Publications by authors named "Makoto Mochizuki"

28 Publications

  • Page 1 of 1

Renal Involvement as Rare Acute Tubulointerstitial Nephritis in a Patient with Eosinophilic Disorder Treated with Early Add-on Administration of Mepolizumab.

Intern Med 2021 Jun 5. Epub 2021 Jun 5.

Department of Internal Medicine, Teikyo University School of Medicine, Japan.

A 39-year-old man presented with peripheral eosinophilia, pulmonary eosinophilic infiltrate, and renal failure due to acute tubulointerstitial nephritis (TIN). He had experienced childhood asthma and was negative for anti-neutrophil cytoplasmic antibody (ANCA). He was tentatively diagnosed with ANCA-negative eosinophilic granulomatous polyangiitis (EGPA) or idiopathic hypereosinophilic syndrome (HES). Renal involvement of isolated TIN with eosinophil infiltration is rare in EGPA and HES and does not seem to have a good prognosis in the literature. However, his condition improved well with corticosteroids and mepolizumab. The revised classification of EGPA based on the etiology should dictate the proper treatment in suspected EGPA patients with nonsystemic vasculitis.
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http://dx.doi.org/10.2169/internalmedicine.7490-21DOI Listing
June 2021

Pyuria without Casts and Bilateral Kidney Enlargement Are Probable Hallmarks of Severe Acute Kidney Injury Induced by Acute Pyelonephritis: A Case Report and Literature Review.

Intern Med 2021 Jan 5;60(2):293-298. Epub 2020 Sep 5.

Department of Internal Medicine, Teikyo University School of Medicine, Japan.

The patient was a 38-year-old man who had experienced nausea and fever for a few days and presented with back pain, oliguria, and pyuria, suggesting acute pyelonephritis (APN). He showed acute kidney injury (AKI) with bilateral kidney enlargement and was using nonsteroidal anti-inflammatory drugs (NSAIDs). AKI-induced by APN was confirmed by kidney biopsy. The AKI was successfully treated with antibiotic therapy. A search of the relevant literature for reports on histopathologically-proven APN-induced severe AKI revealed that the key characteristics were bilateral kidney enlargement with pyuria without casts. Oligoanuria was frequently associated with APN-induced severe AKI, and NSAID use may be a possible risk factor. Prompt antibiotic treatment based on the clinical characteristics of APN-induced AKI can improve the renal outcome.
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http://dx.doi.org/10.2169/internalmedicine.5721-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872795PMC
January 2021

Assessment of preoperative pancreatic biopsy, cytological/histological review of cell-block-specimens obtained by endoscopic ultrasound-guided fine-needle aspiration: Laboratory-based study.

Diagn Cytopathol 2020 Apr 11;48(4):408-413. Epub 2019 Dec 11.

Department of Gastroenterology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.

Background: Pancreatic cancer is among the most lethal cancers worldwide due to the limited availability of techniques for early detection of signs and symptoms. Reportedly, it is the fourth-leading cause of cancer-related mortality among Japanese adults. With the advent of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing pancreatic cancer, the rate of the cytological and histological diagnoses of cell-block-specimens has significantly increased in Japan.

Methods: The cytological specimens of 165 patients with pancreatic lesions obtained using EUS-FNA between January 2010 and July 2016 at the Kyorin University Hospital were investigated. The clinical course of 153 patients was assessed from their clinical records, which included information on their imaging diagnosis, laboratory data, final clinical diagnosis and treatment; moreover, the accuracy of the cytological/histological examination and clinical diagnosis at our hospital were analysed.

Results: The number of cells in cell-block-specimens was too small to estimate data. However, cytological specimens were sufficient to observe the findings of suspected malignancy such as necrosis. Biopsy was deemed necessary for diagnosis using both histological and cytological specimens.

Conclusion: EUS-FNA can be used not only to diagnose benign or malignant types of pancreatic cancers but also to assess the sensitivity of molecular target drugs and chemotherapy methods. Therefore, both histological and cytological diagnoses are required to enhance diagnostic precision both in our hospital and at other institutions.
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http://dx.doi.org/10.1002/dc.24358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079018PMC
April 2020

Late-stage myeloma invades kidney without significant effect on renal function: findings from 53 autopsies in a single institute.

