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1.
Hepatol Res ; 52(12): 1020-1033, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36001355

RESUMO

AIM: The mitochondria are highly plastic and dynamic organelles; mitochondrial dysfunction has been reported to play causative roles in diabetes, cardiovascular diseases, and nonalcoholic fatty liver disease (NAFLD). However, the relationship between mitochondrial fission and NAFLD pathogenesis remains unknown. We aimed to investigate whether alterations in mitochondrial fission could play a role in the progression of NAFLD. METHODS: Mice were fed a standard diet or choline-deficient, L-amino acid-defined (CDAA) diet with vehicle or mitochondrial division inhibitor-1. RESULTS: Substantial enhancement of mitochondrial fission in hepatocytes was triggered by 4 weeks of feeding and was associated with changes reflecting the early stage of human nonalcoholic steatohepatitis (NASH), steatotic change with liver inflammation, and hepatocyte ballooning. Excessive mitochondrial fission inhibition in hepatocytes and lipid metabolism dysregulation in adipose tissue attenuated liver inflammation and fibrogenesis but not steatosis and the systemic pathological changes in the early and chronic fibrotic NASH stages (4- and 12-week CDAA feeding). These beneficial changes due to the suppression of mitochondrial fission against the liver and systemic injuries were associated with decreased autophagic responses and endoplasmic reticulum stress in hepatocytes. Injuries to other liver cells, such as endothelial cells, Kupffer cells, and hepatic stellate cells, were also attenuated by the inhibition of mitochondrial fission in hepatocytes. CONCLUSIONS: Taken together, these findings suggest that excessive mitochondrial fission in hepatocytes could play a causative role in NAFLD progression by liver inflammation and fibrogenesis through altered cell cross-talk. This study provides a potential therapeutic target for NAFLD.

2.
Am J Pathol ; 186(4): 829-43, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26878212

RESUMO

Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury.


Assuntos
Hepatócitos/metabolismo , Histonas/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Lesão Pulmonar/etiologia , Pulmão/metabolismo , Animais , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Proteína HMGB1/metabolismo , Fígado/lesões , Masculino , Camundongos Endogâmicos C57BL
3.
Lab Invest ; 95(10): 1130-44, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26214582

RESUMO

Liver sinusoidal endothelial cells (LSECs) are involved in the transport of nutrients, lipids, and lipoproteins, and LSEC injury occurs in various liver diseases including nonalcoholic fatty liver disease (NAFLD). However, the association between LSEC injury and NAFLD progression remains elusive. Accordingly, in this study, we aimed to elucidate the precise role of LSEC in the pathophysiology of NAFLD using two different mouse models, namely the choline-deficient, L-amino acid-defined and high-fat diet models. Administration of these diets resulted in liver metabolic dysregulation mimicking human NAFLD, such as steatosis, ballooning, lobular inflammation, and fibrosis, as well as central obesity, insulin resistance, and hyperlipidemia. LSEC injury appeared during the simple steatosis phase, and preceded the appearance of activated Kupffer cells and hepatic stellate cells (HSCs). These results indicate that LSEC injury may have a 'gatekeeper' role in the progression from simple steatosis to the early nonalcoholic steatohepatitis (NASH) stage, and LSEC injury may be necessary for the activation of Kupffer cells and HSCs, which in turn results in the development and perpetuation of chronic liver injuries. Taken together, our data provide new insights into the role of LSEC injury in NAFLD/NASH pathogenesis.


Assuntos
Modelos Animais de Doenças , Progressão da Doença , Endotélio Vascular/patologia , Células Estreladas do Fígado/patologia , Células de Kupffer/patologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Deficiência de Colina/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/metabolismo , Hiperlipidemias/etiologia , Imunoquímica , Resistência à Insulina , Células de Kupffer/imunologia , Células de Kupffer/metabolismo , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/fisiopatologia , Cirrose Hepática/etiologia , Ativação de Macrófagos , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Abdominal/etiologia , Organismos Livres de Patógenos Específicos
4.
Forensic Sci Med Pathol ; 11(2): 249-54, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25724839

