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Hisako Karube, Koju Kamoi, Kyoko Ohno-Matsui Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Background: Ocular symptoms in Behçet’s disease (BD) begin mostly before 30 years of age according to international surveys, and BD activity may decrease with age. Information regarding the treatment of ocular symptoms in elderly BD patients is thus scant. Anti-TNFα antibody has recently demonstrated strong effects against recurrent uveitis in BD, but the efficacy and safety of anti-TNFα therapy in elderly patients remain unclear. We report herein the case of an elderly patient with long-standing uveitis due to BD who was successfully treated with two types of anti-TNF therapy. Case: An 81-year-old Japanese man presented with a 33-year history of ocular inflammation due to BD. As immunosuppressive agents, such as cyclosporine A, were difficult to use because he had undergone removal of the left kidney due to cancer, he was treated with colchicine. However, attacks of ocular inflammation persisted around nine times a year. After colchicine had been changed to infliximab, ocular inflammation was fairly well controlled, but ocular attacks still occurred once or twice a year. As soon as intestinal hemorrhage related to BD occurred, infliximab was switched to adalimumab. After this switch, ocular attacks resolved and visual acuity was maintained at 1.0. Intestinal lesions were also well controlled, and no side effects were seen. Conclusion: This represents the first report of the application of two types of anti-TNFα therapy for ocular attacks in an elderly BD patient. In addition to infliximab, adalimumab appears to offer an alternative therapy for refractory, long-standing BD-related uveitis in elderly patients. Keywords: Behçet’s disease, anti-tumor necrosis factor-α antibody, infliximab, adalimumab, elderly patient

Chronic hepatic encephalopathy (CHE) is a neurological syndrome caused by liver disease. It results when products of digestion escape breakdown by liver processes and enter the circulation. Ammonia, a product of protein metabolism, is a probable contributor to CHE. CHE is usually treated by restricted dietary protein and by lactulose, a synthetic sugar that alters colonic bacteria and is a cathartic, but such treatment is not always effective. Vancomycin, an antibiotic, has previously been shown to be effective in treating CHE. The effects of vancomycin on 12 patients with cirrhosis and lactulose-resistant CHE was studied. Encephalopathy resolved completely in 10 patients within two to three days, and only minimum grade encephalopathy persisted in the other patients. When patients who had improved were given lactulose again, and vancomycin was not use, their condition worsened. The medical improvement correlated with a decrease in blood ammonia levels and colonic anaerobic bacteria. The study suggests that the colonic bacteria may be responsible for a large part of the ammonia levels found in encephalopathy. Other mechanisms may also be important in the disorder as well. Further study is needed to determine why vancomycin is so effective in treating lactulose-resistant CHE. (Consumer Summary produced by Reliance Medical Information, Inc.)

Preventing the occurrence of high-rank multiple pregnancies without reducing the pregnancy rate remains a high priority of in-vitro fertilization and embryo transfer programmes. Our previous study demonstrated that, if there is at least one embryo with a good morphological grade, then the transfer of two (a double embryo transfer) instead of three embryos does not result in a lower pregnancy rate, and that the influence of the number of embryos transferred becomes significant only when poor-quality embryos are transferred. This result allowed us to employ the simple policy of systematically selecting double embryo transfer cycles without affecting the pregnancy rate. Since January 1994, when patients < 37 years of age had more than two embryos available for transfer, only two instead of three embryos were transferred if at least one of the embryos demonstrated a good morphological grade. After a 1 year application of this policy, of the 147 cycles (group A) that fulfilled the above criteria, two embryos were transferred in 92 cycles, while three embryos were transferred in the other 55 cycles. The results of these cycles were compared to those of the control 144 cycles (group B) in which three embryos were transferred, prior to the application of this policy. The on-going pregnancy rates and the incidence of multiple and triplet pregnancies were 24% and 28%, 22% and 23%, and 2% and 9% in groups A and B respectively. The rates were not significantly different. In conclusion, although our prospective trial demonstrated a tendency of decreasing pregnancy rate and an invariable incidence of multiple pregnancies, the very low occurrence of triplets during this period indicated that this policy provided a practical compromise between achieving a high pregnancy rate and an acceptable incidence of triplet pregnancies. [ABSTRACT FROM AUTHOR]

