Reiko Shimokawa

Anatomic Properties of Myocardial Bridge Predisposing to Myocardial Infarction

Background— A myocardial bridge (MB) that partially covers the course of the left anterior descending coronary artery (LAD) sometimes causes myocardial ischemia, primarily because of hemodynamic deterioration, but without atherosclerosis. However, the mechanism of occurrence of myocardial infarction (MI) as a result of an MB in patients with spontaneously developing atherosclerosis is unclear. Methods and Results— One hundred consecutive autopsied MI hearts either with MBs [MI(+)MB(+) group; n=46] or without MBs (n=54) were obtained, as were 200 normal hearts, 100 with MBs [MI(−)MB(+) group] and 100 without MBs. By microscopy on LADs that were consecutively cross-sectioned at 5-mm intervals, the extent and distribution of LAD atherosclerosis were investigated histomorphometrically in conjunction with the anatomic properties of the MB, such as its thickness, length, and location and the MB muscle index (MB thickness multiplied by MB length), according to MI and MB status. In the MI(+)MB(+) group, the MB showed a significantly greater thickness and greater MB muscle index (P<0.05) than in the MI(−)MB(+) group. The intima-media ratio (intimal area/medial area) within 1.0 cm of the left coronary ostium was also greater (P<0.05) in the MI(+)MB(+) group than in the other groups. In addition, in the MI(+)MB(+) group, the location of the segment that exhibited the greatest intima-media ratio in the LAD proximal to the MB correlated significantly (P<0.001) with the location of the MB entrance, and furthermore, atherosclerosis progression in the LAD proximal to the MB was largest at 2.0 cm from the MB entrance. Conclusions— In the proximal LAD with an MB, MB muscle index is associated with a shift of coronary disease more proximally, an effect that may increase the risk of MI.

Expression of dentin matrix protein 1 (DMP1) in nonmineralized tissues

Dentin matrix protein 1 (DMP1) is an Arg-Gly-Asp-containing acidic phosphoprotein that was originally identified from a rat incisor cDNA library and was thought to be a dentin-specific protein. DMP1 was later shown to express in a number of hard tissue-forming cells, including osteoblasts, osteocytes, ameloblasts, and cementoblasts, and was considered to play important roles in mineralization. Further, DMP1 gene expression was also detected in fetal bovine brain and in newborn mouse brain. These findings indicate the possibility of DMP1 expression in other soft tissues. In the present study, to clarify the significance of DMP1 expression in nonmineralized tissues, we made a specific antibody to mouse DMP1 peptides and demonstrated that DMP1 protein was localized in mouse brain, pancreas, and kidney by immunohistochemistry. Further DMP1 mRNA was detected in nonmineralized mouse tissues including liver, muscle, brain, pancreas, and kidney by RT-PCR. Based on the evidence that the localization and the expression of DMP1 are not restricted to mineralized tissues, we assume that DMP1 may have functions other than the regulation of mineralization.

Expression of transcriptional repressor ATF3/LRF1 in human atherosclerosis: colocalization and possible involvement in cell death of vascular endothelial cells

Vascular endothelial cell death contributes to the progression of atherosclerotic lesion, and several transcriptional regulators are involved in the process. Activating transcription factor 3/liver regenerating factor-1 (ATF3/LRF-1), a stress-inducible transcriptional repressor, was shown to be highly expressed in vascular endothelial cells and macrophages of human atherosclerotic lesions by immunohistological assay. The expression was colocalized in these cells which were positive for TdT-mediated dUTP nick-end labeling (TUNEL) and annexin V. Treatment of human umbilical vein endothelial cells (HUVECs) by tumor necrosis factor (TNF)-alpha, oxidized low density lipoprotein (oxLDL), and lysophosphatidylcholine (LPC) rapidly induced ATF3/LRF-1, which showed an increased DNA binding to the consensus ATF/CRE sequence by supershift of gel shift assay. Flow cytometry analysis and immunostaining analysis with TUNEL assay showed that ATF3/LRF-1 was highly expressed in cell death induced by these agents. Moreover, antisense ATF3/LRF-1 cDNA partly suppressed the cell death induced by TNF-alpha, oxLDL, and LPC. From these results, it is indicated that ATF3/LRF-1 is one of the immediate early response genes in vascular endothelial cells in response to atherogenic stimuli, and may play a role in the endothelial cell death associated with atherogenesis.