RESUMO

Bilateral spontaneous pneumothorax secondary to disease is rare and seldom encountered in forensic autopsies; however, traumatic bilateral pneumothorax occurs often. Herein, we present a forensic case involving a 50-year-old woman who died 4 days after ingesting a wristwatch. Postmortem computed tomography and autopsy findings demonstrated that the wristwatch was lodged at the pharyngoesophageal junction, that she had a bilateral pneumothorax unaccompanied by any thoracic wound, and that macular hemorrhagic lesions on the lung surfaces were responsible for the pneumothorax. A histological examination of the macular lesions revealed that they were aspiration pneumonia foci with many birefringent foreign materials. Furthermore, a necrotic process secondary to aspiration pneumonia with a one way check-valve hyperinflation caused by foreign materials in the bronchioles was the most probable pathogenesis of her pneumothorax. To our knowledge, this is the first reported case of a bilateral secondary spontaneous pneumothorax caused by a large foreign body at the pharyngoesophageal junction leading to death.


Assuntos
Corpos Estranhos/complicações , Pneumonia Aspirativa/complicações , Pneumonia Aspirativa/etiologia , Pneumotórax/etiologia , Esôfago/diagnóstico por imagem , Esôfago/patologia , Feminino , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/patologia , Patologia Legal , Humanos , Pessoa de Meia-Idade , Faringe/diagnóstico por imagem , Faringe/patologia , Pneumotórax/diagnóstico por imagem , Pneumotórax/patologia , Radiografia , Psicologia do Esquizofrênico
5.
Leg Med (Tokyo) ; 67: 102387, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154310

RESUMO

Williams syndrome (WS) is a rare genetic disorder caused by a microdeletion of chromosome 7q11.23. Although the mortality rate of patients with WS is not very high, sudden cardiac death can occur, particularly in cases complicated by coronary artery stenosis. A 3-month-old female infant with supravalvular aortic stenosis and peripheral pulmonary stenosis was discovered unconscious in bed by her mother. She was immediately transferred to an emergency hospital but succumbed despite multiple attempts as resuscitation. DNA microarray analysis revealed microdeletions of 7q11.23 and 16p11.2, confirming WS and unexpectedly identifying 16p11.2 deletion syndrome which is known to be associated with neurodevelopmental disorders. Postmortem computed tomography revealed a severely enlarged heart, indicative of cardiac dysfunction. External examination revealed moderate-to-severe developmental delays in height and body weight. The heart, on internal examination, revealed whitish-discolored lesions; histologically severe fibrotic changes and thickening of the intima in the coronary arteries and aorta. In the brain, the dentate gyrus of the hippocampus appeared malformed. Taken together, these findings suggest that the cause of death was cardiac dysfunction due to WS. In addition, it could be possible that 16p11.2 deletion syndrome and dentate gyrus malformation contributed to her death. Future autopsy studies are warranted to clarify the precise role of microdeletion disorders in sudden death to reduce future preventable deaths in children.


Assuntos
Transtorno Autístico , Transtornos Cromossômicos , Estenose Coronária , Deficiência Intelectual , Síndrome de Williams , Humanos , Criança , Lactente , Feminino , Síndrome de Williams/complicações , Síndrome de Williams/genética , Deleção Cromossômica , Morte Súbita Cardíaca/etiologia , Cromossomos Humanos Par 16
6.
BMC Genet ; 14: 72, 2013 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23962363

RESUMO

BACKGROUND: DNA profiling is essential for individual identification. In forensic medicine, the likelihood ratio (LR) is commonly used to identify individuals. The LR is calculated by comparing two hypotheses for the sample DNA: that the sample DNA is identical or related to a reference DNA, and that it is randomly sampled from a population. For multiple-fatality cases, however, identification should be considered as an assignment problem, and a particular sample and reference pair should therefore be compared with other possibilities conditional on the entire dataset. RESULTS: We developed a new method to compute the probability via permanents of square matrices of nonnegative entries. As the exact permanent is known as a #P-complete problem, we applied the Huber-Law algorithm to approximate the permanents. We performed a computer simulation to evaluate the performance of our method via receiver operating characteristic curve analysis compared with LR under the assumption of a closed incident. Differences between the two methods were well demonstrated when references provided neither obligate alleles nor impossible alleles. The new method exhibited higher sensitivity (0.188 vs. 0.055) at a threshold value of 0.999, at which specificity was 1, and it exhibited higher area under a receiver operating characteristic curve (0.990 vs. 0.959, P = 9.6E-15). CONCLUSIONS: Our method therefore offers a solution for a computationally intensive assignment problem and may be a viable alternative to LR-based identification for closed-incident multiple-fatality cases.