This study was aimed at assessing the outcome of in-vitro fertilization (IVF) and embryo transfer in patients with polycystic ovarian syndrome (PCOS). The results of IVF and embryo transfer in PCOS patients (PCOS group, 78 cycles of 26 patients) were compared with those of a control group (423 cycles in 202 patients without male factor; age and ovarian stimulation protocol were matched). Although the pregnancy rate per transfer was not different in the two groups of patients (25 versus 34%, PCOS versus control group), the PCOS group had a significantly lower pregnancy rate per follicle aspiration (19 versus 31%, P < 0.05). A notable result was a significantly higher incidence of embryo transfer cancellations in the PCOS group (22 versus 8%, P < 0.01), which resulted from unpredictable failure of either oocyte recovery or fertilization. The incidence of unexplained complete failure of fertilization was significantly higher in the PCOS group (18 versus 5%, P < 0.01). These results may reflect a reduced quality of the oocytes in the PCOS group, and there was a subgroup of PCOS patients who repeatedly produced poor results of treatment. Although the ovarian stimulation regimen best suited to PCOS patients remains to be determined, special care should be taken during ovarian stimulation, especially when the PCOS patients had experienced unexplained failure of oocyte recovery or fertilization in the previous treatment cycle(s). [ABSTRACT FROM AUTHOR]

Introduction: HTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1-associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti-vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF 165 , the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF 165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro ., Methods: We used MT2 and TL-Om1 cells as HTLV-1-infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1-infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments., Results: Anti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1-infected T cells., Conclusion: This preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1-related inflammation and thus may be safe for use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MM declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2023 Zong, Kamoi, Kurozumi-Karube, Zhang, Yang and Ohno-Matsui.)

Human T-cell lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified as the causative agent of human diseases, such as adult T-cell leukemia, HTLV-1-associated myelopathy, and HTLV-1 uveitis (HU). HU is one of the most frequent ocular inflammatory diseases in endemic areas, which has raised considerable public health concerns. Approximately 30% of HU patients develop secondary glaucoma, which is higher than the general uveitis incidence. We therefore investigated the mechanism underlying the high incidence of glaucoma secondary to HU in vitro. After contact with HTLV-1-producing T cells (MT-2), human trabecular meshwork cells (HTMCs) were infected. The infected cells increased in number, and nuclear factor (NF)-κB expression was activated. Contact between MT-2 cells and HTMCs resulted in significantly upregulated production of inflammatory cytokines, such as IL-6, and chemokines, such as CXCL10, CCL2, and CXCL-8. These findings indicate that the mechanism underlying secondary glaucoma in HU may involve proliferation of trabecular meshwork tissue after contact with HTLV-1-infected cells, resulting in decreased aqueous humor outflow. Upregulated production of inflammatory cytokines and chemokines simultaneously disrupts the normal trabecular meshwork function. This mechanism presumably leads to increased intraocular pressure, eventually resulting in secondary glaucoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zong, Kamoi, Ando, Kurozumi-Karube and Ohno-Matsui.)

HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves' disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.

Twelve Planaeschna McLachlan, 1895 species recorded in Vietnam are presented and their subgroupings based on nuclear DNA analysis are discussed. Three new species are described (Planaeschna crux sp. nov. [holotype: Pia Oac NP, Cao Bang Prov.], Planaeschna samurai sp. nov. [holotype: Khau Pha, Tu Le, Yen Bai Prov.] and Planaeschna tsuchi sp. nov. [holotype: Xuan Son NP, Phu Tho Prov.]. Planaeschna celia Wilson Reels, 2001 is recorded from Vietnam for the first time. Planaeschna guentherpetersi Sasamoto, Do Vu, 2013 is shown to be a subspecies of Planaeschna ishigakiana Asahina, 1951. The female of Planaeschna cucphuongensis Karube, 1999 is described for the first time. Additional records are provided for Planaeschna asahinai Karube, 2011, Planaeschna tamdaoensis Asahina, 1996, Planaeschna tomokunii Asahina, 1996, and Planaeschna viridis Karube, 2004. Lastly, the females of two unidentified Planaeschna spp. are illustrated. Information on the ecology of all species is provided.

Chlorogomphus danhkyi sp. nov. (Holotype ♂: Khe Ro, Vu Quang National Park, Ha Tinh Province, 15.0444 N, 107.9270 E, altitude 1480 m) based on both sexes is described. The new species differs from Chlorogomphus piaoacensis Karube, 2013 mainly by the shape of male cerci. Other species of Chlorogomphus Selys, 1854 from Vu Quang National Park are also recorded.

Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro . We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kurozumi-Karube, Kamoi, Ando, Uchida, Hamaguchi and Ohno-Matsui.)

