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[A case of leptospirosis infected in Borneo Island, Malaysia]

Sakamoto M, Sagara H, Koizumi N, Watanabe H

Kansenshogaku Zasshi, 2001 Dec;75(12):1057-61.
PMID: 11806141

We report a case of leptospirosis infected in Sabah, Borneo island, Malaysia. The case is 25-year-old male who had participated in the EcoChallenge Sabah 2000 Expedition Race, a multisport event held during August 20 to September 3, 2000 at various sites in Sabah in Malaysian Borneo. He developed a high fever and headache on September 7, and he was admitted to our hospital on September 9. On admission he also had conjunctivitis and myalgias. Laboratory findings on admission revealed leukocytosis with left shift, slightly elevated transaminase levels, high CRP levels and proteinuria. Plasmodium spp. were negative on blood smears, and no bacteria were isolated from blood and feces cultures. We performed the laboratory tests for leptospirosis, based on the information about the probable leptospirosis outbreak among athletes who participated in the EcoChallenge Race, however both Leptospira antigens and antibodies were negative at that time. We diagnosed leptospirosis clinically because he manifested persistent symptoms, and minocycline 100 mg b.i.d. was administered intravenously resulting in excellent efficacy. Serum antibody tests by microscopic agglutination test (MAT) at convalescent stage revealed significant increased antibodies against Leptospira interrogans serovar hebdomadis, and the diagnosis of leptospirosis was confirmed. Infectious diseases have been global and it is important to have information concerning worldwide infectious disease situations as much as possible for accurate diagnosis.
Attitudes of medical school deans toward interprofessional education in Western Pacific Region countries

Lee B, Celletti F, Makino T, Matsui H, Watanabe H

J Interprof Care, 2012 Nov;26(6):479-83.
PMID: 22830530 DOI: 10.3109/13561820.2012.706336

To examine the attitudes of medical school deans toward interprofessional education (IPE) and collaborative practice (CP), we conducted survey research in the Western Pacific Region. This regional survey was conducted as a collaborative research project with the World Health Organization. A survey was distributed to the medical school deans in Malaysia, the Philippines, Republic of Korea and Japan. Thirty-five surveys were returned from four countries. The survey demonstrated that many medical school deans have positive attitudes toward IPE and CP. However, respondents also reported that it is not easy to introduce interprofessional learning in their academic settings. It is suggested that collaboration between education systems and health systems is needed to introduce IPE in the academic setting. The possible role of international organizations is mentioned. This information helps to identify local efforts on which global health organizations and national governments can build.
Characterization of drug resistant Salmonella enterica serotype Typhimurium by antibiograms, plasmids, integrons, resistance genes and PFGE

Benacer D, Thong KL, Watanabe H, Puthucheary SD

J Microbiol Biotechnol, 2010 Jun;20(6):1042-52.
PMID: 20622506

Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. Presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of S. Typhimurium were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulphonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%) and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%) and cephalexin (17.0%). Resistance genes, blaTEM, strA, aadA, sul1, sul2, tet(A), tet(B) and tet(C) were detected among the drug resistant strains. Thirty-three strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1 and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1 - 6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug-resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.
Isolation of an Escherichia coli O157:H7 strain producing Shiga toxin 1 but not Shiga toxin 2 from a patient with hemolytic uremic syndrome in Korea

Kim YB, Okuda J, Matsumoto C, Morigaki T, Asai N, Watanabe H, et al.

FEMS Microbiol Lett, 1998 Sep 01;166(1):43-8.
PMID: 9741083

Escherichia coli strains isolated from patients with diarrhea or hemolytic uremic syndrome (HUS) at Pusan University Hospital, South Korea, between 1990 and 1996 were examined for traits of the O157:H7 serogroup. One strain isolated from a patient with HUS belonged to the O157:H7 serotype, possessed a 60-MDa plasmid, the eae gene, and ability to produce Shiga toxin 1 but not Shiga toxin 2. Arbitrarily primed PCR analysis suggested that this strain is genetically very close to a O157:H7 strain isolated in Japan.
Molecular characterization of Salmonella enterica serovar Typhimurium isolated from human, food, and animal sources in Malaysia

