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Plasmid DNA encoding neutralizing human monoclonal antibody without enhancing activity protects against dengue virus infection in mice

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Asian Pacific Journal of Tropical Medicine 2021年第7期14卷 299-308页

作者： Surachet Benjathummarak Atsushi yamanaka Thanyaluk Krasae Chonlatip Pipattanaboon Subenya Injampa Pannamthip Pitaksajjakul Pongrama Ramasoota Department of Social and Environmental Medicine Faculty of Tropical MedicineMahidol UniversityBangkokThailand Center of Excellence for Antibody Research(CEAR) Faculty of Tropical MedicineMahidol UniversityBangkokThailand Mahidol-Osaka Center for Infectious Diseases(MOCID) Faculty of Tropical MedicineMahidol UniversityBangkokThailand Mahidol-Osaka Center for Infectious Diseases Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan Laboratory Animal Science Unit Faculty of Tropical MedicineMahidol UniversityBangkokThailand Department of Microbiology Faculty of MedicineKhon Kaen UniversityThailand Faculty of Medicine King Mongkut’s Institute of Technology LadkrabangBangkokThailand

Objective: To evaluate the expression of DNA plasmid-harboring modified antibody gene that produces neutralizing human monoclonal antibodies against four serotypes of dengue virus(DENV) without enhancing activity in BALB/c mice. Methods: We constructed pFUSE-based vectors(pFUSE1 G7 C2hVH and pFUSE1 G7 C2hVL) containing genes encoding the variable domains of the heavy or light chain of the anti-dengue virus antibody 1 G7 C2, a human IgG1 that has been characterized for its neutralizing activity to DENV-1-4. Leucine(L) at positions 234 and 235 on the Fc CH2 domain in pFUSE1 G7 C2hVH was mutated to alanine(A)(LALA mutation) by site direct mutagenesis, and the new plasmid was termed pFUSE1 G7 C2hVHLALA. An equal amount of pFUSE1 G7 C2hVL and 1 G7 C2hG1-LALA plasmids were co-transfected into Chinese hamster ovary cells(CHO-K1) and a single dose of 100 μg 1 G7 C2hG1-LALA plasmid was intramuscularly injected, followed by electroporation in BALB/c mice. The secreted 1 G7 C2hG1-LALA antibodies in cell culture supernatant and mouse serum were examined for their biological functions, neutralization and enhancing activity. Results: The co-transfection of heavy-and light-chain 1 G7 C2hG1-LALA plasmids in CHO-K1 cells produced approximately 3 900 ng/mL human IgG and neutralized 90%-100% all four DENV, with no enhancing activity. Furthermore, the modified human IgG was produced more than 1 000 ng/mL in mouse serum on day 7 post plasmid injection and showed cross-neutralization to four DENV serotypes. Subsequently, antibody production and neutralization decreased rapidly. Nevertheless, the secreted neutralizing 1 G7 C2hG1-LALA in mouse serum demonstrated complete absence of enhancing activities to all DENV serotypes. Conclusions: These findings reveal that a new modified 1 G7 C2h G1-LALA expressing plasmid based on gene transfer is a possible therapeutic antibody candidate against DENV infection.

关键词： Dengue virus LALA mutation Antibodydependent enhancement(ADE) Antibody plasmid Electroporation

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Investigation of Specifics of Self-Management towards Dealing with Cancer Pain among Adult Outpatients

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Health 2018年第11期10卷 1520-1538页

作者： Masako yamanaka Department of Nursing Science Faculty of Health Care Tenri Health Care University Nara Japan Doctoral Program Graduate School of Nursing Osaka Medical College Osaka Japan