Assuntos
Algoritmos , DNA/análise , Medicina Legal/métodos , Área Sob a Curva , Simulação por Computador , Homicídio , Humanos , Curva ROC , Software
7.
Am J Forensic Med Pathol ; 34(3): 242-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23949140

RESUMO

Triphenyltetrazolium chloride (TTC) is one of the most conventional stains to detect infarcted area of the heart in animal experiments. However, its availability and limitations have not been thoroughly discussed in the forensic field. Here, authors stained human hearts with TTC soon after the harvest. Photographs of the samples were analyzed using image analysis software, which evaluated the occupying ratio of the stained area on the surface of each slice. The results showed that the stainability of TTC declines with the length of the postmortem interval (PMI). Specimens reacted well to TTC within 1.5 days after death and then decreased the stainability logarithmically with PMI (y = - 0.294 In (x) + 1.0441; x = PMI, y = TTC-stained area / total myocardial area, R = 0.5673). Samples with old myocardial infarction produced clear TTC contrast; normal tissue is vivid red, and fibrotic myocardium is white discoloration. In acute myocardial infarction cases where death occurred within 9 hours after the attack, however, the detection of infarcted area was very difficult even when PMI was less than 1.5 days. In summary, the TTC method may be useful within 1.5 days after death, but short suffering period before death disturbs its staining efficiency.


Assuntos
Corantes , Infarto do Miocárdio/diagnóstico , Miocárdio/patologia , Sais de Tetrazólio , Idoso , Feminino , Fibrose , Patologia Legal , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Análise de Regressão , Coloração e Rotulagem , Fatores de Tempo
8.
Leg Med (Tokyo) ; 60: 102158, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36308842

RESUMO

High-density single nucleotide polymorphisms (SNPs) can detect distant relatives even in the context of pairwise kinship analysis. Although DNA microarrays conveniently generate genome-wide SNP data, they require large quantities of high-quality DNA. Genotyping data obtained from low-quantity and low-quality samples are likely unreliable owing to the incidence of no-called or mistyped SNPs. In this study, we examined the effects of insufficient sample densities and sample degradation on the efficacy of kinship analysis. While low DNA amounts had a minor effect, DNA degradation led to a significant increase in no-call rates and error rates. Posterior probabilities of kinship determination, calculated using the index of chromosomal sharing, were markedly lower in proportion to the no-call rates and error rates. We also investigated the effect of genotype imputation to complement the no-called genome data utilizing SNPs reference panels. We found that the posterior probability of the relative-assumed person increased with genotype complementation in case of mild degradation, even with mistyped genotypes. Therefore, DNA microarray with imputation is a promising method for analyzing forensic DNA samples taken from situations where DNA quantity and quality may be compromised, such as disaster victim identification using pairwise kinship analysis.


Assuntos
Cromossomos , Polimorfismo de Nucleotídeo Único , Humanos , Polimorfismo de Nucleotídeo Único/genética , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos , DNA/genética
9.
Leg Med (Tokyo) ; 60: 102167, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36279710

