Publications by authors named "Kentaro Sakai"

45 Publications

Unexpected death in a young child associated with anomalous aortic origin of the left main coronary artery without physical exertion: A case of an anomalous coronary artery with highly abundant elastic fibers.

Leg Med (Tokyo) 2021 Nov 15;53:101965. Epub 2021 Sep 15.

Tokyo Medical Examiner's Office, Tokyo Metropolitan Government, Tokyo, Japan.

Sudden death due to anomalous aortic origin of a coronary artery is far less common among young children in the absence of exercise stress. This report describes the case of a 2-year-old boy with a lower respiratory tract infection who suffered sudden cardiac arrest in his bed at home. The autopsy revealed that the left coronary artery (LCA) originated from the right sinus of Valsalva with an acute angle takeoff and traveled between the aorta and the pulmonary trunk (an interarterial course). Upon histological examination, the LCA, before reaching its major branches, was located adjacent to the outside of the aortic wall without an intramural passage, and the arterial wall was composed almost exclusively of elastic fibers without media containing smooth muscle cells throughout the entire length of the abnormal running. Screening tests for respiratory virus infection detected enterovirus in the lung tissue. In association with an acute angle takeoff and interarterial course, the wall structure with highly abundant elastic fibers that are more flexible tissues among blood vessel components might suggest their vulnerability to compression during the great vessels' systolic expansion in the sympathetic activation induced by the viral infection, leading to fatal myocardial ischemia without physical exertion.
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http://dx.doi.org/10.1016/j.legalmed.2021.101965DOI Listing
November 2021

Fatal intracranial hemorrhage due to infantile acute lymphoblastic leukemia mimicking abusive head trauma.

J Forensic Sci 2021 Jul 23. Epub 2021 Jul 23.

Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.

We report the case of a 2-month-old infant who was found moribund in her crib. Postmortem computed tomography (PMCT) was performed before autopsy. As the baby had a severe subdural hematoma, retinal hemorrhage, and encephalopathy on PMCT, abusive head trauma (AHT) was tentatively diagnosed. At autopsy, no scalp hemorrhages or skull fractures were found; however, the classic triad of AHT was present, mainly on the right side. Additionally, there was dark red discoloration around the heart, and the liver, spleen, and pancreas were enlarged. Peripheral blood was macroscopically cloudy with marked leukocytosis. After careful histological examination, B-cell precursor acute lymphoblastic leukemia (ALL) was diagnosed. All the macroscopic lesions could be attributed to ALL. The manner of death was natural. To the best of our knowledge, this is the first report of infantile ALL mimicking AHT on PMCT images. This case demonstrates the importance of a comprehensive systematic approach to considering differential diagnosis when PMCT shows multiple intracranial hemorrhages suggestive of AHT in an infant.
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http://dx.doi.org/10.1111/1556-4029.14815DOI Listing
July 2021

Dissecting lesions in a culprit artery of a hemorrhagic focus in the basal ganglia: Histopathological analysis by serial sectioning.

Neuropathology 2021 Aug 21;41(4):301-305. Epub 2021 Mar 21.

Department of Forensic Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.

In a hypertensive hemorrhagic focus of the basal ganglia, the culprit arteries have been reported to be associated with dissecting lesions, whose topographical relationship to the rupture sites remains to be clarified. Herein we describe multiple dissecting lesions in the culprit artery of hypertensive hemorrhage of the basal ganglia. A 1.0 × 0.8 × 0.8 cm-sized bleeding globe was confirmed at a left lenticulostriate artery and histologically analyzed by serial sectioning. Three independent dissecting lesions were identified in the culprit artery. They were situated near the bifurcations, ranging from 240 to 3200 μm in length. The dissections mainly occurred between the intima and media with disruption of the internal elastic lamina (IEL), forming a fresh thrombus within the false lumen. Two rupture sites causing the cerebral hematoma were confirmed away from the dissecting lesions. One was situated close but not adjacent to the longest dissecting lesion; the other, measuring approximately 150 μm in diameter, was adjacent to the bifurcation of an artery. The histopathological findings suggest that the dissecting lesion resulted from medial detachment following IEL disruption in the process of arterial rupture of the culprit artery. We conclude that this was a secondary manifestation during the rupture rather than a cause of the arterial rupture.
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http://dx.doi.org/10.1111/neup.12736DOI Listing
August 2021

Catalytic and Aerobic Oxidative Biaryl Coupling of Anilines Using a Recyclable Heterogeneous Catalyst for Synthesis of Benzidines and Bicarbazoles.

J Org Chem 2020 Dec 23;85(23):15154-15166. Epub 2020 Nov 23.

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihama-Boji, Yamashiro-cho, Tokushima 770-8514, Japan.

