Akihiko Kimura

Wakayama Medical University, Wakayama, Wakayama, Japan

Are you Akihiko Kimura?

Claim your profile

Publications (85)287.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Endothelial progenitor cells (EPCs), a newly identified cell type, are bone marrow-derived progenitor cells that co-express stem cell markers and vascular endothelial growth factor (VEGF) receptor (Flk-1). In this study, a double-color immunofluorescence analysis was carried out using anti-CD34 and anti-Flk-1 antibodies to examine the time-dependent appearance of EPCs, using 52 human skin wounds with different wound ages (Group I, 0-1 days; Group II, 2-6 days; Group III, 7-14 days; and Group IV, 17-21 days). In wound specimens with an age of less than one day, CD34(+)/Flk-1(+) EPCs were not detected. EPCs were initially observed in wounds aged two days, and their number was increased in lesions with advances in wound age. In morphometrical analysis, the average number of EPCs was the highest in the wounds of Group III. Especially, 20 out of 21 wounds aged 7-12 days had >20 EPCs, and all wound samples with postinfliction intervals of 14-21 days had <15 EPCs. These observations at least showed that >20 EPCs would indicate a wound age of 7-12 days. Taken together, our observations indicate the detection of EPCs would be useful for wound age determination.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 04/2015; DOI:10.1007/s00414-015-1181-7 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We performed immunohistochemical study combined with morphometrical analyses in order to examine the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 using 55 human skin wounds of different ages: group I, 0-3 days (n = 16); II, 4-7 days (n = 11); III, 9-14 days (n = 16); and IV, 17-21 days (n = 12). Immunopositive reactions for MMP-2 were observed in all human skin specimens including uninjured skin as control. The number of MMP-2(+) macrophages was significantly increased in accordance with wound ages. In contrast to MMP-2, no MMP-9(+) signals were detected in uninjured and wound specimens aged less than 1 day. However, the number of MMP-9(+) macrophages profoundly appeared in groups II and III. Morphometrically, in all of wound samples aged 9-12 days, MMP-2(+) cell number was more than 20. On the contrary, most of the remaining samples had <20 positive cells. However, only one sample (a 7-day-old wound) showed 21 positive cells. Thus, with regard to practical applicability with forensic safety, MMP-2(+) macrophages of >20 would indicate a wound age of 7-12 days. Additionally, 10 out of 12 wound specimens aged 9-12 days showed the MMP-2(+) cell number of >25, implying that MMP-2(+) cell number of >25 would indicate the wound age of 9-12 days. On the contrary, all wound samples aged 3-14 days except for only one sample had MMP-9(+) cell number of >30, indicating that MMP-9(+) cell number of >30 would indicate the wound age of 3-14 days. Collectively, MMP-2 seemed to be more distinct marker, compared with MMP-9.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 03/2015; DOI:10.1007/s00414-015-1167-5 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Detection of vitality of mechanical wounds in human cadavers is one of the important issues in forensic medicine. In order to explore novel markers for vitality of acute mechanical wounds, we investigated autophagy in mouse and human skin wounds. Western blotting analysis of mouse skin wounds showed marked reduction of LC3-II and reciprocal increase of p62 in wound samples with the postinfliction intervals of ≥0.5 h, compared with the uninjured skin tissues. These observations indicated that autophagy level was reduced in the wound sites. In postmortem wound samples, there were no remarkable changes in LC3-II and p62 levels. Furthermore, the postmortem intervals of 1-4 days have no significant effects on the changes of LC3-II and p62 in the antemortem skin wounds. Like murine wound samples, these alterations of LC3-II and p62 could be detected in human skin wound samples. Collectively, our study using animal and human samples implied that the detection of autophagy-related molecules such as LC3-II and p62 might be useful for forensic practice as markers of wound vitality.