RESUMO

Systemic amyloidosis is a rare but potentially lethal disease characterized by amyloid accumulation in all organs. Amyloid goiter is an extremely rare pathological lesion characterized by thyroid gland enlargement with fat deposition due to local or systemic amyloidosis. A 60 s woman with rheumatoid arthritis was found unconscious on her bed and declared dead after failed cardiopulmonary resuscitation. Postmortem computed tomography showed severe enlargement of the heart and thyroid glands, suggestive of cardiac hypertrophy and thyroidism. Histological examination revealed amorphous eosinophilic deposits with parenchymal cell destruction in all organs, including the heart and thyroid gland. Abnormal amorphous deposits in the tissues were positive for amyloid A as noted upon Congo red immunohistochemical staining and birefringence microscopy, confirming systemic amyloidosis with amyloid goiter. Serum biochemical analysis revealed increased levels of C-reactive protein; anti-cyclic citrullinated peptide antibody; creatinine kinase-myoglobin binding and N-terminal pro-brain natriuretic peptide; and thyroglobulin, free triiodothyronine, and free thyroxine, indicating systemic inflammation, active rheumatoid arthritis, heart failure, and destructive hyperthyroidism, respectively. These findings suggested that the cause of death was undiagnosed heart failure due to secondary systemic amyloid A (AA) amyloidosis related to rheumatoid arthritis. In addition, destructive hyperthyroidism caused by systemic AA amyloidosis may have also been one of the causes of death as indicated by cardiac overload. To the best of our knowledge, this is the first forensic autopsy report of cardiac amyloidosis with amyloid goiter. In conclusion, this autopsy report highlights the importance of increased awareness and early intervention for severe but treatable complications of systemic amyloidosis.


Assuntos
Amiloidose , Bócio , Insuficiência Cardíaca , Hipertireoidismo , Humanos , Feminino , Autopsia , Amiloidose/diagnóstico , Bócio/complicações , Bócio/diagnóstico , Bócio/patologia , Amiloide/metabolismo , Hipertireoidismo/complicações
10.
J Neuroinflammation ; 9: 256, 2012 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-23176072

RESUMO

INTRODUCTION: The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with corresponding SHAM control that used 0.9% saline injection. METHODS: Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent) and two-dimensional gel electrophoresis (2-DGE) coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. RESULTS: Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral) treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral). Previously known (such as the interleukin family) and novel (Gabra6, Crtam) genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2). The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining) at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. CONCLUSIONS: This study provides a detailed inventory of PACAP influenced gene expressions and protein targets in mice ischemic brain, and suggests new targets for thereaupetic interventions.


Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica/fisiologia , Infarto da Artéria Cerebral Média/patologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Transcriptoma/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional , Proteínas da Matriz Extracelular , Lateralidade Funcional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Chaperonas Moleculares , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Proteínas/genética , Proteínas/metabolismo , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fatores de Tempo
11.
Am J Pathol ; 178(3): 1374-86, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21356387

RESUMO

Murine leukemia retrovirus (MLV) vectors are highly effective tools for introducing a foreign gene into a target host genome. However, it remains unclear how integrated retroviral promoter activity is influenced by the upstream or downstream sequences and how the host cell phenotype is influenced by the integrated promoter activity. Herein, we analyzed a set of pre-B lymphoma clones in which the MLV genome was integrated into the signal transducer and activator of transcription factor 5a (Stat5a) gene. Among the clones, the lymphoma clones with a provirus integrating into the middle position of the palindromic target sequences showed significantly higher transcription of the Stat5a gene; and p300 and other transcriptional factors formed complexes, with binding to the proviral-host junctional DNA segment. By using a luciferase assay, the upstream and downstream sequences of the provirus contributed to the up-regulation of proviral promoter activity. In concomitance with the higher Stat5a transcription, the immunoglobulin gene recombination was arrested. Antiapoptotic activity was significantly higher, with an increase in Bcl-xL, one of the targets of STAT5A, when IL-7 was supplied. Thus, a minute difference between MLV integration sites can lead to large differences in the host phenotype through the formation of transcription factor complexes on the proviral-host junctional DNA segment, suggesting that caution is necessary in monitoring integration sites when working with MLV vectors.


Assuntos
Sequências Repetidas Invertidas/genética , Vírus da Leucemia Murina/genética , Linfoma de Células B/genética , Lesões Pré-Cancerosas/genética , Fator de Transcrição STAT5/genética , Fatores de Transcrição/metabolismo , Integração Viral/genética , Animais , Apoptose/genética , Sequência de Bases , Diferenciação Celular , Células Clonais , Fator de Transcrição GATA2/metabolismo , Genes Reporter/genética , Cadeias Leves de Imunoglobulina/genética , Linfoma de Células B/patologia , Camundongos , Modelos Biológicos , Dados de Sequência Molecular , Lesões Pré-Cancerosas/patologia , Regiões Promotoras Genéticas/genética , Ligação Proteica , Provírus/genética , Receptores de Interleucina-7/metabolismo , Recombinação Genética/genética
12.
Transpl Int ; 25(9): 956-66, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22775391

