Publications by authors named "Asami Yamamoto"

10 Publications

  • Page 1 of 1

Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases.

Commun Biol 2020 10 16;3(1):588. Epub 2020 Oct 16.

Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-020-01305-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567837PMC
October 2020

Capturing the differences between humoral immunity in the normal and tumor environments from repertoire-seq of B-cell receptors using supervised machine learning.

BMC Bioinformatics 2019 May 28;20(1):267. Epub 2019 May 28.

Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.

Background: The recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments. However, given the high diversity of BCRs/Igs and the rarity of recurrent sequences among individuals, it is far more difficult to capture such differences in BCR/Ig sequences than in TCR sequences. The aim of this study was to explore the possibility of discriminating BCRs/Igs in tumor and in normal tissues, by capturing these differences using supervised machine learning methods applied to RNA sequences of BCRs/Igs.

Results: RNA sequences of BCRs/Igs were obtained from matched normal and tumor specimens from 90 gastric cancer patients. BCR/Ig-features obtained in Rep-Seq were used to classify individual BCR/Ig sequences into normal or tumor classes. Different machine learning models using various features were constructed as well as gradient boosting machine (GBM) classifier combining these models. The results demonstrated that BCR/Ig sequences between normal and tumor microenvironments exhibit their differences. Next, by using a GBM trained to classify individual BCR/Ig sequences, we tried to classify sets of BCR/Ig sequences into normal or tumor classes. As a result, an area under the curve (AUC) value of 0.826 was achieved, suggesting that BCR/Ig repertoires have distinct sequence-level features in normal and tumor tissues.

Conclusions: To the best of our knowledge, this is the first study to show that BCR/Ig sequences derived from tumor and normal tissues have globally distinct patterns, and that these tissues can be effectively differentiated using BCR/Ig repertoires.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-019-2853-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537402PMC
May 2019

Compositional and Functional Shifts in the Epibiotic Bacterial Community of Shinkaia crosnieri Baba & Williams (a Squat Lobster from Hydrothermal Vents) during Methane-Fed Rearing.

Microbes Environ 2018 Dec 17;33(4):348-356. Epub 2018 Oct 17.

Japan Agency for Marine-Earth Science and Technology (JAMSTEC).

The hydrothermal vent squat lobster Shinkaia crosnieri Baba & Williams harbors an epibiotic bacterial community, which is numerically and functionally dominated by methanotrophs affiliated with Methylococcaceae and thioautotrophs affiliated with Sulfurovum and Thiotrichaceae. In the present study, shifts in the phylogenetic composition and metabolic function of the epibiont community were investigated using S. crosnieri individuals, which were reared for one year in a tank fed with methane as the energy and carbon source. The results obtained indicated that indigenous predominant thioautotrophic populations, such as Sulfurovum and Thiotrichaceae members, became absent, possibly due to the lack of an energy source, and epibiotic communities were dominated by indigenous Methylococcaceae and betaproteobacterial methylotrophic members that adapted to the conditions present during rearing for 12 months with a supply of methane. Furthermore, the overall phylogenetic composition of the epibiotic community markedly changed from a composition dominated by chemolithotrophs to one enriched with cross-feeding heterotrophs in addition to methanotrophs and methylotrophs. Thus, the composition and function of the S. crosnieri epibiotic bacterial community were strongly affected by the balance between the energy and carbon sources supplied for chemosynthetic production as well as that between the production and consumption of organic compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1264/jsme2.ME18072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308002PMC
December 2018

Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies.

Cell Rep 2017 08;20(5):1073-1087

Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, 113-8510 Tokyo, Japan. Electronic address:

Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2017.07.016DOI Listing
August 2017

Molecular evidence of digestion and absorption of epibiotic bacterial community by deep-sea crab Shinkaia crosnieri.

ISME J 2015 Mar 17;9(4):821-31. Epub 2015 Mar 17.

Department of Subsurface Geobiological Analysis and Research (D-SUGAR), Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Kanagawa, Japan.