Infliximab (IFX) was the first biologic introduced for refractory uveitis treatment in Behçet's syndrome (BS). However, there have been few reports on the safety and efficacy of IFX monotherapy over follow-up periods of more than 10 years. This retrospective study evaluated the 10-year safety and efficacy of IFX monotherapy compared to IFX combination therapies with colchicine or corticosteroid for refractory uveitis in BS patients. Monotherapy was performed in 30 eyes of 16 patients while combination therapies were performed in 20 eyes of 11 patients. Continuation of IFX occurred in 70.3% of enrolled patients for 10 years without any significant difference noted in the retention rate between the monotherapy and combination therapies (p = 0.86). Reduction of ocular inflammatory attacks and improvement of best corrected visual acuity occurred in the monotherapy group after 10 years, which was equivalent to that for the combination therapies. Although adverse events (AEs) or therapy discontinuation occurred during the initial 5 years in both therapies, no AEs were observed for either therapy after 6 years. Our results suggested that IFX monotherapy proved to be effective and not inferior to combination therapies over a 10-year follow-up. Although loss of response and AEs may be noticed during the initial 5-year period, a safe and effective continuation can be expected thereafter.

Rationale: Proliferation of retinal pigment epithelium (RPE) is typically observed in limited ocular disorders, in connection with the local mechanism of RPE proliferation-mediated wound repair. Bilateral and diffuse type RPE proliferation is considered to be associated with paraneoplastic syndromes, such as a bilateral diffuse uveal melanocytic proliferation. However, other reported diseases that induce bilateral diffuse RPE proliferation are quite rare, especially for patients who are considered to have a non-malignant status., Patient Concerns: The bilateral eyes of a 47-year-old woman with bilateral ocular inflammation, presented united multiple small to medium white retinal lesions during the disease progress., Diagnoses: Optical coherence tomography showed scattered serous retinal detachments, choroidal folds, choroidal thickening and diffuse RPE proliferation. As autofluorescence and angiography showed a "giraffe pattern", bilateral diffuse uveal melanocytic proliferation was suspected. However, systemic investigations identified no malignancy. In consideration of the above findings, choroidal inflammation was thought to be the major cause of this condition., Interventions: The patient was administered intensive systemic steroids. Over the next 2 months, the amount of steroid was tapered off., Outcomes: After administration, the bilateral diffuse RPE proliferation settled down. During the 2-year follow-up, there was no recurrence of ocular inflammation and diffuse RPE proliferation, or any other malignancy found., Lessons: This finding demonstrates that bilateral diffuse RPE proliferation can be generated as a secondary phenomenon of choroidal inflammation in patients with a non-malignant status.

Use of biologics has been widely advocated for inflammatory diseases recently. Anti-tumor necrosis factor (TNF)-α antibody therapy is reportedly effective against ocular inflammation. However, side effects of TNF-α inhibition have been reported, particularly in the form of exacerbation of infections such as tuberculosis. Paradoxical reactions such as exacerbated inflammation are also well known. Around 20 million humans are infected with human T-cell leukemia virus type 1 (HTLV-1) globally, and this virus can cause adult T-cell leukemia, HTLV-1-associated myelopathy and HTLV-1 uveitis. As for ophthalmic concerns, it has not been identified whether anti-TNF-α antibody stimulates HTLV-1-infected cells and ocular cells to induce HTLV-1 uveitis in HTLV-1 carriers. Here we investigated the effects of anti-TNF-α antibody on ocular status under HTLV-1 infectious conditions using ocular cells and HTLV-1-infected cells in vitro . We used the ARPE-19 human retinal pigment epithelial cell line as ocular cells considered to play an important role in the blood-ocular barrier, and the MT2 HTLV-1-infected cell line. Jurkat cells were used as controls. Infliximab (IFX) was used as an anti-TNF-α antibody to achieve TNF-α inhibition. We evaluated the production of inflammatory cytokines and intercellular adhesion molecule (ICAM)-1, proliferation of ARPE-19, expression of TNF-α receptor (TNF-R) and HTLV-1 proviral DNA, and the percentage of apoptotic ARPE-19. Inflammatory cytokines such as interleukin (IL)-6, IL-8, TNF, and ICAM-1 were significantly elevated through contact between ARPE-19 and MT2. Treatment with IFX tented to inhibit TNF production, although the level of production was low, but changes in IL-6, IL-8, and ICAM-1 remained unaffected. Expression of TNFR was unaltered by IFX treatment. HTLV-1 proviral DNA was not significantly changed with treatment. No change in cell growth rate or apoptotic rate of ARPE-19 was seen with the addition of IFX. In conclusion, IFX did not exacerbate production of inflammatory cytokines, and did not affect expression of TNFR, proliferation of ARPE-19, HTLV-1 proviral load, or apoptosis of ARPE-19. These results suggest that IFX does not exacerbate HTLV-1-related inflammation in the eye and represents an acceptable treatment option under HTLV-1 infectious conditions., (Copyright © 2019 Uchida, Kamoi, Ando, Wei, Karube and Ohno-Matsui.)

