Publications by authors named "Yukako Shintani-Domoto"

9 Publications

  • Page 1 of 1

Autopsy case with concurrent transthyretin and immunoglobulin amyloidosis.

Pathol Int 2021 Oct 12. Epub 2021 Oct 12.

Department of Diagnostic Pathology, Nippon Medical School Hospital, Tokyo, Japan.

An 85-year-old man with a history of aortic dissection suddenly fainted, underwent cardiac heart arrest, and died. An autopsy was performed, but the cause of death was not grossly identified. Congo red staining detected amyloid deposits in systemic organs, including the heart, lungs, liver, and kidneys. Immunohistochemical (IHC) analysis revealed immunoglobulin (Ig) λ light chain (-λ) in systemic blood vessels and transthyretin (TTR) in the heart and lungs. Ig-λ was predominantly positive in the blood vessels of the lungs, while TTR was detected in the alveolar septum. In the heart, Ig-λ was positive in the endocardium and blood vessels, and TTR was positive in nodular deposits between cardiomyocytes. The concurrent deposition of Ig-λ and TTR in the heart was further substantiated by laser microdissection (LMD)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) at each deposition site. Despite systemic deposition of Ig-λ, bone marrow biopsy findings were not diagnostic for multiple myeloma. In summary, we present an autopsy case of concurrent Ig-λ and TTR deposition as revealed by IHC and LC-MS/MS. When Congo red staining and IHC results are indeterminate due to the deposition of multiple amyloid proteins, LMD-LC-MS/MS is useful for determining the precursor protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.13179DOI Listing
October 2021

Predominant mesangial IgM, C3, and λ light chain depositions and interstitial nephritis in a patient with overlap syndrome and positivity for anti-mitochondrial M2 antibody: a case report.

Mod Rheumatol Case Rep 2021 Sep 10. Epub 2021 Sep 10.

Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Overlap syndrome refers to a group of conditions that have clinical features of more than one well-characterised rheumatic disease and meet the respective classification criteria. There are no typical renal histological findings in overlap syndrome. When patients with overlap syndrome develop renal dysfunction, various potential causes, including lupus nephritis (LN), renal crisis by systemic sclerosis, interstitial nephritis, and so on, need to be distinguished. Here, we report a 44-year-old woman with overlap syndrome involving systemic lupus erythematosus (SLE), diffuse cutaneous systemic scleroderma, and Sjogren's syndrome, who was also positive for anti-mitochondrial M2 antibody. She developed glomerular haematuria, proteinuria, and increase in creatinine appeared gradually. Suspecting LN, renal biopsy was performed. However, in the interstitium, mild infiltration of lymphocytes and plasma cells and very partial fibrosis were observed. Immunofluorescence microscopy revealed predominant mesangial immunoglobulin M, C3, and λ light chain staining. Overall, LN was not diagnosed based on these findings. Renal dysfunction was normalised by glucocorticoid treatment for 3 months. This case suggests the importance of a renal diagnosis based on renal pathological findings, especially in a case of overlap syndrome including SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/mrcr/rxab017DOI Listing
September 2021

Glomerular Classification Using Convolutional Neural Networks Based on Defined Annotation Criteria and Concordance Evaluation Among Clinicians.

Kidney Int Rep 2021 Mar 13;6(3):716-726. Epub 2020 Dec 13.

Department of Biomedical Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Introduction: Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN).

Method: To generate appropriate labeled data, annotation criteria including 12 features (e.g., "fibrous crescent") were defined. The concordance among 5 clinicians was evaluated for 100 images using the kappa (κ) coefficient for each feature. Using the annotation criteria, 1 clinician annotated 10,102 images. We trained the CNNs to classify the features with an average κ ≥0.4 and evaluated their performance using the receiver operating characteristic-area under the curve (ROC-AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN's focusing point with a heat map when the CNN classifies the glomerular image for a feature.

Results: The average κ coefficient of the features ranged from 0.28 to 0.50. The ROC-AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, "capillary collapse" and "fibrous crescent" had high ROC-AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed that the CNN could not distinguish between 2 different features that had similar visual structures or that occurred simultaneously.

