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ABSTRACT: The effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF.
FEBS Letters 12/2001; 509(1):95-100. · 3.54 Impact Factor
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ABSTRACT: To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.
International Journal for Vitamin and Nutrition Research 10/2001; 71(5):261-7. · 0.88 Impact Factor
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T Tomomasa,
K Kobayashi,
H Kaneko,
H Shimura, T Fukusato,
M Tabata,
Y Inoue,
S Ohwada,
M Kasahara,
Y Morishita,
M Kimura,
T Saheki,
A Morikawa
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ABSTRACT: We describe 2 patients with adult-onset type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed a marked fatty change and fibrosis. After the patients had lived without symptoms to the ages of 5 and 16 years, respectively, the diagnosis was made by genetic analysis.
Journal of Pediatrics 06/2001; 138(5):741-3. · 4.11 Impact Factor
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ABSTRACT: BACKGROUND: Although some Japanese Galerina species poisonings manifest as gastrointestinal symptoms followed by late-onset hepatorenal failure (phalloides syndrome), the toxin responsible for this has not been determined. CASE REPORT: We report a 6-year-old boy who developed characteristic cholera-like diarrhea and late-onset severe hepatic deterioration after eating mushrooms, later identified as a Galerina species, most likely Galerina fasciculata. A residual mushroom revealed alpha-amanitin. This account is the first known reported case of poisoning by Japanese Galerina species where an amatoxin was demonstrated to be responsible for the toxicity.
Journal of toxicology. Clinical toxicology 02/2001; 39(4):413-6.
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H Fujii,
X G Zhu,
T Matsumoto,
M Inagaki,
Y Tokusashi,
N Miyokawa, T Fukusato,
T Uekusa,
T Takagaki,
N Kadowaki,
T Shirai
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ABSTRACT: Combined hepatocellular-cholangiocarcinoma (combined HCC/ CC) is a rare form of liver neoplasms showing both hepatocellular (HCC) and bile duct differentiation (CC). In an attempt to clarify the clonality and genetic/phenotypic relationships in the evolution of these neoplasms, we microdissected multiple HCC and CC foci and studied allelic status of chromosome arms 1p, 1q, 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, 18q, and 22q. Overall, the highest frequency of loss of heterozygosity (LOH) was seen on 4q and 17p, followed by 8p and 16q. Of the 11 cases studied, 3 cases did not show any of the identical allelic losses between HCC and CC foci, indicating the biclonal nature. The remaining 8 cases showed multiple allelic losses shared between both components, strongly suggestive of a single clonal derivation. Moreover, 4 of the 8 cases showed additional or divergent allelic losses at more than 1 chromosomal locus only in HCC and/or CC foci. Thus, this heterogeneity was shown to affect the phenotypic diversity of the tumor. Summarizing the genetic patterns, combined HCC/CC could be classified into the following 3 possibilities: (1) collision tumor in which 2 independent neoplastic clones develop at close proximity; (2) single clonal tumor with homogeneous genetic background in both components--histological diversity is thus a manifestation of divergent differentiation potential of a single clone; (3) single clonal process in which genetic heterogeneity in the process of clonal evolution within the tumor parallels histologic diversity; therefore, the tumor in this category is mainly composed of mosaics of closely related subclones.
Human Pathlogy 10/2000; 31(9):1011-7. · 2.88 Impact Factor
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ABSTRACT: We report here a 13-year-old woman with cough, sputum and fever. The patient had both chronic sinusitis and bronchitis. Chest X-ray and computed tomographic scan of the chest revealed mucous bronchial filling and bronchiectasia in bronchi of bilateral lower lobes, right middle lobe and left upper lobe. Aerosol inhalation scintigraphy with 99mTechnetium demonstrated delays of the discharged tracer. On the basis of these findings, primary ciliary dyskinesia was suggested. This was confirmed by the findings from nasal biopsy with transmission electron microscopy where all of the microtubules were segmentally defected near the basal body in the cilia. On the basis of these findings, we diagnosed the patient with primary ciliary dyskinesia which may be due, at least in part, to segmental defect of ciliary microtubules.
