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2.
J Forensic Leg Med ; 93: 102474, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36577210

RESUMO

A woman in her 80s was found unconscious after being hit by a car while crossing a road. After admission to hospitals, computed tomography (CT) scans revealed traumatic brain injury (TBI), and the patient was treated symptomatically. However, despite improvement of TBI in CT images, she died unexpectedly. Postmortem CT demonstrated cerebral infarction in the territory of the right middle cerebral artery (MCA). Histopathological examination revealed lumen-obstructing thrombosis and intimal injury upstream of the thrombosis in the right MCA. These findings suggested that the intimal injury in the MCA had led to thrombus formation, and thromboembolism in the region distal to the injury leading to post-traumatic cerebral infarction (PTCI). Both postmortem CT and autopsy were able to reveal the final condition of the deceased, which had not been fully anticipated by the clinicians who had treated her after the accident. The longitudinal antemortem to postmortem course revealed by multiple CT images and the histopathological examination provided crucial clues to the pathogenesis of PTCI in this case.


Assuntos
Lesões Encefálicas Traumáticas , Trombose , Humanos , Feminino , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/patologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Autopsia , Tomografia Computadorizada por Raios X , Trombose/complicações , Lesões Encefálicas Traumáticas/complicações
3.
J Forensic Sci ; 67(3): 1124-1131, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35088897

RESUMO

Forensic pathologists are required to investigate lethal trauma or disease at autopsy. In addition to massive contusions of various organs, a number of small features with potentially fatal implications also need to be sought. Since such lesions may need microscopic examinations for detailed evaluation, it is important to select suitable anatomic locations for tissue sampling. For practical screening of small lesions, we have developed a tissue optical clearing (TOC) technique for forensic autopsy. The technique involves clearing with a non-toxic organic solvent, ethyl cinnamate, which renders excised organs transparent, while hemorrhages or blood-containing vessels remain opaque. Using this technique, tiny hemorrhages in the spinal cord were able to be identified by gross examination, allowing proper selection of locations for tissue sampling. Subsequent histopathological evaluation was successfully performed with no apparent artifacts related with the TOC procedure. In addition, a combination of TOC and targeted CT angiography allowed feasible examination of the arterial occlusive lesion in the superior mesenteric artery, and when combined with micro-CT scanning it was useful for evaluating the lumen of the coronary artery with stent implantation. The results obtained so far indicated that TOC could complement routine forensic autopsy procedures when detailed evaluation of small lesions is required.


Assuntos
Vasos Coronários , Tomografia Computadorizada por Raios X , Autopsia/métodos , Patologia Legal/métodos , Hemorragia , Humanos
4.
Transfusion ; 62(2): 469-480, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34918362

RESUMO

BACKGROUND: Reduction of blood group ABO antigens on red blood cells (RBCs) is well known in patients with leukemias, and this reduction of ABO expression is strongly associated with DNA methylation of the ABO promoter. Previously, we reported a two-nucleotide deletion in RUNX1 encoding an abnormally elongated protein lacking the trans-activation domain in a patient with myelodysplastic syndrome (MDS) showing A-antigen loss on RBCs. This prompted us to investigate the underlying mechanism responsible for A-antigen reduction on RBCs in another patient with MDS. STUDY DESIGN AND METHODS: Screening of somatic mutations was carried out using a targeted sequencing panel with genomic DNA from peripheral blood mononuclear cells from the patient and eleven MDS controls without A- or B-antigen loss. DNA methylation of the ABO promoter was examined by bisulfite genomic sequencing. Transient transfection assays were performed for functional evaluation of mutations. RESULTS: Screening of somatic mutations showed missense mutations in RUNX1 and GATA2 in the patient, while no mutation was found in exons of those genes in the controls. There was no significant difference in ABO promoter methylation between the patient and the controls. Transient transfection experiments into COS-7 and K562 cells suggested that the amino acid substitutions encoded by those mutations reduced or lost the trans-activation potential of the ABO expression. CONCLUSION: Considering the discrepancy between the variant frequencies of these mutations and the ratios of the RBCs with A-antigens loss, the antigen reduction might be associated with these somatic mutations and hypermethylation of the ABO promoter.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Síndromes Mielodisplásicas , Sistema ABO de Grupos Sanguíneos/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Eritrócitos/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Humanos , Leucócitos Mononucleares , Mutação , Síndromes Mielodisplásicas/genética
5.
Leg Med (Tokyo) ; 52: 101898, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33962163

RESUMO

Postmortem computed tomography is now being used more commonly for routine forensic investigation. The use of 3D reconstruction techniques including virtual gastroscopy is effective and also improves the speed of interpretation, recognition, and description of specific clinical conditions. However, it has been unclear whether postmortem virtual endoscopy could be applicable for medicolegal autopsy or whether it could complement pathological examination at autopsy. Here, we investigated the applicability of postmortem virtual gastroscopy by reviewing 295 medicolegal autopsy cases seen at our institution, and found four cases in which the technique had been able to demonstrate features corresponding to changes that were evident at autopsy. Thus,postmortem virtual gastroscopy would have only rarely been effective forvisualizing any change in the stomach in such cases. In addition, we describe in detail three of those cases in which virtual gastroscopy had been able to visualize changes in the stomach, including a gastric ulcer, a polyp, and the presence of foamy fluid, which were all verified at autopsy. In those cases, virtual gastroscopy was useful for understanding features in the stomach of the deceased, which were revealed by axial images of the abdomen, to forensic pathologists who were not familiar with PMCT 2D images. Taken together, our findings suggest that postmortem virtual gastroscopy might help facilitate clear, straightforward sharing of information about PMCT images of complex anatomical structures among radiologists and forensic pathologists, as well as non-medical professionals with a limited knowledge of anatomy and physiology.


