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Roughly 250 million people are infected with hepatitis B virus (HBV) worldwide, and perhaps 15 million also carry the satellite virus HDV, which confers even greater risk of severe liver disease. Almost ten years ago the HBV receptor was identified as NTCP (sodium taurocholate co-transporting polypeptide), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large (L) protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria, and these models with ten transmembrane helices are believed to resemble strongly both NTCP and ASBT. Using cryo-electron microscopy we have solved the structure of NTCP bound to an antibody, clearly showing the transporter has no equivalent to the first transmembrane helix of other SLC10 models, leaving the N-terminus exposed on the extracellular face. Comparison of the different structures indicates a common mechanism of bile acid transport, but the NTCP structure also displays a pocket formed by residues known to interact with preS1, presenting new and enticing opportunities for structure-based drug design., B型肝炎ウイルスの受容体“胆汁酸輸送体”の立体構造を解明. 京都大学プレスリリース. 2022-05-18.

During dissection for oral cancer, there is a high probability of bacteria indigenous to the oral cavity migrating to the surgical field in the neck due to the opening of new pathways of communication with the oral cavity. The risk of postoperative surgical site infection (SSI) in such patients is high due to malnutrition arising from perioperative eating disorders and dysphagia. Neck infections after neck dissection in oral cancer patients were investigated to elucidate the development of SSIs and their relationship with the results of bacterial culture.A total of 86 patients with oral squamous cell carcinoma who underwent neck dissection between January 2012 and December 2016 were enrolled. Ten factors were selected for investigation: (1) sex; (2) age; (3) primary site; (4) type of dissection; (5) whether or not there was a new pathway of communication between the oral cavity and the neck; (6) operative time; (7) blood loss; (8) number of drainage days; (9) amount of drainage at the time of drain removal; and (10) whether or not there was an SSI. Bacteria isolated from the catheter tip on drain removal were also investigated. Significant differences were observed between patients with and without SSIs (p-0.010) according to the presence of a new pathway of communication between the oral cavity and the neck (p-0.004); operative time (p-0.007); number of drainage days (p-0.029); or the amount of drainage at the time of drain removal. The present results indicate that selecting antibiotics appropriate to each patient and administering perioperative oral care are important in preventing SSIs.

Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here, we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite–helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.

Background In daily practice, three-dimensional patient-specific jawbone models (3D models) are a useful tool in surgical planning and simulation, resident training, patient education, and communication between the physicians in charge. The progressive improvements of the hardware and software have made it easy to obtain 3D models. Recently, in the field of oral and maxillofacial surgery, there are many reports on the benefits of 3D models. We introduced a desktop 3D printer in our department, and after a prolonged struggle, we successfully constructed an environment for the “in-house” fabrication of the previously outsourced 3D models that were initially outsourced. Through various efforts, it is now possible to supply inexpensive 3D models stably, and thus ensure safety and precision in surgeries. We report the cases in which inexpensive 3D models were used for orthodontic surgical simulation and discuss the surgical outcomes. Review We explained the specific CT scanning considerations for 3D printing, 3D printing failures, and how to deal with them. We also used 3D models fabricated in our system to determine the contribution to the surgery. Based on the surgical outcomes of the two operators, we compared the operating time and the amount of bleeding for 25 patients who underwent surgery using a 3D model in preoperative simulations and 20 patients without using a 3D model. There was a statistically significant difference in the operating time between the two groups. Conclusions In this article, we present, with surgical examples, our in-house practice of 3D simulation at low costs, the reality of 3D model fabrication, problems to be resolved, and some future prospects.