Int J Hematol 2019 Feb 16;109(2):147-153. Epub 2018 Oct 16.

Division of Hematology, Internal Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan.

Renal manifestations of multiple myeloma (MM) including cast nephropathy, amyloidosis, and renal calcification have been widely recognized. However, the severity of histopathological findings has not been addressed so far, and the clinical significance of these pathological findings is unclear. We sought to clarify the relationship between the severity of renal pathology and clinical characteristics. We analyzed 53 autopsies performed on patients who died from MM. The kidneys were evaluated using light microscopy, and the severity of pathological findings was recorded. The most common renal lesion was cast nephropathy (n = 27). Other findings included amyloidosis (n = 10), renal calcification (n = 5), microbial infection (n = 4), and MM infiltration (n = 17). The incidence of MM infiltration was substantially higher than previously reported. Renal MM infiltration was detected even when bone marrow plasmacytosis was limited. However, a significantly higher degree of renal MM infiltration was observed when MM cells invaded the liver. No correlation was observed between serum creatinine levels and degree of MM infiltration, but these tended to be elevated when cast nephropathy was severe. These findings may provide clues to understand both renal injury and extramedullary diseases in patients with MM.
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http://dx.doi.org/10.1007/s12185-018-2546-8DOI Listing
February 2019

A Caucasian American patient with celiac disease diagnosed in Japan and successfully treated with a gluten-free diet.

Clin J Gastroenterol 2018 Feb 1;11(1):23-28. Epub 2017 Nov 1.

Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.

We report the case of a 33-year-old Caucasian American man diagnosed with celiac disease in Japan. He presented to a community hospital because of chronic watery diarrhea and weight loss for 6 months. The laboratory data showed low serum albumin and serum cholesterol. A colonoscopy was normal. He was referred to our hospital for further work-up. Serum tissue transglutaminase immunoglobulin A (IgA) and endomysial antibody were positive. The HLA type was DQ2. Esophagogastroduodenoscopy (EGD) revealed nodular and mosaic-patterned mucosa from the bulb to the second part of the duodenum. The histopathological findings were consistent with Marsh type 3c of the modified Marsh classification for celiac disease. The patient was instructed to follow a gluten-free diet (GFD). Six months after the initiation of the GFD, his symptom and the levels of serum albumin and cholesterol were improved, and the serum tissue transglutaminase IgA and endomysial antibody became negative. However, EGD showed little improvement. Capsule endoscopy also revealed mosaic-patterned mucosa, nodular mucosa, and scalloping of the folds of the duodenum and proximal small intestine. There was no definite improvement in histopathological findings. Collectively, the GFD was effective in this patient with celiac disease, but it should be maintained to achieve endoscopic and histopathologic healing.
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http://dx.doi.org/10.1007/s12328-017-0794-4DOI Listing
February 2018

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.

Oncol Lett 2017 Jul 11;14(1):119-126. Epub 2017 May 11.

Department of Pathology, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.

The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.
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http://dx.doi.org/10.3892/ol.2017.6156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494860PMC
July 2017

Finegoldia magna myometritis with uterine necrosis after uterine artery embolisation.

J Obstet Gynaecol 2017 Jul 20;37(5):688-689. Epub 2017 Mar 20.

a Department of Obstetrics and Gynecology , Kyorin University School of Medicine , Tokyo , Japan.

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http://dx.doi.org/10.1080/01443615.2017.1286303DOI Listing
July 2017

Non-uniform Progression of Chronic Tubulointerstitial Nephritis and Widespread Nephrocalcification in a Patient with Anorexia Nervosa.

Intern Med 2017 1;56(5):545-549. Epub 2017 Mar 1.

Department of Nephrology, National Center for Global Health and Medicine, Japan.

Although patients with anorexia nervosa (anorexia) are known to show tubulointerstitial nephritis (TIN), the pathophysiology of its progression is not fully understood. We herein report a 31-year-old woman with anorexia who showed acute exacerbation of chronic kidney disease. Renal biopsy showed non-uniform chronic TIN; some areas were obsolete lesions and other areas were active lesions. In addition, many calcium-containing crystals were widely deposited in the distal tubules. The results suggest that chronic TIN in the setting of anorexia does not uniformly progress and that not only TIN but also widespread calcification of distal tubules might aggravate the renal function of anorexia patients.
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http://dx.doi.org/10.2169/internalmedicine.56.7594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399208PMC
April 2017

Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases.