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 03/2015; 129(3). DOI:10.1007/s00414-015-1168-4 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We immunohistochemically examined intrathrombotic IL-6 expression using a murine model of deep vein thrombosis induced by the ligation of the inferior vena cava (IVC) and discussed the availability of intrathrombotic IL-6 for thrombus age estimation. IL-6(+) cells could be first detected at 1 day after IVC ligation in three of five samples, and all samples with postligation intervals of 3 days or more had intrathrombotic IL-6(+) cells. Thereafter, the numbers of IL-6(+) cells were elevated with the increase of postligation intervals. Double-color immunofluorescence analyses demonstrated that IL-6 was mainly expressed by intrathrombotic macrophages. In all samples with postligation intervals of 5 days or less, the IL-6/macrophage ratio (IL-6/Mϕ) was <0.5. In contrast, the IL-6/Mϕ was greater than 0.5 at ≥7 days after the IVC ligation. These observations implied that IL-6/Mϕ ratios of >0.5 would strongly indicate thrombus ages of ≥7 days. Reciprocally, the ratios of less than 0.5 would suggest thrombus ages of ≤5 days. The present study demonstrated that the immunohistochemical detection of IL-6 was suitable to estimate the age of venous thrombi.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 01/2015; DOI:10.1007/s00414-015-1147-9 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We immunohistochemically examined the expression of IFNγ, TNFα, and TNF receptor p55 (TNF-Rp55) in a stasis-induced venous thrombus murine model. IFNγ(+), TNFα(+), and TNF-Rp55(+) cells could be first detected 7, 3, and 3 days after inferior vena cava (IVC) ligation. Thereafter, the numbers of these positive cells increased with time after IVC ligation. Double-color immunofluorescence analyses demonstrated that each molecule was expressed by intrathrombotic macrophages. In all samples with postligation intervals of 7 days or less, IFNγ/macrophage ratio (IFNγ/Mϕ), TNFα/macrophage ratio (TNFα/Mϕ), and TNF-Rp55/macrophage ratio (TNF-Rp55/Mϕ) were <0.2, <0.2, and <0.4, respectively. In contrast, IFNγ/Mϕ and TNFα/Mϕ were greater than 0.2 and 0.3 at ≥10 days after the IVC ligation, respectively. These observations suggested that IFNγ/Mϕ ratios of >0.2 and TNFα/Mϕ ratios of >0.3 indicated thrombus age of ≥10 days. Moreover, TNF-Rp55/Mϕ ratios of >0.7 strongly suggested thrombus age of >14 days. The present study demonstrated that the immunohistochemical detection of IFNγ, TNFα, and TNF-Rp55 was suitable to estimate the age of venous thrombi. However, the variation in TNF-Rp55/Mϕ ratios is wider than those of the other two markers. Thus, IFNγ and TNFα could be more practical markers.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 05/2013; 127(5). DOI:10.1007/s00414-013-0873-0 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of sudden unexpected death due to late onset neonatal group B streptococcal sepsis. A male neonate weighing 2731g was born at 35week gestational age, and discharged at the age of 4days after the birth. At 6days after the discharge (10days after the birth), because of consciousness loss and hypothermia, the neonate was conveyed to an emergency hospital, eventually followed by his death. Forensic autopsy revealed neither severe trauma nor cardiac anomaly. Both lungs were edematous. Histopathologically, a lot of bacterial clusters were found in the lungs and intracerebral vessels. Cerebrospinal fluid contained a lot of leukocytes. Streptococcus agalactiae was detected in the specimens from the feces and the blood. Collectively, we diagnosed that the cause of the neonate's death was late onset group B streptococcal sepsis. In autopsy cases of neonates, careful macroscopic and microscopic observations and bacteriological/virological examination should be performed.
