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Biomedical subjects

K Naruse

Publications and source records attributed to K Naruse.

At least 55 records · Page 3Linked to original sources

Adenoid basal carcinoma of the uterine cervix: a case report with ultrastructural findings.

Adenoid basal carcinoma of the uterine cervix is a rare tumor with a favorable prognosis. A case of adenoid basal carcinoma (ABC) of the uterine cervix was studied using light and electron microscopy. The patient was a 74-year-old Japanese woman who had undergone hysterectomy due to cervical intraepithelial neoplasia 3. Incidentally, ABC was found in the resected uterus. The tumor cells made small nests and infiltrated the cervical portion of the uterus. In the nests, glands, cribriform patterns with glandlike structures, and squamous differentiation were seen. Immunohistochemically, the glandlike structures were positive for laminin and type IV collagen. Ultrastructurally, the tumor cells had irregular nuclei, scanty cytoplasm, and cribriform patterns in which glandlike structures were covered with basal lamina. No myoepithelial differentiation of the tumor cells was seen. These findings suggest a similarity between adenoid basal carcinomas and adenoid cystic carcinomas. Furthermore, both tumors are considered to originate in the reserve cells of the uterine cervix. Because their outcomes are different, they should be distinguished from each other.

Aged↗

Mesangial myofibroblastic transformation in steroid-dependent minimal change nephrotic syndrome.

Patients with minimal change nephrotic syndrome (MCNS) occasionally show frequent relapses with proteinuria after cessation of steroid treatment, even though no significant pathological abnormalities are found in the glomeruli, compared with those in nonrelapsed and good-prognosis cases of MCNS. To resolve this contradiction, we immunohistochemically and ultrastructurally examined a biopsied renal tissue of a patient who showed glomerular features of MCNS and frequent clinical relapses. Immunohistochemistry demonstrated the overexpression of alpha-smooth muscle actin (ASMA) and vimentin in glomerular mesangial cells despite no mesangial cell proliferation, compared with nine nonrelapsed cases of MCNS. These facts may be an important clue to the investigation of the pathogenesis of steroid-dependent MCNS with frequent relapses. Furthermore, the immunohistochemical examination of ASMA and vimentin may be useful to detect mesangial myofibroblastic transformation that is not demonstrated in conventional light microscopy and immunofluorescence study.

Actins↗

Vinculin: its possible use as a marker of normal collecting ducts and renal neoplasms with collecting duct system phenotype.

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Biomarkers, Tumor↗

Anaplastic carcinoma of the pancreas with rhabdoid features.

The malignant rhabdoid tumor (MRT) is histologically characterized by the invasive proliferation of polygonal to ovoid cells with abundant eosinophilic cytoplasm and eccentric vesicular nuclei with a prominent nucleolus. MRT frequently occurs in the kidney, but may also arise in other organs. However, MRT should be strictly distinguished from carcinomas with rhabdoid features. A post-mortem examination of a 68-year-old woman found an anaplastic carcinoma of the pancreas with rhabdoid features displaying extensive invasion into the neighboring tissues. To the best of our knowledge, this is the first case of a pancreatic tumor with rhabdoid features. Pathologists should consider that carcinomas showing rhabdoid features may also appear in the pancreas. As pancreatic tumors with rhabdoid features have characteristic histopathological features and poor prognosis compared to other pancreatic tumors, careful histopathological differential diagnosis is important.

Aged↗

Adult-onset giant juxtaglomerular cell tumor of the kidney.

The juxtaglomerular cell tumor (JGCT) of the kidney is a rare neoplasm which commonly secretes renin. This tumor often occurs in teenagers. This paper documents the 14th adult-onset (over 30-years-old) case with a giant JGCT which measured 9.0 x 8.0 x 7.5 cm. Histologically, this tumor was composed of both vascular and tubular components. Immunohistochemically, the vascular component reacted with renin, cytokeratin 7, ulex europaeus agglutinin-1, vascular endothelial growth factor (VEGF) and Flk-1 (VEGF-R2), whereas the tubular component was positive for renin, epithelial membrane antigen (EMA), cytokeratin 7, alpha-1-antitrypsin, VEGF and Flk-1. This finding suggests that both vascular and tubular components of JGCT may promote neoplastic proliferation via an autocrine mechanism through the action of VEGF.

Female↗

Bronchial granular cell tumor with osteopontin and osteonectin expression: a case report.

