Publications by authors named "Takahiro Kamiya"

50 Publications

Ankylosing spondylitis, Crohn's disease, and myelodysplasia in an adolescent.

Pediatr Int 2022 01;64(1):e15215

Department of Lifetime Clinical Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.15215DOI Listing
January 2022

The ontogeny of two species of the family Notodromadidae (Cypridoidea, Ostracoda, Crustacea); taxonomic and palaeogeographic significance.

Zootaxa 2022 Feb 4;5094(3):351-395. Epub 2022 Feb 4.

Institute of Science and Engineering, Faculty of Geosciences and Civil Engineering , Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.

Details of the post-embryonic development of two Notodromadidae species, Notodromas trulla Smith Kamiya, 2014 and Newnhamia fenestrata King, 1855, (subfamily Notodromadinae) are provided, and compared with previous ontogenetic studies on other podocopid families and superfamilies. The ontogenetic development is generally similar to other families, consisting of eight free-living juvenile stages and one adult stage, but the first instar, with a leg-like mandible, resembles that of the Cyprididae, rather than other families. From the A-7 instar onwards, the ventral margin of the carapace is a flattened ovoid, and the dorsolateral eye cups are separated, resembling those of the adults, suggesting that a neustonic lifestyle, similar to that of the adults, is embraced from a very early age. In addition to the ventral margin, other apomorphies of the Notodromadinae include spur-like protrusions on the walking legs of juveniles, which become reduced in adults, and features of the mandibles, probably related to neustonic feeding. Overall, Ne. fenestrata has more plesiomorphic features than No. trulla, and most differences between the two species are related to sexually selected characters, such as different sexually dimorphic features of the antennae. This suggests that sexual selection has been the main evolutionary driving force causing morphological divergence in the subfamily. The two taxa, one from Japan (No. trulla), the other Australia (Ne. fenestrata), have perhaps been separated since the breakup of Pangaea, which started in the Middle Jurassic. This suggests that despite the long geographical isolation, many aspects of ostracod anatomy have remained unchanged over long periods of time. On reviewing the taxonomy of the family, we conclude that monophyly needs to be confirmed with further work, and the subfamily Notodromadinae can be divided into two groups: the Notodromas-group and the Newnhamia-group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11646/zootaxa.5094.3.1DOI Listing
February 2022

Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control.

Drug Test Anal 2022 Jul 7;14(7):1244-1254. Epub 2022 Mar 7.

Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.

IOX4, a hypoxia-inducible factor stabilizer, is classified as a banned substance for horses in both horse racing and equestrian sports. We recently reported the pharmacokinetic profiles of IOX4 in horse plasma and urine and also identified potential monitoring targets for the doping control purpose. In this study, a long-term longitudinal analysis of IOX4 in horse hair after a nasoesophageal administration of IOX4 (500 mg/day for 3 days) to three thoroughbred mares is presented for the first time for controlling the abuse/misuse of IOX4. Six bunches of mane hair were collected at 0 (pre), 1, 2, 3, and 6 month(s) postadministration. Our results showed that the presence of IOX4 was identified in all postadministration horse hair samples, but no metabolite could be detected. The detection window for IOX4 could achieve up to 6-month postadministration (last sampling point) by monitoring IOX4 in hair. In order to evaluate the longitudinal distribution of IOX4 over 6 months, a validated quantification method of IOX4 in hair was developed for the analysis of the postadministration samples. Segmental analysis of 2-cm cut hair across the entire length of postadministration hair showed that IOX4 could be quantified up to the level of 1.84 pg/mg. In addition, it was found that the movement of the incorporated IOX4 band in the hair shaft over 6 months varied among the three horses due to individual variation and a significant diffusion of IOX4 band up to 10 cm width was also observed in the 6-month postadministration hair samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.3247DOI Listing
July 2022

Successful ruxolitinib administration for a patient with steroid-refractory idiopathic pneumonia syndrome following hematopoietic stem cell transplantation: A case report and literature review.

Clin Case Rep 2021 Dec 22;9(12):e05242. Epub 2021 Dec 22.

Department of Pediatrics and Developmental Biology Tokyo Medical and Dental University Tokyo Japan.

Idiopathic pneumonia syndrome (IPS) is an acute lung complication observed after the early posthematopoietic stem cell transplantation (HSCT) period. Ruxolitinib was effective for a patient with myelodysplastic syndrome who developed severe IPS after second HSCT. No severe adverse effects were observed. Ruxolitinib may be an alternative choice for HSCT-related IPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.5242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693824PMC
December 2021

Efficacy of ondansetron against emesis induced by a multiple-day cisplatin-based chemotherapy regimen for malignant lymphoma.