Background Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis B patients. Antiretroviral therapy (ART) in hepatitis B virus/human immunodeficiency virus-1 (HBV/HIV-1)–coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss. Methods This was a retrospective study of 58 HBV/HIV-1–coinfected subjects HBsAg-positive for ≥6 months before ART initiation and followed for ≥1 year (median 9.9 years) after ART initiation. We examined humoral factors in sera from healthy volunteers, HIV-monoinfected patients, and HBV/HIV-1–coinfected patients with IRIS-HF or acute hepatitis B infection. Results During ART, HBsAg loss was observed in 20 of 58 HBV/HIV-1–coinfected patients (34.5%). Of the 58 patients, 15 (25.9%) developed IRIS-HF within 12 months of ART initiation. HBsAg loss was more frequent among patients who developed IRIS-HF (11/15, 73.3%) than those who did not (9/43, 20.9%). Multivariate analysis showed IRIS-HF was an independent predictor of subsequent HBsAg loss. Younger age and higher baseline HBV DNA titer were associated with IRIS-HF. Elevation of sCD163, not CXCL9, CXC10, CXCXL11, or CXCL13, was observed at IRIS-HF. Conclusions IRIS-HF was associated with HBsAg loss in HBV/HIV-1–coinfected patients.

Viruses exploit host factors and environment for their efficient replication. The virus-host interaction mechanisms for achieving an optimal hepatitis B virus (HBV) replication have been largely unknown. Here, a single cell cloning revealed that HepAD38 cells, a widely-used HBV-inducible cell line, contain cell clones with diverse permissiveness to HBV replication. The HBV permissiveness was impaired upon treatment with microtubule inhibitor nocodazole, which was identified as an HBV replication inhibitor from a pharmacological screening. In the microtubule-disrupted cells, the efficiency of HBV capsid assembly was remarkably decreased without significant change in pre-assembly process. We further found that HBV core interacted with tubulin and co-localized with microtubule-like fibriforms, but this association was abrogated upon microtubule-disassembly agents, resulting in attenuation of capsid formation. Our data thus suggest a significant role of microtubules in the efficient capsid formation during HBV replication. In line with this, a highly HBV permissive cell clone of HepAD38 cells showed a prominent association of core-microtubule and thus a high capacity to support the capsid formation. These findings provide a new aspect of virus-cell interaction for rendering efficient HBV replication.

Background & Aims The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function. Methods We characterized a series of cyclosporine (CsA) derivatives for their anti-HBV activity and NTCP binding specificity using HepG2 cells overexpressing NTCP and primary human hepatocytes. The four most potent derivatives were tested for their capacity to prevent HBV entry, but maintain NTCP transporter function. Their antiviral activity against different HBV genotypes was analysed. Results We identified several CsA derivatives that inhibited HBV infection with a sub-micromolar IC 50 . Among them, SCY446 and SCY450 showed low activity against calcineurin (CN) and cyclophilins (CyPs), two major CsA cellular targets. This suggested that instead, these compounds interacted directly with NTCP to inhibit viral attachment to host cells, and have no immunosuppressive function. Importantly, we found that SCY450 and SCY995 did not impair the NTCP-dependent uptake of bile acids, and inhibited multiple HBV genotypes including a clinically relevant nucleoside analog-resistant HBV isolate. Conclusions This is the first example of small molecule selective inhibition of HBV entry with no decrease in NTCP transporter activity. It suggests that the anti-HBV activity can be functionally separated from bile acid transport. These broadly active anti-HBV molecules are potential candidates for developing new drugs with fewer adverse effects. Lay summary In this study, we identified new compounds that selectively inhibited hepatitis B virus (HBV) entry, and did not impair bile acid uptake. Our evidence offers a new strategy for developing anti-HBV drugs with fewer side effects.

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) and 4′-ethynyl-2′-deoxyadenosine (EdA) are nucleoside analogues which inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. EdAP, a cyclosaligenyl (cycloSal) phosphate derivative of EdA, inhibits the replication of the influenza A virus. The common structural feature of these compounds is the ethynyl group at the 4′-position. In this study, these nucleoside analogues were prepared by a common synthetic strategy starting from the known 1,2-di-O-acetyl-D-ribofuranose. Biological evaluation of EdAP revealed that this compound reduced hepatitis B virus (HBV) replication dose-dependently without cytotoxicity against host cells tested in this study.