The hydrothermal vent crab Shinkaia crosnieri is considered to obtain nutrition from the epibiotic bacteria found on the setae, but previous studies have not shown how nutrients can be transferred from the epibionts to the host. In this study, microscopic observations of S. crosnieri intestinal components detected autofluorescent setae fragments and pigmentation derived from the digestion of epibionts in a dye-stained epibiont tracer experiment. An in vitro digestion experiment with epibiotic populations using an intestinal extract demonstrated the degradation of epibiotic cells by digestive enzymes. A phylogenetic analysis showed that many of the bacterial 16S ribosomal RNA gene sequences obtained from the intestine were closely related to the sequences of the epibionts, thus they were probably derived from the epibionts. A stable isotope tracer experiment also indicated that (13)C assimilated by the epibionts provided a carbon (nutrition) source for the host. Both activity measurements and isotope studies showed that chemosynthetic metabolism by the gut microbial components were inactive. Together with the feeding behaviour of living S. crosnieri, these results indicate that S. crosnieri ingests the epibionts using maxillipeds and assimilates them via its digestive organs as a nutrient source. The results of this study elucidate the mechanism of nutritional transfer in ectosymbiosis between chemosynthetic bacteria and deep-sea invertebrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ismej.2014.178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817695PMC
March 2015

Diversity and methane oxidation of active epibiotic methanotrophs on live Shinkaia crosnieri.

ISME J 2014 May 9;8(5):1020-31. Epub 2014 Jan 9.

Subsurface Geobiology Advanced Research (SUGAR) Project, Extremobiosphere Research Program (XBR), Institute of Biogeosciences, Japan Agency for Marine-Earth Science and Technology (JAMSTEC), Yokosuka, Kanagawa, Japan.

Shinkaia crosnieri is a galatheid crab that predominantly dwells in deep-sea hydrothermal systems in the Okinawa Trough, Japan. In this study, the phylogenetic diversity of active methanotrophs in the epibiotic microbial community on the setae of S. crosnieri was characterized by reverse transcription-polymerase chain reaction (RT-PCR) of a functional gene (pmoA) encoding a subunit of particulate methane monooxygenase. Phylogenetic analysis of pmoA transcript sequences revealed that the active epibiotic methanotrophs on S. crosnieri setae consisted of gammaproteobacterial type Ia and Ib methanotrophs. The effect of different RNA stabilization procedures on the abundance of pmoA and 16S rRNA transcripts in the epibiotic community was estimated by quantitative RT-PCR. Our novel RNA fixation method performed immediately after sampling effectively preserved cellular RNA assemblages, particularly labile mRNA populations, including pmoA mRNA. Methane consumption in live S. crosnieri was also estimated by continuous-flow incubation under atmospheric and in situ hydrostatic pressures, and provided a clear evidence of methane oxidation activity of the epibiotic microbial community, which was not significantly affected by hydrostatic pressure. Our study revealed the significant ecological function and nutritional contribution of epibiotic methanotrophs to the predominant S. crosnieri populations in the Okinawa Trough deep-sea hydrothermal systems. In conclusion, our study gave clear facts about diversity and methane oxidation of active methanotrophs in the epibiotic community associated with invertebrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ismej.2013.226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996700PMC
May 2014

Antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats.

J Vet Med Sci 2014 Mar 8;76(2):173-82. Epub 2013 Oct 8.

Laboratory of Veterinary Internal Medicine, Joint Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, 4-101 Koyama-Minami, Tottori 680-8553, Japan.

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 40 µg/kg medetomidine intramuscularly and saline (as the control), 160 µg/kg prazosin, or 40, 160 or 480 µg/kg atipamezole or yohimbine intravenously 0.5 hr later. Volume, pH and specific gravity of urine; plasma arginine vasopressin (AVP) level; and creatinine, osmolality and electrolyte levels in both urine and plasma were measured. Both atipamezole and yohimbine, but not prazosin, antagonized medetomidine-induced diuresis. The antidiuretic effect of atipamezole was more potent than that of yohimbine, but was not dose dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed medetomidine-induced decreases in both urine specific gravity and osmolality and increases in plasma osmolality and free-water clearance. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP level, although the highest dose of both atipamezole and yohimbine initially and temporarily increased plasma AVP levels, suggesting that this may partly influence the antidiuretic effects of both agents. The diuretic effect of medetomidine in cats may be mediated by α2-adrenoceptors, but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against medetomidine-induced diuresis in healthy cats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982822PMC
http://dx.doi.org/10.1292/jvms.13-0398DOI Listing
March 2014

[Steroid responsive anti-Hu-associated paraneoplastic encephalitis with bilateral frontal lobe lesions].