A new species of the genus Ochthebius , O. (O.) sasakii sp. nov. , is described from the Ogasawara Islands, Japan, with a description of the larva. This record is the first of the family Hydraenidae from the Ogasawara Islands. This species belongs to the punctatus species group and is similar to two Japanese species, O. (O.) inermis Sharp, 1884 and O. (O.) danjo Nakane, 1990, but it differs from them in both adult and larval characters. The larva of O. (O.) inermis is also described for comparison.

Heliogomphus bidentatus sp. nov. (holotype male: Tam Dao National Park, Vinh Phuc Prov., northern Vietnam) is described from north and central Vietnam. This new species is similar to H. scorpio (Ris, 1912), but can be separated by the coloration of the thorax and details of the male caudal appendages. Information on its biology and ecology is provided.

Oncolytic virus therapy (OVT) represents a new class of therapeutic agents in cancer treatment. The molecular and cellular mechanisms of action of OVTs have been evaluated in nonclinical/clinical phase trials. Various genetically modified viruses have been developed as oncolytic agents, and the first approval of an OVT for clinical use was issued by the US Food and Drug Administration in 2015. In this context, more and more clinical development of OVTs is anticipated in the future. This article provides a risk assessment of OVT based on the safety data obtained from all clinical trials to date using a publicly available database. The most common adverse events (AEs) observed in clinical trials have been infection-related symptoms such as fatigue, chills, fever, and nausea; few serious AEs have been observed, regardless of the kind of virus or transfected genes. In vivo systemic infusion of OVTs demonstrated a high percentage of AEs, but most AEs were manageable using common drugs. This paper describes OVTs' specific safety/toxicity profiles and encourages the performance of further clinical trials of OVTs to address the most serious challenges anticipated in the development of OVTs as a new class of drugs for the treatment of cancer.

Chlorogomphus canhvang sp. nov. [holotype male: Along QL15, Quang Binh Province (appr. 17.488 N, 106.302 E), 6.V.2016] is described from the Truong Son Mountains (Quang Binh and Thua Thien-Hue Provinces) in central Vietnam. Detailed differences are given to distinguish the new species from the very similar C. auratus Martin, 1910 for both males and females, and information on its ecology is provided.

23 species of Euphaeidae (Odonata: Zygoptera) are reported from Vietnam including two new species of Euphaea, E. saola Phan Hayashi, sp. nov. and E. sanguinea Kompier Hayashi, sp. nov., and four species not recorded previously, Bayadera continentalis Asahina, 1973, B. hyalina Selys, 1879, B. nephelopennis Davies Yang, 1996 and Euphaea pahyapi Hämäläinen, 1985. The females of Anisopleura bipugio Hämäläinen Karube, 2013, Bayadera serrata Davies Yang, 1996 and Euphaea hirta Hämäläinen Karube, 2001 are described for the first time. The mutual taxonomic status of Bayadera hyalina and B. strigata Davies Yang, 1996 is discussed. Distribution maps of all known Vietnamese species, with detailed distribution records, are provided.

Descriptions are given of two new species of Calicnemia: C. akahara sp. nov. from central and southern Vietnam and C. hamata sp. nov. from central Laos. C. soccifera Yu & Chen, 2013, and C. haksik Wilson & Reels, 2003, are recorded for the first time from Vietnam; C. uenoi Asahina, 1997, is redescribed with new illustrations provided of its anal appendages and genital ligula; and the occurrence of C. mortoni (Laidlaw, 1917) in Vietnam is discussed.