RESUMO

The long-term fate of aged liver allografts in young recipients who received grafts from older donors is unknown. We evaluated graft aging by analyzing hepatocytic telomere length and karyotypic changes. Seventeen pediatric individuals who underwent living-donor liver transplantation for congenital biliary diseases were selected. At a median of 10.4 years post-transplant, ten had tolerated grafts with weaned off immunosuppressants, and seven had idiopathic post-transplantation hepatitis. Fluorescence in situ hybridization was used to evaluate the telomere signal intensity (TI) and karyotypic changes. First, we measured predictive age-dependent TI decline with regression analysis of donor livers. The mean TI at the earliest (within a year) and latest biopsies was significantly lower than the predicted TI of the studied allografts. With univariate analysis, a higher abnormal karyotype ratio in the donor liver was correlated with development of idiopathic post-transplantation hepatitis. With multivariate analysis that included clinical parameters, a greater TI decline at the earliest biopsy was correlated with the development of idiopathic post-transplantation hepatitis. In conclusion, graft aging as measured by TI decline and donor abnormal karyotype ratio was associated with idiopathic post-transplantation hepatitis of long-term transplanted liver allografts.


Assuntos
Hepatócitos/patologia , Falência Hepática/genética , Falência Hepática/terapia , Transplante de Fígado/métodos , Telômero/ultraestrutura , Adolescente , Aneuploidia , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Hepatite/complicações , Hepatite/etiologia , Humanos , Imunossupressores , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , Masculino , Análise Multivariada , Transplante Homólogo , Resultado do Tratamento
13.
Am J Forensic Med Pathol ; 33(3): 280-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22835970

RESUMO

Pituitary abscess is a rare disease presenting with nonspecific clinical symptoms, and diagnosis is often difficult. This disease is potentially life-threatening, but most cases have a chronic and indolent course. We report a case of a 60-year-old man with a pituitary abscess associated with pituitary adenoma who died 5 days after the onset of clinical symptoms without a definitive diagnosis. Postmortem computed tomography and autopsy findings revealed a sellar mass with cystic change and extension toward the optic chiasm. Histopathology of the lesion demonstrated an abscess with suppurative meningitis and encephalitis. The disturbance of the cardiac autonomic nervous system because of hypothalamus involvement was suggested as the cause of rapid progression and death. This case provides useful information for clinicians to avoid a lethal outcome.


Assuntos
Abscesso/patologia , Doenças da Hipófise/patologia , Abscesso/etiologia , Adenoma/complicações , Adenoma/patologia , Progressão da Doença , Patologia Legal , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/etiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/patologia , Tomografia Computadorizada por Raios X
14.
Leg Med (Tokyo) ; 54: 101972, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34629243

RESUMO

Probabilistic genotyping software based on continuous models is effective for interpreting DNA profiles derived from DNA mixtures and small DNA samples. In this study, we updated our previously developed Kongoh software (to ver. 3.0.1) to interpret DNA profiles typed using the GlobalFiler™ PCR Amplification Kit. Recently, highly sensitive typing systems such as the GlobalFiler system have facilitated the detection of forward, double-back, and minus 2-nt stutters; therefore, we implemented statistical models for these stutters in Kongoh. In addition, we validated the new version of Kongoh using 2-4-person mixtures and DNA profiles with degradation in the GlobalFiler system. The likelihood ratios (LRs) for true contributors and non-contributors were well separated as the information increased (i.e., larger peak height and fewer contributors), and these LRs tended to neutrality as the information decreased. These trends were observed even in profiles with DNA degradation. The LR values were highly reproducible, and the accuracy of the calculation was also confirmed. Therefore, Kongoh ver. 3.0.1 is useful for interpreting DNA mixtures and degraded DNA samples in the GlobalFiler system.