Internal Medicine 08/1999; 38(7):602-6. · 0.94 Impact Factor
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ABSTRACT: Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with alpha-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.
Oncology 02/1999; 57(2):157-63. · 2.27 Impact Factor
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ABSTRACT: Mutations in the transforming growth factor beta type II receptor (TGFbetaRII), Smad2, and Smad4 genes have been detected in several human cancers. However, there are no reports of mutation analysis of the entire coding regions in these genes in hepatocellular carcinoma, and the roles of these genes in hepatocarcinogenesis remain unknown. We screened 30 hepatocellular carcinomas for mutations of these genes using polymerase chain reaction single-strand conformation polymorphism. We detected no mutations, but did find 3 cases of loss of heterozygosity of chromosome 17p13.1. These results suggest that mutations of the TGFbetaRII, Smad2, and Smad4 genes are rare, and that genetic instability is uncommon in human hepatocellular carcinoma.
International Journal of Oncology 02/1999; 14(1):127-31. · 2.40 Impact Factor
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Transplantation Proceedings 12/1998; 30(7):3730-1. · 1.00 Impact Factor
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ABSTRACT: It has been reported that hepatitis C virus-related hepatocellular carcinoma (HCC) patients survive longer than hepatitis B virus-related patients. In this study, since HCC patients positive for anti-HCV antibody had significantly longer disease-free survival (p<0.05), we evaluated the proliferative activity of 58 resected HCCs and the status of their viral infections. Ki-67 (MIB-1) immunostaining, argyrophilic nucleolar organizer regions and c-myc gene amplification were examined as parameters of proliferation, and p53 overexpression was examined in relation to clinicopathologic features and prognosis. Thirty-nine patients with HCC (67%) were positive for anti-HCV antibody alone, five (9%) were negative for both anti-HCV and HBV antibodies, two (3%) were positive for both anti-HCV and HBV antibodies, and 12 (21%) had HBsAg alone. HCC patients with anti-HCV antibody had a lower MIB-1 labeling index (LI) than HCC patients negative for the antibody (p<0.05), irrespective of the serum HBsAg status. However, there was no significant correlation between anti-HCV antibody and other proliferative parameters. MIB-1 could simply be related to cellular proliferation. On the other hand, the other parameters may be related to tumor progression as well as proliferation. HCV-related HCC does have lower proliferative activity and a better prognosis.
International Journal of Oncology 11/1998; 13(5):1017-22. · 2.40 Impact Factor
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ABSTRACT: The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.
American Journal of Clinical Oncology 02/1998; 21(1):39-41. · 2.01 Impact Factor
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ABSTRACT: The expression of the alpha and beta isoforms of phosphatidylinositol transfer protein (PI-TP alpha and PI-TP beta) in the adult rat brain was examined by in situ hybridization analysis with isoform-specific RNA probes. PI-TP alpha mRNA was detected in rather restricted regions of the brain whereas PI-TP beta mRNA was widely distributed in the brain. PI-TP alpha mRNA signals were remarkable in neocortex layers II/III and V/VI, Purkinje cell layer, deep cerebellar nuclei of the cerebellum, red nucleus and most part of brain stem. Low levels of PI-TP alpha transcript were present in CA3 of the hippocampus, ventral and dorsal thalamic nuclei, and motoneurons of spinal cord. No hybridization signals was obtained in the olfactory bulb, basal ganglia, amygdala, hypothalamus, and pituitary gland. In contrast, strong signals of PI-TP beta mRNA were detected in the dentate gyrus. The beta isoform mRNA was moderately expressed in olfactory bulb, layers II/III of the neocortex, striatum, CA1-CA4 regions of the hippocampus, medial habenula, cerebellum, amygdala, hypothalamus, spinal cord, and pituitary gland. Thalamus and brain stem contained relatively low, but significant levels of PI-TP beta transcript. The distinct distribution of PI-TP alpha and PI-TP beta mRNAs suggests different functional roles for each of the gene products in the mature nervous system.