    Legal Medicine 03/2013; 15(5). DOI:10.1016/j.legalmed.2013.02.002 · 1.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiac hypertrophy is an adaptive response of the heart to prolonged increases in hemodynamic workload. This compensatory process is initially beneficial in normalizing wall stress, and sustained left ventricular hypertrophy significantly increases the risk of developing heart failure. Although various molecules have been shown to be involved in the compensatory process, its molecular mechanism still remains unclear. We investigated roles of IFN-γ in the process of compensatory cardiac hypertrophy induced by pressure overload.Methods Male Balb/c (WT) and IFN-γ-deficient (IFN-γ-KO) mice were subjected to transverse aortic constriction (TAC).Aortic constriction was achieved by tying around the transverse thoracic aorta against a 28-gauge needle using a 7–0 silk suture, and then removing the needle. As the control, sham operation was also performed without constricting the aorta. Cardiac hypertrophy, survival rate and hypertrophy related signaling pathways were examined.ResultsIntracardiac gene expression for IFN-γ was rapidly increased in TAC mice. Although TAC induced rapid increase of heart weight/body weight ratio (HW/BW ratio) in WT mice even at 3 days after TAC, most mice survived for 3 weeks after TAC. On the other hand, IFN-γ-KO mice showed no significant increase of HW/BW ratio at 3 days after TAC, and about 60% of them died within 6 days after TAC. Western blotting analysis showed that AKT phosphorylation in the left ventricles of WT mice was significantly increased at 3 days after TAC, compared with sham operated mice. The downstream signal molecules, GSK-3β and GATA4, were also highly phosphorylated in the left ventricles of WT mice, compared with sham operated mice. However, the activation of PI3K/AKT signals were significantly attenuated in the left ventricles of IFN-γ-KO mice, indicating that IFN-γ plays a crucial role in the hypertrophic response through PI3K/AKT signaling.Conclusion Our results demonstrate blunted hypertrophy with reduced survival rate and attenuated PIK3/AKT signaling following pressure overload in IFN-γ-KO mice, and suggest that IFN-γ plays a crucial role in the compensatory hypertrophic response.
    Cytokine 09/2012; 59(3):531. DOI:10.1016/j.cyto.2012.06.122 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bone marrow-derived cells are known to play important roles in repair/regeneration of injured tissues, but their roles in pathological fibrosis are less clear. Here, we report a crucial role for CX3C chemokine receptor 1 (CX3CR1) in the recruitment of lung fibrocytes.Methods An intratracheal injection of bleomycin into wild-type mice caused a massive infiltration of leukocyte subsets, such as neutrophils, T lymphocytes, and macrophages, followed by the development of diffuse pulmonary fibrosis with accumulation of fibrocytes characterized by CD45+/collagen type I+ cells.ResultsIntrapulmonary CX3CR1 and its ligand CX3CL1 expression were enhanced significantly and remained at elevated levels until pulmonary fibrosis developed. Compared with wild-type mice, collagen deposition was attenuated in CX3CR1−/− mice with reduced number of lung fibrocytes although bleomycin increased leukocyte infiltration to a similar extent in wild-type and CX3CR1−/− mice, implying that less intrapulmonary recruitment of fibrocytes directly correlated with decreased collagen deposition in CX3CR1 deficiency. Furthermore, bone marrow transplantation from CX3CR1−/− to wild-type mice, but not that from wild-type to CX3CR1−/− mice, recapitulated the phenotypes in CX3CR1−/−- mice. Conclusion: These results demonstrated that CX3CL1-CX3CR1 interaction was involved in bleomycin-induced recruitment of bone marrow-derived fibrocytes and subsequent development of pulmonary fibrosis.
    Cytokine 09/2012; 59(3):573. DOI:10.1016/j.cyto.2012.06.268 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The chemotherapeutic agent cisplatin often causes severe renal dysfunction; however, the molecular mechanism causing renal injury remains unclear. In wild-type mice, intrarenal interferon (IFN)-γ gene expression was found to be enhanced while CD3(+) T cells and Ly-6G neutrophils were the main cellular source of IFN-γ following cisplatin injection. Compared to wild-type mice, cisplatin-treated IFN-γ-deficient (IFN-γ(-/-)) mice exhibited exaggerated histopathological changes with higher blood urea nitrogen and creatinine levels. Cisplatin-induced apoptosis was associated with enhanced caspase-3 activation in renal proximal tubular epithelial cells, with effects suppressed by IFN-γ resulting in increased cell viability. IFN-γ significantly reduced the levels of the autophagic markers LC3-II and p62, and enhanced cathepsin D expression in cisplatin-treated renal proximal tubule epithelial cells, implying that IFN-γ can accelerate autophagic flux. Tubular cell apoptosis was more evident with enhanced caspase-3 activation in IFN-γ-deficient compared to wild-type mice. Elevated intrarenal LC3-II and increased p62 accumulation were associated with reduced cathepsin D activation in IFN-γ-deficient mice, implying that the absence of IFN-γ suppressed autophagic flux. Thus, IFN-γ can accelerate autophagic flux by augmenting cathepsin D levels and reciprocally increasing the viability of renal tubular cells, thereby attenuating cisplatin-induced acute renal injury.Kidney International advance online publication, 11 July 2012; doi:10.1038/ki.2012.240.
