Search

Background and Summary: We review the transcriptional regulation of ABO expression and discuss variants in the promoter and erythroid cell-specific regulatory region in individuals with weak ABO phenotypes such as Bm, Am, B3, and A3. We also review the molecular mechanisms responsible for variations in ABO expression in development and disease including the cell type-specific expression of ABO during erythroid cell differentiation, and reduction of A- or B-antigens in cancer cells or on red blood cells in patients with leukemia. Although the relationship between ABO blood group antigens and diseases has been characterized, the physiological significance of the ABO blood group system remains unclear. Key Messages: This review discusses accumulated knowledge of the ABO gene regulation and potential reasons for conservation of ABO during evolution. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABBREVIATIONS ABOi ABO-incompatible AML acute myeloid leukemia CGIs CpG islands ChIP chromatin immunoprecipitation DHSs DNase I-hypersensitive sites EMSAs electrophoretic mobility shift assays HGVS Human Genome Variation Society MDS myelodysplastic syndrome SSP single specific primer TFs transcription factors vWF von Willebrand factor The ABO blood group system, discovered by Karl Landsteiner in 1900,[1] is fundamental to the safety of blood transfusion, which requires identification of weak phenotypes or subgroups. Thus, it remains controversial whether I ABO i transcription is influenced by the CCAAT-binding factor/NF-Y enhancer region in erythroid cells.[[36], [52]] Distal promoter of ABO At the 5' end of the CGI involving the I ABO i proximal promoter in cultured cells expressing I ABO i , an alternative starting Exon 1a comprising 27 base pairs was found by 5'-RACE (Fig. The region proximal to the proximal ABO promoter The plasmid-based reporter assays demonstrated a negative regulatory element just upstream from the proximal I ABO i promoter in KATOIII cells and HEL cells,[54] suggesting that I ABO i transcription is regulated by negative elements in the -307 to -150 region from the translation start site. Cell differentiation-specific regulation In vitro erythroid differentiation of CD34 SP + sp cells and AC133 SP - sp CD34 SP + sp cells from peripheral blood mononuclear cells indicated that I ABO i was expressed at an early stage and disappeared later,[[35], [42]] and that the period when I ABO i was expressed at a higher level preceded that of I FUT1 i expression (Fig.). [Extracted from the article]

Background: Loss of blood group ABO antigens on red blood cells (RBCs) is well known in patients with leukemias, and such decreased ABO expression has been reported to be strongly associated with hypermethylation of the ABO promoter. We investigated the underlying mechanism responsible for A-antigen reduction on RBCs in a patient with myelodysplastic syndrome.Study Design and Methods: Genetic analysis of ABO was performed by PCR and sequencing using peripheral blood. RT-PCR were carried out using cDNA prepared from total bone marrow (BM) cells. Bisulfite genomic sequencing was performed using genomic DNA from BM cells. Screening of somatic mutations was carried out using a targeted sequencing panel with genomic DNA from BM cells, followed by transient transfection assays.Results: Genetic analysis of ABO did not reveal any mutation in coding regions, splice sites, or regulatory regions. RT-PCR demonstrated reduction of A-transcripts when the patient's RBCs were not agglutinated by anti-A antibody and did not indicate any significant increase of alternative splicing products in the patient relative to the control. DNA methylation of the ABO promoter was not obvious in erythroid cells. Targeted sequencing identified somatic mutations in ASXL1, EZH2, RUNX1, and WT1. Experiments involving transient transfection into K562 cells showed that the expression of ABO was decreased by expression of the mutated RUNX1.Conclusion: Because the RUNX1 mutation encoded an abnormally elongated protein without a transactivation domain which could act as dominant negative inhibitor, this frame-shift mutation in RUNX1 may be a genetic candidate contributing to A-antigen loss on RBCs. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) has been suggested to cause epigenetic changes to genes in the brain, such as the Nuclear Receptor Subfamily 3, Group C, Member 1 gene (NR3C1). Conversely, evaluation of the epigenetic status in the postmortem brain might provide clues to the antemortem ELS experience. We examined DNA methylation of the 1F promoter region of NR3C1 in the postmortem brains of eight children including four ELS cases. As a result, DNA methylation was evident in ELS cases due to severe physical abuse. Epigenetic status may have potential application as a biomarker for clarifying the antemortem experiences of deceased. [ABSTRACT FROM AUTHOR]

Background: The ABO system is of fundamental importance in the fields of transfusion and transplantation and has apparent associations with certain diseases, including cardiovascular disorders. ABO expression is reduced in the late phase of erythroid differentiation in vitro, whereas histone deacetylase inhibitors (HDACIs) are known to promote cell differentiation. Therefore, whether or not HDACIs could reduce the amount of ABO transcripts and A or B antigens is an intriguing issue.Study Design and Methods: Quantitative polymerase chain reactions were carried out for the ABO transcripts in erythroid-lineage K562 and epithelial-lineage KATOIII cells after incubation with HDACIs, such as sodium butyrate, panobinostat, vorinostat, and sodium valproate. Flow cytometric analysis was conducted to evaluate the amounts of antigen in KATOIII cells treated with panobinostat. Quantitative chromatin immunoprecipitation (ChIP) assays and luciferase assays were performed on both cell types to examine the mechanisms of ABO suppression.Results: HDACIs reduced the ABO transcripts in both K562 and KATOIII cells, with panobinostat exerting the most significant effect. Flow cytometric analysis demonstrated a decrease in B-antigen expression on panobinostat-treated KATOIII cells. ChIP assays indicated that panobinostat altered the modification of histones in the transcriptional regulatory regions of ABO, and luciferase assays demonstrated reduced activity of these elements.Conclusion: ABO transcription seems to be regulated by an epigenetic mechanism. Panobinostat appears to suppress ABO transcription, reducing the amount of antigens on the surface of cultured cells. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • We report a case of post-traumatic cerebral infarction caused by vascular injury. • Both postmortem computed tomography scan and autopsy revealed the final condition of the deceased. • The longitudinal antemortem to postmortem course of multiple CT images clarified this pathogenesis. • Histopathological examination was able to confirm the intimal injury and thromboembolism. • The cerebral infarction was considered to have resulted from vascular injury. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the association of a single-nucleotide polymorphism (SNP) in growth hormone receptor (GHR) gene. The facts that GHR is association with GH permitted researchers to anticipate possible connections of the SNPs in the GHR gene having physical traits. The study focused on examining the possible effect of polymorphic SNP rs6180 on human organ weight's GHR gene with the use of autopsy samples.

It is essential for medical students to learn and comprehend human anatomy in three dimensions (3D). With this in mind, a new system was designed in order to integrate anatomical dissections with diagnostic computed tomography (CT) radiology. Cadavers were scanned by CT scanners, and students then consulted the postmortem CT images during cadaver dissection to gain a better understanding of 3D human anatomy and diagnostic radiology. Students used handheld digital imaging and communications in medicine viewers at the bench-side (OsiriX on iPod touch or iPad), which enabled 'pixel-to-tissue' direct comparisons of CT images and cadavers. Students had lectures and workshops on diagnostic radiology, and they completed study assignments where they discussed findings in the anatomy laboratory compared with CT radiology findings. This teaching method for gross and radiological anatomy was used beginning in 2009, and it yielded strongly positive student perspectives and significant improvements in radiology skills in later clinical courses. Anat Sci Educ 7: 438-449. © 2014 American Association of Anatomists. [ABSTRACT FROM AUTHOR]