In this study, a heterogeneous rhodium-catalyzed oxidative homocoupling reaction of anilines utilizing molecular oxygen as the sole oxidant is reported. Employing a commercially available and recyclable Rh/C catalyst enabled the oxidative dimerization of various anilines, including ,-disubstituted and -monosubstituted anilines, as well as diarylamines, triarylamines, and carbazoles. Additionally, the catalytic protocol was extended to the ortho-ortho coupling of anilines, affording 2,2'-diaminobiphenyls with high regioselectivity. Notably, the developed approach provides rapid access to diversely functionalized benzidines and diaminobiphenyls in an operationally simple, practical, and environmentally friendly manner.
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http://dx.doi.org/10.1021/acs.joc.0c02020DOI Listing
December 2020

c-Phycocyanin primed silver nano conjugates: Studies on red blood cell stress resilience mechanism.

Colloids Surf B Biointerfaces 2020 Oct 25;194:111211. Epub 2020 Jun 25.

Department of Applied Physiology, School of Medicine, University of Miyazaki, Miyazaki, 889 1692, Japan.

Green synthesis of metal-encased nutraceutical nano-hybrids has been a target for research over the last few years. In the present investigation, we have reported temperature dependent facile synthesis of silver nanoparticles using FDA approved c phycocyanin (cPC). The cPC conjugated silver nanoparticles (AgcPCNPs) were characterized by TEM, Zeta Potential, UV-vis, XPS, FTIR, and CD Spectroscopy. The temperature optimization studies suggested the synthesis of stable AgcPCNPs at 40 °C while at higher temperature system shows aggregated appearance. Molecular docking studies predicted the exclusive interaction of C, D, I, and J chains of cPC with the surface of AgNPs. Moreover, AgcPCNPs significantly (p < 0.1 %) counteract the toxic nature of AgNPs on red blood cell by measuring parameters like total RBC count, % hemolysis, % hematocrit, coagulation time, pH, electrolyte concentrations and degree of blood cell lipid peroxidation by the anti-oxidation mechanism. Skin fibroblast in vitro cell migration result suggeststhat AgcPCNPs enhanced the degree of cell movement towards the wound area. Data obtained collectively demonstrate that AgcPCNPs can be a better agent in the dermal wound healing with reduced toxicity with the bi-phasic advantage of cPC as a wound healer and Ag nano-metal as an anti-bacterial agent.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111211DOI Listing
October 2020

Probing molecular bond-length using molecular-frame photoelectron angular distributions.

J Chem Phys 2019 May;150(17):174306

Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577, Japan.

The molecular-frame photoelectron angular distributions (MFPADs) in O 1s photoemission from CO molecule were measured. Patterns due to photoelectron diffractions were observed in the MFPADs. The polarization-averaged MFPADs were compared with theoretical calculation and were found to be useful in determining the molecular bond-length, which is a component to determine molecular structures.
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http://dx.doi.org/10.1063/1.5091946DOI Listing
May 2019

Sudden unexpected death due to coronary thrombosis associated with isolated necrotizing vasculitis in the coronary arteries of a young adult.

Forensic Sci Med Pathol 2019 Jun 27;15(2):252-257. Epub 2019 Feb 27.

Tokyo Medical Examiner's Office, Tokyo Metropolitan Government, 4-21-18 Otsuka, Bunkyo-ku, Tokyo, 112-0012, Japan.

Coronary arteritis is an uncommon cause of sudden death in non-atherosclerotic coronary diseases, and is mostly associated with systemic vasculitis or systemic autoimmune diseases; therefore, sudden death due to isolated coronary arteritis rarely occurs. The case described in this report is that of a 34-year-old man with no significant personal medical history who died suddenly after presenting with nausea. Postmortem examination revealed a significant infiltration of lymphocytes predominantly on the adventitia and periadventitial tissues of the coronary arteries in the epicardium. The lymphocytic infiltrate partially extended to the thickened intima with fibrosis, destructing the media and internal elastic lamina, and the lumen was occluded by a thrombus in the left main stem and left anterior descending branch. The arterial walls exhibited focal fibrinoid necrosis with regression in the intima and fibrous scars with angiogenesis in the media and adventitia. Focal myocardial infarction was detected in the left ventricle as a fibrotic change of the myocardium. No findings associated with vasculitis were discerned in the aorta, other peripheral arteries, or major organs. Laboratory tests of postmortem blood samples returned negative results for antinuclear antibodies, cryoglobulin, immunoglobulin G4, and cytoplasmic anti-neutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3. These autopsy findings suggest that the sudden death was caused by isolated necrotizing vasculitis that is assumed to be polyarteritis nodosa localized at the coronary arteries. However, pathological characteristics may not be exactly the same between isolated necrotizing vasculitis in the coronary arteries and polyarteritis nodosa.
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http://dx.doi.org/10.1007/s12024-019-00099-1DOI Listing
June 2019

C(sp )-H Cyanation Promoted by Visible-Light Photoredox/Phosphate Hybrid Catalysis.