Int J Hematol 2016 Dec 7;104(6):669-681. Epub 2016 Sep 7.

Center for AIDS Research, Kumamoto University, Kumamoto, Kumamoto, Japan.

Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011-12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.
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http://dx.doi.org/10.1007/s12185-016-2082-3DOI Listing
December 2016

Glioblastoma with Rhabdoid Features: Report of Two Young Adult Cases and Review of the Literature.

World Neurosurg 2016 Feb 5;86:515.e1-9. Epub 2015 Nov 5.

Department of Neurosurgery, National Center for Global Health and Medicine, Tokyo, Japan.

Background: There are few previous reports of glioblastoma in young adults, in particular, of the very rare recently proposed rhabdoid or epithelioid types.

Case Description: We report 2 cases of glioblastoma with rhabdoid features involving a 27-year-old woman and a 41-year-old man. In case 1, the patient presented with generalized seizures, and the initial magnetic resonance imaging showed a very small region of contrast in the left parahippocampal area. After 1 year, the mass suddenly increased in size. Treatment with multiple therapies was administered, but 5 months later, the patient died from multiple systemic metastases. In case 2, the patient presented with a chief complaint of headache for a few weeks. Computed tomography and magnetic resonance imaging showed a left parietal mass with calcification and meningeal dissemination. After undergoing surgical removal, his condition rapidly deteriorated until brain death occurred.

Conclusions: Glioblastoma with rhabdoid features may represent a specific pattern of clinical progression that emerges from histologic glioblastoma types.
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http://dx.doi.org/10.1016/j.wneu.2015.10.065DOI Listing
February 2016

Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into the nucleus.

Elife 2015 Apr 8;4. Epub 2015 Apr 8.

Graduate School of Life Science, University of Hyogo, Kobe, Japan.

tRNAs are unique among various RNAs in that they shuttle between the nucleus and the cytoplasm, and their localization is regulated by nutrient conditions. Although nuclear export of tRNAs has been well documented, the import machinery is poorly understood. Here, we identified Ssa2p, a major cytoplasmic Hsp70 in Saccharomyces cerevisiae, as a tRNA-binding protein whose deletion compromises nuclear accumulation of tRNAs upon nutrient starvation. Ssa2p recognizes several structural features of tRNAs through its nucleotide-binding domain, but prefers loosely-folded tRNAs, suggesting that Ssa2p has a chaperone-like activity for RNAs. Ssa2p also binds Nup116, one of the yeast nucleoporins. Sis1p and Ydj1p, cytoplasmic co-chaperones for Ssa proteins, were also found to contribute to the tRNA import. These results unveil a novel function of the Ssa2p system as a tRNA carrier for nuclear import by a novel mode of substrate recognition. Such Ssa2p-mediated tRNA import likely contributes to quality control of cytosolic tRNAs.
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http://dx.doi.org/10.7554/eLife.04659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432389PMC
April 2015

Detection of trichodysplasia spinulosa-associated polyomavirus in a fatal case of myocarditis in a seven-month-old girl.

Int J Clin Exp Pathol 2014 15;7(8):5308-12. Epub 2014 Jul 15.

Department of Pathology, National Institute of Infectious Diseases Tokyo, Japan.

Trichodysplasia spinulosa-associated polyomavirus (TSV) was identified in a seven-month-old girl with myocarditis. The number of TSV genomes detected was higher in the heart than in the other organs. The full-length TSV genome was cloned from the heart. This suggests a possible role of TSV infection in the pathogenesis of myocarditis in infants.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152105PMC
June 2015

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BMC Infect Dis 2014 Apr 29;14:229. Epub 2014 Apr 29.

Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Background: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies.

Methods: A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records.

Results: Mean CD4 counts of patients were 77.0 cells/μL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/μL in naïve patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026).

Conclusions: The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.
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http://dx.doi.org/10.1186/1471-2334-14-229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016795PMC
April 2014

Perivascular epithelioid cell tumor of the uterus.