Purpose: This study aimed to identify specifics of self-management towards dealing with cancer pains among adult outpatients. Methods: Semi-structured interviews were conducted with 16 adult outpatients (9 males and 7 females) who suffered from cancer pain and the data obtained were analyzed using the qualitative synthesis method of KJ Ho. Results: An analysis of the results revealed these key findings for the following symbolic wording of the semi-structured interviews: Cooperative relationship with medical professionals;Problems originating from cancer pain;Self-regulation of analgesic medications based on the interactions with medical professionals;Self-regulation of the analgesic medications based on the physical perceptions of the effects;Self-regulation to maintain a balanced and calm mind, Fulfilling life by the pain alleviation and liberation from the restrictions imposed by the cancer;and Efforts to maintain their lives by themselves. Conclusion: Based on the cooperative relationship established with medical professionals, the patient carried out the self-regulation of cancer pain using analgesics, and self-regulation to maintain a balanced and calm mind. Nurses must therefore sufficiently educate patients regarding how to communicate successfully with medical professionals in order to improve cancer patients’ pain management regarding both physical and mental aspects.

关键词： Self-Management Cancer Pain Adult Outpatients

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Involvement of A5/A7 noradrenergic neurons and B2 serotonergic neurons in nociceptive processing:a fiber photometry study

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Neural Regeneration Research 2022年第4期17卷 881-886页

作者： Shunpei Moriya Akira Yamashita Daiki Masukawa Junichi Sakaguchi Yoko Ikoma Yoshimune Sameshima Yuki Kambe Akihiro yamanaka Tomoyuki Kuwaki Department of Physiology Kagoshima University Graduate School of Medical and Dental ScienceKagoshimaJapan Department of Molecular Pharmacologyand Neurobiology Yokohama City University Graduate School of MedicineYokohamaJapan Department of Pharmacology Kagoshima University Graduate School of Medical and Dental ScienceKagoshimaJapan Research Institute of Environmental Medicine Nagoya UniversityNagoyaJapan

In the central nervous system,the A6 noradrenaline(NA)and the B3 serotonin(5-HT)cell groups are well-recognized players in the descending antinociceptive system,while other NA/5-HT cell groups are not well characterized.A5/A7 NA and B25-HT cells project to the spinal horn and form descending *** recorded G-Ca MP6 green fluorescence signal intensities in the A5/A7 NA and the B25-HT cell groups of awake mice in response to acute tail pinch stimuli,acute heat stimuli,and in the context of a non-noxious control test,using fiber photometry with a calcium imaging *** first introduced G-Ca MP6 in the A5/A7 NA or B25-HT neuronal soma,using transgenic mice carrying the tetracycline-controlled transactivator transgene under the control of either a dopamineβ-hydroxylase or a tryptophan hydroxylase-2 promoters and by the site-specific injection of adeno-associated virus(AAV-Tet O(3 G)-G-Ca MP6).After confirming the specific expression patterns of G-Ca MP6,we recorded G-Ca MP6 green fluorescence signals in these sites in awake mice in response to acute nociceptive stimuli.G-Ca MP6 fluorescence intensity in the A5,A7,and B2 cell groups was rapidly increased in response to acute nociceptive stimuli and soon after,it returned to baseline fluorescence *** was not observed in the non-noxious control *** results indicate that acute nociceptive stimuli rapidly increase the activities of A5/A7 NA or B25-HT neurons but the non-noxious stimuli do *** present study suggests that A5/A7 NA or B25-HT neurons play important roles in nociceptive processing in the central nervous *** suggest that A5/A7/B2 neurons may be new therapeutic *** performed procedures were approved by the Institutional Animal Use Committee of Kagoshima University(MD17105)on February 22,2018.

关键词： A5 NA neurons A7 NA neurons B25-HT neurons DBH-tTA mice fiber photometry G-CaMP6 mCherry monoaminergic signaling nociception TPH-t TA mice

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Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease

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World Journal of Gastroenterology 2005年第4期11卷 476-481页

作者： Yukiko Saitou Katsuya Shiraki Yutaka yamanaka Yumi Yamaguchi Tomoyuki Kawakita Norihiko Yamamoto Kazushi Sugimoto Kazumoto Murata Takeshi Nakano First Department of Internal Medicine Mie University School of Medicine TsuMie 514-8507Japan