Nitric Oxide Synthase Expression in Ischemic Rat Retinas

PURPOSE To investigate the expression of nitric oxide synthase (NOS) in the ischemic retina. METHODS Retinal ischemia was induced in rats by bilateral common carotid artery occlusion (BCCAO) for various lengths of time. Using the retina after BCCAO, expression of neuronal NOS (nNOS) and inducible NOS (iNOS) and identification of their positive cells were studied by histological and immunohistochemical examinations. RESULTS Histological examinations revealed significant reduction in the thickness of the inner plexiform layer and the outer plexiform layer of the retina. Expression of nNOS was detected in retinal ganglion cells, amacrine cells, and Müller cells after BCCAO. The expression of nNOS and iNOS detected in Müller cells became stronger and persisted long after BCCAO. CONCLUSIONS In the ischemic retina, Müller cells and retinal ganglion cells expressed nNOS and iNOS. These phenomena may be involved in the ischemic damage to the retina.

MUCOEPIDERMOID CARCINOMA OF THE THYMIC REGION

A case of mucoepidermold carcinoma in thymus in a 59‐year‐old Japanese female is presented. She died of cardiac tamponade due to tumor invasion after a 5 years clinical course. At autopsy the main tumor was found in the thymic region with metastases to the sternum, regional lymph nodes, pericardial, and left pleural cavity. The mucoepidermold carcinoma might be probably originated from a hens egg‐sized cyst which was located in the upper posterior aspect of the tumor‐Involved thymus. No teratomatous components were present. The cyst was most likely to be of thymic or bronchogenic cyst origin, though it was not determined, in view of the lining with pseudo‐stratified ciliated columnar epithelium of the cystic wall and the surrounding with the thymic tissue outside. Moreover, there was thymic hyperplasia with germinal center that was compatible with SLE‐like symptoms in her past history and autoimmune nature of the autopsy findings of pulmonary fibrosis.

Lymphangiogenesis in myocardial remodelling after infarction.

Aims:  The lymphatic system is involved in fluid homeostasis of the cardiac interstitium, but lymphangiogenesis in myocardial remodelling has not previously been examined histopathologically. The aim was to investigate by D2‐40 immunohistochemistry the sequential changes in lymphatic distribution in the process of myocardial remodelling after myocardial infarction (MI).

Histopathological predictors of regional lymph node metastasis at the invasive front in early colorectal cancer

Akishima‐Fukasawa Y, Ishikawa Y, Akasaka Y, Uzuki M, Inomata N, Yokoo T, Ishii R, Shimokawa R, Mukai K, Kiguchi H, Suzuki K, Fujiwara M, Ogata K, Niino H, Sugiura H, Ichinose A, Kuroda Y, Kuroda D & Ishii T
(2011) Histopathology59, 470–481

Hepatoma-derived growth factor, a new trophic factor for motor neurons, is up-regulated in the spinal cord of PQBP-1 transgenic mice before onset of degeneration

Hepatoma‐derived growth factor (HDGF) is a nuclear protein homologous to the high‐mobility group B1 family of proteins. It is known to be released from cells and to act as a trophic factor for dividing cells. In this study HDGF was increased in spinal motor neurons of a mouse model of motor neuron degeneration, polyglutamine‐tract‐binding protein‐1 (PQBP‐1) transgenic mice, before onset of degeneration. HDGF promoted neurite extension and survival of spinal motor neurons in primary culture. HDGF repressed cell death of motor neurons after facial nerve section in newborn rats in vivo. We also found a significant increase in p53 in spinal motor neurons of the transgenic mice. p53 bound to a sequence in the upstream of the HDGF gene in a gel mobility shift assay, and promoted gene expression through the cis‐element in chloramphenicol acetyl transfer (CAT) assay. Finally, we found that HDGF was increased in CSF of PQBP‐1 transgenic mice. Collectively, our results show that HDGF is a novel trophic factor for motor neurons and suggest that it might play a protective role against motor neuron degeneration in PQBP‐1 transgenic mice.

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Background and Aims:  Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.

Significance of Lymphatic Invasion and Proliferation on Regional Lymph Node Metastasis in Renal Cell Carcinoma

We studied the associations of lymphatic invasion and lymphatic vessel density around tumors with lymph node (LN) status in renal cell carcinoma (RCC) by immunohistochemical analysis using D2-40 antibody as a lymphatic marker. Surgically removed specimens from 76 cases with RCC, including 16 cases with LN metastasis, were used. Lymphatic vessel density around the tumor increased compared with normal kidneys but was not significant by LN status. Tumor size, tumor cell types, patterns of tumor growth, nuclear grade of tumor cells, venous invasion, lymphatic invasion, and primary tumor stage were predictive factors for LN metastasis. Based on multivariate regression analysis, only lymphatic invasion was an independent risk factor for LN metastasis. The immunohistochemical detection of lymphatics was useful for identifying the lymphatic invasion of RCC, and the presence of lymphatic invasion around RCC was an independent predictive factor for LN metastasis.