Pathol Int 2014 Mar;64(3):151-3

Department of Pathology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan; Department of Pathology, Kyorin University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.1111/pin.12137DOI Listing
March 2014

Classification of AIDS-related lymphoma cases between 1987 and 2012 in Japan based on the WHO classification of lymphomas, fourth edition.

Cancer Med 2014 Feb 10;3(1):143-53. Epub 2014 Jan 10.

Department of Pathology and Laboratory Medicine, Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo, 108-8639, Japan.

The introduction of combined antiretroviral therapy (ART) has reduced the mortality of patients with human immunodeficiency virus-1 infection worldwide. However, malignant lymphoma is a severe and frequent complication seen in patients with acquired immunodeficiency syndrome (AIDS). The diagnostic criteria for some categories of AIDS-related lymphoma were revised in the World Health Organization International Classification of Lymphoma, fourth edition. The purpose of this study was to assess the clinicopathological characteristics of Japanese patients with AIDS-related lymphoma according to the revised classification. In this retrospective study, 207 AIDS-related lymphoma cases diagnosed between 1987 and 2012 in Japan were subjected to histological subtyping and clinicopathological analyses. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype throughout the study period (n = 104, 50%). Among the DLBCL cases, 24% were of the germinal center (GC) type and 76% were of the non-GC type. Non-GC-type cases showed a significantly lower 1-year survival rate (43%) than the GC-type cases (82%). Cases of Burkitt lymphoma (n = 57, 28%), plasmablastic lymphoma (n = 16, 8%), primary effusion lymphoma (n = 9, 4%), Hodgkin lymphoma (n = 8, 4%), and large B-cell lymphoma arising in Kaposi sarcoma-associated herpesvirus-associated multicentric Castleman disease (n = 2, 1%) were also observed. Hodgkin lymphoma was more common in patients receiving ART (11.1%) than in ART-naïve patients (1.4%). Statistical analyses identified CD10 negativity, BCL-6 negativity, Epstein-Barr virus positivity, and Kaposi sarcoma-associated herpesvirus positivity as risk factors for poor prognosis. This information will help in the early diagnosis of lymphoma in patients with AIDS.
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http://dx.doi.org/10.1002/cam4.178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930399PMC
February 2014

DNA methylation profiling can classify HIV-associated lymphomas.

AIDS 2014 Feb;28(4):503-10

aDepartment of Intractable Diseases, Research Institute, National Center for Global Health and Medicine, Shinjuku bDepartment of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Honkomagome, Bunkyo cBiostatistics Section, Department of Clinical Research and Informatics, Clinical Research Center, National Center for Global Health and Medicine, Shinjuku dDepartment of Human Genetic, School of Medicine, The University of Tokyo, Bunkyo, Tokyo eGraduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba fDepartment of Pathology gAIDS Clinical Center hDivision of Hematology, Internal Medicine, National Center for Global Health and Medicine Hospital, Shinjuku iDepartment of Pathology, School of Medicine, Kyorin University, Mitaka, Tokyo, Japan.

Background: HIV-positive patients have a 60-fold to 200-fold increased incidence of non-Hodgkin lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, and primary central nervous system lymphoma. HIV-associated lymphomas frequently have features such as extranodal involvement, decreased responses to standard chemotherapy, and high relapse rates, which indicate a poor prognosis. General pathological features do not clearly differentiate HIV-associated lymphomas from non-HIV lymphomas.

Methods: To investigate the features of HIV-associated lymphomas, we performed genome-wide DNA methylation profiling of HIV and non-HIV lymphomas using Illumina GoldenGate Methylation Cancer Panel I and Illumina Infinium HumanMethylation450 BeadChip microarrays. DNA methylation profiles in HIV-associated and non-HIV lymphomas were characterized using unsupervised hierarchical clustering analyses.

Results: The analyses of promoter regions revealed unique DNA methylation profiles in HIV-associated lymphomas, suggesting profile differences compared with non-HIV lymphomas, which implies specific gene regulation in HIV-associated lymphoma involving DNA methylation. Based on HumanMethylation450 BeadChip data, 2541 target sites were selected as differing significantly in comparisons between HIV-associated and non-HIV-associated lymphomas using Wilcoxon's rank-sum test (P <0.05) and Δβ values more than 0.30. Recurrent cases of HIV-associated lymphoma had different profiles compared with nonrecurrent HIV lymphomas.