    Kidney International 07/2012; 82(10). DOI:10.1038/ki.2012.240 · 8.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of fatal intoxication caused by the ingestion of an organophosphate pesticide, methidathion (DMTP). An 80-year-old male was found dead in his bed. Forensic autopsy revealed no remarkable morphological changes. However, in a toxicological screening test, methidathion was qualitatively detected in extracts of stomach contents. Concentrations of methidathion (μg/g) in body fluids and organ tissues, determined by gas chromatography-mass spectrometry, were as follows; 66.2 in heart blood, 8.33 in peripheral blood, 8.80 in urine, 2000 in the brain (frontal lobe), 4800 in the left lung, 810 in the liver, 150 in the left kidney, and 64,000 in the stomach contents (total 1.9 g). These results strongly suggested that the victim orally ingested methidathion. Additionally, xylene was determined in body fluids and organ tissues. From the toxicological data together with autopsy findings, the cause of his death was diagnosed as acute poisoning by an emulsion of methidathion.
    Legal Medicine 06/2012; 14(5):263-6. DOI:10.1016/j.legalmed.2012.04.007 · 1.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immunohistochemical study combined with morphometry was carried out to examine the expression of cyclooxygenase-2 (COX-2) using 60 human skin wounds of different ages: group I, 0-4 h (n = 11); II, 8 h-2 days (n = 21); III, 3-9 days (n = 14); and IV, 12-21 days (n = 14). In wound specimens aged 2 h to 2 days, anti-myeloperoxidase-positive neutrophils observed at the wound site expressed immunopositive reaction to COX-2. In wound specimens of more than 3 days, CD68-positive macrophages as well as neutrophils were positively immunostained with anti-COX-2. In group II, all 21 wound samples had COX-2-positive ratios of >40 %, and 15 out of them showed >50 %. In group III, only three wound samples with the postinfliction intervals of 3 days showed positive ratios of 40-50 % and the remaining 11 cases less than 40 %. In groups I and IV, all 25 wound specimens had COX-2-positive ratio of <40 %. With regard to the practical applicability with forensic safety, these observations suggested that a COX-2-positive ratio of >40 % indicated a wound age of 8 h to 3 days. Moreover, COX-2-positive ratios, considerably exceeding a ratio of 50 %, indicate a wound age of 8 h to 2 days. Collectively, COX-2 would be a useful marker for the determination of early wound age.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 03/2012; 126(3):435-40. DOI:10.1007/s00414-012-0685-7 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We immunohistochemically examined the expression of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen-activator inhibitor type-1 (PAI-1) using venous thrombi developed by ligation of the inferior vena cava (IVC) in mice. The uPA-, tPA- and PAI-1-positive cells could be firstly detected 5, 7, and 3 days, respectively, after IVC ligation. Morphometrically, the number of PAI-1-positive cells was significantly higher than those of uPA- and tPA-positive cells at later than 7 days. In all of the thrombus samples aged 10-21 days, the uPA/PAI-1 and tPA/PAI-1 ratios were >0.1 and >0.2, respectively. In contrast, all of the thrombus samples aged 1-7 days had uPA/PAI-1 of <0.1 and tPA/PAI-1 ratios of <0.2. These findings implied that uPA/PAI-1 of >0.1 and tPA/PAI-1 of >0.2 indicated an age of 10 days or more. Moreover, in four of five samples aged 10 days, uPA/PAI-1 ratios were <0.3, and the remaining one had uPA/PAI-1 of 0.32. All thrombi aged 14-21 days showed values greater than 0.3. Thus, uPA/PAI-1 ratios, markedly exceeding 0.3, strongly indicated an age of more than 14 days. The present study demonstrated that the immunohistochemical detection of uPA, tPA, and PAI-1 was suitable to estimate the age of venous thrombi.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 02/2012; 126(3):421-5. DOI:10.1007/s00414-012-0680-z · 2.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BM-derived endothelial progenitor cells (EPCs) are critical and essential for neovascularization in tissue repair and tumorigenesis. EPCs migrate from BM to tissues via the bloodstream, but specific chemotactic cues have not been identified. Here we show in mice that the absence of CCR5 reduced vascular EPC accumulation and neovascularization, but not macrophage recruitment, and eventually delayed healing in wounded skin. When transferred into Ccr5-/- mice, Ccr5+/+ BM cells, but not Ccr5-/- cells, accumulated in the wound site, were incorporated into the vasculature, and restored normal neovascularization. Consistent with these observations, CCL5 induced in vitro EPC migration in a CCR5-dependent manner. Moreover, expression of VEGF and TGF-β was substantially diminished at wound sites in Ccr5-/- mice, which suggests that EPCs are important not only as the progenitors of endothelial cells, but also as the source of growth factors during tissue repair. Taken together, these data identify the CCL5/CCR5 interaction as what we believe to be a novel molecular target for modulation of neovascularization and eventual tissue repair.