Background: Carcinoma of unknown primary site (CUP) is said to account for approximately 3 to 5% of all carcinomas. However, an isolated lesion in the abdominal cavity is rare, and there are no reports describing associated abscess formation., Case Presentation: A 76-year-old woman had consulted a previous physician complaining of fever and right lower quadrant abdominal pain. Enhanced computed tomography (CT) showed an abscess formation around the cecum. She was treated conservatively with antibiotics, but the symptoms relapsed and she consulted our hospital. Enhanced CT showed a persistent abscess, a tumorous lesion in the mesentery and right hydronephrosis. Because malignancy could not be ruled out, surgical treatment was selected. At laparotomy, encapsulated abscesses were found on the mesenteric side and outside of the ileocecal region. When we raised the ileocecal region, a tumor was found to be fixed to the right ureter, and there was leakage of white, solid tumor content. This tumor content was submitted to intraoperative frozen section diagnosis which revealed a carcinoma. Ileocecal resection with D3 lymph node dissection and retroperitoneal tumor resection was thus performed. There were no abnormal findings in the uterus and adnexa, nor any evidence of peritoneal dissemination. We regarded this case as an incomplete resection and chemotherapy with paclitaxel and carboplatin was administered. The patient has remained alive and disease-free for almost one year since the primary operation., Conclusion: We described a case with mesenteric CUP discovered during surgery for an intra-abdominal abscess. It is necessary to pay attention to treatment-resistant intraperitoneal abscesses as they may accompany a tumor.

Objective: The aim of this study is to clarify the effects of zinc chloride (ZnCl2) exposure on the induction of heme oxygenase-1 (HO-1) expression and its regulatory mechanisms in MDPC-23 mouse odontoblast-like cells., Methods: MDPC-23 cells were incubated with ZnCl2, and the levels of HO-1 protein, phosphorylated forms of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, and phosphorylated forms of amino kinase terminal (Akt) and nuclear factor-κB (NF-κB) p65 were determined with western immunoblotting. The level of HO-1 mRNA was determined with RT-PCR analysis. After pretreatment with inhibitors of ERK, JNK, p38, phosphoinositide-3 kinase (PI3K), and NF-κB, HO-1 protein level was determined in MDPC-23 cells exposed to ZnCl2., Results: Following exposure to 500μM ZnCl2, the levels of both HO-1 mRNA and protein were markedly increased. The phosphorylated forms of ERK, JNK, and p38 increased after ZnCl2 exposure. Furthermore, the expression of HO-1 was markedly suppressed by treatment with the p38 inhibitor, SB203580, and mildly suppressed by the MAPK/ERK kinase inhibitor, U0126. However, treatment with the JNK inhibitor, SP600125, did not suppress ZnCl2-induced HO-1 expression. In addition, the phosphorylated forms of Akt, a downstream kinase of PI3K, and NF-κB p65 increased after ZnCl2 exposure. Treatment with the PI3K inhibitor, LY294002, and the NF-κB inhibitor, Bay11-7082, suppressed ZnCl2-induced HO-1 expression., Conclusion: These results suggest that ZnCl2 exposure induces HO-1 expression via multiple intracellular signalling pathways, including p38, ERK, PI3K/Akt, and NF-κB, in this odontoblast-like cell line., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Exposure of alpha-synuclein (alphaS), a major component of Lewy bodies in Parkinson's disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble alphaS oligomers. Here, we demonstrate that PUFA binds recombinant alphaS protein through its N-terminal region (residues 2-60). In HEK293 cells, alphaS mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced alphaS oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of alphaS; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization.

Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of alpha-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with alpha-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of alpha-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

POEMS syndrome is a rare plasma cell disorder, characterized by polyneuropathy, organomegaly, endocrinopathy, serum monoclonal protein, and skin lesions. Although not included in the acronym, renal lesions also are characteristic of this disease and sometimes require dialysis therapy. We treated a 61-year-old woman with POEMS syndrome with high-dose melphalan therapy (HDT) supported by autologous blood stem cell transplantation (SCT), and clinical remission was achieved. A repeated renal biopsy showed the striking effectiveness of this therapy on renal lesions. Pathological features of the renal lesions, such as membranoproliferative glomerulonephritis-like lesions, microangiopathic glomerulopathy, and mesangiolytic lesions with microcapillaries, almost completely disappeared. This treatment also markedly decreased serum levels of vascular endothelial growth factor (VEGF). These findings indicate that HDT with SCT is effective, even on renal lesions in patients with POEMS syndrome, and suggest that high serum VEGF concentrations are associated closely with the development of renal lesions in patients with this type of plasma cell disorder.