Conclusion: DNA methylation profiling indicated that 2541 target sites differed significantly in HIV-associated lymphoma, which may partly explain the poor prognosis. Our data indicate that the methylation profiles of target genes have potential in elucidating HIV-associated lymphomagenesis and can serve as new prognostic markers.
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http://dx.doi.org/10.1097/QAD.0000000000000120DOI Listing
February 2014

Depression of local cell-mediated immunity and histological characteristics of disseminated AIDS-related Mycobacterium avium infection after the initiation of antiretroviral therapy.

Intern Med 2013 1;52(16):1793-803. Epub 2012 Mar 1.

Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Japan.

Objective: The aim of the present study was to examine the immunohistological characteristics of disseminated Mycobacterium avium infection after the initiation of antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS).

Methods: We histologically investigated five autopsied AIDS patients with systemic M. avium infection.

Results: The inflammatory cell composition in the affected tissues was assessed using immunohistochemistry. The celiac lymph nodes and intestinal canal were the most commonly involved organs in the AIDS cases. The most common histological feature was unstructured aggregation of histiocytes. Immunohistochemistry revealed depression of CD4(+), CD8(+) and CD57(+) cells in the gut lamina propria and mesenteric lymph nodes.

Conclusion: These findings suggest that local cell-mediated immunity is depressed in affected tissues and that the primary histological feature is poor organization of granulomas in mycobacterial lesions, despite the administration of adequate ART.
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http://dx.doi.org/10.2169/internalmedicine.52.9311DOI Listing
April 2014

Amyloid imaging mismatch.

Clin Nucl Med 2012 Aug;37(8):807-9

Division of Nuclear Medicine, Department of Radiology, National Center for Global Health and Medicine, Tokyo, Japan.

An 82-year-old man with suspected systemic amyloidosis and complete atrioventricular block underwent vascular biopsy during his pacemaker implantation with pathology showing amyloid deposits. 99mTc-aprotinin SPECT revealed increased radiotracer uptake along the left ventricular wall, consistent with cardiac amyloidosis. 11C-PiB PET/CT performed for the evaluation of amyloid deposits in the brain showed findings suggestive of Alzheimer disease without abnormal radiotracer concentration in the myocardium to match the 99mTc-aprotinin SPECT findings. Dynamic PET images showed increased 11C-PiB concentration in the left ventricular myocardium at 2 minutes after injection, with subsequent tracer clearance by approximately 5 minutes, consistent with normal 11C-PiB biodistribution.
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http://dx.doi.org/10.1097/RLU.0b013e318251e1d3DOI Listing
August 2012

A case of vasoproliferative retinal tumor complicated by neovascular glaucoma.

Retin Cases Brief Rep 2013 ;7(4):338-42

Departments of *Ophthalmology †Pathology, Hospital, National Center for Global Health and Medicine, Tokyo, Japan.

Purpose: To report a case of vasoproliferative retinal tumor complicated by neovascular glaucoma that showed remission after vitrectomy surgery to remove the tumor.

Methods: A 78-year-old man was referred to the hospital with a complaint of visual loss in his right eye. Corrected visual acuity was 0.5 in the right eye and 1.2 in the left eye. The right eye showed mild vitreous hemorrhage and an elevated lesion in the lower fundus. Fluorescein angiography demonstrated leakage from the tumor, and a 4-mm lesion of high density was seen on computed tomography, and we diagnosed it as retinal capillary hemangioma. In this case, von Hippel-Lindau disease was negative. During the course of the disease, peripheral anterior synechia and neovascularization was seen in the iris and angle, and vitreous surgery was enforced to remove the tumor because of increased intraocular pressure. The tumor was removed as almost one mass. Histologically, the tumor was composed of glial cells and small vessels proliferation. We diagnosed vasoproliferative retinal tumor.

Results: Seven months after surgery, the intraocular pressure stabilized, and neovascularization of the iris and angle disappeared. Visual acuity was 0.03 due to epiretinal membrane and optic atrophy. There were no signs of recurrence.