Chemistry 2018 Jun 4;24(32):8051-8055. Epub 2018 May 4.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a C(sp )-H cyanation reaction promoted by visible-light photoredox/phosphate hybrid catalysis was developed. Phosphate radicals, generated by one-electron photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst to produce nucleophilic carbon radicals from C(sp )-H bonds with a high bond-dissociation energy. The resulting carbon radicals were trapped by a cyano radical source (TsCN) to produce the C-H cyanation products. Due to the high functional-group tolerance and versatility of the cyano group, the reaction will be useful for realizing streamlined building block syntheses and late-stage functionalization of drug-like molecules.
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http://dx.doi.org/10.1002/chem.201801746DOI Listing
June 2018

Sulfonamides as new hydrogen atom transfer (HAT) catalysts for photoredox allylic and benzylic C-H arylations.

Chem Commun (Camb) 2018 Mar;54(26):3215-3218

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

A catalytic amount of a sterically and electronically tuned diarylsulfonamide promoted allylic and benzylic C-H arylations in cooperation with a visible light photoredox catalyst. This is the first example of the catalytic use of a sulfonamidyl radical to promote the hydrogen atom transfer process.
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http://dx.doi.org/10.1039/c7cc09457dDOI Listing
March 2018

Exploration of Predictive Biomarkers for Sudden Unexplained Cardiac Death in Nonelderly People: A Case-Control Study With Biochemical Parameters Related to Heart Failure.

Am J Forensic Med Pathol 2018 Mar;39(1):41-45

From the *Tokyo Medical Examiner's Office, Tokyo Metropolitan Government; and †Department of Forensic Medicine, Jikei University School of Medicine, Tokyo, Japan.

Sudden unexplained cardiac death (SUCD) can occasionally occur in nonelderly patients with epilepsy, psychiatric disorders, or no medical history. This study was conducted to aim to analyze whether values of the biomarkers for heart failure are associated with the SUCD. Serum concentrations of N-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α were analyzed in 57 nonelderly patients with SUCD who was diagnosed at medicolegal autopsy. The subjects were divided into 3 subgroups according to the medical history: (1) epilepsy, (2) psychiatric disorders, and (3) no specific medical history. The results showed that serum hs-CRP levels were significantly high in patients with epilepsy (P = 0.01) or psychiatric disorders (P = 0.01) as compared with the controls. Also, significantly high concentrations of hs-CRP were observed in psychiatric patients with schizophrenia, compared with the controls (P = 0.003) or the other psychiatric diseases (P = 0.01). The level of N-terminal probrain natriuretic peptide and tumor necrosis factor α did not show a significant difference between the SUCD and the controls. These results might suggest the association between high serum hs-CRP levels and the potential impairment of the cardiac function before the fatal event.
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http://dx.doi.org/10.1097/PAF.0000000000000361DOI Listing
March 2018

Maintenance treatment using the purine-synthesis inhibitor mizoribine in a patient with relapsing thrombotic thrombocytopenic purpura.

CEN Case Rep 2018 May 9;7(1):24-28. Epub 2017 Nov 9.

Department of Nephrology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening disease. Although plasma exchange (PE) therapy and corticosteroids are standard remission induction and maintenance therapies, some patients are easily refractory and frequently relapse under treatment with this therapy, and require additional treatment. However, there are limited data about additional treatment interventions. We report a case of 56-year-old man who was hospitalized for fever, general fatigue and hemoglobinuria. Owing to the symptoms and the laboratory findings of hemolysis, he was diagnosed with TTP. He was treated with PE therapy and corticosteroids, and the TTP went into remission. However, his TTP relapsed and remission induction was attempted again. As a remission maintenance treatment, we used combination therapy with the purine-synthesis inhibitor mizoribine (MZR) and corticosteroids. The administration of MZR maintained disease activity with no adverse event for long periods and allowed us to gradually reduce the corticosteroids dose. Hence, we propose that MZR is an effective treatment for TTP maintenance.
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http://dx.doi.org/10.1007/s13730-017-0285-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886917PMC
May 2018

Deaths Associated With Brotizolam Poisoning From a Single Drug Overdose: Four Reported Cases.

Am J Forensic Med Pathol 2018 Mar;39(1):82-84

From the *Tokyo Medical Examiner's Office, Tokyo Metropolitan Government, Tokyo; †Department of Legal Medicine, Dokkyo Medical University School of Medicine, Tochigi; ‡Department of Forensic Medicine, Saitama Medical University, Saitama; and §Department of Forensic Medicine, Juntendo University School of Medicine, Tokyo, Japan.

Brotizolam is a short-acting hypnotic in the benzodiazepine family, and fatal poisonings by an overdose of brotizolam are rare. This report describes 4 cases of deaths associated with brotizolam poisoning from a single drug overdose. The ages ranged from 51 to 90 years, and the postmortem interval between death and tissue sampling was 1.5 to 2.5 days. These deaths were classified as 1 homicide and 3 suicides. The concentration of the brotizolam ranged from 0.05 to 0.21 mg/L in the blood samples. Ethanol, which could cause mild alcohol intoxication, was detected in the blood samples from 2 cases. Postmortem examinations did not find any significant pathologic conditions, except for a case of death by drowning in a bathtub due to brotizolam poisoning. These 4 cases suggest that a brotizolam overdose should not be underestimated in terms of its fatal effects, particularly when situations involve alcohol intoxication, injury subsequent to the poisoning, or underlying medical conditions including aging.
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http://dx.doi.org/10.1097/PAF.0000000000000358DOI Listing
March 2018

Expression of transcription factors in MEN1-associated pancreatic neuroendocrine tumors.