Conclusion: The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2020.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938073PMC
March 2021

Mass spectrometry-based absolute quantification of amyloid proteins in pathology tissue specimens: Merits and limitations.

PLoS One 2020 1;15(7):e0235143. Epub 2020 Jul 1.

Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, including serum amyloid A (SAA), transthyretin (TTR), immunoglobulin kappa light chain (IGK), immunoglobulin lambda light chain (IGL), beta-2-microglobulin (B2M), apolipoprotein (Apo) A1, Apo A4, Apo E, lysozyme, Apo A2, gelsolin, and fibrinogen alpha chain; leukocyte cell-derived chemotaxin-2 was not detected. The quantification of SAA, TTR, IGK, IGL, and B2M confirmed the responsible proteins, even when the immunohistochemical results were not decisive. Considerable amounts of Apo A1, Apo A4, and Apo E were deposited in parallel amounts with the responsible proteins. Quantification of amyloid protein by MS-QBIC is feasible and useful for the classification of and research on systemic amyloidoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235143PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329117PMC
September 2020

Pulmonary postmortem computed tomography of bacterial pneumonia and pulmonary edema in patients following non-traumatic in-hospital death.

Leg Med (Tokyo) 2020 May 19;45:101716. Epub 2020 May 19.

Radiology, Graduate School of Medicine, The University of Tokyo, Japan.

In this study, we compared the postmortem computed tomography (PMCT) findings among nonpathological lungs, lungs with bacterial pneumonia, and lungs with pulmonary edema in patients following non-traumatic in-hospital death. We studied 104 consecutive adult patients (208 lungs) who died in our tertiary care hospital and underwent PMCT and pathological autopsy (both within 2.5 days after death), and were pathologically diagnosed with nonpathological lungs, bacterial pneumonia, and pulmonary edema. Thirteen pulmonary features were assessed on the CT scans. We also examined the association between the time elapsed since death and the pulmonary findings. We observed increased lung opacities with horizontal plane formation, diffuse opacities, diffuse bronchovascular bundle thickening, symmetric opacities to the contralateral lung, and decreased segmental opacities with time elapsed since death (Cochran-Armitage test for trend). Multiple logistic regression revealed that the presence of opacities without horizontal plane formation or centrilobular opacities, and the absence of diffuse bronchovascular bundle thickening were associated with histopathological pneumonia, whereas the presence of opacities with horizontal plane formation, diffuse opacities, and interlobular septal thickening were associated with histopathological pulmonary edema. In conclusion, specific pulmonary PMCT findings increased with time elapsed since death, and some lung findings may facilitate the diagnosis of bacterial pneumonia and pulmonary edema.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.legalmed.2020.101716DOI Listing
May 2020

Utility of unenhanced postmortem computed tomography for investigation of in-hospital nontraumatic death in children up to 3 years of age at a single Japanese tertiary care hospital.

Medicine (Baltimore) 2020 May;99(19):e20130

Department of Radiology.

To evaluate the utility of unenhanced postmortem computed tomography (PMCT) for the investigation of in-hospital nontraumatic death in children up to 3 years of age.This study included the cadavers of children who died from intrinsic diseases before 3 years of age. The major underlying disease and the main organ-disease systems associated with the immediate causes of death were determined by clinical evaluation, PMCT, and autopsy, which were used as a reference standard. The rates of concordance between the former two methods and autopsy were calculated for all cases.In total, 22 cadavers (12 male and 10 female; mean age, 6.1 ± 8.2 months) were included. The rates of concordance between clinical evaluation/PMCT and autopsy for diagnosis of the major underlying disease and main organ-disease systems associated with the immediate causes of death were 100%/36% (P = .0015) and 59%/41% (P = .37), respectively. In cases where the respiratory system was associated with the immediate cause of death, PMCT showed greater diagnostic sensitivity (90%) than did clinical evaluation (20%). In contrast, the diagnostic sensitivity of PMCT was lower than that of clinical evaluation in cases involving disorders of the cardiac system and multiple organ systems (0% vs 100% for both).The findings of this study suggest that the use of unenhanced PMCT with clinical evaluation can result in improved detection of the immediate cause of death in select cases of in-hospital nontraumatic death before 3 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220630PMC
May 2020

Nutcracker Syndrome with the Superimposition of Thin Basement Membrane Syndrome.