Hematology 2021 Dec;26(1):945-949

Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Objectives: This study aimed to evaluate the antiemetic efficacy of a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), ondansetron, in patients with malignant lymphoma receiving multi-day cisplatin-based combination chemotherapy.

Methods: We conducted a single-institution retrospective analysis of patients receiving the first course of an ESHAP (etoposide, cisplatin, methylprednisolone, cytarabine) regimen including 4-day continuous infusion of cisplatin (25 mg/m/day). All patients received ondansetron 4 mg intravenously during 5-day administration of ESHAP. The primary endpoint was complete response (CR) for emesis, which was defined as absence of both emesis and rescue medications. Total control (TC) was defined as an absence of emetic episodes, including nausea and emesis, and complete protection (CP) was defined as an absence of emesis with addition of rescue antiemetics. Nausea and vomiting were assessed and graded daily by medical staff.

Results: Eighty-two patients were analyzed. Nausea and vomiting were generally well controlled, with the CR rates of emesis being 79% in the overall phase, 82% in the early phase (days 1-6), and 89% in the delayed phase (days 7-10). TC and CP were achieved in 51 patients (62%) and 77 patients (94%) in the overall phase.

Discussion: Most of the chemotherapy regimens for lymphoid malignancies include high-dose corticosteroid which may be also effective as antiemetics. Although NK1 receptor antagonist (NK1RA) is generally recommended for cisplatin-containing chemotherapy, it can interact with variety drugs.

Conclusion: Although NK1RA is generally recommended for cisplatin-containing regimen, our results suggest that ondansetron effectively controlled emesis in patients receiving ESHAP therapy which includes high-dose corticosteroid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/16078454.2021.2001150DOI Listing
December 2021

Vedolizumab therapy for pediatric steroid-refractory gastrointestinal acute graft-versus-host disease.

Int J Hematol 2022 Apr 1;115(4):590-594. Epub 2021 Nov 1.

Department of Pediatrics, Tokyo Medical and Dental University Hospital, Tokyo, Japan.

Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.5-4.4 years. It was significantly effective in two patients and did not cause serious side effects in any patient. Vedolizumab might be effective and safe for pediatric GI-aGVHD refractory to other treatments, but this must be confirmed in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-021-03245-0DOI Listing
April 2022

Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometer for the purpose of doping control.

Drug Test Anal 2022 Feb 21;14(2):233-251. Epub 2021 Oct 21.

Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Tochigi, Japan.

IOX4 is a hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitor, which was developed for the treatment of anemia by exerting hematopoietic effects. The administration of HIF-PHD inhibitors such as IOX4 to horses is strictly prohibited by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale. To the best of our knowledge, this is the first comprehensive metabolic study of IOX4 in horse plasma and urine after a nasoesophageal administration of IOX4 (500 mg/day, 3 days). A total of four metabolites (three mono-hydroxylated IOX4 and one IOX4 glucuronide) were detected from the in vitro study using homogenized horse liver. As for the in vivo study, post-administration plasma and urine samples were comprehensively analyzed with liquid chromatography/electrospray ionization high-resolution mass spectrometry to identify potential metabolites and determine their corresponding detection times. A total of 10 metabolites (including IOX4 glucuronide, IOX4 glucoside, O-desbutyl IOX4, O-desbutyl IOX4 glucuronide, four mono-hydroxylated IOX4, N-oxidized IOX4, and N-oxidized IOX4 glucoside) were found in urine and three metabolites (glucuronide, glucoside, and O-desbutyl) in plasma. Thus, the respective quantification methods for the detection of free and conjugated IOX4 metabolites in urine and plasma with a biphase enzymatic hydrolysis were developed and applied to post-administration samples for the establishment of elimination profiles of IOX4. The detection times of total IOX4 in urine and plasma could be successfully prolonged to at least 312 h.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.3172DOI Listing
February 2022

[Viral infections after hematopoietic cell transplantation and treatment with virus-specific T-cell therapies].

Rinsho Ketsueki 2021 ;62(8):1334-1342

Department of Pediatrics, Tokyo Medical and Dental University Medical hospital.