Assuntos
Impressões Digitais de DNA , Repetições de Microssatélites , Alelos , DNA , Humanos , Funções Verossimilhança , Software
15.
Leg Med (Tokyo) ; 57: 102059, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35413664

RESUMO

Dieulafoy lesions are rare vascular malformations of the gastrointestinal tract; however, they can lead to fatal vascular bleeding. Immunoglobulin G4-related disease (IgG4-RD) is a rare systemic fibroinflammatory disease involving multiple organs, including the vasculature. To date, no autopsy reports of Dieulafoy lesions with IgG4-RD have been described in the literature. A 48-year-old man was found dead in his home with hematochezia. Postmortem computed tomography revealed high-density gastric contents and an enlarged iso-density area in the pancreas, indicating gastric hemorrhage and mass-forming lesions. Macroscopic and histological examinations revealed an ulcer of the body of the stomach with a large amount of hemorrhage from the enlarged artery in the submucosal layer, confirming the rupture of the Dieulafoy lesion. Moreover, lymphocyte infiltrations with increased IgG4 positive cells were found in the pancreas, thyroid gland, and arteries in non-ulcer regions of the stomach, suggesting IgG4-RD. Serum biochemical analysis showed elevated levels of inflammatory mediators, such as IgE, soluble-interleukin-2 receptor, and C-reactive protein. These findings suggest that systemic inflammation caused by IgG4-RD could, at least in part, contribute to the development of Dieulafoy lesions and fatal rupture of the lesion. This case report highlights the importance of autopsy research focusing on Dieulafoy lesions and IgG4-RD to promote awareness and a better understanding of the relationships between these treatable diseases to establish earlier and effective interventional strategies for better patient outcomes.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Autopsia , Humanos , Imunoglobulina G/análise , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/patologia , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Úlcera
16.
Sci Rep ; 12(1): 9773, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35697924

RESUMO

Sudden infant death syndrome (SIDS) remains a leading cause of infant death in high-income countries. Supporting models for categorization of sudden unexpected infant death into SIDS/non-SIDS could reduce mortality. Therefore, we aimed to develop such a tool utilizing forensic data, but the reduced number of SIDS cases renders this task inherently difficult. To overcome this, we constructed Bayesian network models according to diagnoses performed by expert pathologists and created conditional probability tables in a proof-of-concept study. In the diagnostic support model, the data of 64 sudden unexpected infant death cases was employed as the training dataset, and 16 known-risk factors, including age at death and co-sleeping, were added. In the validation study, which included 8 new cases, the models reproduced experts' diagnoses in 4 or 5 of the 6 SIDS cases. Next, to confirm the effectiveness of this approach for onset prediction, the data from 41 SIDS cases was employed. The model predicted that the risk of SIDS in 0- to 2-month-old infants exposed to passive smoking and co-sleeping is eightfold higher than that in the general infant population, which is comparable with previously published findings. The Bayesian approach could be a promising tool for constructing SIDS prevention models.


Assuntos
Morte Súbita do Lactente , Poluição por Fumaça de Tabaco , Teorema de Bayes , Humanos , Lactente , Recém-Nascido , Fatores de Risco , Sono , Morte Súbita do Lactente/epidemiologia , Morte Súbita do Lactente/etiologia
17.
Leg Med (Tokyo) ; 59: 102151, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36191412

RESUMO

In human identification methods that target short tandem repeats (STRs), massively parallel sequencing (MPS) technology has made it possible to genotype at the level of the specific sequence itself. This allows for the detection of repeat unit variants and single nucleotide polymorphisms (SNPs) adjacent to the STRs. Using the GlobalFiler™ NGS STR Panel v2, Ion S5, and Converge software, this study constructed a Japanese database of 31 autosomal STRs (auSTRs) and two sex markers from 322 individuals. After excluding some sequence errors and stutters, a total of 31 novel alleles were identified. Additionally, using the allele frequencies of 31 auSTR loci, the match probabilities for the length-based and sequence-based data were calculated to be 1.433 × 10-34 and 9.163 × 10-38, respectively. These values are at least nine orders of magnitude higher than that obtained from 21 auSTR loci in the Japanese population using the conventional capillary electrophoresis method. The database generated in this study is expected to be implemented in forensic practice and used to solve difficult casework.


