently received considerable attention. This cytokine has multiple splice variants and shows a wide variety of behaviors, depending on the tumor type and primary organ. Although some hypotheses have been proposed to explain the activity of IL-32, a unified view has not been agreed. In the present study, through the establishment of highly invasive cells from pancreatic cancer and a comprehensive gene analysis, it is suggested that IL-32 may serve an important role as a molecule involved in the invasiveness of this neoplasm.

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.

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.

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.

In this paper, we propose a trajectory estimation method using sparsely deployed anchor nodes. Whenever mobile nodes encounter each other, they record the encounter time and ID of the encounter node. Moreover, when they encounter anchor nodes, they forward the encounter records to the anchor nodes. The anchor nodes then send the encounter records to a cloud server. In our proposed method, the cloud server estimates the trajectory of the mobile nodes based on the encounter records, the positions of the anchor nodes, and the average moving speed of the mobile nodes. Through simulation experiments, we show the effectiveness of our proposed method.

Background/aim Angiosarcoma is a rare and aggressive soft tissue sarcoma with poor prognosis. Chemotherapy and radiotherapy do not improve the prognosis. SIRT1, a class III histone deacetylase, is up-regulated in many malignant tumours. This study aimed at exploring the role of SIRTl in angiosarcoma. Materials and methods The effect of suppressing SIRT1 expression with siRNA on the proliferation and invasion ability of ISO-HAS-B angiosarcoma cells was investigated. Additionally, SIRT1 expression in tissues from surgical specimens was immunohistochemically evaluated and compared to that from benign tumours. Results Suppression of SIRT1 expression by siRNA resulted in the down-regulation of cell growth, proliferation, migration, and invasion. An immunohistochemical analysis disclosed that SIRT1 expression in angiosarcoma was stronger than that in haemangioma. Conclusion SIRT1 may be involved in the invasive proliferation and malignant transformation of angiosarcoma, and may be considered a future target for angiosarcoma therapy.

Peripheral electrical stimulation (PES) modulates the excitability of the corticospinal tract (CST). This modulation of CST excitability depends on the PES intensity, defined by the amplitude and the width of each pulse, the total pulse number, the stimulation frequency, and the intervention duration. Another key PES parameter is the stimulation pattern; little is known about how PES pattern affects CST excitability, as previous studies did not control other PES parameters. Here, we investigated the effect of the net difference in PES pattern on CST excitability. We use three controlled PESs, intermittent PES (30 Hz) (stimulation trains at 30 Hz with pauses), continuous PES (12 Hz) (constant stimulation at 12 Hz without pauses), and continuous PES (30 Hz) with the same stimulation frequency as the intermittent PES (30 Hz), to compare the effect of the stimulation frequency. The motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) of healthy subjects were recorded before and after these three types of PESs in separate sessions. We found that intermittent PES (30 Hz) increased MEP amplitudes, whereas continuous PES (12 and 30 Hz) decreased amplitudes. A significant change in subcortical SEP component occurred during continuous PES (12 and 30 Hz), but not intermittent PES (30 Hz), whereas cortical SEP components showed similar behavior in three types of PESs. We conclude that (1) opposing modulations of CST excitability were induced by the differences in the PES pattern, and (2) these modulations appear to be mediated through different processes in the sensorimotor system. Our findings suggest the possibility that it may be preferable to select the PES pattern in therapeutic interventions based on the putative desired effect and the neural structure being targeted.