Viral infections are one of the leading causes of death in hematopoietic cell transplantation (HCT) and are a problem that should be resolved. For post-HCT viral infections, reduction of antiviral treatment or immunosuppressive drug dose is generally performed; however, the effect of antiviral drug is sometimes limited, and reduction of immunosuppressive treatment might worsen the graft-versus-host disease. Therefore, appropriate infection preventive measures and early diagnosis and therapeutic intervention for viral infections are important. In addition, virus-specific T-cell (VST) therapy is attracting attention as a new treatment method for intractable and refractory post-HCT viral infections. Various methods have been developed to establish VSTs, from a single- to multiple-virus targeting and from related- to third-party-derived donors. Its safety and efficacy have already been reported in clinical trials, and thereby, it is expected to be established as one of the important treatments for post-HCT viral infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.62.1334DOI Listing
September 2021

Myelodysplastic Syndrome in a Patient with IPEX Syndrome.

J Clin Immunol 2021 10 12;41(7):1683-1685. Epub 2021 Jul 12.

Department of Pediatrics, Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-021-01092-6DOI Listing
October 2021

Hematopoietic Cell Transplantation Rescues Inflammatory Bowel Disease and Dysbiosis of Gut Microbiota in XIAP Deficiency.

J Allergy Clin Immunol Pract 2021 10 8;9(10):3767-3780. Epub 2021 Jul 8.

Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address:

Background: X-linked inhibitor of apoptosis protein (XIAP) deficiency is an infrequent inborn error of immunity that is often associated with refractory inflammatory bowel disease (IBD). The natural course of XIAP deficiency is typically associated with poor prognosis, and hematopoietic cell transplantation (HCT) is the only curative treatment.

Objective: To study (1) the effect of HCT on patients with XIAP deficiency undergoing HCT, (2) the status of XIAP deficiency-associated IBD after HCT, and (3) the gut microbiota of XIAP deficiency-associated IBD before and after HCT.

Methods: A nationwide survey of patients with XIAP deficiency was conducted. A spreadsheet questionnaire was collected from the physicians. Feces samples collected from the patients before and after HCT and their healthy family members were analyzed.

Results: Twenty-six patients with XIAP deficiency underwent HCT by the end of March 2020, and 22 patients (84.6%) survived. All the survivors underwent a fludarabine-based reduced-intensity condition regimen. Acute graft-versus-host disease was observed in 17 patients (65.4%). Nineteen patients experienced refractory IBD before undergoing HCT. IBD improved remarkably after HCT. After HCT, the colonoscopic and pathological symptoms were restored to normal, and the pediatric ulcerative colitis activity index improved significantly. Gut microbiota indicated dysbiosis before HCT; however, it was improved to resemble that of the healthy family members after HCT.

Conclusions: This study revealed that HCT has a favorable outcome for XIAP deficiency. HCT rescues gut inflammation and dysbiosis in patients with XIAP deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaip.2021.05.045DOI Listing
October 2021

Therapeutic options for CTLA-4 insufficiency.

J Allergy Clin Immunol 2022 02 7;149(2):736-746. Epub 2021 Jun 7.

The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania.

Background: Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness.

Objective: Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level.

Methods: Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated.

Results: Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed.

Conclusion: Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.04.039DOI Listing
February 2022

Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases.

J Clin Immunol 2021 07 1;41(5):944-957. Epub 2021 Feb 1.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Purpose: The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID).

Methods: We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID.

Results: The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival.

Conclusions: RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-021-00966-zDOI Listing
July 2021

Duodenal nodular lymphoid hyperplasia in a patient with IgA deficiency.

Clin Case Rep 2020 Dec 8;8(12):3594-3595. Epub 2020 Sep 8.

Department of Hematology National Cancer Center Hospital Tokyo Japan.

Most patients with IgA deficiency are asymptomatic, but duodenal nodular lymphoid hyperplasia is one symptom known to be associated with common variable immunodeficiency (CVID), including selective IgA deficiency and agammaglobulinemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccr3.3298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752382PMC
December 2020

Cytomegalovirus Laryngitis in Primary Combined Immunodeficiency Diseases.

J Clin Immunol 2021 01 8;41(1):243-247. Epub 2020 Oct 8.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-020-00873-9DOI Listing
January 2021

[Systemic varicella-zoster infection during ixazomib-containing multiagent chemotherapy for multiple myeloma].

Rinsho Ketsueki 2020 ;61(8):870-873

Division of Hematology, Department of Medicine, Keio University School of Medicine.