Sodium taurocholate cotransporting polypeptide (NTCP) is a host cell receptor required for hepatitis B virus (HBV) entry. However, the susceptibility of NTCP-expressing cells to HBV is diverse depending on the culture condition. Stimulation with epidermal growth factor (EGF) was found to potentiate cell susceptibility to HBV infection. Here, we show that EGF receptor (EGFR) plays a critical role in HBV virion internalization. In EGFR-knockdown cells, HBV or its preS1-specific fluorescence peptide attached to the cell surface, but its internalization was attenuated. PreS1 internalization and HBV infection could be rescued by complementation with functional EGFR. Interestingly, the HBV/preS1–NTCP complex at the cell surface was internalized concomitant with the endocytotic relocalization of EGFR. Molecular interaction between NTCP and EGFR was documented by immunoprecipitation assay. Upon dissociation from functional EGFR, NTCP no longer functioned to support viral infection, as demonstrated by either (i) the introduction of NTCP point mutation that disrupted its interaction with EGFR, (ii) the detrimental effect of decoy peptide interrupting the NTCP–EGFR interaction, or (iii) the pharmacological inactivation of EGFR. Together, these data support the crucial role of EGFR in mediating HBV–NTCP internalization into susceptible cells. EGFR thus provides a yet unidentified missing link from the cell-surface HBV–NTCP attachment to the viral invasion beyond the host cell membrane.

Background Le Fort I osteotomy is one of the surgical procedures now routinely and safely performed. It is possible to move the maxilla in three dimensions, but it is necessary to separate the bones around the maxillary sinus. Therefore, with surgery, maxillary sinus mucosal thickening occurs. By knowing the changes in the sinus mucosa after surgery and the factors affecting it, it is possible to better predict the outcomes of surgery and contribute to safer surgery. In this study, thickening of maxillary sinus mucosa before and after surgery in Le Fort I osteotomy was evaluated using multidetector-row computed tomography (MDCT) images, and the changes in mucosal thickening and the related factors were examined. Methods Using MDCT images, the maxillary sinus mucosa of 125 patients who had undergone Le Fort I osteotomy was retrospectively evaluated before surgery, 1 month after surgery, and 1 year after surgery. On the MDCT images, the maxillary sinus was judged as mucosal thickening and classified into three grades according to the proportion occupying the maxillary sinus. In the evaluation of factors related to mucosal thickening, the following eight factors were examined: sex, age, diagnosis, operating time, amount of postoperative bleeding, with/without bone graft, with/without multisegmental osteotomy, and with/without macrolide therapy after surgery. Results The mean age at the time of surgery was 25.6 ± 8 years. Of all 125 patients, 66 had bilateral thickening, 19 had unilateral thickening, and 40 had no thickening. Factors that were significantly related to mucosal thickening were the operative time for the maxilla, bone grafts, and macrolide therapy after surgery. Conclusions Operative time for the maxilla, bone grafts, and macrolide therapy after surgery were found to be related to mucosal thickening. In addition, MDCT scanning 1 month after surgery was considered to be appropriate for evaluation of maxillary sinus mucosal thickening.

Hepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, from fish to human. Hepadnaviruses and their hosts have a long history of acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and their hosts. Here, we present evidence suggesting that the adaptive evolution of the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by virus infection. Evolutionary analysis of the NTCP-encoding genes from 20 mammals showed that most NTCP residues are highly conserved among species, exhibiting evolution under negative selection (dN/dS ratio [ratio of nonsynonymous to synonymous evolutionary changes] of 1). Notably, a substitution at amino acid (aa) 158, a positively selected residue, converting the human NTCP to a monkey-type sequence abrogated the capacity to support HBV infection; conversely, a substitution at this residue converting the monkey Ntcp to the human sequence was sufficient to confer HBV susceptibility. Together, these observations suggested a close association of the aa 158 positive selection with the pressure by virus infection. Moreover, the aa 158 sequence determined attachment of the HBV envelope protein to the host cell, demonstrating the mechanism whereby HBV infection would create positive selection at this NTCP residue. In summary, we provide the first evidence in agreement with the function of hepadnavirus as a driver for inducing adaptive mutation in host receptor. IMPORTANCE HBV and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary arms race between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidence supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species specificity.