Ngoi ST, Lindstedt BA, Watanabe H, Thong KL

Jpn J Infect Dis, 2013;66(3):180-8.
PMID: 23698477

Salmonella Typhimurium is an important nontyphoidal Salmonella serovar associated with foodborne diseases in many parts of the world. This organism is the major causative agent of nontyphoidal salmonellosis in Malaysia. We aimed to investigate the genetic profiles of the strains isolated from clinical, zoonotic, and dietary sources in Malaysia using multilocus variable number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). By focusing on the 5 common variable number tandem repeat (VNTR) loci, we found that PFGE (D = 0.99) was more discriminative than MLVA (D = 0.76). The low MLVA score might be because of a lack of VNTR loci STTR6 (81.0%) and STTR10pl (76.2%). Both subtyping methods suggested that our S. Typhimurium strains were largely endemic with limited genetic variation. Furthermore, we observed that biphasic S. Typhimurium strains were dominant (99%) and multidrug resistance was prevalent (50%) within our sample pool. The most frequently observed phenotypes were resistance to compound sulfonamides (49%), tetracycline (51%), and streptomycin (52%). In this study, we documented the genetic relationship, antimicrobial resistance characteristics, and flagellar-phase dominance among S. Typhimurium strains found in Malaysia.
Fulltext Gluconobacter dominates the gut microbiome of the Asian palm civet Paradoxurus hermaphroditus that produces kopi luwak

Watanabe H, Ng CH, Limviphuvadh V, Suzuki S, Yamada T

PeerJ, 2020;8:e9579.
PMID: 32821539 DOI: 10.7717/peerj.9579

Coffee beans derived from feces of the civet cat are used to brew coffee known as kopi luwak (the Indonesian words for coffee and palm civet, respectively), which is one of the most expensive coffees in the world owing to its limited supply and strong market demand. Recent metabolomics studies have revealed that kopi luwak metabolites differ from metabolites found in other coffee beans. To produce kopi luwak, coffee beans are first eaten by civet cats. It has been proposed that fermentation inside the civet cat digestive tract may contribute to the distinctively smooth flavor of kopi luwak, but the biological basis has not been determined. Therefore, we characterized the microbiome of civet cat feces using 16S rRNA gene sequences to determine the bacterial taxa that may influence fermentation processes related to kopi luwak. Moreover, we compared this fecal microbiome with that of 14 other animals, revealing that Gluconobacter is a genus that is, uniquely found in feces of the civet cat. We also found that Gluconobacter species have a large number of cell motility genes, which may encode flagellar proteins allowing colonization of the civet gut. In addition, genes encoding enzymes involved in the metabolism of hydrogen sulfide and sulfur-containing amino acids were over-represented in Gluconobacter. These genes may contribute to the fermentation of coffee beans in the digestive tract of civet cats.
Fulltext Characterization of Shigella sonnei in Malaysia, an increasingly prevalent etiologic agent of local shigellosis cases

Koh XP, Chiou CS, Ajam N, Watanabe H, Ahmad N, Thong KL

BMC Infect Dis, 2012;12:122.
PMID: 22606962 DOI: 10.1186/1471-2334-12-122

Shigellosis is a major public health concern worldwide, especially in developing countries. It is an acute intestinal infection caused by bacteria of the genus Shigella, with a minimum infective dose as low as 10-100 bacterial cells. Increasing prevalence of Shigella sonnei as the etiologic agent of shigellosis in Malaysia has been reported. As there is limited information on the genetic background of S. sonnei in Malaysia, this study aimed to characterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.
The mediating role of Internet addiction in depression, social anxiety, and psychosocial well-being among adolescents in six Asian countries: a structural equation modelling approach

Lai CM, Mak KK, Watanabe H, Jeong J, Kim D, Bahar N, et al.

Public Health, 2015 Sep;129(9):1224-36.
PMID: 26343546 DOI: 10.1016/j.puhe.2015.07.031