A 58-year-old man received high-dose melphalan with autologous peripheral blood stem cell transplantation for multiple myeloma in stringent complete response (sCR). Relapse occurred 4 years after the transplantation, and he was placed on ixazomib, lenalidomide, and dexamethasone (IRd) and achieved sCR. On the 10th day of the 10th course of IRd, he developed fever followed by generalized skin eruption with vesicles, headache, and dizziness. Varicella-zoster virus (VZV) antigen from the vesicle and VZV-DNA from the cerebrospinal fluid were detected, and he was diagnosed with systemic VZV infection. He was placed on intravenous acyclovir (ACV), and the infection resolved completely. VZV infection has been recognized as an important complication associated with the use of proteasome inhibitors; however, to our knowledge, there have been no reported cases of serious systemic VZV infection associated with ixazomib. The clinical course of this case strongly suggests the importance of prophylaxis for VZV infection during treatment with ixazomib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.61.870DOI Listing
October 2020

Interleukin-6-producing Intravascular Large B-cell Lymphoma with Lymphadenopathy Mimicking the Histology of Multicentric Castleman Disease.

Intern Med 2020 Dec 4;59(23):3061-3065. Epub 2020 Aug 4.

Division of Hematology, Department of Medicine, Keio University School of Medicine, Japan.

An inguinal lymph node biopsy of a woman with a one-month history of a progressive fever, fatigue, dyspnea, skin rash, and lymphadenopathy revealed a well-preserved basic structure, hyperplastic germinal centers, and an interfollicular region containing polyclonal plasma cell sheets, suggesting plasma cell-type multicentric Castleman disease (MCD). We initiated prednisolone and anti-interleukin (IL)-6 antibody (tocilizumab), without success. A biopsy specimen re-evaluation detected CD20-positive atypical large B cells infiltrating the small vessels within and around the lymph node and its capsule. We diagnosed her with intravascular large B-cell lymphoma (IVLBCL). Lymphoma cells were weakly positive for IL-6 by immunohistochemical staining. IL-6 from lymphoma cells may have caused the MCD-like presentation as a paraneoplastic etiology. Malignant lymphoma should be excluded before diagnosing MCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.5046-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759707PMC
December 2020

Inherited chromosomally integrated human herpesvirus-6 in a patient with XIAP deficiency.

Transpl Infect Dis 2020 Oct 8;22(5):e13331. Epub 2020 Jun 8.

Deprtment of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Human herpesvirus-6 (HHV-6) is a common pathogen affecting the human population. Primary HHV-6 infection generally occurs during infancy and causes exanthema subitum. Moreover, HHV-6 may exhibit inherited chromosomally integrated HHV-6 (iciHHV-6) in certain individuals. Although iciHHV-6 is generally known to be nonpathogenic, it may cause reactivation in patients with primary immunodeficiency disease (PID). XIAP deficiency is a rare PID characterized by recurrent hemophagocytic lymphohistiocytosis (HLH). It has been reported that the Epstein-Barr virus primarily causes HLH; however, the other pathogens, including HHV-6, can also cause this complication. We encountered a case of XIAP deficiency accompanied by iciHHV-6. He suffered from recurrent HLH, for which allogeneic bone marrow transplantation (BMT) was performed as a curative therapy. During the course of BMT, the patient experienced HLH three times, but there was no reactivation of endogenous HHV-6 from iciHHV-6. Finally, the patient achieved complete donor chimerism and a decline in HHV-6 DNA copy number in whole blood. This case report demonstrates no evidence of reactivation of iciHHV-6 during BMT in a patient with XIAP deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tid.13331DOI Listing
October 2020

The prognostic value of the controlling nutritional status score in patients with multiple myeloma.

Leuk Lymphoma 2020 08 19;61(8):1894-1900. Epub 2020 Apr 19.

Department of Hematology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.

The Controlling Nutritional Status (CONUT) score predicts the prognosis in several tumors. However, its prognostic significance in multiple myeloma (MM) remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of MM patients. A total of 178 patients newly diagnosed with MM were retrospectively enrolled. Patients with a high CONUT score (≥5) had a significantly shorter median overall survival (OS) than those with a low CONUT score (≤4) (33 vs. 57 months,  < .001). In a multivariate analysis among patients with International Staging System (ISS) score of ≤2, a high CONUT score was an independent prognostic covariate for the OS after adjusting for other significant factors (hazard ratio 2.364; 95% confidence interval 1.324-4.220,  = .004). Our results suggest that the CONUT score is a predictor of a poor outcome in patients with MM, particularly in low-ISS-score cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1749608DOI Listing
August 2020

Hematopoietic stem cell transplantation recovers insulin deficiency in type 1 diabetes mellitus associated with IPEX syndrome.