Objectives Tokyo Dental College started oral cancer screening in cooperation with a local dental association in 1992. Reveal the usefulness of Countermeasure and Opportunistic Screening Systems for Oral Cancer. The actual results of countermeasure and opportunistic oral cancer screening systems are reported. Materials and Methods Countermeasure screening for the public was performed in each region, and opportunistic screening was performed in a general dental clinic of a cooperating physician. Results In countermeasure screening, 19,721 persons were checked from 1992 to 2018; the gender ratio was 1:3. The close examination rate was 4.45%. The detection rates of oral cancer and oral potentially malignant disorders were 0.13% and 1.85%, respectively. In opportunistic screening, 29,912 persons were checked from 2006 to 2018; the gender ratio was 2:3. The close examination rate was 2.33%. The detection rates of oral cancer and oral potentially malignant disorders were 0.08% and 2.15%, respectively. The close examination rate was significantly lower in opportunistic screening than in countermeasure screening. The oral cancer detection rates and the positive predictive value for cancer were equivalent. In addition, the detection rate of oral potentially malignant disorders was significantly higher in opportunistic screening than in countermeasure screening. Conclusion Oral cancer detection rates were equivalent between countermeasure and opportunistic screenings, and opportunistic screening were more effective on number of participants and the close examination rate, and the detection rate of oral potentially malignant disorders.

Hepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates from fish to human. Hepadnaviruses and their hosts have a long history of acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and their hosts. Here, we present evidence suggesting the adaptive evolution of the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by virus infection. Evolutionary analysis of the NTCP-encoding genes from 20 mammals showed that most NTCP residues are highly conserved among species, exhibiting evolution under negative selection (dN/dS < 1); this observation implies that the evolution of NTCP is restricted by maintaining its original protein function. However, 0.7 % of NTCP amino acid (aa) residues exhibit rapid evolution under positive selection (dN/dS > 1). Notably, a substitution at aa 158, a positively selected residue, converting the human NTCP to a monkey-type sequence abrogated the capacity to support HBV infection; conversely, a substitution at this residue converting the monkey Ntcp to the human sequence was sufficient to confer HBV susceptibility. Together, these observations suggested that positive selection at aa 158 was induced by virus infection. Moreover, the aa 158 sequence determined attachment of the HBV envelope protein to host cell, demonstrating the mechanism whereby HBV infection would create positive selection at this residue in NTCP. In summary, we provide the first evidence in agreement with the function of hepadnavirus as a driver for inducing an adaptive mutation in host receptor.ImportanceHepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection, while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidences supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species-specificity.

Sodium taurocholate cotransporting polypeptide (NTCP) is an entry receptor for hepatitis B virus (HBV) and is regarded as one of the determinants that confer HBV permissiveness to host cells. However, how host factors regulate the ability of NTCP to support HBV infection is largely unknown. We aimed to identify the host signaling that regulated NTCP expression and thereby permissiveness to HBV. Here, a cell-based chemical screening method identified that Ro41-5253 decreased host susceptibility to HBV infection. Pretreatment with Ro41-5253 inhibited the viral entry process without affecting HBV replication. Intriguingly, Ro41-5253 reduced expression of both NTCP mRNA and protein. We found that retinoic acid receptor (RAR) regulated the promoter activity of the human NTCP (hNTCP) gene and that Ro41-5253 repressed the hNTCP promoter by antagonizing RAR. RAR recruited to the hNTCP promoter region, and nucleotides -112 to -96 of the hNTCP was suggested to be critical for RAR-mediated transcriptional activation. HBV susceptibility was decreased in pharmacologically RAR-inactivated cells. CD2665 showed a stronger anti-HBV potential and disrupted the spread of HBV infection that was achieved by continuous reproduction of the whole HBV life cycle. In addition, this mechanism was significant for drug development, as antagonization of RAR blocked infection of multiple HBV genotypes and also a clinically relevant HBV mutant that was resistant to nucleoside analogs. Thus, RAR is crucial for regulating NTCP expression that determines permissiveness to HBV infection. This is the first demonstration showing host regulation of NTCP to support HBV infection.