OBJECTIVES: This study examines the associations of Internet addiction with social anxiety, depression, and psychosocial well-being among Asian adolescents. A self-medication model conceptualizing Internet addiction as a mediating role in relating depression and social anxiety to negative psychosocial well-being was tested.
STUDY DESIGN: A cross-sectional survey.
METHODS: In the Asian Adolescent Risk Behavior Survey (AARBS), 5366 adolescents aged 12-18 years from six Asian countries (China, Hong Kong, Japan, South Korea, Malaysia, and Philippines) completed a questionnaire with items of the Internet Addiction Test (IAT), Social Anxiety Scale for Adolescents (SAS-A), Center for Epidemiological Studies Depression Scale (CESD), Self-Rated Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA-SR) in the 2012-2013 school year. Structural equation modelling was used to examine the mediating role of Internet addiction in depression, social anxiety, and subjective psychosocial well-being.
RESULTS: Significant differences on the scores of IAT, SAS-A, CESD, and HoNOSCA-SR across the six countries were found. The proposed self-medication model of Internet addiction received satisfactory goodness-of-fit with data of all countries. After the path from social anxiety to Internet addiction had been discarded in the revised model, there was a significant improvement of the goodness-of-fit in the models for Japan, South Korea, and the Philippines.
CONCLUSIONS: Depression and social anxiety reciprocally influenced, whereas depression associated with poorer psychosocial well-being directly and indirectly through Internet addiction in all six countries. Internet addiction mediated the association between social anxiety and poor psychosocial well-being in China, Hong Kong, and Malaysia.
KEYWORDS: Adolescents; Asian; Depression; Internet addiction; Social anxiety; Structural equation modelling
Fulltext Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway

Bhidayasiri R, Phokaewvarangkul O, Shang HF, Lim TT, Cho JW, Pal PK, et al.

Front Neurol, 2024;15:1356761.
PMID: 38419696 DOI: 10.3389/fneur.2024.1356761

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.
Fulltext Neurological perspectives should be integrated into the management of tardive dyskinesia - expert opinion and proposed educational initiatives in Asia

Bhidayasiri R, Phokaewvarangkul O, Lim TT, Pal PK, Watanabe H, Cho JW, et al.

J Mov Disord, 2024 Apr 11.
PMID: 38600683 DOI: 10.14802/jmd.24068
Measurement Invariance of the Internet Addiction Test Among Hong Kong, Japanese, and Malaysian Adolescents

Lai CM, Mak KK, Cheng C, Watanabe H, Nomachi S, Bahar N, et al.

Cyberpsychol Behav Soc Netw, 2015 Oct;18(10):609-17.
PMID: 26468915 DOI: 10.1089/cyber.2015.0069

There has been increased research examining the psychometric properties on the Internet Addiction Test (IAT) in different populations. This population-based study examined the psychometric properties and measurement invariance of the IAT in adolescents from three Asian countries. In the Asian Adolescent Risk Behavior Survey (AARBS), 2,535 secondary school students (55.9% girls) aged 12-18 years from Hong Kong (n=844), Japan (n=744), and Malaysia (n=947) completed a survey in 2012-2013 school year. A nested hierarchy of hypotheses concerning the IAT cross-country invariance was tested using multigroup confirmatory factor analyses. Replicating past findings in Hong Kong adolescents, the construct of the IAT is best represented by a second-order three-factor structure in Malaysian and Japanese adolescents. Configural, metric, scalar, and partial strict factorial invariance was established across the three samples. No cross-country differences on Internet addiction were detected at the latent mean level. This study provided empirical support for the IAT as a reliable and factorially stable instrument, and valid to be used across Asian adolescent populations.
Fulltext S-Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics

Ishima Y, Watanabe K, Chuang VTG, Takeda I, Kuroda T, Ogawa W, et al.

FASEB Bioadv, 2019 Mar;1(3):137-150.
PMID: 32123826 DOI: 10.1096/fba.1018

Alpha-1-acid glycoprotein (AGP) is a major acute-phase protein. Biosynthesis of AGP increases markedly during inflammation and infection, similar to nitric oxide (NO) biosynthesis. AGP variant A (AGP) contains a reduced cysteine (Cys149). Previously, we reported that S-nitrosated AGP (SNO-AGP) synthesized by reaction with a NO donor, possessed very strong broad-spectrum antimicrobial activity (IC50 = 10-9-10-6 M). In this study, using a cecal ligation and puncture animal model, we confirmed that AGP can be endogenously S-nitrosated during infection. Furthermore, we examined the antibacterial property of SNO-AGP against multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa to investigate the involvement of SNO-AGP in the host defense system. Our results showed that SNO-AGP could inhibit multidrug efflux pump, AcrAB-TolC, a major contributor to bacterial multidrug resistance. In addition, SNO-AGP decreased biofilm formation and ATP level in bacteria, indicating that SNO-AGP can revert drug resistance. It was also noteworthy that SNO-AGP showed synergistic effects with the existing antibiotics (oxacillin, imipenem, norfloxacin, erythromycin, and tetracycline). In conclusion, SNO-AGP participated in the host defense system and has potential as a novel agent for single or combination antimicrobial therapy.
Epidemiology of internet behaviors and addiction among adolescents in six Asian countries

Mak KK, Lai CM, Watanabe H, Kim DI, Bahar N, Ramos M, et al.