The case of a 52-year-old Japanese man with bronchial granular cell tumors with osteopontin and osteonectin expression is reported here because there have been few investigations of their expression in benign tumors. He was admitted because of sudden hematemesis. A bronchoscopic examination revealed a lobulated polypoid tumor located in the left and right bronchi. Histologically, most tumor cells had abundant granular eosinophilic cytoplasm and were immunoreactive for S-100, neuron-specific enolase (NSE), CD68 and vimentin. Moreover, osteopontin-positive tumor cells were randomly distributed in the tumor tissue, but few stromal cells were positive. In contrast, osteonectin was mainly expressed in the peripheral tumor cells and was also distributed in the stromal cells. Blood vessels at the tumor border in which osteonectin-positive tumor cells were distributed, proliferated moderately. These results suggest that osteopontin and osteonectin may play a role in the progression of granular cell tumors and in the interaction between the tumor and host or angiogenesis around the tumor, respectively.

Biomarkers, Tumor↗

An immunohistochemical study of developing glomeruli in human fetal kidneys.

BACKGROUND: In the glomerulonephritis, mesenchymal cells frequently repeat the expression of fetal immunohistochemical phenotypes. However, in human glomerulogenesis the phenotypic alteration of mesangial and other types of glomerular cells has not been clearly defined. Our aim was to clarify the characteristics of fetal mesangial cells and glomerular capillary endothelial cells, as well as their changes during glomerulogenesis using immunohistochemistry. METHODS: We examined the renal tissues of 34 autopsied fetuses and neonates, 5 children, and 5 adults using immunohistochemistry and immunoelectron microscopy, using antibodies for cytoskeletons, contraction-associated proteins, and endothelial cell markers. RESULTS: In the V and S stages, there were no cells showing mesangial and endothelial features within the vesicles and the S-shaped bodies. In the S stage, small blood vessels, consisting of endothelial cells (CD31+, CD34+) and primitive perivascular mesenchymal cells (alpha-smooth muscle actin+, low molecular caldesmon+, vimentin+), were branched from developing interlobular arteries and appeared to extend to the lower clefts of the S-shaped bodies. In the C stage, the perivascular mesenchymal cells aggregated at the root of the immature glomeruli. In the M stage, they migrated toward the periphery of immature glomeruli and gradually lost their fetal immunohistochemical features. Similarly, with further maturation, the fetal glomerular capillary endothelial cells gradually lost the immunostaining for CD34, while the strong staining intensity of CD31 remained unchanged, just as that in the adult glomerular capillary endothelial cells. CONCLUSIONS: In human glomerulogenesis, we demonstrate that fetal mesangial and capillary endothelial cells change their immunohistochemical phenotypes with maturation. They gradually lose fetal immunohistochemical phenotypes. Already before birth, the mesangial cells in almost all glomeruli at the late M stage acquire the adult phenotype.

Adolescent↗

A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution.

We mapped 633 markers (488 AFLPs, 28 RAPDs, 34 IRSs, 75 ESTs, 4 STSs, and 4 phenotypic markers) for the Medaka Oryzias latipes, a teleost fish of the order Beloniformes. Linkage was determined using a reference typing DNA panel from 39 cell lines derived from backcross progeny. This panel provided unlimited DNA for the accumulation of mapping data. The total map length of Medaka was 1354.5 cM and 24 linkage groups were detected, corresponding to the haploid chromosome number of the organism. Thirteen to 49 markers for each linkage group were obtained. Conserved synteny between Medaka and zebrafish was observed for 2 independent linkage groups. Unlike zebrafish, however, the Medaka linkage map showed obvious restriction of recombination on the linkage group containing the male-determining region (Y) locus compared to the autosomal chromosomes.

Animals↗

Hydralazine decreases blood pressure and endothelin-1 mRNA expression in tissues but not cardiac weight in SHR-SP/Izm rats.

Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac hypertrophy and ET-1 gene expression in various tissues of spontaneously hypertensive rats (SHR-SP/Izm). Hydralazine (20 mg/kg/day) was administered orally from the age of 4 weeks for 8 weeks. Tissues of the kidney, heart, aorta and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Administration of hydralazine resulted in a significant decrease in the blood pressure (156 +/- 1 mmHg vs 212 +/- 4 mmHg in controls) and an increase in the heart rate (470 +/- 20 bpm vs 402 +/- 23 bpm in controls). ET-1 mRNA expression was significantly decreased in the heart (x 1/2), kidney (x 1/4) and brain (x 1/2). There was no significant change of the cardiac weight (309 +/- 4 mg/100 g body weight vs 307 +/- 5 mg/100 g body weight in controls). The dissociation between ET-1 mRNA expression and cardiac hypertrophy in hydralazine-treated rats may suggest that the increased tissue ET-1 is not an indispensable factor of cardiac hypertrophy in hypertension. Sympathetic activation, as shown by the reactive tachycardia, may overcome the effects on the blood pressure and ET-1 expression.

