Asuka Araki

Noticeable Decreased Expression of Tenascin-X in Calcific Aortic Valves

Calcification of aortic valves results in valvular aortic stenosis and is becoming a common valvular condition in elderly populations. An understanding of the molecular mechanisms of this valve lesion is important for revealing potential biomarkers associated with the development and progression of this disease. In order to identify proteins that are differentially expressed in calcific aortic valves (CAVs) compared with those in adjacent normal valvular tissues, comprehensive analysis of differentially expressed proteins in the tissues was done by a quantitative proteomic approach with isobaric tag for absolute and relative quantitation labeling followed by nanoliquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. The proteomic analysis revealed 105 proteins differentially expressed in CAVs in contrast to adjacent normal valvular tissues with high confidence. Significantly increased expression (>_1.3-fold) was found in 34 proteins, whereas decreased expression (<0.77-fold) was found in 39 proteins in CAVs. Among them, α-2-HS-glycoprotein showed the greatest increase in expression (6.54-fold) and tenascin-X showed the greatest decrease in expression (0.37-fold). Numerous extracellular matrix proteins such as collagens were identified as proteins with significantly decreased expression. Panther pathway analysis showed that some of the identified proteins were linked to blood coagulation and integrin signaling pathways. Cluster analysis of the 105 proteins differentially expressed in CAVs based on the expression pattern revealed that tenascin-X was clustered with proteins controlling collagen structure and function, especially collagen fibrillogenesis, such as decorin and fibromodulin. We confirmed decreased levels of these proteins in CAVs by Western blot analyses. These results indicated that massive destruction of the extracellular matrix occurs in CAVs.

The number and distribution of eosinophils in the adult human gastrointestinal tract: a study and comparison of racial and environmental factors.

There are surprisingly limited data regarding normal counts or distribution of eosinophils in the gastrointestinal tract, despite the increasing incidence of eosinophilic gastrointestinal tract diseases. Moreover, there are no published reports on the eosinophil number throughout the gastrointestinal tract of adults or Asian populations, or those investigating the effect of race on eosinophil count. First, in our study, the number of eosinophils from each portion of the gastrointestinal mucosa was quantified on biopsy slides from a Japanese adult population (132 samples). Next, the surgical resections from Japanese (110 samples), Japanese Americans (64), and Caucasians (57) were used to investigate the racial and environmental effects. Our results with the Japanese biopsy samples showed a significant increase in the number of eosinophils from the esophagus to the right colon (mean±SD/mm2: 0.07±0.43 for the esophagus, 12.18±11.39 for the stomach, and 36.59±15.50 for the right colon), compared with a decrease in the left colon (8.53±7.83). Investigation using surgical samples showed that the distribution patterns in the gastrointestinal tract were very similar among the 3 ethnic groups, and there were no significant differences in the number of eosinophils among these groups, except in the esophageal epithelium. This study is the first report on the normal numbers and distribution of eosinophils throughout the gastrointestinal tract not only of an Asian population but also of adults. Our data suggest that a cutoff value for eosinophil counts, when rendering a diagnosis of eosinophilic gastrointestinal tract disease, should be individualized to the different biopsy sites. Interestingly, race and environmental factors did not seem to have a significant effect on eosinophil densities and distributions.

Steroid-induced crisis and rhabdomyolysis in a patient with pheochromocytoma: A case report and review

A 66-year-old Japanese woman was urgently referred to our hospital. Two days prior to admission, her general practitioner began to administer prednisolone for treatment of a diagnosis of polymyalgia rheumatica. At the time of admission, laboratory results indicated multiorgan failure with rhabdomyolysis. Abdominal ultrasonography and computed tomography revealed a tumor in the right adrenal gland. On the same day, we measured serum and urine cathecholamines, which were markedly elevated. Additionally, magnetic resonance imaging revealed an adrenal mass and metaiodobenzylguanidine scintigraphy showed labeling of the tumor. Then, the patient underwent surgical resection of the tumor via laparoscopy. Histological examination confirmed the diagnosis of pheochromocytoma. One week after the operation, serum and urinary catecholamine levels returned to normal. The patient was discharged 10 days after the operation, and has remained stable at home. This report indicates that steroid should be avoided if possible in patients with pheochromocytoma. Furthermore, pheochromocytoma should be recalled as a differential diagnosis whenever patients take a sudden turn for the worse, or have acute uncontrollable hypertension following steroid administration and/or whenever patients present with unexplained rhabdomyolysis.