Endocrinol Diabetes Metab Case Rep 2017 4;2017. Epub 2017 Sep 4.

Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan.

MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma. A 70-year-old woman was found to manifest hypoglycemia with non-suppressed insulinemia and hypercalcemia with elevated PTH level. She was diagnosed as MEN1 based on the manifestation of primary hyperparathyroidism, pituitary adenoma and insulinoma, with genetic variation of MEN1 gene. She had pylorus-preserving pancreaticoduodenectomy because CT scan and SACI test indicated that insulinoma was localized in the head of the pancreas. Histopathological finding was MEN1-associated NET, G1. Interestingly, immunohistological examination of the resected pancreas revealed that two insulinomas, a glucagon-positive NET and a multiple hormone-positive NET coexisted. Hence, we examined the expression of transcription factors immunohistochemically to elucidate the role of the transcription factors in MEN1-associated hormone-producing pNETs. We observed homogeneous expressions of MafA and Pdx1 in insulinomas and Arx in glucagon-positive NET, respectively. Moreover, multiple hormone-positive NETs expressed several transcription factors heterogeneously. Collectively, our results suggested that transcription factors could play important roles in the production of specific hormones in MEN1-associated pNETs, similar to islet differentiation.

Learning Points: To date, it has been shown that different hormone-producing tumors coexist in MEN1-associated pNETs; however, the underlying mechanism of the hormone production in MEN1-associated pNETs has not been well elucidated.Although this case presented symptomatic hypoglycemia, several hormone-producing pNETs other than insulinoma also coexisted in the pancreas.Immunohistochemical analysis showed MafA and Pdx1 expressions distinctly in insulinoma, and Arx expression particularly in a glucagon-positive NET, while a multiple hormone-positive NET expressed MafA, Pdx1 and Arx.Collectively, clinicians should consider that several hormone-producing pNETs may coexist in a MEN1 case and examine both endocrinological and histopathological analysis of pNETs, regardless of whether symptoms related to the excess of hormones are observed or not.
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http://dx.doi.org/10.1530/EDM-17-0088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592709PMC
September 2017

Temporal Changes in Post-Infectious Glomerulonephritis in Japan (1976-2009).

PLoS One 2016 10;11(6):e0157356. Epub 2016 Jun 10.

Department of Nephrology, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Background: The incidence of post-infectious glomerulonephritis (PIGN) in developed countries has decreased over the last 50 years. Here we identified the trends of the incidence of PIGN in Japan during the past four decades.

Methods: We explored the frequency, clinicopathological findings, and prognosis of PIGN based on 6,369 cases from the Renal Biopsy Database of our institute in the Kanto region of Japan, diagnosed histologically from 1976 to 2009.

Results: The numbers of PIGN cases were 131 (2.1%) in total, and 2.4%, 1.1%, 2.6% and 2.1% identified in the 1970s, 1980s, 1990s, and 2000s, respectively. Acute glomerulonephritis (AGN), including post-streptococcal glomerulonephritis (PSGN), accounted for almost all of the PIGN cases in the 1970s, but decreased to approx. 40%-50% since the 1990s. In the 1990s, Staphylococcus aureus infection-related nephritis (SARN) showed a rapid increase in rate, reaching 30%. The incidence of hepatitis C virus infection-associated GN (HCVGN) has increased since the 1990s. The average age at onset rose from 33 to 51 years over the study period. These transitions can be summarized as increases in SARN and HCVGN and decreases in PSGN and other types of AGN, since SARN and HCVGN have older onsets compared to PSGN and other AGN types. The clinicopathological features were marked for each PIGN. Regarding the prognosis, the renal death rates of both the SARN and HCVGN groups were significantly higher than those of other PIGN.

Conclusion: Based on our analysis of the Renal Biopsy Database, the incidence of PIGN in Japan reached its peak in the 1990s. The temporal changes in the incidence of PIGN reflected the trends in infectious diseases of each decade and the continual aging of the population, with a related higher susceptibility to infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157356PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902309PMC
July 2017

Infant death associated with maternal methamphetamine use during pregnancy and delivery: A case report.

Leg Med (Tokyo) 2015 Sep 20;17(5):409-14. Epub 2015 Jun 20.

Department of Forensic Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

The case described in this report is of a male infant who was found dead in a closet. His mother delivered the infant in the kitchen, left him wrapped in a towel, and called emergency medical services 4days after the delivery. At the autopsy, the growth suggests a full-term delivery, significant pathological findings were not observed, and the infant was estimated to be stillborn. After the autopsy, the police investigation discovered that the mother used a stimulant during the pregnancy and shortly before the rupture of the membrane. Toxicological analysis showed 1.60mg/L of methamphetamine in the blood, strongly suggesting that the fetal death was associated with this acute intoxication. Thus far, only a few cases of infant deaths have been reported in association with methamphetamine intoxication. The present case showed the highest blood concentration of methamphetamine compared to the past infant cases with this intoxication.
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http://dx.doi.org/10.1016/j.legalmed.2015.06.004DOI Listing
September 2015

Membranous nephropathy with solitary immunoglobulin A deposition.