AIM: To evaluate the clinical utility of serum fibrosis markers, including YKL-40, in patients with HCV-associated liver disease. METHODS: A total of 109 patients with HCV-associated liver disease were enrolled. We measured serum type IV collagen, amino-terminal peptide of type III procollagen (PIIIP), hyaluronic acid (HA), YKL-40 levels and biochemical. Parameters by RIA or ELISA. Eighty-eight patients underwent liver biopsy, and 67 of 109 patients received interferon (IFN) therapy. We also investigated the relationship between the concentrations of serum fibrosis markers and histological fibrosis scores (METAVIR), and evaluated the changes of the levels of fibrosis markers before and after the IFN therapy. RESULTS: The increase in serum levels of all markers, particularly HA, was correlated with the progression of liver fibrosis (for type IV collagen, F= 9.076, P<0.0001; for PIIIP, F= 9.636, P<0.0001; for HA, F=13.128, P<0.0001; and for YKL-40, F= 8.016, P<0.0001). YKL-40 had strong correlation with HA (r= 0.536, P<0.0001). Based on the receiver operating curve (ROC), the ability of serum HA exceeded the abilities of other serum markers to determine fibrosis score 4 from fibrosis score 0-3 (AUC = 0.854). While YKL-40 was superior to other fibrosis markers for predicting severe fibrosis (F2-F4) from mild fibrosis (FO-F1) (YKL-40, AUC = 0.809; HA, AUC = 0.805). After IFN therapy, only YKL-40 values significantly decreased not only in the responder group, but also in the nonresponder group (P = 0.03). CONCLUSION: YKL-40 may be a useful non-invasive serum marker to estimate the degree of liver fibrosis and to evaluate the efficacy of IFN therapies in patients with HCV-associated liver disease.

关键词： HCV Liver fibrosis YKL-40 Interferon

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Large mucinous cystic neoplasm of the pancreas associated with pregnancy

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World Journal of Gastroenterology 2008年第47期14卷 7252-7255页

作者： Shin-ichi Ikuta Tsukasa Aihara Chiaki Yasui Hiroya Iida Hidenori Yanagi Masao Mitsunobu Ayako Kakuno Naoki yamanaka Department of Surgery Meiwa General HospitalHyogo 663-8186Japan Department of Pathology Meiwa General HospitalHyogo 663-8186Japan

Mucinous cystic neoplasms (MCNs) of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.

关键词： Mucinous cystic neoplasm Pancreatic tumor Pregnancy

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发现“不可见” PRODUCTS FROM KAZUHIRO yamanaka

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室内设计与装修 2017年第9期 122-125页

作者： Kazuhiro yamanaka(日)

可折叠的月亮灯（图01-图05）打开灯的瞬间，柔和的光充盈了整个大大的白色圆盘，犹如一轮明月，这款灯因此得名。月亮灯是山中一宏为意大利品牌Pallucco设计的一款产品，其灵感来自于摄影。这款灯的特点是可以轻松地折叠和展开，方便... 详细信息

可折叠的月亮灯（图01-图05）打开灯的瞬间，柔和的光充盈了整个大大的白色圆盘，犹如一轮明月，这款灯因此得名。月亮灯是山中一宏为意大利品牌Pallucco设计的一款产品，其灵感来自于摄影。这款灯的特点是可以轻松地折叠和展开，方便使用者携带。

关键词：可折叠意大利使用者月亮灯

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Temporal changes in nitrogen acquisition of Japanese black pine(Pinus thunbergii) associated with black locust(Robinia pseudoacacia)

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Journal of Forestry Research 2014年第3期25卷 585-589页

作者： M.L.Lopez C. C.Mizota Y.Nobori T.Sasaki T.yamanaka Faculty of Agriculture Yamagata University1-23 Wakabamachi Tsuruoka Yamagata 997-8555 Japan Faculty of Agriculture Iwate University Division of Earth Science Graduate School of Natural Science and Technology Okayama University1-1 Naka 3-chome Tsushima Okayama Japan