Cyberpsychol Behav Soc Netw, 2014 Nov;17(11):720-8.
PMID: 25405785 DOI: 10.1089/cyber.2014.0139

Internet addiction has become a serious behavioral health problem in Asia. However, there are no up-to-date country comparisons. The Asian Adolescent Risk Behavior Survey (AARBS) screens and compares the prevalence of Internet behaviors and addiction in adolescents in six Asian countries. A total of 5,366 adolescents aged 12-18 years were recruited from six Asian countries: China, Hong Kong, Japan, South Korea, Malaysia, and the Philippines. Participants completed a structured questionnaire on their Internet use in the 2012-2013 school year. Internet addiction was assessed using the Internet Addiction Test (IAT) and the Revised Chen Internet Addiction Scale (CIAS-R). The variations in Internet behaviors and addiction across countries were examined. The overall prevalence of smartphone ownership is 62%, ranging from 41% in China to 84% in South Korea. Moreover, participation in online gaming ranges from 11% in China to 39% in Japan. Hong Kong has the highest number of adolescents reporting daily or above Internet use (68%). Internet addiction is highest in the Philippines, according to both the IAT (5%) and the CIAS-R (21%). Internet addictive behavior is common among adolescents in Asian countries. Problematic Internet use is prevalent and characterized by risky cyberbehaviors.
Fulltext Distribution of Polysulfide in Human Biological Fluids and Their Association with Amylase and Sperm Activities

Ikeda M, Ishima Y, Chuang VTG, Sakai M, Osafune H, Ando H, et al.

Molecules, 2019 Apr 30;24(9).
PMID: 31052207 DOI: 10.3390/molecules24091689

Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confirmed the presence of polysulfide in other biological fluids, such as semen and nasal discharge. The levels of polysulfide in these biological fluids from healthy volunteers (n = 9) with identical characteristics were compared. Additionally, the circadian rhythm of plasma polysulfide was also investigated. The polysulfide levels detected from nasal discharge and seminal fluid were approximately 400 and 600 μM, respectively. No correlation could be found between plasma polysulfide and the polysulfide levels of tear, saliva, and nasal discharge. On the other hand, seminal polysulfide was positively correlated with plasma polysulfide, and almost all polysulfide contained in semen was found in seminal fluid. Intriguingly, saliva and seminal polysulfide strongly correlated with salivary amylase and sperm activities, respectively. These results provide a foundation for scientific breakthroughs in various research areas like infertility and the digestive system process.
Fulltext Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment

Ishima Y, Mimono A, Tuan Giam Chuang V, Fukuda T, Kusumoto K, Okuhira K, et al.

IUBMB Life, 2020 04;72(4):641-651.
PMID: 31794135 DOI: 10.1002/iub.2203

Deposition of amyloid protein, particularly Aβ1-42 , is a major contributor to the onset of Alzheimer's disease (AD). However, almost no deposition of Aβ in the peripheral tissues could be found. Human serum albumin (HSA), the most abundant protein in the blood, has been reported to inhibit amyloid formation through binding Aβ, which is believed to play an important role in the peripheral clearance of Aβ. We identified the Aβ binding site on HSA and developed HSA mutants with high binding capacities for Aβ using a phage display method. HSA fragment 187-385 (Domain II) was found to exhibit the highest binding capacity for Aβ compared with the other two HSA fragments. To elucidate the sequence that forms the binding site for Aβ on Domain II, a random screening of Domain II display phage biopanning was constructed. A number of mutants with higher Aβ binding capacities than the wild type were identified. These mutants exhibited stronger scavenging abilities than the wild type, as revealed via in vitro equilibrium dialysis of Aβ experiments. These findings provide useful basic data for developing a safer alternative therapy than Aβ vaccines and for application in plasma exchange as well as extracorporeal dialysis.
Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape

Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Ikegami K, Chuang VTG, et al.