Animals↗

Augmented expression of tissue endothelin-1 messenger RNA is a common feature in hypertensive rats.

Recent studies revealed important roles for endothelin-1 (ET-1) in the pathogenesis of hypertension. Whether ET-1 could be a primary cause of hypertension or a secondary factor associated with hypertension, however, remains unknown. In this study, we determined plasma ET-1 levels and the expression of ET-1 mRNA in tissues of rats rendered hypertensive using distinct mechanisms: deoxycorticosterone acetate (DOCA)-salt hypertension: N(G)-nitro-L-arginine-methyl ester- (L-NAME) induced hypertension; and spontaneously hypertensive rats (SHR-SP). ET-1 mRNA expression level was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blotting. There was no significant difference in plasma ET-1 levels between the hypertensive rats and normotensive rats. By contrast, ET-1 mRNA level was significantly increased in various tissues including the adrenal, lung, kidney and brain of these hypertensive rats compared with control rats. Thus, ET-1 gene expression was ubiquitously augmented in tissues of hypertensive rats irrespective of the cause of the hypertension. The results suggest that the increase in ET-1 expression is not the primary cause of hypertension but a secondary outcome which may further exacerbate the hypertension.

Animals↗

Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissues in rats.

Although smoking has been suggested to be involved in the development of cardiovascular diseases, details of the mechanism still need to be revealed. We investigated the effects of cigarette smoking on the tissue mRNA expression of endothelin-1 (ET-1). Male Wistar rats of 4 weeks of age were exposed to smoke from six cigarettes for 30 min (acute exposure) and six cigarettes for 30 min/day, 5 days a week for 6 months (chronic exposure). Half of the rats exposed to 6 months smoking were kept in clean-air conditions for a further 3 months to clear the effects. Tissue expression of ET-1 mRNA in the kidney, aorta, heart and lung was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. There was no significant difference in body and organ weight of the heart and kidney between the control and smoking group in either the acute or chronic experiment. In the acute-exposure experiment, expression of ET-1 mRNA was increased in the heart and lung, while that in the kidney and aorta was unchanged. In the chronic-exposure experiment, however, there was no significant difference in the expression of ET-1 mRNA in all the tissues between the smoking and control groups. These results suggest that cigarette smoking could cause cardiovascular and pulmonary diseases by modulating ET-1 mRNA expression in the tissues.

Animals↗

Hemodynamic and biochemical effects of endothelin-A- and -B-receptor antagonist TAK-044 in stroke-prone spontaneously hypertensive rats.

We have demonstrated previously that endothelin-1 (ET-1) mRNA expression is increased in hypertensive rats. The aim of the study reported here was to elucidate the effects of the endothelin (ET) receptor antagonist on the hemodynamic and biochemical parameters in stroke-prone spontaneously hypertensive rats (SHRSPs/Izm). The endothelin-A- and -B- (ETA/ETB) receptor antagonist (TAK-044, Takeda Chemical Industries, Osaka, Japan) was administered subcutaneously at a dose of 10 mg/kg/day from the age of 8 weeks for 4 weeks. Blood samples and tissues of the kidney, heart and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Treatment with TAK-044 resulted in a significant decrease in systolic blood pressure (SBP), blood urea nitrogen (BUN), serum creatinine concentration, plasma aldosterone level, heart weight, and kidney weight. In addition, ET-1 contents and mRNA expression level in the kidney, heart and brain were significantly decreased by the treatment with TAK-044. These results suggest that the ET receptor antagonist TAK-044 is able to attenuate ET-1 gene expression in addition to its specific antagonism of the biological actions of ET via the receptors.

Animals↗

Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumour stroma.