Conclusion: The vitreous surgery is one of the effective treatment methods against vasoproliferative retinal tumor complicated by neovascular glaucoma.
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http://dx.doi.org/10.1097/ICB.0b013e3182598eeaDOI Listing
January 2015

Hemophagocytic lymphohistiocytosis complicated by central nervous system lesions in a patient with dermatomyositis: a case presentation and literature review.

Mod Rheumatol 2013 Mar 11;23(2):386-92. Epub 2012 May 11.

Division of Rheumatic Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

We report a case of dermatomyositis (DM) and hemophagocytic lymphohistiocytosis (HLH) complicated by central nervous system (CNS) lesions and review eight literature cases of DM and HLH. A 17-year-old woman, admitted to our hospital because of severe muscle weakness and high fever, was diagnosed with DM based on elevated serum levels of muscle enzymes and a typical skin rash. Pancytopenia, high serum ferritin and soluble interleukin (IL)-2 receptor, and hepatosplenomegaly were also noted. Bone-marrow examination was negative for hemophagocytosis. Steroid therapy combined with immunoglobulin i.v. was ineffective against the DM, pancytopenia, hepatic dysfunction, and hyperferritinemia. On the 27th hospital day, seizures and acute respiratory failure occurred. In the course of improving muscle enzyme levels after starting adjunctive treatment with cyclosporine, the patient suffered disturbed consciousness, dyskinesia, and tremor. Brain magnetic resonance imaging (MRI) revealed T2 hyperintense lesions in the pons. Additional cyclophosphamide pulse therapy successfully decreased serum ferritin. Unfortunately, the diffuse alveolar damage (DAD) confirmed by biopsy progressed and the patient died. Autopsy findings revealed DAD throughout both lungs, HLH liver lesions, and a hemorrhagic necrotic lesion of the pons in the brain. Even when pathological examination yields no findings of hemophagocytosis, it is important to comprehensively and rapidly diagnose HLH based on the clinical picture. Because DM complicated by HLH may be associated with abnormal production of cytokines and systemic autoimmune responses, it may be necessary to immediately administer additional immunosuppressive therapy. We describe and discuss the extraordinary, severe form of DM in our patient, along with cases in the literature.
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http://dx.doi.org/10.1007/s10165-012-0661-6DOI Listing
March 2013

Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy.

Rare Tumors 2011 Mar 30;3(1):e11. Epub 2011 Mar 30.

Division of Hematology, Internal Medicine, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo;

Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine), etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation.
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http://dx.doi.org/10.4081/rt.2011.e11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070448PMC
March 2011

(18)F-FDG-PET/CT findings of granulocyte colony stimulating factor (G-CSF)-producing lung tumors.

Ann Nucl Med 2008 Aug 29;22(7):635-9. Epub 2008 Aug 29.

Division of Nuclear Medicine, Department of Radiology, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

Tumors producing granulocyte colony stimulating factor (G-CSF), malignant lung tumors in most cases, are rare, and patients present with abnormal elevations of the white blood cell (WBC) count in the absence of any infectious disease. We present the (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) imaging findings of two cases of G-CSF-producing tumor. PET-CT showed abnormally high uptake of (18)F-FDG not only by the tumor itself but also diffusely throughout the bone marrow. Following resection of the tumor, the blood G-CSF level as well as the WBC count dropped down to normal range in both cases. Histopathological examination of the resected tumor specimens revealed the presence of an enormous number of inflammatory cells within the tumors and positive immunostaining of the tumor cells for G-CSF. The (18)F-FDG-PET/CT findings could be explained by the elevated bone marrow metabolism associated with the excessively active production of granulocytes under G-CSF stimulation, and the (18)F-FDG uptake by the inflammatory cells also contributing to the total tumor uptake of (18)F-FDG. These characteristic imaging findings are expected to be useful for the diagnosis of G-CSF-producing tumors.
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http://dx.doi.org/10.1007/s12149-008-0146-zDOI Listing
August 2008

Rheumatoid arthritis fibroblast-like synoviocytes express BCMA and are stimulated by APRIL.

Arthritis Rheum 2007 Nov;56(11):3554-63

International Medical Center of Japan, Shinjuku, Tokyo, Japan.