The alien woody legume, black locust （Robinia pseudoaca-cia）, has invaded Japanese black pine （Pinus thunbergii） forests located in Japan’s coastal plain and hill regions where gaps are formed in pine forests after nematode infestation. Nitrogen fixation by legumes acceler-ates N cycling in forest ecosystems. We studied temporal change in the annual tree-ring resolution N stable isotope composition （δ15N, a per mil deviation of δ15N/14N ratio, relative to atmospheric N2δ15N=0‰） at two natural locations of Japanese black pine forest with black locust that differed in the time since black locust establishment （Shohnai in north-east and Kita-Kyushu in southwest Japan）. Analyzed tree-rings covered the period from 1990/1992 to 2009. N acquisition by Japanese black pine from black locust N input to the soil was evidenced by temporal shifting of N stable isotope composition on the annual pine tree rings. With pro-gressive development of the forest stand,δ15N values of earlier tree-ringsδ15N of -5‰） from black pine associated with black locust shifted to-wards values similar to those of black locustδ15N values nearly to-1‰）, which suggests acquisition of N by N2 fixation （Shohnai site）. In con-trast, in a forest where black locust had settled for two or three genera-tions, in a black pine stand （Kita-Kyushu site）, longer periods of N en-richment in the soil were reflected in the elevated tree-ringδ15N values of newly established black pine trees. Based on tree-ringδ15N data from the Shohnai site, we determined that about 10 years after black locust establishment, soil N had already been enriched by black locust N, this, in turn, contributed to N fertilization of surrounding trees in mixed stands.

关键词： δ15N natural abundance Japanese black pine black locust,nitrogen acquisition tree-ring

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Impact Values : 30 Discussion topics to help you explore your own values / Richard ***, Junko yamanaka, Joseph Shaules.

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2003年

作者： Richard R.Day Junko yamanaka Joseph Shaules.

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The Impact of Orographically-Induced Gravity Waves on the Diurnal Cycle of Rainfall over Southeast Kalimantan Island

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Atmospheric and Oceanic Science Letters 2009年第1期2卷 35-39页

作者： Jun-Ichi HAMADA Manabu D.yamanaka Jun MATSUMOTO Masayuki HARA Institute of Observational Research for Global Change JAMSTECYokosukaJapan Graduate School of Urban Environmental Sciences Tokyo Metropolitan UniversityHachiojiJapan Frontier Research Center for Global Change JAMSTECYokohamaJapan

Precipitation measurements from the Tropical Rainfall Measuring Mission (TRMM) satellite indicate that the southeastern area of Kalimantan (Borneo) Island receives much less rainfall than elsewhere on the island during the period from July to *** from sur-face meteorological observations show that the diurnal cycle of rainfall differs greatly between the eastern and western coasts of the *** on the western coast of the island is frequent in the afternoon and evening,whereas almost all rainfall on the eastern coast occurs in the ***,the Global Positioning System (GPS)-derived precipitable water (PW) on the eastern coast shows a substantial decrease in moisture in the af-ternoon and *** experiments with a mesoscale model reveal that gravity waves driven by di-urnal heating of the elevated land surface of the moun-tains on Sulawesi Island,which lies approximately 300 kilometers to the east of Kalimantan Island,significantly affect the diurnal cycle of rainfall over southeast Kali-mantan Island.

关键词： diurnal cycle rainfall precipitable water Kalimantan (Borneo) Island gravity wave

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Watery diarrhea,hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

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World Journal of Gastroenterology 2007年第34期13卷 4649-4652页

作者： Shin-ichi Ikuta Chiaki Yasui Masahiro Kawanaka Tsukasa Aihara Hidenori Yoshie Hidenori Yanagi Masao Mitsunobu Ayako Sugihara Naoki yamanaka Department of Surgery Meiwa General Hospital Hyogo 663-8186 Japan Department of Internal Medicine Meiwa General Hospital Hyogo 663-8186 Japan Department of Pathology Meiwa General Hospital Hyogo 663-8186 Japan

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

关键词： Pheochromocytoma Vasoactive intestinalpolypeptide Watery diarrhea, hypokalemia andachlorhydria syndrome

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