Intern Med 2019 Feb 12;58(3):411-414. Epub 2018 Sep 12.

Division of Nephrology and Endocrinology, The University of Tokyo Hospital, Japan.

A 21-year-old woman was referred to our hospital because of proteinuria and hematuria. She had occasional flank pain. A renal biopsy was performed and revealed a thin basement membrane. Therefore, she was diagnosed with thin basement membrane disease. However, the frequency of her flank pain increased. Since her left kidney was slightly larger than the right, nutcracker syndrome (NCS) was suspected. Renal vein ultrasonography and venography were performed, and NCS was confirmed. Her hematuria was multifactorial, and NCS can go unnoticed if there is a comorbidity that also causes hematuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.1433-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395115PMC
February 2019

Laminar crystal deposition in large vessels in a patient with crystalglobulinemia.

Pathol Int 2017 May 31;67(5):269-272. Epub 2017 Mar 31.

Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.

Crystalglobulinemia is an extremely rare complication of monoclonal gammopathy and is characterized by crystal thrombi within systemic organs. We herein report the first described case of crystalglobulinemia accompanied by laminar crystal deposition in the large vessels. A 44-year-old man presented with a history of numbness, pain, and swelling of the left leg in addition to visual impairment. Renal and skin biopsies revealed crystal thrombi within the capillary lumens. The patient was finally diagnosed with crystalglobulinemia associated with multiple myeloma. He was treated with hemodialysis and chemotherapy but died of the disease 15 months after admission. Autopsy demonstrated a huge amount of crystal deposition in the subintimal layer of the vascular wall throughout the thoracic to abdominal aorta. The characteristic deposition extended to the iliac arteries, common carotid arteries, and subclavian arteries but did not affect the bilateral renal arteries. Antemortem computed tomography demonstrated higher intensity in the wall of the abdominal aorta but not in the walls of the renal arteries, suggesting that a finding of high intensity on computed tomography could be a clinical marker of systemic crystal deposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.12526DOI Listing
May 2017

Different desmin peptides are distinctly deposited in cytoplasmic aggregations and cytoplasm of desmin-related cardiomyopathy patients.

Biochim Biophys Acta Proteins Proteom 2017 Jul 21;1865(7):828-836. Epub 2017 Mar 21.

Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address:

Desmin-related cardiomyopathy is a heterogeneous group of myofibrillar myopathies characterized by aggregates of desmin and related proteins in myocytes. It has been debated how the expression and protein structure are altered in the aggregates and other parts of myocytes in patients. To address this question, we investigated the proteome quantification as well as localization in formalin-fixed and paraffin-embedded specimens of the heart of patients by imaging mass spectrometry and liquid chromatography-mass spectrometry analyses. Fifteen tryptic peptide signals were enriched in the desmin-related cardiomyopathy myocardium, twelve of which were identified as desmin peptides with 14.3- to 27.3-fold increase compared to normal hearts. High-intensity signals at m/z 1032.5 and 1002.5, which were desmin peptides 59-70 at the head portion and 213-222 at the 1B domain, were with infrequent colocalization distributed not only in desmin-positive intracytoplasmic aggregates but also in histologically normal cytoplasm, indicating that desmin protein is fragmented and different types of naturally-occurring truncated proteins ectopically assemble throughout the heart of patients. Thus, in addition to conventional histological identification of protein aggregates, specific desmin peptides show a marked difference in quantity and localization in a tissue section of desmin-related cardiomyopathy and differentiate from other cardiomyopathies. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbapap.2017.03.006DOI Listing
July 2017
-->