A 41-year-old female smoker presented with a vaginal mass. Gynecological examination showed a mass filling the uterine corpus, cervix, and vagina. A total abdominal hysterectomy was performed. Macroscopic findings included a large fragile mass involving the uterine cavity, cervix, and vagina. Histology revealed atypical ducts admixed with solid components consisting of large atypical cells. The initial pathological diagnosis was grade 3 endometrioid adenocarcinoma. The patient was designated as stage II according to the 2008 International Federation of Gynecology and Obstetrics (FIGO) staging. Two years later, two nodules were found in the upper lobe of the left lung, and the patient underwent an upper lobectomy. The masses, which exhibited solid and organoid growth patterns of large atypical cells, had histological characteristics of large cell neuroendocrine carcinoma (LCNEC) of the lung. However, the tumor was immunohistochemically positive for neuroendocrine markers, such as synaptophysin in addition to estrogen receptor and progesterone receptor, and the tumor was negative for thyroid transcription factor-1. These immunohistochemical results were almost identical to those of the solid portions of the uterine carcinoma. The final diagnosis was LCNEC combined with endometrioid adenocarcinoma of the uterine corpus and lung metastasis of the LCNEC component of the endometrial carcinoma. LCNEC often arises in the lung, but it rarely arises in other organs. Some patients with metastatic components exhibited only a LCNEC pattern although the primary tumor was a mixed carcinoma consisting of LCNEC and other histology, like the present case. LCNEC is often poorly differentiated, especially in extrapulmonary primary organ LCNEC. Therefore, pathologists should consider metastatic carcinoma when they encounter lung LCNEC in a patient with a preceding extrapulmonary carcinoma composed of a poorly differentiated component or LCNEC component, and they should clarify tumor immunohistochemical characteristics to confirm the diagnosis.

The coverage of rabies vaccinations has been reported at 70-80% of dogs in annual reports. However, there are still outbreaks of rabies among humans and dogs in Thailand, thus indicating the necessity of ensuring seroprevalence in vaccinated dogs and efficacy of human immunization. A cost effective easy competitive enzyme-linked immunosorbent assay (CEE-cELISA) was developed here for monitoring protective immunity against the rabies virus in human and dog serum samples using monoclonal antibody clone 1-46-12, which recognizes a conformational epitope of the rabies G protein. The ELISA plate is coated with the whole viral antigen from a commercial vaccine. The serotiter measured by the CEE-cELISA and by the gold standard assay (rapid fluorescent focus inhibition test), detecting the neutralizing antibody, showed a strong correlation, with an R value of 0.958 and 0.931 in humans and dogs, respectively. These correlations were detected in the serum samples from humans and dogs at antibody concentrations up to 100 and 10 IU/ml, respectively. This CEE-cELISA could be an alternative assay for evaluating mass rabies vaccination rapidly at a low cost as well as for detecting antirabies antibodies in the serum of not only humans but also other animal species.

Prenylated indole alkaloid okaramines selectively target insect glutamate-gated chloride channels (GluCls). Because of their highly complex structures, including azocine and azetidine rings, total synthesis of okaramine A or B has not been achieved, preventing evaluation of the biological activities of okaramines. Biosynthetic approaches provide alternatives to accessing structurally diverse derivatives and enabling the elucidation of structure-activity relationships. To explore the biosynthetic potential of okaramines, gene knockout experiments of an okaramine-producer fungus were performed. The deletion mutants of the oxygenase genes okaB, okaD, okaE, and okaG provided analogues that were unlikely to be accumulated in the normal biosynthetic process of the wild-type strain. Analysis of the structure-activity relationships of okaramines collected from the fungal cultures revealed that 1,4-dihydroazocine and N-aliphatic group attached to the indole were crucial for GluCl-activating activity. This provided insights into further derivatization of the complex structure of okaramines in order to facilitate the development of new insecticides.

Expression of the protein deacetylase SIRT1 is associated with either poor or favorable prognosis in cancer patients, depending on the cancer type. In head and neck squamous cell carcinoma (HNSCC), SIRT1 expression is associated with favorable prognosis. However, the molecular mechanism underlying the tumor-suppressive function of SIRT1 in HNSCC is unknown. SIRT1 promotes differentiation in epithelial cells; therefore, we investigated whether SIRT1 promotes differentiation in HNSCC cells by studying the correlations between the expression of SIRT1 and several genes implicated in stemness or differentiation in HNSCC-derived cell lines. Our results suggest that SIRT1 does not contribute to differentiation in HNSCC cells. RNA interference-mediated reduction of SIRT1 revealed that SIRT1 supports the expression of TAp63, which has been implicated in tumor suppression, in addition to epithelial differentiation. A positive correlation was observed between SIRT1 and TAp63 expression in HNSCC tissues, as determined by quantitative reverse transcription-polymerase chain reaction analysis of RNA extracted from formalin-fixed paraffin-embedded biopsy samples. Together, these results suggest that although SIRT1 does not regulate differentiation of HNSCC cells, it functions as a tumor suppressor in HNSCC by supporting the transcription of tumor-suppressive TAp63. This finding supports the notion that SIRT1-activating drugs could be useful for the treatment of HNSCC.

Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P