Pediatr Diabetes 2019 11 24;20(7):1035-1040. Epub 2019 Jul 24.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is an autoimmune disorder caused by the dysfunction of FOXP3, which leads to regulatory T-(Treg) cell dysfunction and subsequently autoimmunity including type 1 diabetes mellitus (T1D). Presently, allogeneic hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for IPEX syndrome, but not for T1D. Generally, after complete loss of pancreatic β-cells, HSCT cannot improve the prognosis of T1D. Here, we report the case of a 16-year-old adolescent with late-onset of FOXP3 R347H mutation associated IPEX syndrome with T1D, where insulin dependency was ameliorated following HSCT. This patient with insulin-dependent diabetes mellitus required insulin dosage of 1.28 U/kg/day for 1 month before HSCT. Although the results of glucose homeostasis before HSCT revealed impaired insulin secretion and low ΔC-peptide immunoreactivity (CPR, 1.0 ng/mL), the patient withdrew insulin infusion and remained euglycemic at 15 months after HSCT, and had normal β-cell function with improved ΔCPR (3.4 ng/mL) at 20 months after HSCT. The present case suggests that HSCT for T1D-associated IPEX syndrome improves Treg deficiency and prevents elimination of β-cells. We speculate that the period from the onset of T1D to HSCT could affect the therapeutic efficacy for T1D with IPEX, and early intervention with HSCT before or immediately after the onset of DM can rescue β-cells and remit T1D completely. Our study elaborates not only the therapeutic strategy for T1D with IPEX, but also the pathogenic mechanism in general T1D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pedi.12895DOI Listing
November 2019

The prognostic value of geriatric nutritional risk index in patients with follicular lymphoma.

Ann Hematol 2019 Jul 30;98(7):1777-1779. Epub 2019 Apr 30.

Division of Hematology, Keio University School of Medicine, Tokyo, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-019-03703-0DOI Listing
July 2019

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells.

J Clin Invest 2019 05 12;129(5):2094-2106. Epub 2019 Mar 12.

Department of Pediatrics and National University Cancer Institute Singapore, National University of Singapore, Singapore.

A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA-E in tumor cells, which suppresses natural killer (NK) cell activity via ligation of the NK inhibitory receptor CD94/NKG2A. Gene expression data from approximately 10,000 tumor samples showed widespread HLAE expression, with levels correlating with those of KLRC1 (NKG2A) and KLRD1 (CD94). To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. Constructs containing a single-chain variable fragment derived from an anti-NKG2A antibody were linked to endoplasmic reticulum-retention domains. After retroviral transduction in human peripheral blood NK cells, these NKG2A Protein Expression Blockers (PEBLs) abrogated NKG2A expression. The resulting NKG2Anull NK cells had higher cytotoxicity against HLA-E-expressing tumor cells. Transduction of anti-NKG2A PEBL produced more potent cytotoxicity than interference with an anti-NKG2A antibody and prevented de novo NKG2A expression, without affecting NK cell proliferation. In immunodeficient mice, NKG2Anull NK cells were significantly more powerful than NKG2A+ NK cells against HLA-E-expressing tumors. Thus, NKG2A downregulation evades the HLA-E cancer immune-checkpoint, and increases the anti-tumor activity of NK cell infusions. Because this strategy is easily adaptable to current protocols for clinical-grade immune cell processing, its clinical testing is feasible and warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI123955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486333PMC
May 2019

Epstein-Barr Virus-Associated γδ T-Cell Lymphoproliferative Disorder Associated With Hypomorphic Mutation.

Front Pediatr 2019 4;7:15. Epub 2019 Feb 4.

Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an EBV-associated lymphoproliferative disease characterized by repeated or sustainable infectious mononucleosis (IM)-like symptoms. EBV is usually detected in B cells in patients who have IM or Burkitt's lymphoma and even in patients with X-linked lymphoproliferative syndrome, which is confirmed to have vulnerability to EBV infection. In contrast, EBV infects T cells (CD4 T, CD8 T, and γδT) or NK cells mono- or oligoclonally in CAEBV patients. It is known that the CAEBV phenotypes differ depending on which cells are infected with EBV. CAEBV is postulated to be associated with a genetic immunological abnormality, although its cause remains undefined. Here we describe a case of EBV-related γδT-cell proliferation with underlying hypomorphic mutation. The immunological phenotype consisted of γδT-cell proliferation in the peripheral blood. A presence of EBV-infected B cells and γδT cells mimicked γδT-cell-type CAEBV. Although the patient had normal expression of CD132 (common γ chain), the phosphorylation of STAT was partially defective, indicating impaired activation of the downstream signal of the JAK/STAT pathway. Although the patient was not diagnosed as having CAEBV, this observation shows that CAEBV might be associated with immunological abnormality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2019.00015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369201PMC
February 2019

The prognostic value of circulating myeloblasts in patients with myelodysplastic syndromes treated with azacitidine.