Molecular Brain Research 07/1997; 46(1-2):256-64. · 2.00 Impact Factor
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ABSTRACT: Hypertrophic gastric mucosa in transgenic mice overexpressing transforming growth factor (TGF)-alpha showed mucosal cellular hyperplasia with dysplasia, suppression of gastric acid secretion, and chief and parietal cell depletion. In order to clarify the effects of TGF-alpha on the gastric mucosa, we analyzed the stomach of TGF-alpha transgenic mice by mucin histochemical staining and immunohistochemical analysis of TGF-alpha. In transgenic mice, especially those older than 3 months, the fundic gland was notably atrophic but the total mucosa was thickened. The mucous neck cells were hypersecretory and associated with abnormal sulfation. Mucosal hyperplasia was caused by proliferation of surface epithelial cells, associated with formation of intracytoplasmic lumina. The hyperplastic foveolar cells revealed production of a high amount of sialomucin. In addition, the involved stomach regionally revealed collagenous fibrosis in the submucosal layer. The wide distribution of TGF-alpha in the hyperplastic foveolar cells was in sharp contrast to negative expression in the foveolar cells in the control mice. These findings demonstrated the various regulatory functions of TGF-alpha in mucin production, fibrogenesis, and neck cell proliferation in the stomach.
Digestive Diseases and Sciences 02/1997; 42(1):91-8. · 2.12 Impact Factor
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 12/1996; 93(11):857-61.
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H Oshimoto,
S Saitoh,
F Makita,
T Matsumoto,
K Konaka,
K Takehara,
H Takagi,
T Nagamine,
M Mori, T Fukusato,
K Abe
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 09/1996; 93(8):573-7.
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 07/1996; 93(6):428-32.
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Ryōikibetsu shōkōgun shirīzu. 02/1996;
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ABSTRACT: We present three women with hypokalemic myopathy in whom serum creatine phosphokinase (CPK) was bound to serum immunoglobulin (macro-CPK). In all three cases, CPK isozyme electrophoresis demonstrated an extra CPK band between CPK-MM and CPK-MB. The bound immunoglobulins were identified as IgA/A-kappa and lambda, IgA-lambda and IgA-kappa and lambda, respectively. In all cases, histological examination of the biopsied muscles revealed necrotic and/or regenerating fibers. In each patient, potassium replacement therapy returned the macro-CPK as well as the marked elevations of serum muscle enzymes to normal. Taken together with other recent reports, our findings suggested that CPK-immunoglobulin binding may be related to the emergence of pathophysiology of hypokalemic myopathy.
Internal Medicine 01/1996; 34(12):1210-4. · 0.94 Impact Factor
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ABSTRACT: The accuracy of a technique that uses chemical-shift misregistration in magnetic resonance (MR) imaging to quantify vertebral bone marrow cellularity was tested on cadaveric specimens. In order to estimate the cellularity of 11 unfixed vertebral bodies, mid-sagittal MR images were obtained using a 1.5T magnet with a proton-density-weighted spin-echo sequence (repetition time/echo time, 2500/22 ms) and a narrow bandwidth. These values were subsequently compared to the histomorphometrical values for cellularity, amount of trabecular bone and deposited iron. The image-derived values for cellularity (VI, %) correlated well with values determined by histomorphometry (VH, %) (VI = 21.2 + 0.72 VH, r = 0.92) regardless of the presence of trabecular bone and small amount of stored iron in the specimens. This simple technique may be applicable in the estimation of marrow cellularity.
Australasian Radiology 12/1995; 39(4):411-4. · 0.51 Impact Factor
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ABSTRACT: We report three cases of extrahepatic portal-systemic encephalopathy (EHPSE), two of which did not show portal hypertension (PH) and in the other of which precirrhotic state with chronic active hepatitis was detected at liver biopsy. Our review of the literature regarding EHPSE without PH leads us to conclude that a part of the shunts is congenitally or spontaneously formed, that PH is not always essential to shunt formation. Since the clinical symptoms most often do not manifest until middle age, cases with only mild disturbance of consciousness are not easily distinguished from dementia. Furthermore, all reported patients underwent shunt closure followed by marked improvement of clinical symptoms and uneventful postoperative course. EHPSE without PH which can be corrected by shunt closure should always be differentiated from EHPSE with PH.
The Tohoku Journal of Experimental Medicine 03/1995; 175(2):77-90. · 1.24 Impact Factor