Rinsho Shinkeigaku 2013 ;53(4):273-7

Department of Internal Medicine, Division of Neurology, Hyogo College of Medicine.

A 46-year-old woman was admitted to our hospital because of behavioral changes. Her mentality was fluctuating vigorously and neurological examination revealed disorientation and word finding difficulty. MRI demonstrated bilateral frontal and right temporal lesions. Cerebrospinal fluid examination showed predominantly lymphocytic pleocytosis. Brain biopsy disclosed inflammation but not neoplasm. Repeated steroid therapy gave her a recovery in neurological manifestations and MRI findings. As we got a positive result of anti-Hu antibody after her complete recovery, we did screening for tumors and found small cell lung cancer. She got a chemotherapy and remains free of relapse of any symptoms. There have been few reports in that anti-Hu associated paraneolastic syndrome showed steroid responsive frontal lesions. We suggest that anti-Hu associated paraneoplastic encephalitis should be considered for steroid responsive encephalitis with brain lesions other than limbic system, because early detection of paraneoplastic encephalitis and timely antitumor treatment are important for patient's prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5692/clinicalneurol.53.273DOI Listing
February 2014

Correlation of subthalamic nuclei T2 relaxation times with neuropsychological symptoms in patients with Parkinson's disease.

J Neurol Sci 2012 Apr 26;315(1-2):96-9. Epub 2011 Nov 26.

Department of Internal Medicine, Division of Neurology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.

The subthalamic nucleus (STN) is a frequent target of deep brain stimulation (DBS), which is used to treat patients with advanced Parkinson's disease (PD). However, few studies have assessed the relationship between the STN and the clinical characteristics of PD patients. We identified the STN of 17 PD patients and 7 control subjects using coronal Short TI Inversion Recovery (STIR) magnetic resonance imaging (MRI) and estimated the T2 relaxation time (T2) of the STN on the subsequent coronal images that were acquired from T2-weighted MRI. The relationships between the STN T2 measurements and the PD patients' age, disease duration, laterality, and clinical scores were examined. STN T2 measurements tended to be lower in PD patients than in controls, although the difference was not significant. STN T2 measurements were significantly and inversely correlated (p=0.03) with scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part 1, which was applied to evaluate the mentation, behavior, and mood of PD patients. However, no significant correlations were found between the STN T2 measurements and the patients' age, disease duration, laterality, or motor clinical scores. These results suggest that degeneration of the STN in PD patients may contribute to their neuropsychological symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2011.11.018DOI Listing
April 2012

Susceptibility of juvenile humpback grouper Cromileptes altivelis to grouper sleepy disease iridovirus (GSDIV).

Dis Aquat Organ 2004 Apr;59(1):1-9

Gondol Research Institute for Mariculture, PO Box 140, Singaraja, Bali, Indonesia.

Susceptibility of juvenile humpback grouper Cromileptes altivelis to the grouper sleepy disease iridovirus (GSDIV) was examined. GSDIV-containing inocula for challenge were obtained using a filtrate of spleen tissues from donor fish (orange-spotted grouper Epinephelus coioides) infected with GSDIV. Groups injected with the primary filtrate showed lower mortalities (30 to 60%) than groups receiving the 10(-4) diluted inoculum (90 to 100% mortality). This result was contrary to the expectation that fish challenged with a higher concentration of virus would show higher mortality. Electron microscopy revealed that moribund fish receiving the 10(-4) diluted inoculum displayed massive formation of typical inclusion body-bearing cells (IBCs) containing an intracytoplasmic inclusion body with many virions in the 180-200 nm size range propagated within a virus assembly site. In contrast, survivors in fish receiving the primary filtrate showed the formation of unusual IBCs containing an abnormal inclusion body that was characterized by the assembly of a small number of deformed virions. This impaired virus assembly appeared to prevent mortality in the challenged fish and was assumed to be due to an interferon-like effect of a previously unknown substance that was passed on to the challenged fish with the tissue filtrate from the donor fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3354/dao059001DOI Listing
April 2004