    The Journal of clinical investigation 01/2012; 122(2):711-21. DOI:10.1172/JCI43027 · 13.77 Impact Factor
  • International journal of cardiology 11/2011; 158(2):e23-5. DOI:10.1016/j.ijcard.2011.10.038 · 6.18 Impact Factor
  • Cytokine 10/2011; 56(1):79-79. DOI:10.1016/j.cyto.2011.07.220 · 2.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism, a leading cause of death in individuals with DVT. Several lines of evidence indicate proinflammatory cytokines such as TNF-α are involved in thrombus formation and resolution, but the roles of IFN-γ remain unclear. To address this issue, we performed ligation of the inferior vena cava to induce DVT in WT and IFN-γ-deficient (Ifng-/-) mice. In WT mice, intrathrombotic IFN-γ levels were elevated progressively as the postligation interval was extended. Thrombus size was substantially smaller at 10 and 14 days in Ifng-/- mice than in WT mice. Intrathrombotic collagen content was remarkably reduced at more than 10 days after the ligation in Ifng-/- mice compared with WT mice. The expression and activity of MMP-9, but not MMP-2, was higher at the late phase in Ifng-/- mice than in WT mice. Moreover, intrathrombotic recanalization was increased in Ifng-/- mice, with enhanced Vegf gene expression, compared with that in WT mice. Activation of the IFN-γ/Stat1 signal pathway suppressed PMA-induced Mmp9 and Vegf gene expression in peritoneal macrophages. Furthermore, administration of anti-IFN-γ mAbs accelerated thrombus resolution in WT mice. Collectively, these findings indicate that IFN-γ can have detrimental roles in thrombus resolution and may be a good molecular target for the acceleration of thrombus resolution in individuals with DVT.
    The Journal of clinical investigation 06/2011; 121(7):2911-20. DOI:10.1172/JCI40782 · 13.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The injection of Clostridium difficile toxin A into the ileal loops caused fluid accumulation with the destruction of intestinal epithelial structure and the recruitment of neutrophils and macrophages. Concomitantly, intraileal gene expression of CX3CL1/fractalkine (FKN) and its receptor, CX3CR1, was enhanced. When treated with toxin A in a similar manner, CX3CR1-deficient (CX3CR1(-/-)) mice exhibited exaggerated fluid accumulation, histopathological alterations, and neutrophil recruitment, but not macrophage infiltration. Mice reconstituted with CX3CR1(-/-) mouse-derived bone marrow cells exhibited exacerbated toxin A-induced enteritis, indicating that the lack of the CX3CR1 gene for hematopoietic cells aggravated toxin A-induced enteritis. A heme oxygenase-1 (HO-1) inhibitor, tin-protoporphyrin-IX, markedly increased fluid accumulation in toxin A-treated wild-type mice, indicating the protective roles of HO-1 in this situation. HO-1 expression was detected mainly in F4/80-positive cells expressing CX3CR1, and CX3CR1(-/-) mice failed to increase HO-1 expression after toxin A treatment. Moreover, CX3CL1/FKN induced HO-1 gene expression by isolated lamina propria-derived macrophages or a mouse macrophage cell line, RAW264.7, through the activation of the ERK signal pathway. Thus, CX3CL1/FKN could induce CX3CR1-expressing macrophages to express HO-1, thereby ameliorating toxin A-induced enteritis.