J Control Release, 2019 06 28;304:156-163.
PMID: 31082432 DOI: 10.1016/j.jconrel.2019.05.015

We recently developed a cell-penetrating drug carrier composed of albumin (HSA) combined with palmitoyl-cyclic-(D-Arg)12. While it is possible that the palmitoyl-cyclic-(D-Arg)12/HSA enters the cell mainly via macropinocytosis, the mechanism responsible for the induction of macropinocytosis and endosomal escape remain unknown. We report herein that palmitoyl-cyclic-(D-Arg)12/HSA might interact with heparan sulfate proteoglycan and the chemokine receptor CXCR4 followed by multiple activations of the PKC/PI3K/JNK/mTOR signaling pathways to induce macropinocytosis. This result was further confirmed by a co-treatment with 70 kDa dextran, a macropinocytosis marker. Using liposomes that mimic endosomes, the leakage of 5,6-carboxyfluorescein from liposome was observed in the presence of palmitoyl-cyclic-(D-Arg)12/HSA only in the case of the anionic late endosome-like liposomes but not the neutral early endosome-like liposomes. Heparin largely inhibited this leakage, suggesting the importance of electrostatic interactions between palmitoyl-cyclic-(D-Arg)12/HSA and the late-endosomal membrane. Immunofluorescence staining and Western blotting data indicated that the intact HSA could be transferred from endosomes to the cytosol. These collective data suggest that the palmitoyl-cyclic-(D-Arg)12/HSA is internalized via macropinocytosis and intact HSA is released from the late endosomes to the cytoplasm before the endosomes fuse with lysosomes. Palmitoyl-cyclic-(D-Arg)12/HSA not only functions as an intracellular drug delivery carrier but also as an inducer of macropinocytosis.
α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents

Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, et al.

J Pharm Sci, 2019 11;108(11):3592-3598.
PMID: 31288036 DOI: 10.1016/j.xphs.2019.07.002

Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.
Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

Ogura A, Kawabata K, Watanabe H, Choy SW, Bagarinao E, Kato T, et al.

Eur J Neurol, 2022 Feb;29(2):432-440.
PMID: 34632672 DOI: 10.1111/ene.15136

BACKGROUND AND PURPOSE: To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis.
METHODS: We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables.
RESULTS: The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p
Erythrocyte Alloimmunity and Genetic Variance: Results from the Collaborative Study of Alloimmunity to Antigen Diversity in Asian Populations (All ADP)

Takeshita A, Watanabe H, Yamada C, Nadarajan VS, Permpikul P, Sinkitjasub A, et al.

Transfus Apher Sci, 2020 Oct;59(5):102944.
PMID: 33228922 DOI: 10.1016/j.transci.2020.102944

As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.
Fulltext Development of Kupffer cell targeting type-I interferon for the treatment of hepatitis via inducing anti-inflammatory and immunomodulatory actions

Minayoshi Y, Maeda H, Yanagisawa H, Hamasaki K, Mizuta Y, Nishida K, et al.

Drug Deliv, 2018 Nov;25(1):1067-1077.
PMID: 29688069 DOI: 10.1080/10717544.2018.1464083

Because of its multifaceted anti-inflammatory and immunomodulatory effects, delivering type-I interferon to Kupffer cells has the potential to function as a novel type of therapy for the treatment of various types of hepatitis. We report herein on the preparation of a Kupffer cell targeting type-I interferon, an albumin-IFNα2b fusion protein that contains highly mannosylated N-linked oligosaccharide chains, Man-HSA(D494N)-IFNα2b, attached by combining albumin fusion technology and site-directed mutagenesis. The presence of this unique oligosaccharide permits the protein to be efficiently, rapidly and preferentially distributed to Kupffer cells. Likewise IFNα2b, Man-HSA(D494N)-IFNα2b caused a significant induction in the mRNA levels of IL-10, IL-1Ra, PD-L1 in RAW264.7 cells and mouse isolated Kupffer cells, and these inductions were largely inhibited by blocking the interferon receptor. These data indicate that Man-HSA(D494N)-IFNα2b retained the biological activities of type-I interferon. Man-HSA(D494N)-IFNα2b significantly inhibited liver injury in Concanavalin A (Con-A)-induced hepatitis model mice, and consequently improved their survival rate. Moreover, the post-administration of Man-HSA(D494N)-IFNα2b at 2 h after the Con-A challenge also exerted hepato-protective effects. In conclusion, this proof-of-concept study demonstrates the therapeutic effectiveness and utility of Kupffer cell targeting type-I interferon against hepatitis via its anti-inflammatory and immunomodulatory actions.

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