Intern Med 2015 1;54(9):1081-4. Epub 2015 May 1.

Department of Nephrology, Faculty of Medicine, University of Tsukuba, Japan.

A 71-year-old woman was admitted with nephrotic syndrome. Light and electron microscopic analyses of renal biopsy tissue showed typical diffuse membranous features. In contrast, granular deposition of immunoglobulin A (IgA), but not IgG, IgM, C3 or C1q, was observed along the capillary walls on immunofluorescence. The patient was pathologically diagnosed with diffuse membranous nephropathy with solitary IgA deposition. Secondary membranous nephropathy was suspected; however, no underlying cause was found. The clinical and pathological findings, except for those of immunofluorescence, were all compatible with a diagnosis of primary membranous nephropathy. This is the first reported case of membranous nephropathy associated with solitary IgA deposition.
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http://dx.doi.org/10.2169/internalmedicine.54.3655DOI Listing
September 2015

Is the denervation or hyperinnervation of the cardiac sympathetic nerve in the subepicardium related to unexpected cardiac death?

Cardiovasc Pathol 2014 Jul-Aug;23(4):211-6. Epub 2014 Mar 27.

Department of Forensic Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Background: Past studies have reported that abnormal innervation of cardiac sympathetic nerve can cause sudden cardiac death through the arrythmogenesis; however, the severe cardiac sympathetic degeneration does not necessarily cause clinical problems. This study aimed to examine whether denervation or hyperinnervation of cardiac sympathetic nerves in the subepicardium is associated with unexpected cardiac death (UCD).

Methods: Cardiac tissues of 278 forensic autopsy cases within 48 h after death were analyzed by double-staining immunohistochemistry for tyrosine hydroxylase and neurofilament. The density of nerve fascicles and the degeneration rate in the subepicardium of the left ventricular anterior wall were compared between the UCD group and the non-UCD group.

Results: The density of nerve fascicles was lower in the SCD group (median: 51.9/cm(2)) than in the non-SCD group (median: 58.9/cm(2)); however, the difference was not significant (P = .08). The degeneration rate was higher in the SCD group (median: 0.19) than in the non-SCD group (median: 0.17), but again, the difference was not significant (P = .43). The multiple logistic regression model did not show a significant association between the incidence of UCD and the density of nerve fascicles or the degeneration rate.

Conclusions: It cannot be concluded that the denervation or hyperinnervation of cardiac sympathetic nerves in the subepicardium is related to UCD. Abnormal innervation of cardiac sympathetic nerves in the subepicardium may not have a substantial effect on UCD, compared to other arrhythmogenic factors.
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http://dx.doi.org/10.1016/j.carpath.2014.03.006DOI Listing
May 2015

A fatal fall associated with undiagnosed parenchymatous neurosyphilis.

Am J Forensic Med Pathol 2014 Mar;35(1):4-7

From the *Department of Forensic Medicine and †Division of Neuropathology, Department of Neuroscience, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.

A fall from a great height is often associated with altered mental status. Aside from the usual contributing factors, for example, alcohol consumption or mental illness, natural disease leading to a fatal fall is seldom identified by autopsy. The case described in this report is that of a 57-year-old man who had been clinically diagnosed with presenile Alzheimer disease and fell head first into a river from the bridge. These events were captured by a surveillance camera on the bridge; an acquaintance reported that he had previous suicidal ideation. At autopsy, the cervical spinal cord was determined to have been severely injured, and the sixth cervical vertebra was observed to have been fractured. Histological examination showed chronic meningoencephalitis including neuronal loss, perivascular cuffing, and the proliferation of microglia and astrocytes in the cerebral cortex. Serologic evaluation consisting of the nontreponemal antigen test (rapid plasma reagin [RPR]) and treponemal antibody test (Treponema pallidum latex agglutination) was positive in both cases (RPR: 18.2 RPR units, T. pallidum latex agglutination: 7718 U/mL). These findings suggested that the patient had been affected by a syphilis infection and that his suicidal behavior was associated with parenchymatous neurosyphilis.
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http://dx.doi.org/10.1097/PAF.0000000000000068DOI Listing
March 2014

Immunohistochemical analysis of the ubiquitin proteasome system and autophagy lysosome system induced after traumatic intracranial injury: association with time between the injury and death.

Am J Forensic Med Pathol 2014 Mar;35(1):38-44

From the Department of *Forensic Medicine and †Division of Neuropathology, Department of Neuroscience, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.