Magnetic resonance imaging features of angiomyofibroblastoma-like tumor of the scrotum with pathologic correlates

Various tumors can occur in the scrotum. Among them, angiomyofibroblastoma-like tumors are very rare mesenchymal tumors. We report a case of an angiomyofibroblastoma-like tumor that arose in the right half of the scrotum in a 72-year-old man. It is difficult to separate angiomyofibroblastoma-like tumors from other malignant tumors invading the male genital tract on the basis of clinical characteristics and magnetic resonance imaging findings.

Characteristics of gastritis in patients with Helicobacter pylori-positive reflux esophagitis.

Background and Aim:  The influence of Helicobacter pylori on gastric acid secretion differs with the status of gastritis. The histological characteristics of gastritis in H. pylori‐positive patients with reflux esophagitis have not been fully investigated. We therefore studied the pattern of endoscopic gastric mucosal atrophy and degree of histological gastritis in such patients.

Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis.

The serotonin reuptake transporter (SERT) terminates serotonin activity by removing it from interstitial space. Downregulated colonic SERT expression has been reported in irritable bowel disease (IBS), and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission; thus, a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing.

Increased vulnerability of hippocampal CA1 neurons to hypoperfusion in ataxia and male sterility (AMS) mouse.

The nna1 gene mutation is associated with spontaneous degeneration of cerebellar Purkinje cells and germ cells in Ataxia and Male Sterility (AMS) mouse. Since nna1 is also expressed in hippocampal neurons, we investigated their vulnerability to hypoperfusion in AMS mouse. Eight-week-old male wild type (WT) and AMS mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 10 min and sacrificed 1, 3, 7 and 28 days after BCCAO. Nissl staining revealed the neuronal cell loss and pyknotic change in the CA1 of AMS mice. TUNEL(+) apoptotic cells were found in the area at 7 days in AMS mice. Bcl-2 mRNA and protein in WT hippocampus were increased, while they were not increased in AMS. Bax mRNA was increased in AMS. Moreover, Bax activation was immunohistochemically demonstrated only in AMS at 3 and 7 days after BCCAO. An oxidative DNA damage marker, 8-hydroxydeoxyguanosine-positive cells were increased in both strains at 1 day; decreased in WT at 3 days but remained high in AMS. BCCAO increased glutathione, an antioxidant, in WT, but not in AMS at 3 days. The mRNA level of mitochondrial uncoupling protein 2, a regulator of oxidative stress, was increased only in WT at 1 day. Nna1 mRNA was similarly expressed in WT and AMS, but the protein was undetectable in AMS. Thus, our results indicate the increased vulnerability of hippocampal CA1 neurons of AMS mice to cerebral hypoperfusion could be due to an imbalance between oxidative stress and antioxidative defense system.

CNS high-grade neuroepithelial tumor with BCOR internal tandem duplication: A comparison with its counterparts in the kidney and soft tissue