Med Oncol 2019 Jan 31;36(3):25. Epub 2019 Jan 31.

Department of Hematology, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama, 240-8555, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12032-019-1247-3DOI Listing
January 2019

Novel Cardinium strains in non-marine ostracod (Crustacea) hosts from natural populations.

Mol Phylogenet Evol 2019 01 21;130:406-415. Epub 2018 Sep 21.

Royal Belgian Institute of Natural Sciences, OD Nature, Freshwater Biology, Brussels, Belgium; University of Ghent, Dept Biology, Ghent, Belgium.

Endosymbiotic bacteria are known from many metazoan taxa, where they manipulate host biology and reproduction. Here, we used classic PCR amplification and direct DNA sequencing with universal primers for four different endosymbionts to test for their presence in more than 300 specimens of three recent non-marine ostracod superfamilies from different geographic areas and aquatic habitats. We verified these results with "high throughput" amplicon sequencing of 16S of nine selected specimens and evolutionary placement algorithms. The phylogenetic position of endosymbionts detected in ostracod hosts was compared to known endosymbionts from other metazoans. While Wolbachia, Spiroplasma and Rickettsia are absent, we find evidence for the general presence of Cardinium bacteria in natural populations of various non-marine ostracod species. Phylogenetic reconstructions based on Cardinium 16S data and estimates of genetic distances both indicate that Cardinium from ostracods are distantly related to Cardinium from Diptera and Nematoda but represent novel strains with a monophyletic origin. Cardinium bacteria from different ostracod hosts have genetic distances of up to 3.8%, providing evidence against recent and frequent horizontal transmissions amongst the three ostracod superfamilies. High throughput sequencing reveals more than 400 different 16S amplicon sequence variants in the investigated ostracods as well as the presence of different Cardinium strains within individual Eucypris virens and Heterocypris hosts. These results call for future, more in-depth investigations. Mapping Cardinium infections on COI trees of non-marine ostracod hosts shows that the occurrence of these endosymbionts is not linked to genetic species identity or phylogenetic host groups and, except for one ostracod morphospecies, prevalence never reaches 100%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ympev.2018.09.008DOI Listing
January 2019

A novel method to generate T-cell receptor-deficient chimeric antigen receptor T cells.

Blood Adv 2018 03;2(5):517-528

Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Practical methods are needed to increase the applicability and efficacy of chimeric antigen receptor (CAR) T-cell therapies. Using donor-derived CAR-T cells is attractive, but expression of endogenous T-cell receptors (TCRs) carries the risk for graft-versus-host-disease (GVHD). To remove surface TCRαβ, we combined an antibody-derived single-chain variable fragment specific for CD3ε with 21 different amino acid sequences predicted to retain it intracellularly. After transduction in T cells, several of these protein expression blockers (PEBLs) colocalized intracellularly with CD3ε, blocking surface CD3 and TCRαβ expression. In 25 experiments, median TCRαβ expression in T lymphocytes was reduced from 95.7% to 25.0%; CD3/TCRαβ cell depletion yielded virtually pure TCRαβ-negative T cells. Anti-CD3ε PEBLs abrogated TCRαβ-mediated signaling, without affecting immunophenotype or proliferation. In anti-CD3ε PEBL-T cells, expression of an anti-CD19-41BB-CD3ζ CAR induced cytokine secretion, long-term proliferation, and CD19 leukemia cell killing, at rates meeting or exceeding those of CAR-T cells with normal CD3/TCRαβ expression. In immunodeficient mice, anti-CD3ε PEBL-T cells had markedly reduced GVHD potential; when transduced with anti-CD19 CAR, these T cells killed engrafted leukemic cells. PEBL blockade of surface CD3/TCRαβ expression is an effective tool to prepare allogeneic CAR-T cells. Combined PEBL and CAR expression can be achieved in a single-step procedure, is easily adaptable to current cell manufacturing protocols, and can be used to target other T-cell molecules to further enhance CAR-T-cell therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2017012823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851418PMC
March 2018
-->