Chronic hepatitis B virus (HBV) infection is a major public health problem worldwide. Although nucleos(t)ide analogs inhibiting viral reverse transcriptase are clinically available as anti-HBV agents, emergence of drug-resistant viruses highlights the need for new anti-HBV agents interfering with other targets. Here we report that cyclosporin A (CsA) can inhibit HBV entry into cultured hepatocytes. The anti-HBV effect of CsA was independent of binding to cyclophilin and calcineurin. Rather, blockade of HBV infection correlated with the ability to inhibit the transporter activity of sodium taurocholate cotransporting polypeptide (NTCP). We also found that HBV infection-susceptible cells, differentiated HepaRG cells and primary human hepatocytes expressed NTCP, while nonsusceptible cell lines did not. A series of compounds targeting NTCP could inhibit HBV infection. CsA inhibited the binding between NTCP and large envelope protein in vitro. Evaluation of CsA analogs identified a compound with higher anti-HBV potency, having a median inhibitory concentration

Hepatitis B virus (HBV) entry has been analyzed using infection-susceptible cells, including primary human hepatocytes, primary tupaia hepatocytes, and HepaRG cells. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) membrane transporter was reported as an HBV entry receptor. In this study, we established a strain of HepG2 cells engineered to overexpress the human NTCP gene (HepG2-hNTCP-C4 cells). HepG2-hNTCP-C4 cells were shown to be susceptible to infection by blood–borne and cell culture-derived HBV. HBV infection was facilitated by pretreating cells with 3% dimethyl sulfoxide permitting nearly 50% of the cells to be infected with HBV. Knockdown analysis suggested that HBV infection of HepG2-hNTCP-C4 cells was mediated by NTCP. HBV infection was blocked by an anti-HBV surface protein neutralizing antibody, by compounds known to inhibit NTCP transporter activity, and by cyclosporin A and its derivatives. The infection assay suggested that cyclosporin B was a more potent inhibitor of HBV entry than was cyclosporin A. Further chemical screening identified oxysterols, oxidized derivatives of cholesterol, as inhibitors of HBV infection. Thus, the HepG2-hNTCP-C4 cell line established in this study is a useful tool for the identification of inhibitors of HBV infection as well as for the analysis of the molecular mechanisms of HBV infection.

Background: Cytokines and host factors triggering innate immunity against hepatitis B virus (HBV) are not well understood. Results: IL-1 and TNFα induced cytidine deaminase AID, an anti-HBV host factor, and reduced HBV infection into hepatocytes. Conclusion: IL-1/TNFα reduced host susceptibility to HBV infection through AID up-regulation. Significance: Proinflammatory cytokines modulate HBV infection through a novel innate immune pathway involving AID., Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.

A schwannoma is a benign tumor composed of schwann cells which forms on the periphery of nerves. We report a case of a schwannoma derived from a lingual nerve occurring in the floor of the mouth. The patient was a 27-year-old woman who presented with the complaint of a swelling in the floor of the mouth. It is difficult to distinguish a swelling from a sublingual gland tumor, cyst, or malignant tumor by MRI alone. Therefore, a biopsy and cytological examination were performed one week prior to surgery to determine whether the growth represented a malignancy. The results revealed a class II growth which was suspected to be a schwannoma. Intraoperatively, it became clear that the tumor and lingual nerve were inseparable, making excision of the nerve unavoidable. On the other hand, there was a clear border between the tumor and the sublingual gland, so it was possible to preserve the sublingual gland. In the postoperative pathological diagnosis, a definitive diagnosis was difficult based solely on H-E staining. Therefore, immunohistochemical staining was performed, resulting in a diagnosis of schwannoma. Currently, the patient is still being followed up. The results of this case indicate that preoperative aspiration biopsy cytology is useful in deciding the operative method to be employed.

Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps). These cells were susceptible to HBV infection, produced HBV particles and maintained innate immune responses. The infection efficiency of HBV in iPS-HPCs predominantly depended on the expression levels of sodium taurocholate cotransporting polypeptide (NTCP) and was low relative to iPS-Heps: however, long-term culture of iPS-Heps was difficult. To provide a model for HBV persistence, iPS-HPCs overexpressing NTCP were established. The long-term persistence of HBV cccDNA was detected in iPS-HPCs overexpressing NTCP and depended on the inhibition of the Janus-kinase signaling pathway. In conclusion, this study provides evidence that iPS-derived hepatic cell lines can be utilized for novel HBV culture models with genetic variation to investigate the interactions between HBV and host cells and the development of anti-HBV strategies.