Background/aims: Pelvic autonomic nerve preservation for rectal cancer has become more common in recent years. Therefore, we evaluated the usefulness of bipolar scissors for this procedure., Methodology: This study included 30 consecutive patients with lower rectal cancer who underwent pelvic autonomic nerve preservation at our hospital between April 1998 and August 2001. The bipolar scissors group comprised 10 patients who received the procedure using bipolar scissors, while the conventional group included 20 patients who received the procedure without the use of bipolar scissors. The two groups were compared in terms of operating time, blood loss, postoperative urinary and sexual function., Results: Blood loss in the bipolar scissors group was 394.4 +/- 201.8mL, which was a significantly lower volume than that in the conventional group (881.8 +/- 582.9ml) (p=0.0049). All the patients in the bipolar scissors group (10/10=100%) and 19 cases in the conventional group (19/20=95.0%) answered that they were satisfied with the results of their voiding function. In the bipolar scissors group, 100% were capable of erection (5/5) and 80.0% preserved ejaculation (4/5). In the conventional group, 100.0% (10/10) and 77.8% (7/9) preserved erection and ejaculation, respectively., Conclusions: The use of bipolar scissors is quite beneficial when patients with rectal cancer receive pelvic autonomic nerve preservation.

A 41-year-old man was found to have advanced gastric cancer with simultaneous multiple bone metastases when pyloric stenosis was being diagnosed in our hospital. We performed gastrojejunostomy from the lower third of the stomach to the upper third of the duodenum to relieve the obstruction. However, at 8 days after surgery, disseminated intra-vascular coagulation (DIC) occurred. Therefore, the patient was administered combined chemotherapy with TS-1 plus low-dose cisplatin in addition to anti-DIC therapy. TS-1 (150 mg/day) and cisplatin (10 mg/body intravenously over the course of 30 minutes) were administered on days 1 to 5, 8 to 12, and 15 to 19 (weekday-on/weekend-off schedule). There was remarkable response to this chemotherapy, and the patient was shifted from inpatient to outpatient treatment. The treatment course was repeated for 4 cycles until remission was observed. Because of hematologic relapse due to DIC at 6 months after the first treatment, he was readmitted for administration of combined chemotherapy. Fortunately, DIC once again responded to the same chemotherapy regimen. In this pathologic condition, combined chemotherapy is unavoidable when DIC occurs with cancer. Accordingly, it is necessary that an effective combined chemotherapy with mild bone marrow suppression be chosen. A companion drug should be chosen in consideration of delayed homo-toxicity and of the possibility of relapse into DIC in the drug withdrawal period. In addition, it is indispensable that careful consideration be given to the most favorable dose and regimen.

The patient was a 50-year-old female with peritoneal metastasis of Type 4 gastric cancer. She underwent a relative curative resection with total gastrectomy and peritonectomy. Postoperative chemotherapy with 5'-DFUR following 5-FU and CDDP was performed. Thirteen months after surgery, cancer recurrence was suspected due to elevated levels of the serum tumor markers carcinoembryonic antigen (8.9 ng/ml) and alpha fetoprotein (85.8 ng/ml). She was additionally treated with UFT 300 mg/day and Lentinan 2 mg/week. The serum tumor markers decreased gradually returned to normal levels. At 5 years and 8 months after surgery, she is alive without any sign of recurrence.

A 66-year-old man was found to have both advanced cancer of the middle thoracic esophagus and advanced cancer of the middle third of the stomach with paraaortic lymph node metastases. The prognosis was poor because of local advanced disease and distant metastasis. The patient was therefore given combined chemotherapy with TS-1 and cisplatin. TS-1 (80 mg/day) was administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 (weekday-on/weekend-off schedule), and cisplatin (70 mg/m2 intravenously over the course of 2 hours) was administered on days 1 and 15 of a 28-day cycle. After 2 courses of chemotherapy the esophageal lesion had a complete response, and the gastric lesion had a partial response (reduction ratio, 71.4%). However, stomatitis and anorexia of grade 2 (NCI-CTC) occurred. Two courses of TS-1 alone (80 mg/m2) were therefore given. The esophageal lesion continued to show a complete response and the gastric lesion a partial response (reduction ratio, 85.7%). There was no change in the para-aortic lymph node metastasis (No. 16a2 latero). No adverse reaction to chemotherapy was severer than grade 3, and a good response was obtained. These findings indicate that chemotherapy with a combination of TS-1 and cisplatin is effective against advanced esophageal cancer and advanced gastric cancer.