AIMS: To investigate the role of CD34 positive stromal cells, namely dendritic interstitial cells, in the desmoplastic stroma formation of malignant epithelial neoplasms the distribution of CD34 positive stromal cells was examined in human colorectal adenocarcinomas, peritumoral inflammatory tissue, and normal tissue. METHODS: Forty one surgically resected human colorectal adenocarcinomas and their corresponding peritumoral inflammatory and normal tissues were examined. To distinguish CD34 positive stromal cells from vascular endothelial cells, immunostaining for both CD34 and CD31 was performed. The distribution of myofibroblasts was also analysed immunohistochemically, and double staining with CD34 and alpha smooth muscle actin (ASMA) was performed. RESULTS: Most of the stromal cells in the normal colorectal submucosa, muscularis propria, subserosa, and perirectal tissue were positive for CD34. In contrast, the peritumoral inflammatory tissue and the tumour stroma had no CD34 positive stromal cells. The distribution of myofibroblasts was almost the same as in the aforementioned series. No stromal cells double positive for CD34 and ASMA were detected in the peritumoral inflammatory tissues. CONCLUSIONS: Most stromal fibroblasts are CD34 positive stromal cells (dendritic interstitial cells). In colorectal adenocarcinomas, a lack of CD34 expression in stromal cells is associated with desmoplastic reaction.

Adenocarcinoma↗

A boy with normal growth in spite of growth hormone deficiency after resection of a suprasellar teratoma.

We reported a boy with panhypopituitarism after removal of a suprasellar teratoma and pituitary stalk transection at the age of 3 months. His growth was accelerated after 5 years of age without growth hormone (GH) therapy, although he had poor height growth until age 4 under treatment with hydrocortisone, levothyroxine sodium, and desamino-D-arginine vasopressin (DDAVP). Hyperphagia and obesity developed after surgery. Endocrinological examination revealed no GH response to glucagon, low serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3). Serum prolactin was normal, but serum insulin was high. Some patients who received an operation for craniopharyngioma were reported to achieve normal growth without GH secretion, but the mechanism is still unknown. High serum levels of prolactin or insulin can be associated with normal IGF in GH deficient patients. This patient had obesity and high serum insulin, which may be related to growth without GH secretion.

Growth↗

Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation.

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.

Animals↗

Epalrestat, an aldose reductase ihibitor, reduces the levels of Nepsilon-(carboxymethyl)lysine protein adducts and their precursors in erythrocytes from diabetic patients.

OBJECTIVE: To clarify the role of the polyol pathway in the intracellular formation of advanced glycation end products in human tissues, we examined the effects of epalrestat, an aldose reductase inhibitor, on the level of Nepsilon-(carboxymethyl)lysine (CML) along with 3-deoxyglucosone (3-DG) and triosephosphates in erythrocytes from diabetic patients. Plasma thiobarbituric acid-reactive substances (TBARS) were also determined as indicators of oxidative stress. RESEARCH DESIGN AND METHODS: Blood samples were collected from 12 nondiabetic volunteers, 38 untreated type 2 diabetic patients, and 16 type 2 diabetic patients who had been treated with 150 mg epalrestat/day. Blood samples were also collected from 14 of the untreated type 2 diabetic patients before and after the administration of epalrestat for 2 months. The amount of erythrocyte CML was determined by a competitive enzyme-linked immunosorbent assay, and 3-DG was measured by high-performance liquid chromatography RESULTS: In diabetic patients not treated with epalrestat, the erythrocyte CML level was significantly elevated above levels seen in nondiabetic individuals (49.9 +/- 5.0 vs. 31.0 +/- 5.2 U/g protein, P < 0.05) and was significantly lower in patients receiving epalrestat (33.1 +/- 3.8 U/g protein, P < 0.05). Similar results were observed with 3-DG. The treatment of patients with epalrestat for 2 months significantly lowered the level of erythrocyte CML (46.2 +/- 5.6 at baseline vs. 34.4 +/- 5.0 U/g protein, P < 0.01) along with erythrocyte 3-DG (P < 0.05), triosephosphates (P < 0.05), fructose (P < 0.05), sorbitol (P < 0.05), and plasma TBARS (P < 0.05) without changes in plasma glucose and HbA(1c) levels. A positive correlation was evident between the erythrocyte CML and sorbitol (r = 0.49, P < 0.01) or fructose (r = 0.40, P < 0.05) levels in diabetic patients. CONCLUSIONS: The results indicate that epalrestat administration lowers CML and associated variables and that polyol metabolites are correlated with CML in the erythrocytes of diabetic patients. The observed results suggest that aldose reductase activity may play a substantial role in the intracellular formation of CML in the mediation of reactive intermediate metabolites and oxidative stress.

Aldehyde Reductase↗