Objective: Fibroblast-like synoviocytes (FLS) are among the principal effector cells in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the variety of stimulating effects of APRIL and its specific effect on FLS in the affected RA synovium.

Methods: Synovium and serum samples were obtained from patients with RA, patients with osteoarthritis (OA), and healthy subjects. Soluble APRIL proteins were assayed by enzyme-linked immunosorbent assay. The relative gene expression of APRIL, BCMA, interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), IL-1beta, and RANKL was assessed in RA and OA FLS by polymerase chain reaction. Effects of APRIL on the production of proinflammatory cytokines and RANKL in RA FLS were investigated by flow cytometry and with the use of a BCMA-Fc fusion protein.

Results: A significantly higher level of soluble APRIL was detected in RA serum compared with normal serum. Among the 3 receptors of APRIL tested, RA FLS expressed only BCMA, whereas OA FLS expressed none of the receptors. APRIL stimulated RA FLS, but not OA FLS, to produce IL-6, TNFalpha, IL-1beta, and APRIL itself. In addition, APRIL increased RA FLS expression of RANKL and also enhanced progression of the cell cycle of RA FLS. Neutralization of APRIL by the BCMA-Fc fusion protein attenuated all of these stimulating effects of APRIL on RA FLS.

Conclusion: RA FLS are stimulated by APRIL and express the APRIL receptor BCMA. These results provide evidence that APRIL is one of the main regulators in the pathogenesis of RA.
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http://dx.doi.org/10.1002/art.22929DOI Listing
November 2007

A case of spontaneous regression of small cell lung cancer with progression of paraneoplastic sensory neuropathy.

Lung Cancer 2007 Nov 18;58(2):291-5. Epub 2007 Jun 18.

Department of Respiratory Medicine, International Medical Center of Japan, 1-21-1, Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.

We report here a rare case of small cell lung cancer (SCLC) accompanied by a partial spontaneous regression with a progression of paraneoplastic sensory neuropathy (PSN). A 55-year-old woman was admitted to our hospital with dry cough and progressive numbness in the distal extremities over 1 month. She was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. About 1 month later, partial spontaneous regression of tumor with a progression of paraneoplastic sensory neuropathy was observed. A complete response was achieved through chemotherapy and concurrent radiotherapy. As the tumor size decreased, her neurological symptoms improved. A short interval between onset of PSN and the start of therapy may be essential for successful treatment for not only SCLC but also PSN.
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http://dx.doi.org/10.1016/j.lungcan.2007.05.005DOI Listing
November 2007

Pulmonary tumor thrombotic microangiopathy.

J Clin Oncol 2007 Feb;25(5):597-9

Department of Respiratory Medicine, International Medical Center of Japan, Shinjuku-Ku, Tokyo, Japan.

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http://dx.doi.org/10.1200/JCO.2006.09.0670DOI Listing
February 2007

[A case of Peutz-Jeghers type polyp of the duodenum treated by endoscopic resection].

Nihon Shokakibyo Gakkai Zasshi 2005 Aug;102(8):1039-44

Department of Gastroenterology, Hachiouji Medical Center of Tokyo Medical University.

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August 2005

Seasonal influence on testicular function of male raccoons, Procyon lotor.

J Reprod Dev 2005 Aug 10;51(4):477-82. Epub 2005 Jun 10.

Department of Veterinary Obstetrics and Gynecology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.

In order to clarify the breeding capability of male raccoons in Japan, the testes of raccoons, a nuisance animal, collected in Kanagawa Prefecture and Hokkaido were histologically inspected. Furthermore, testosterone concentrations in their blood were measured. The testosterone concentrations increased in winter and the diameter of seminiferous tubules and the spermatogenetic score decreased in summer for the animals captured in Kanagawa Prefecture. For the animals captured in Hokkaido, the diameter of seminiferous tubules did not change and the decrease of the spermatogenetic score in summer was slight. As the above results show, there is a breeding season in male raccoons in Japan, and the reduction of testicular function in summer was greater in animals captured in Kanagawa Prefecture than in animals captured in Hokkaido.
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http://dx.doi.org/10.1262/jrd.16069DOI Listing
August 2005