Objective: The role of E-cadherin in the metastatic process remains controversial. In this study, we examined what role E-cadherin plays in relation to tumor size and microvessel density (MVD) of the liver metastatic lesion., Materials and Methods: In F344 male rats, metastatic lesions were made by injecting RCN-9 cells into the spleen. We performed an immunohistochemical evaluation of E-cadherin and MVD in the metastatic lesions. According to a previous report, we focused on tumor sizes ranging from 2 to 3 mm, and the metastatic nodules were divided into two groups considering the value of the MVD., Results: The expression of E-cadherin was inversely proportional to tumor size (r = -0.882, P < 0.0001). MVD was directly proportional to metastatic tumor size (r = 0.726, P = 0.001). MVD in group A, in which the tumor size was 2.3 mm or more, was significantly higher than that in group B, in which the tumor size was less than 2.3 mm (3.13 +/- 1.65% vs 1.75 +/- 0.27%; P = 0.0069). The expression ratio of E-cadherin in group A was 28.21 +/- 16.36%, while it was 82.33 +/- 16.35% in group B (P = 0.0003)., Conclusion: In liver metastasis, E-cadherin's function is preserved when the tumor is small and E-cadherin's expression is reduced in large tumors in which neovascularization is increased.

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Background/aims: We have demonstrated that colorectal cancer with fatty liver had few liver metastases clinically as well as experimentally. In this study, to clarify why colorectal cancer with fatty liver had few liver metastases, we focused on the angiogenesis of carcinomas., Methodology: The rat colon cancer cells (RCN-9) were injected into 40 rats (the fatty liver group = FL group includes 20 rats, the non-fatty liver group = NFL group includes 20 rats). In each group, the PyNPase (pyrimidine nucleoside phosphorylase) activity in the metastatic lesion of the liver was examined using the high-performance liquid chromatographic method. In addition, the microvessel density in the metastatic lesion of the liver was assessed by Von Willebrand factor-related antigen immunostaining., Results: 1) The PyNPase activity in the FL group was 33.34 +/- 6.27 (microgram FU/mg protein/hr), which was significantly lower than that of the NFL group (49.30 +/- 14.82) (P = 0.0021). 2) Microvessel density in the FL group was 1.845 +/- 0.357 (%), while that in the NFL group was 2.777 +/- 1.371 (%). The microvessel density of the FL group was significantly lower than that of the NFL group (P = 0.0365). 3) The regression coefficient between PyNPase activity and microvessel density was 0.480, which indicated a significant correlation (P = 0.0098)., Conclusions: We think that, in colorectal carcinomas with fatty liver, the decreased activity of PyNPase and the decreased neovascularization in the metastatic lesion are closely related to fewer liver metastasis compared with colorectal cancer patients without fatty liver.

Gallium arsenide (GaAs), a chemical compound of gallium and arsenic, causes various toxic effects including pulmonary diseases in animals. Since the toxicity is not completely investigated, GaAs has been used in workplaces as the material of various semiconductor products. The present study was conducted to clarify the toxicity of GaAs particles in the alveolar macrophages of hamsters using magnetometry, enzyme release assays and morphological examinations. Alveolar macrophages obtained from hamsters by tracheobronchial lavage and adhered to the disks in the bottom of wells were exposed to ferrosoferric oxide and GaAs particles. Ferrosoferric oxide particles were magnetized externally and the remanent magnetic field was measured. Relaxation, a fast decline of the remanent magnetic fields radiated from the alveolar macrophages, was delayed and decay constants were decreased dose-dependently due to exposure to GaAs. Because the relaxation is thought to be associated with cytoskeleton, the exposure of GaAs may have impaired the motor function of them. Enzyme release assay and morphological findings indicated the damage to the macrophages. Thus the cytotoxicity causes cytostructural changes and cell death. According to DNA electrophoresis and the TUNEL method, necrotic changes occur more frequently than apoptotic changes.

Dogs were exposed to 1% (v/v) (10,000 ppm) vapor of 1,1,1-Trichloroethane (1,1,1-TCE) by inhalation for 3 min repeated four times at 4 hr intervals under continuous anesthesia. Changes in the 1,1,1-TCE concentration in blood with time, as well as distribution of 1,1,1-TCE in the organs and tissues (lungs, liver, kidneys, heart, brain, and fat around the kidneys and on the abdominal wall) upon completion of the four exposures were studied. Concentrations of 1,1,1-TCE in blood showed the highest level immediately after exposure, and fairly decreased in about 30 min after exposure. The half life of 1,1,1-TCE in blood was 4-12 min after exposure. Upon completion of the exposures (3 min inhalations repeated four times), 1,1,1-TCE concentrations per gram wet weight of each organ ranged from 0.1 to 0.5 microgram/g in the lungs, liver, kidneys, heart and brain. On the other hand, the 1,1,1-TCE concentration in fat ranged from 16.9 to 54.6 micrograms/g, greatly exceeding those in other organs.