This study aimed to analyze how the ubiquitin proteasome system (UPS) or autophagy lysosome system (autophagy) are induced in brain tissues at different intervals after traumatic intracranial injury in humans. Injured cerebral cortices of 36 forensic autopsy cases were analyzed by immunohistochemistry using antibodies as the UPS marker (ubiquitin and lysine 48-linked polyubiquitin chains [K48]) and autophagy marker (lysine 63-linked polyubiquitin chains [K63], p62/sequestome 1 and microtubule-associated protein 1 light chain 3 [LC3]). The number of neurons and glial cells with cytoplasmic inclusions that stained positive for ubiquitin, K48, and p62 began to increase within 1 hour after intracranial injury, particularly at contusion sites. From 3.5 hours onward, an increase in cytoplasmic inclusions that stained positive for K63 and LC3 began to be detected. LC3-positive cytoplasmic inclusions were not identified after 37 days; however, the increased immunoreactivity to ubiquitin and anti-K48 antibody was maintained for 7 months. These results suggest that the UPS is activated earlier and lasts longer than autophagy, that autophagy is activated for a relatively short term (between a few hours and approximately 1 month), and that the activation occurs especially in severely damaged brain tissues following head trauma in humans.
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http://dx.doi.org/10.1097/PAF.0000000000000067DOI Listing
March 2014

Beading of the astrocytic processes (clasmatodendrosis) following head trauma is associated with protein degradation pathways.

Brain Inj 2013 10;27(13-14):1692-7. Epub 2013 Oct 10.

Department of Forensic Medicine , and.

Objectives: To present the incidence of clasmatodendrosis (injured astrocytic processes) and analyse the association between clasmatodendrosis and the ubiquitin proteasome system (UPS) and autophagy lysosome system (autophagy).

Methods: The injured cerebral cortices of 36 autopsy cases were analysed by light microscopy by immunohistochemistry using an anti-glial fibrillary acidic protein (GFAP) antibody and UPS marker antibodies (ubiquitin and lysine 48-linked polyubiquitin chains (K(48)) and autophagy marker (lysine 63-linked polyubiquitin chains (K(63)), p62/sequestosome 1 and microtubule-associated protein 1 light chain 3 [LC3]). Double-immunofluorescence staining was used to detect the relationships between p62-K(48), p62-K(63) and GFAP-K(48).

Results: Clasmatodendrosis that was immunoreactive to GFAP or K(48) was detected by 1 hour up to 14 days following head trauma. The survival time of cases with clasmatodendrosis was significantly shorter than that in cases without clasmatodendrosis (p < 0.01). Involvement of contusion or oedema was significantly frequent in cases with clasmatodendrosis (p < 0.01). There was no significant age difference between cases with clasmatodendrosis and cases without clasmatodendrosis (p = 0.18). Double-immunofluorescence staining for p62-K(48) and GFAP-K(48) demonstrated clasmatodendrosis with overlapping fluorescence signals.

Conclusion: Clasmatodendrosis is associated with UPS-mediated, autophagy and relatively acute pathological findings after traumatic intracranial injury.
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http://dx.doi.org/10.3109/02699052.2013.837198DOI Listing
September 2014

Primary membranoproliferative glomerulonephritis on the decline: decreased rate from the 1970s to the 2000s in Japan.

Clin Exp Nephrol 2013 Apr 13;17(2):248-54. Epub 2012 Sep 13.

Department of Nephrology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.

Background: A prolonged change in the rate of primary membranoproliferative glomerulonephritis (MPGN) was identified using a Japanese database of renal biopsies.

Methods: We retrospectively investigated 6,369 renal biopsies that were performed between 1976 and 2009. Primary MPGN patients were selected, and the clinical and pathological findings were examined. We also statistically analyzed the changing rate of the onset of primary MPGN according to each decade.

Results: Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed. The age of the patients ranged from 6-79 years (average 34.6 years). There were 24 children and 55 adults, including 37 male and 42 female patients. Thirty-six cases of primary MPGN (45.6 %) showed nephrotic syndrome-8 childhood and 28 adult cases. In the pathological classification of 44 samples using electron microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were MPGN type III. The secular change of the rate of primary MPGN onset showed a statistically significant reduction from the 1970s to the 2000s. The rate of primary MPGN onset in the child population also significantly decreased, but not in the adult population. Among the clinical parameters, disease severity and prognosis remained unchanged. Regarding treatment in recent years, steroid pulse therapy became more available but the administration of warfarin and anti-platelet drugs significantly decreased.

Conclusion: We concluded that the rate of total primary MPGN and that of pediatric patients with primary MPGN decreased.
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http://dx.doi.org/10.1007/s10157-012-0690-7DOI Listing
April 2013

Angiopoietin balance in septic shock patients with acute lung injury: effect of direct hemoperfusion with polymyxin B-immobilized fiber.

Ther Apher Dial 2011 Aug;15(4):349-54

Department of Nephrology, Mito Saiseikai General Hospital, Mito, Japan.