    The Journal of Immunology 01/2011; 186(1):423-31. DOI:10.4049/jimmunol.1000043 · 5.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The biological clock may stop at the time of death in a dead body. Therefore, the biological clock seems useful for estimating the time of death. In this study, we tried to read the biological clock in tissues from dead bodies to estimate the time of death using molecular biological techniques. At first, we examined real-time RT-PCR analysis of gene expression for mPer2 and mBmal1, which constitutes a feedback loop in the oscillation system, in the kidney, liver, and heart of mice. We could detect circadian oscillation of these gene expressions in mouse tissues even at <48 h after death. Thus, the ratio of mPer2/mBmal1 was found to be useful for estimating the time of death. We next applied this method to the liver, kidney, and heart obtained from forensic autopsy cases with less than 72 h of postmortem interval. Significant circadian oscillation of hPer2/hBmal1 ratio could be detected in these autopsy samples. We further examined gene expression for hRev-Erbα, a component of another feedback loop. The ratios of hRev-Erbα/hBmal1 showed higher amplitude of oscillation than those of hPer2/hBmal1 and are considered more suitable for estimating the time of death. In particular, a hRev/hBmal1 ratio of >50 indicated the time of death as 0200-0900 hours, and a hRev/hBmal1 ratio that considerably exceeded 75 indicated the time of death as 0200-0800 hours. On the other hand, a hRev/hBmal1 ratio of less than 25 strongly indicated the time of death as 1000-2300 hours. Taken together, these findings indicate that gene expression analyses of the biological clock could be powerful methods for estimation of the time of death.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 11/2010; 125(3):385-91. DOI:10.1007/s00414-010-0527-4 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human brain samples were collected from 70 autopsy cases including 22 freshwater drowning (FWD), 26 saltwater drowning (SWD), and 22 non-drowning cases as controls. Then, immunohistochemical study combined with morphometry was carried out in order to examine the differential expression of AQP1 and AQP4 in the brain samples. Immunohistochemically, star-shaped cells bearing highly branched processes, often surrounding blood vessels, showed positive reactions for AQP1 and AQP4 in FWD, SWD, as well as control groups. Additionally, with double-color immunofluorescence analysis, AQP1- or AQP4-positive cells could be identified as GFAP-positive astrocytes. Moreover, AQP1-positive reaction was also observed in blood vessels. Morphometrically, there were no significant differences in AQP1 expression in astrocytes or in blood vessels among the three groups. In contrast, the average value of AQP4-positive astrocytes was significantly higher in FWD cases than in SWD and control groups. Moreover, AQP4 expression was significantly lower in SWD than in the control group (p < 0.05). Moreover, there was no significant correlation between post-submerged interval and AQP expression in drowning cases. Therefore, immunohistochemical analysis of intracerebral AQP4 expression would be forensically useful for differentiation between FWD and SWD.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 11/2010; 125(1):59-65. DOI:10.1007/s00414-010-0523-8 · 2.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We immunohistochemically examined the expression of matrix metalloproteinase (MMP)-2 and MMP-9 using venous thrombi developed by ligation of the inferior vena cava (IVC) in mice. Both MMP-2- and MMP-9- positive cells could be detected in the whole course of thrombus formation after IVC ligation. Morphometrically, their number was greatest 14 days after IVC ligation and thereafter, gradually decreased at 21 days. The number of MMP-9-positive cells was significantly higher than that of MMP-2-positive cells at 1 to 7 days. The average ratio of MMP-9 to MMP-2 (MMP-9/MMP-2 ratio) was >2.0 in all thrombus samples at 1-5 days. After 7 days, the MMP-9/MMP-2 ratio was less than 2.0. These observations implied that an MMP-9/MMP-2 ratio markedly exceeding 2.0 strongly indicates an age of 5 days or less. Furthermore, an MMP-9/MMP-2 ratio of <2.0 probably indicates an age of more than 7 days. The present study demonstrated that the immunohistochemical detection of intrathrombotic MMP-2 and MMP-9 was suitable to estimate the age of venous thrombi.
    Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 09/2010; 124(5):439-44. DOI:10.1007/s00414-010-0484-y · 2.60 Impact Factor

Publication Stats

935 Citations
287.47 Total Impact Points

Institutions

  • 1991–2015
    • Wakayama Medical University
      • • Department of Forensic Medicine
      • • Department of Legal Medicine
      Wakayama, Wakayama, Japan
  • 2008–2010
    • Kanazawa University
      • Department of Forensic and Social Environmental Medicine
      Kanazawa, Ishikawa, Japan