本研究は, 厨芥のメタン発酵処理を高負荷処理することを目的とし, 水熱反応処理を前処理としたメタン発酵法を開発した。厨芥の水熱反応処理特性に及ぼす処理条件の影響およびメタン発酵の処理性に及ぼす水熱反応処理の影響を検討した結果, 以下の知見が得られた。 (1) 厨芥の水熱反応処理は, 処理温度が高いほど固形物の可溶化が短時間で進むことが確認された。ただし, 処理温度が高いほどガス化による溶存成分の減少が, 可溶化による増加を短時間で上回ることが確認され, DOCが最大となる処理条件は, 160℃, 60minであり, 処理前の1.5倍程度まで増加した。 (2) 粉砕処理のみの厨芥と水熱反応処理した厨芥のメタン発酵処理実験を行い, 処理性を比較した結果, HRT20日では, 大きな違いがみられなかった。しかし, HRT10日では, 水熱反応処理を行うことによりSS, POC, TOC分解率において10～15%程度の向上効果が確認された。また, 粉砕処理のみでは運転の困難であったHRT5日においても, 水熱反応処理を用いることによりSS, POC, TOC分解率がそれぞれ69, 74, 72%で処理が可能となり, 水熱反応処理の利用によるHRT短縮の可能性が示された。

Mucoepidermoid carcinomas in the minor salivary glands usually originate in the palatine gland, and their occurrence in the retromolar region is rare. We report a rare case of mucoepidermoid carcinoma with clear cell components occurring in the retromolar region. The patient was a 63-year-old woman referred to our hospital with the chief complaint of a painless mass in the right retromolar region initially found during treatment at a local dental clinic. The 20×10-mm mass was well-defined, elastic, and flexible. The surface of the mucosa was healthy. The mass was clinically diagnosed as a gingival benign tumor in the right retromolar region. There were no significant findings in the patient's medical history. The tumor was resected under local anesthesia. Histopathology revealed that squamoid cells, undifferentiated intermediate cells, and clear cells were dominant, with mucus-producing cells in some areas. A mucoepidermoid carcinoma with clear cell components was diagnosed. There were no signs of recurrence or metastasis at 15 months postoperatively and the patient's progress has been satisfactory. Because the tumor was a painless, slow-growing mass, it was clinically diagnosed as a benign tumor of the gingiva, and resection was performed under local anesthesia without performing a biopsy. However, even if a mass in the retromolar region is clinically diagnosed as a benign tumor, the course of treatment should be decided after performing fine-needle aspiration cytology, taking into consideration the possibility of mucoepidermoid carcinoma.

The Frequency with which impacted supernumerary teeth are encountered in a clinical setting is relatively high, with the majority of such cases occurrig in the median maxillary region, and very few in the molar region. In the molar region, mandibular distomolars (fourth molars) are very rare. Although a small number of case reports have described impacted supernumerary distomolars, very few have compared third molars and distomolars. Herein, the authors report two cases involving mandibular distomolars and one case a maxillary distomolar. In each of these cases, the third molar and distomolar were extracted and a macroscopic morphological analysis conducted. The results were then compared with those of the latest available literature.

Cataract is one of the most typical age-related eye diseases. As a cataract progress, the crystalline lens becomes hazier and visual ability deteriorates. Since the main cause of visual impairment is light scattered by the hazy lens, both brighter environments and hazier lenses worsen visual ability. In this study, error scores of 50 Hue test were measured for pseudo-cataract subjects (young observer with foggy filters of known as haze factor) when the intensity of scattering light was increased. The rate of increase in error score of 50 Hue test was larger with higher haze factor. We propose, as an easy method for assessing the progress of a cataract, the haze estimation of elderly crystalline lens using the obtained error scores of 50 Hue test as a function of the intensity of scattering light.

not Available.

2017