Central nervous system high‐grade neuroepithelial tumors with BCOR alteration (CNS HGNET‐BCOR) are a recently reported rare entity, identified as a small fraction of tumors previously institutionally diagnosed as so‐called CNS primitive neuroectodermal tumors. Their genetic characteristic is a somatic internal tandem duplication in the 3′ end of BCOR (BCOR ITD), which has also been found in clear cell sarcomas of the kidney (CCSK) and soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and these BCOR ITD‐positive tumors have been reported to share similar pathological features. In this study, we performed a clinicopathological and molecular analysis of six cases of CNS HGNET‐BCOR, and compared them with their counterparts in the kidney and soft tissue. Although these tumors had histologically similar structural patterns and characteristic monotonous nuclei with fine chromatin, CNS HGNET‐BCOR exhibited glial cell morphology, ependymoma‐like perivascular pseudorosettes and palisading necrosis, whereas these features were not evident in CCSK or URCS/PMMTI. Immunohistochemically, diffuse staining of Olig2 with a mixture of varying degrees of intensity, and only focal staining of GFAP, S‐100 protein and synaptophysin were observed in CNS HGNET‐BCOR, whereas these common neuroepithelial markers were negative in CCSK and URCS/PMMTI. Therefore, although CNS HGNET‐BCOR, CCSK and URCS/PMMTI may constitute a group of BCOR ITD‐positive tumors, only CNS HGNET‐BCOR has histological features suggestive of glial differentiation. In conclusion, we think CNS HGNET‐BCOR are a certain type of neuroepithelial tumor relatively close to glioma, not CCSK or URCS/PMMTI occurring in the CNS.

An evaluation of the diagnostic and prognostic significance of p16INK4a/p21WAF1/Cip1 immunostaining in squamous intraepithelial lesions of the uterine cervix using liquid-based cytology specimens

Human papillomavirus (HPV) infection frequently causes squamous intraepithelial lesions (SIL) of the uterine cervix and consequently gives rise to squamous cell carcinoma. It is therefore important to identify cases that potentially develop higher grades of SIL at an early stage of the disease. In this study, we thus investigated whether immunocytochemistry for p21WAF1/Cip1 and p16INK4a could be applicable in the diagnosis and the prognostic prediction of SIL in combination with genomic analyses of HPV. The genomic analysis of high‐risk HPV (hrHPV), which was done by reversed dot blotting and by in situ hybridization, and immunocytochemistry were performed on liquid‐based cytological specimens. A cross‐sectional study comprising 145 cases of NILM, ASC‐US, LSIL, and HSIL indicated that the incidence of the positive cases for p16INK4a and p21WAF1/Cip1 and hrHPV increased with the grade of SIL. A double positive status for p16INK4a and p21WAF1/Cip1 was a significant discriminator between HSIL and LSIL/NILM, even when applied in conjunction with the genomic test for hrHPV (P = 0.006 by logistic regression analysis). However, a prospective study employing 61 NILM/ASC‐US cases, revealed that the p16INK4a/p21WAF1/Cip1 immunostaining was not a significant predictor for the progression of SIL, whereas the cytological diagnosis (NILM vs. ASC‐US) and the infection status of hrHPV conferred significant effects on the prognosis. Immunostaining of p16INK4a and p21WAF1/Cip1 provides additional information on the cytological diagnosis of SIL. A further analysis using a larger population is warranted to obtain a conclusive result regarding the prognostic significance of p16INK4a/p21WAF1/Cip1 immunocytochemistry in the diagnosis of SIL. Diagn. Cytopathol. 2014;42: 125–133.

Different types of neural cell death in the cerebellum of the ataxia and male sterility (AMS) mutant mouse

To investigate the mechanisms(s) of age‐dependent atrophy of the cerebellum of the ataxia and male sterility (AMS) mouse at young age, the morphological changes were evaluated and the nature of neural cell death was examined. Dying Purkinje cells lacked characters of classical apoptosis except for light microscopic morphology, but their death was considered to be autonomous death triggered by the direct effect of ams mutation, because of the acute and near‐complete disappearance and particular change of the cytoplasm. In contrast, in the granular layer, typical apoptotic bodies were recognized by electron microscopy, and substantial numbers of terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end‐labeling (TUNEL)‐positive cells and activated caspase‐3‐positive cells were observed. Granule cell death was considered to be target‐related apoptosis induced after post‐synaptic Purkinje cell death, because the age‐dependent changes in TUNEL‐positive cell counts followed that of Purkinje cell loss and the peak value was still noted 1 week after total loss of Purkinje cells. These results indicate that both total and partial losses of Purkinje cells and granule cells, respectively, contributed to the atrophy of the AMS cerebellum. Furthermore, different types of neuronal death were recognized; the granule cell death was apoptotic while Purkinje cell death was different from that of classical apoptosis.