Assuntos
Impressões Digitais de DNA , Repetições de Microssatélites , Humanos , Impressões Digitais de DNA/métodos , Japão , Análise de Sequência de DNA , Repetições de Microssatélites/genética , Frequência do Gene/genética
18.
Leg Med (Tokyo) ; 48: 101806, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33189063

RESUMO

In forensic genetics, a suspect is assigned to a component of a DNA mixture profile, and a probabilistic interpretation is then usually performed. However, it is difficult to determine what types of body fluid the component is from. Previous studies have reported that the fourth exon of the Dishevelled binding antagonist of beta catenin 1 (DACT1) gene is hypomethylated in a semen DNA-specific manner. In the present study, we evaluated whether the DACT1 gene could be effectively used to identify semen in body fluid mixtures and were able to semi-quantify the semen DNA content in mixed fluids. Our results showed that the DACT1 gene was useful in discriminating semen from venous blood and saliva. However, the amount of sperm in semen can affect semen identification. In addition, SI (the semen DNA content index), which we developed, was useful to determine whether the semen compromised majority, almost half, or was in the minority of the components in a mixed fluid. This technique is based on the methylation-sensitive high-resolution melting (MS-HRM) technology, which is time-, cost-, and labour-effective, and could be adopted in routine criminal investigations.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Líquidos Corporais/química , Metilação de DNA , DNA/análise , Genética Forense/métodos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Sêmen/química , Crime , Vítimas de Crime , Feminino , Humanos , Masculino , Espermatozoides
19.
Leg Med (Tokyo) ; 52: 101906, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34015722

RESUMO

As DNA typing systems have become increasingly sensitive in recent years, probability distribution models for back, forward, double-back, and minus 2-nt stutter ratios have been desired to be considered in DNA evidence interpretation using specific software programs. However, experimental investigations have been insufficient, especially for forward, double-back, and minus 2-nt stutters. In this study, we experimentally reevaluated the probability distribution models for each stutter ratio in the typing systems of GlobalFiler™ PCR Amplification Kit and 3500xL Genetic Analyzer from Thermo Fisher Scientific. In addition, to enhance the reliability of longest uninterrupted stretch (LUS) values and corrected allele numbers used in previously developed models for stutter ratios using sequence information (i.e., LUS model and multi-seq model), we propose the weighted average of LUS values and corrected allele numbers based on the number of observations in sequence-based population data. Back stutter ratios demonstrated a positive correlation with allele numbers (allele model) in eight loci, LUS values (LUS model) in eight loci, and corrected allele numbers (multi-seq model) in five loci. The forward stutter ratios (FSRs) of D22S1045 followed the LUS model. FSRs other than D22S1045 and double-back stutter ratios followed the LUS model by considering multiple loci together. Minus 2-nt stutter ratios observed in SE33 and D1S1656 did not increase with the increase in the allele numbers. The adopted models for each stutter ratio can be implemented in software programs for DNA evidence interpretation and enable a reliable interpretation of crime stain profiles in forensic caseworks.


Assuntos
Impressões Digitais de DNA , Alelos , Humanos , Repetições de Microssatélites , Probabilidade , Reprodutibilidade dos Testes , Análise de Sequência de DNA
20.
Cancer Sci ; 101(3): 800-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20353532

RESUMO

While the molecular mechanisms underlying microsatellite instability (MSI) have been exhaustively investigated, identifying the patterns of MSI distribution within diverse cancer genomes has remained an elusive issue. In the present study, we conducted genome-wide MSI screening in B-cell lymphoblastic lymphomas (B-LBL) which spontaneously develop in the SL/Kh strain of mice. Tumor samples harvested from 16 mice were investigated using a framework map consisting of 150 microsatellite markers spaced at increments of roughly 0.5-3.0 centimorgans, spanning the entirety of mouse chromosomes (mus musculus chromosomes [MMU]) 3-6. MMU3 contains a quantitative trait locus (QTL), Bomb1 (bone marrow pre-B1), known to induce an aberrant expansion of pre-B cells in bone marrow prior to the onset of B-LBL in SL/Kh mice. The remaining chromosomes were selected on the basis of those most closely resembling MMU3 in terms of total estimated length (maximum variance 10 Mb). MSI was confirmed at 2

Assuntos
Linfoma de Células B/genética , Instabilidade de Microssatélites , Locos de Características Quantitativas , Animais , Camundongos
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