Assuntos
Gastroscopia , Tomografia Computadorizada por Raios X , Abdome , Autopsia , Humanos , Estômago/diagnóstico por imagem
6.
Sci Rep ; 11(1): 7325, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795748

RESUMO

The human ABO blood group system is of great importance in blood transfusion and organ transplantation. ABO transcription is known to be regulated by a constitutive promoter in a CpG island and regions for regulation of cell-specific expression such as the downstream + 22.6-kb site for epithelial cells and a site in intron 1 for erythroid cells. Here we investigated whether the + 22.6-kb site might play a role in transcriptional regulation of the gene encoding odorant binding protein 2B (OBP2B), which is located on the centromere side 43.4 kb from the + 22.6-kb site. In the gastric cancer cell line KATOIII, quantitative PCR analysis demonstrated significantly reduced amounts of OBP2B and ABO transcripts in mutant cells with biallelic deletions of the site created using the CRISPR/Cas9 system, relative to those in the wild-type cells, and Western blotting demonstrated a corresponding reduction of OBP2B protein in the mutant cells. Moreover, single-molecule fluorescence in situ hybridization assays indicated that the amounts of both transcripts were correlated in individual cells. These findings suggest that OBP2B could be co-regulated by the + 22.6-kb site of ABO.


Assuntos
Sistema ABO de Grupos Sanguíneos , Células Epiteliais/metabolismo , Lipocalinas/biossíntese , Linhagem Celular Tumoral , Ilhas de CpG , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Humanos , Hibridização In Situ , Hibridização in Situ Fluorescente , Íntrons , Lipocalinas/genética , Mutação , Fenótipo , Reação em Cadeia da Polimerase , RNA-Seq , Espectrometria de Fluorescência , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
7.
Sci Rep ; 11(1): 3379, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564039

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a pandemic throughout 2020. Since the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry, increment of ACE2 would lead to an increased risk of SARS-CoV-2 infection. At the same time, an association of the ABO blood group system with COVID-19 has also been highlighted: there is increasing evidence to suggest that non-O individuals are at higher risk of severe COVID-19 than O individuals. These findings imply that simultaneous suppression of ACE2 and ABO would be a promising approach for prevention or treatment of COVID-19. Notably, we have previously clarified that histone deacetylase inhibitors (HDACIs) are able to suppress ABO expression in vitro. Against this background, we further evaluated the effect of HDACIs on cultured epithelial cell lines, and found that HDACIs suppress both ACE2 and ABO expression simultaneously. Furthermore, the amount of ACE2 protein was shown to be decreased by one of the clinically-used HDACIs, panobinostat, which has been reported to reduce B-antigens on cell surfaces. On the basis of these findings, we conclude that panobinostat could have the potential to serve as a preventive drug against COVID-19.


Assuntos
Sistema ABO de Grupos Sanguíneos/metabolismo , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Panobinostat/farmacologia , Ácido Butírico/farmacologia , COVID-19/prevenção & controle , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Serina Endopeptidases , Tratamento Farmacológico da COVID-19
8.
J Forensic Sci ; 66(3): 1148-1153, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33320985

RESUMO

With the increasing use of postmortem computed tomography (PMCT) in medicolegal autopsies, three-dimensional (3D) models of injured areas can now be generated from multislice computed tomography images. However, since PMCT has low sensitivity for detecting injuries in solid organs in the absence of contrast administration, it has been difficult to demonstrate the tracks of stab wounds leading to solid organ injury using 3D reconstruction. Here, we report one homicide case with two stab wounds. On the skin surface, the stab wounds were located on the neck and anterior chest wall. A medicolegal autopsy revealed that one stab wound in the neck had penetrated the wall of the right pleural cavity and the upper portion of the right lung whereas the other stab wound in the anterior chest wall had penetrated the right diaphragm and the heart. To illustrate the tracks of the stab wounds, superimposed CT images of the body, the excised organ, and a knife model were constructed to obtain a 3D model. This allowed clear and concise visualization of the complex relationship of the knife to the heart incision and the stab wound on the chest surface.


Assuntos
Simulação por Computador , Traumatismos Cardíacos/diagnóstico por imagem , Imageamento Tridimensional/métodos , Ferimentos Perfurantes/diagnóstico por imagem , Medicina Legal/métodos , Homicídio , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Tomografia Computadorizada por Raios X , Imagem Corporal Total
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