The underlying roles of macrophage populations in myocardial fibrosis

Myocardial fibrosis is one of the main structural changes following cardiomyocyte injury such as infarction. Macrophages play a central role in the development of fibrotic lesions. In myocardial fibrosis, three different populations of macrophages are recognized: exudate macrophages, resident macrophages, and interstitial dendritic cells. Exudate macrophages, which are derived from blood monocytes and recruited into injured areas through chemoattractants and cell adhesion molecules, release various fibrogenic growth factors in early stages of the fibrosis. Transforming growth factor-beta and platelet-derived growth factors are proposed as the most probable growth factors produced by exudate macrophages to induce the modulation of fibroblasts towards myofibroblasts. Emerging evidence shows that macrophage-secreted nerve growth factor may also be involved in that process. The myofibroblasts are capable of producing extracellular matrix proteins which contribute to myocardial fibrosis. The exudate macrophages also participate in the induction ofapoptosis in injured myocytes and myofibroblasts in the fibrotic lesions. These apoptotic cells are phagocytized by exudate macrophages, and the macrophages themselves also disappear by apoptosis. The decrease in cellularity by apoptosis leads to the evolution of fibrous granulation tissues into scar tissues (reparative fibrosis). The resident macrophages particiapte exclusively in the late stages of the myocardial fibrosis, when their mitotic activity increases in the lesions; they are presumed to have the same roles as the exudate macrophages. In addition, the resident macrophages and interstitial dendritic cells both act as immune mediators to recruit T-lymphocytes into the lesions. In contrast to hepatic, pulmonary, and renal fibrosis, the roles of macrophage populations in myocardial fibrosis has not yet been extensively investigated.Biomedical Reviews 1999; 10: 89-105

A CASE STUDY OF THROWING MOTION OF A MALE PARA- SHORT STATURE JAVELIN THROWER

The purpose of the present study was to investigate the throwing motion of a male para- short stature javelin thrower (F41) in a real competition using the 3D DLT method, compared with male able-bodied javelin throwers as reference. At the 119th Nippon Sport Science University Athletic Meet (March 27, 2021), one para- athlete who participated in the men\u27s javelin throw was videotaped with two video cameras. The release parameters of javelin such as the initial velocity and projection angle at the release, and body segments angle were calculated for the only one trial, the best. The features of para-athlete were clarified by comparing them with the able-bodied javelin throwers (n=13) as reference. The release parameters of javelin showed that there was large difference in the horizontal velocity of javelin between the para-athlete and the reference throwers (12.59 and 19.35 m/s). The para-athlete of short stature in the present study showed the delayed withdrawal of the left leg at R-on, the delayed initiation of the rotation of the hips and trunk during throwing phase, and the left foot pointing to the right at L-on

Immunohistochemical Expressions of Main PGE2 Biosynthesis-related Enzymes and PGE2 Receptor in Rat Nephrogenesis

Endogenous prostaglandin (PG) E2 plays important roles in renal homeostasis. Immunoexpressions of PGE2 biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE2 synthetase (mPGES)-1 and EP4 (a PGE2 receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on gestation days 18 and 21 and neonates on days 1 to 18. In fetuses and early neonates, the expressions of COX-2, mPGES-1 and EP4 were observed in developing renal tubules, indicating that COX-2 and its product, PGE2, play important roles in blastemal cell-derived renal tubular development via EP4. Cyclin D1 expression was seen in both the nucleus and cytoplasm of the developing tubules. These findings differed from the decreased COX-2 expression and exclusive nuclear expression of cyclin D1 seen in abnormal epithelial regeneration of injured renal tubules in cisplatin-treated rats in our previous articles. Collectively, PGE2, induced by COX-2, regulates renal tubular epithelial formation via EP4

Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS

Detection of the toxicity of a candidate compound at an early stage of drug development is an emerging area of interest. It is difficult to determine all of the effects of metabolism of a compound using traditional approaches such as histopathology and serum biochemistry. The goal of a metabolomics approach is to determine all metabolites in a living system, with the potential to detect and identify biomarkers involved in toxicity onset. Here, we summarize the metabolic fingerprints for detection and identification of metabolic changes and biomarkers related to drug-induced toxicity using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS)

Comparative Gene Expression Analysis in the Skeletal Muscles of Dysferlin-deficient SJL/J and A/J Mice

Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was conducted to determine whether or not there are interstrain or site-dependent differences in the gene expression profiles of skeletal muscles in SJL/J and A/J mice as dysferlinopathy models. Upon analysis by qRT-PCR, SJL/J mice showed a trend of increased gene expression level of uncoupling protein 2 in the rectus femoris and longissimus lumborum at 30 weeks of age when dystrophic lesions became histopathologically pronounced. Heme oxygenase 1 and S100 calcium binding protein A4 were upregulated in the rectus femoris, longissimus lumborum and abdominal muscles, in which dystrophic lesions occur more commonly in SJL mice. The gene expression levels of heat shock protein 70 in most muscles of A/J mice were lower than those of BALB/c mice as control. SJL/J mice exhibited a marked lowering of decay-accelerating factor 1/CD55 gene expression level in all studied muscles except for the heart at all ages compared with that of BALB/c mice. This study showed that there were some interstrain differences in the gene expres sion profiles of skeletal muscles between SJL/J and A/J mice. Further investigation is required to reveal whether these alterations of the expression levels are the cause of dystrophic changes or occur subsequent to muscle damage

Paleolithic stone tools from the Hosono Site in Shunan city, Yamaguchi prefecture

Hosono site is a complex archaeological sites ranging from the Paleolithic Age to the Middle Ages. This sites situated at the upper stream of the Nishiki River in the Chugoku Mountains. This sites is located on a river terrace with an altitude around 255 m.　 In this paper, we report on the Palaeolithic stone tools from Hosono site.　These Paleolithic stone tools mainly consisted of tuff, and can be roughly classified three periods.　The first is a stone spear head, which is positioned at the end of the Upper Paleolithic Age − the early Jomon Age.　The second is a knife blade and a blade, which is positioned in the second half of the Upper Paleolithic Age.　These stone tools are close relation with stone tools of the eastern Kyushu district.　The third is a wide flake, a core, which is positioned in the first half of the late Paleolithic Age.　The stone tools collected from this site are important materials for considering the use of raw materials for stone tools and the relations of human group in the Upper Paleolithic Age in Southwest Japan

Thy-1 Expressing Mesenchymal Cells in Rat Nephrogenesis in Correlation with Cells Immunoreactive for α-Smooth Muscle Actin and Vimentin

Thy-1 expression may influence myofibroblast development. Through the epithelial-mesenchymal transition (EMT), injured renal epithelial cells undergo regression to the metanephric mesenchymal phenotype and then acquire a myofibroblastic nature (expressing α-smooth muscle actin; α-SMA). Because the metanephric blastema differentiates into mesenchymal and renal epithelial cells, we investigated Thy-1 immunoexpression during nephrogenesis in F344 rats in correlation with vimentin and α-SMA expressions. Kidney samples were obtained from fetuses on gestation days 18 and 21, neonates on days 1-18 and adults at 6 weeks of age. Mesangial cells in S-shaped bodies and immature and mature glomeruli continuously expressed both Thy-1 and α-SMA during early nephrogenesis (fetuses and neonates on days 1-9). During early nephrogenesis, loosely-arranged blastemal cell-derived mesenchymal cells in the cortex and medulla also exhibited Thy-1 and α-SMA, although the α-SMA expression was weaker than that of Thy-1. Vimentin expression coincided with that of Thy-1. These findings indicate that the derivation of α-SMA-expressing myofibroblastic cells may be related to mesangial or blastemal cells expressing both Thy-1 and α-SMA. Interestingly, there was a difference in Thy-1 expression between cortical and medullary tubulointerstitial cells from late nephrogenesis (neonates on days 12-18) and those from adults in that the cortical cells reacted faintly or negatively to Thy-1, whereas the medullary cells reacted strongly to Thy-1; additionally, bundle-arranged mesenchymal cells that were only observed in the neonates on days 1-12 reacted strongly to α-SMA, but faintly to Thy-1. Blastemal cell-derived mesenchymal cells seem to alter the immunoexpressions of Thy-1 and α-SMA, depending on the conditions which they develop. Thy-1 immunoexpression would be useful for investigation of reverse embryogenesis, which might occur in fibrotic kidneys

Relationship of Cell Proliferating Marker Expressions with PGE2 Receptors in Regenerating Rat Renal Tubules after Cisplatin Injection

Cisplatin, an anticancer drug, is well known to have nephrotoxicity as an adverse effect. We investigated the expressions of cell cycle markers and prostaglandin E2 (PGE2) receptors (EP) in the affected renal tubules in rats injected with a single dose (6 mg/kg body weight) of cisplatin. On days 1–3 after dosing, the affected renal epithelial cells were almost desquamated, showing necrosis. On day 5 onwards, the renal tubules were rimmed by flattened or cuboidal epithelial cells with basophilic cytoplasm; BrdU-immunopositive cells began to significantly increase, indicating regeneration. Simultaneously, TUNEL-positive apoptotic cells were also seen. On days 1–5, cyclin D1-immunopositive cells were decreased with an increased expression in p21 mRNA, indicating G1 arrest in the cell cycle. The affected renal epithelial cells began to react to EP4 receptor, but not to EP2 receptor. Some EP4 receptor-reacting epithelial cells gave a positive reaction to BrdU or cyclin D1. Collectively, the affected renal tubules underwent various alterations such as necrosis, apoptosis, regeneration and G1 arrest; the aspects might be influenced by endogenous PGE2 through EP4 receptor