Regarding colophony, the use in industries, adverse effects, diagnosis, pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture of resin acids as like abietic acid and neutral substances. Colophony is used everywhere, in industry, daily life and medical supplies. Soldering workers are exposed to the colophony fumes heated up to the temperature of soldering irons. The effects of exposure to colophony are classified into bronchial asthma and contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific irritation. Inhalation challenge test and repeated spirometry during working day may help the diagnosis of colophony induced asthma. Improvement of working environment for soldering and development of new flux instead of colophony will be necessary. A study on contact dermatitis revealed that colophony and its related compounds are one of major causes for contact dermatitis. Cases of dermatitis by depilatory agents used to remove hair from slaughtered swine, anti-slipping cream for ballet shoes or resin for cello strings have been reported. Patch test may contribute to the diagnosis of dermatitis caused by colophony.

Objective: To evaluate the effectiveness of IVF treatment in endometriosis-associated infertility., Design: Nonrandom retrospective study., Setting: Department of Gynecology and Obstetrics, Akita University School of Medicine., Main Outcome Measure(s): Cumulative pregnancy rate., Patient(s): One hundred eighteen infertile patients in whom diagnosis of endometriosis was established by laparoscopic examination., Intervention(s): The prognoses of 60 patients (IVF group) who started IVF treatment within 6 months after laparoscopy were compared with those of 58 patients who were managed expectantly without IVF treatment during the same period., Result(s): The cumulative conception rates at 36 months after laparoscopy were 62% in the IVF group and 43% in the control group, and the difference was not significant (a log-rank test). For patients > or = 32 years of age, the conception rates were significantly higher in the IVF group (59% versus 29%). A relatively large but nonsignificant difference in the conception rate between the two groups was observed in patients with endometriosis at stages III or IV (52% versus 27%)., Conclusion(s): In vitro fertilization treatment provides better prognosis in patients > or = 32 years of age and is recommended for such patients. The benefits of treatment appear to be greater in patients with more advanced stages of endometriosis.

Objective: To elucidate characteristic changes of plasma hemostatic markers in ovarian hyperstimulation syndrome (OHSS) cycles., Design: Prospective study., Setting: The IVF-ET program of the Department of Obstetrics and Gynecology, The University of Akita, School of Medicine., Patients: Forty cycles of 40 IVF patients, including 12 cycles in which a severe form of OHSS occurred., Interventions: Blood samples were taken during IVF treatment to determine the levels of blood markers that reflect activation of the coagulation and fibrinolytic systems., Main Outcome Measures: Thrombin-antithrombin III complexes, plasmin-alpha 2 antiplasmin complexes, and other hemostatic markers related to the coagulation and fibrinolytic system activation., Results: In the OHSS cycles, the levels of thrombin-antithrombin III and plasmin-alpha 2 antiplasmin complexes in the plasma began to rise within a few days after hCG administration and demonstrated significantly higher levels during the midluteal phase. In OHSS cycles with pregnancy, elevation of these markers continued for > or = 3 weeks after the onset of disease. There were some characteristic changes in OHSS cycles in other hemostatic markers, such as a decrease in the levels of antithrombin III and prekallikrein and shortened activated partial thromboplastin time., Conclusion: These data demonstrate the status of the coagulation and fibrinolytic systems in OHSS cycles and provide insight into the mechanism of activation in the hemostatic system.

We aspirated ovarian follicles of an infertile patient who encountered a great risk of ovarian hyperstimulation (OHSS) during her ovulation-induction cycle, which had been stimulated with gonadotropins, in order to avoid OHSS without interrupting the treatment. If this action were to yield a considerable number of immature oocytes, some of which were to achieve in vitro maturation and subsequent fertilization, this method could be an alternative to conventional ovulation-induction methods for patients who repeatedly present imminent signs of hyperstimulation. However, the number of oocytes collected from the patient was disappointingly low, even though a large number of follicles were thoroughly aspirated. One of these oocytes was matured in vitro in a medium containing 30% follicular fluid and granulosa cells of mature follicles, fertilized, cryopreserved, and transferred in a later artificial cycle; but pregnancy was not achieved. A low number of recovered oocytes from patients in this situation might be a factor that greatly limits the clinical applications of this method.