Acute lung injury (ALI) in sepsis is characterized by an increase in microvascular permeability, resulting in pulmonary edema. Several studies have suggested that angiopoietin-1 and -2 play a contributory role in the pathogenesis of ALI. Polymyxin B-immobilized fiber column hemoperfusion is effective for sepsis-induced ALI. We investigated the angiopoietin levels before and after direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) therapy. Enzyme-linked immunoassay was used to measure the serum angiopoietin-1 and -2 levels in 25 patients with septic shock treated with PMX. Eleven of the 25 patients were diagnosed with ALI. There was a significant positive correlation between the angiopoietin-1 level and the PaO(2) /FiO(2) ratio, but there was a significant inverse correlation between the angiopoietin-2 level and the PaO(2) /FiO(2) ratio. The mean angiopoietin-1 level before PMX therapy in the ALI group was significantly lower and the mean angiopoietin-2 level was significantly higher than in the non-ALI group. The mean angiopoietin-1 level of the ALI patients in response to PMX therapy was increased during PMX therapy, but that of the non-ALI patients with newly occurring ALI showed a decreased angiopoietin-1 level. On the other hand, the mean angiopoietin-2 level of the responders was decreased during PMX therapy, but that of patients with newly occurring ALI showed an increased angiopoietin-2 level. This result suggested that each angiopoietin-1 and -2 level may play a role in the pathogenesis of ALI and that PMX therapy ameliorates the angiopoietin balance in patients with ALI in sepsis.
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http://dx.doi.org/10.1111/j.1744-9987.2011.00963.xDOI Listing
August 2011

Longitudinal evaluation of immunohistochemical findings of milk aspiration: an experimental study using a murine model.

Forensic Sci Int 2011 Jun 17;209(1-3):183-5. Epub 2011 Feb 17.

Department of Forensic Medicine, The Jikei University School of Medicine, Tokyo, Japan.

To examine the longitudinal change of pathological findings of the lung and other organs in milk aspiration, an experimental study using a murine model was carried out. Either 0.5 or 1.0 ml cow's milk was instilled into the trachea of rats. From immediately after to 14 days after instillation, the animals were sacrificed, and the lungs, liver, kidneys, and spleen were removed. The results of immunostaining with anti-human α lactalbumin antibody indicated that not only the lung but also the kidney and spleen showed a positive reaction against the antibody over time. Experimentally aspirated milk was detectable in alveoli until 2 days after instillation. It was also detectable in renal tubules from 1 to 6h after instillation. Macrophages containing granules of aspirated milk were observed in splenic red pulp from 3h to 14 days after instillation. Detection of aspirated milk in other organs except the lung would be clear evidence of intravital milk aspiration and would suggest previous or recurrent milk aspiration.
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http://dx.doi.org/10.1016/j.forsciint.2011.01.026DOI Listing
June 2011

Toxicological analysis of 17 autopsy cases of hydrogen sulfide poisoning resulting from the inhalation of intentionally generated hydrogen sulfide gas.

Forensic Sci Int 2011 Apr 20;207(1-3):91-5. Epub 2010 Oct 20.

Department of Forensic Medicine, The Jikei University School of Medicine 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Although many cases of fatal hydrogen sulfide poisoning have been reported, in most of these cases, it resulted from the accidental inhalation of hydrogen sulfide gas. In recent years, we experienced 17 autopsy cases of fatal hydrogen sulfide poisoning due to the inhalation of intentionally generated hydrogen sulfide gas. In this study, the concentrations of sulfide and thiosulfate in blood, urine, cerebrospinal fluid and pleural effusion were examined using GC/MS. The sulfide concentrations were blood: 0.11-31.84, urine: 0.01-1.28, cerebrospinal fluid: 0.02-1.59 and pleural effusion: 2.00-8.59 (μg/ml), while the thiosulfate concentrations were blood: 0-0.648, urine: 0-2.669, cerebrospinal fluid: 0.004-0.314 and pleural effusion: 0.019-0.140 (μmol/ml). In previous reports, the blood concentration of thiosulfate was said to be higher than that of sulfide in hydrogen sulfide poisoning cases, although the latter was higher than the former in 8 of the 14 cases examined in this study. These results are believed to be strongly influenced by the atmospheric concentration of hydrogen sulfide the victims were exposed to and the time interval between exposure and death.
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http://dx.doi.org/10.1016/j.forsciint.2010.09.008DOI Listing
April 2011

Focal segmental glomerulosclerosis as a complication of hepatitis B virus infection.

Nephrol Dial Transplant 2011 Jan 19;26(1):371-3. Epub 2010 Oct 19.

Department of Nephrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Human hepatitis B virus (HBV) is well known as a cause of membranous nephropathy (MN). While the association of HBV infection with MN is strong, data regarding its association with other glomerular diseases are conflicting. Here, we report a case of focal segmental glomerulosclerosis (FSGS) with HBV infection. In this case, we have found HBV-DNA in urinary podocytes by real-time PCR methods. After the administration of anti-viral therapy, FSGS improved, paralleling the decreased level of HBV-DNA in podocytes. The refractory FSGS induced by HBV could be effectively treated with appropriate anti-viral agents.
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http://dx.doi.org/10.1093/ndt/gfq600DOI Listing
January 2011

Sudden death involving inhalation of 1,1-difluoroethane (HFC-152a) with spray cleaner: three case reports.

Forensic Sci Int 2011 Mar 26;206(1-3):e58-61. Epub 2010 Sep 26.

Department of Forensic Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Spray cleaner is a cleaning product containing compressed 1,1-difluoroethane (HFC-152a) to blow dust off electric devices and other sensitive equipment; however, it is also inhaled to induce euphoria. This report describes three cases of death involving HFC-152a inhalation with spray cleaner under different circumstances. In case 1, death was during inhalation for euphoria with which led to having frostbite. In case 2, death may have been associated with suicidal intention. Case 3 was also considered an accidental autoerotic death. In all three cases, HFC-152a was detected at 99.2-136.2mg/l in blood samples, 94.5-191.9 mg/l in urine samples and 3.6-18.4 mg in the gastric contents according to gas chromatography with flame ionization detection. To prevent death associated with HFC-152a inhalation from spray cleaner, the danger of the sudden death should be announced to people, given the ready availability of commercial products containing HFC-152a.
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http://dx.doi.org/10.1016/j.forsciint.2010.08.026DOI Listing
March 2011

Potential medical adverse events associated with death: a forensic pathology perspective.

Int J Qual Health Care 2010 Feb 2;22(1):9-15. Epub 2009 Dec 2.

Department of Forensic Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Objective: To determine the incidence of potential medical adverse events among patients undergoing forensic autopsy, and to present the characteristics of potential medical adverse events.

Design: Retrospective review of consecutive autopsy records.

Setting: Department of Forensic Medicine, the Jikei University School of Medicine, Tokyo, Japan.

Participants: A total of 3355 forensic autopsy cases between 1983 and 2006.

Main Outcome Measures: Incidence of potential medical adverse events identified in decedents undergoing forensic autopsy, classified by actual occurrence as 'confirmed', 'equivocal' and 'negative' cases; proportion of potential diagnostic, performance and system errors among potential medical adverse events.

Results: Of 291 autopsies (8.7%) with potential medical adverse events, 66 cases (22.7%) were confirmed, 42 cases (14.4%) were negative and 183 cases (62.9%) were equivocal. Confirmed cases consisted of potential diagnostic errors in 49 cases (74.2%) and performance errors in 17 cases (25.8%). Equivocal cases included 99 cases associated with potential diagnostic errors (54.1%) and 60 cases associated with potential system errors (32.8%). In 38 of the confirmed cases (57.5%), serious exacerbation of patient condition occurred outside the medical facility.

Conclusions: Potential medical adverse events are not uncommon in decedents undergoing forensic autopsy. They are particularly associated with potential diagnostic errors. Forensic autopsy may provide information that could be used to improve care and reduce deaths due to potential medical adverse events.
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http://dx.doi.org/10.1093/intqhc/mzp058DOI Listing
February 2010

A novel method for the diagnosis of drowning by detection of Aeromonas sobria with PCR method.

Leg Med (Tokyo) 2009 Nov 17;11(6):257-9. Epub 2009 Sep 17.

Department of Forensic Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, 105-8461 Tokyo, Japan.

The acid digestion method has been widely used for the diagnosis of death by drowning, but it is not always sensitive. However, there has been no definitive method to replace acid digestion until now. We speculate that bacteria are more useful markers than plankton for the diagnosis of death by drowning. In this study, from the preserved blood samples of 32 freshwater drowning cases, specific DNA fragments of Aeromonas sobria, one of the most common aquatic bacteria, were examined using PCR. The DNA fragments of the bacterium were detected from 27 of 32 cases with first round PCR or nested-PCR. The remaining 5 cases in which bacterial DNA was not detected had longer storage periods for the blood samples and shorter time intervals from drowning to death. These results indicate that the present method can be applied to the diagnosis of death by drowning.
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http://dx.doi.org/10.1016/j.legalmed.2009.07.003DOI Listing
November 2009

Molecular cloning and allergenicity of Pen j 1, a major allergen of kuruma prawn, Penaeus japonicus.

Biosci Biotechnol Biochem 2009 Apr 7;73(4):840-8. Epub 2009 Apr 7.

Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Kuboki, Soja, Okayama 719-1197, Japan.

Tropomyosins have been identified as a common allergen in crustaceans, but their allergenicity is not well understood. In the present study, we isolated an allergen, Pen j 1, a tropomyosin from kuruma prawn Penaeus japonicus, and determined its N-terminal amino acid sequence. The cDNA encoding the allergen was cloned by 5'- and 3'-rapid amplification of cDNA ends (RACE), and was found to code for a protein which consists of 284 amino acid residues. Sequencing analyses indicated for the first time that mature tropomyosin is formed by the elimination of a leader peptide of nine amino acid residues. To elucidate the binding sites of IgE antibodies in the sera of shrimp-sensitive patients, various recombinant peptides were expressed in Escherichia coli as fusion proteins with glutathione S-transferase (GST), and the examined with regard to reactivity with IgE antibodies. The IgE-binding epitopes were found to locate over the whole sequence of the allergen, and the IgE antibodies in the sera were found to recognize strongly its C-terminal region.
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http://dx.doi.org/10.1271/bbb.80751DOI Listing
April 2009
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