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T Sakatani

Publications and source records attributed to T Sakatani.

At least 19 recordsLinked to original sources
PubMed2001

Epigenetic heterogeneity at imprinted loci in normal populations.

Genomic imprinting is the phenomenon by which the two alleles of certain genes are differentially expressed according to their parental origin. Extensive analysis of allelic expression at multiple imprinted loci in a normal population has not performed so far. In the present study, we examined the allelic expression pattern of three imprinted genes in a panel of 262 Japanese normal individuals. We observed differences in the extent of maintenance of allele-specific expression of the three genes. The allelic expression of small nuclear ribonucleoprotein N (SNRPN) was stringently regulated while that of multimembrane-spanning polyspecific transporter-like gene 1 (IMPT1) showed a large degree of variation. Significant biallelic expression of insulin-like growth factor II (IGF2) was observed in about 10% of normal individuals. Our findings add to the accumulating evidence for variable allelic expression at multiple loci in a normal human population. This epigenetic heterogeneity can be a stable trait and potentially influence individual phenotypes.

Alleles↗
PubMed2001

Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma.

OBJECTIVE: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma. METHODS: In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1-285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (high, intermediate, and low) were used for the classification. RESULTS: The mean CD index of 478 tumors was 12.8% (range: 0-100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only. CONCLUSION: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.

Adenocarcinoma↗
PubMed2000

In vivo transfer of hepatocyte growth factor gene accelerates proliferation of hepatic oval cells in a 2-acetylaminofluorene/partial hepatectomy model in rats.

To clarify the effect of hepatocyte growth factor (HGF) on proliferation of hepatic oval cells, we transferred HGF gene into liver of the Solt-Farber rat model. Male Fisher 344 rats were infected with a recombinant adenovirus carrying the cDNA for HGF (pAxCAHGF) from tail vein. HGF mRNA showed its peak at 4 days, and diminished thereafter. The total and proliferating cell nuclear antigen-positive hepatic oval cells were significantly elevated in HGF-transferred rats, in which stem cell factor and c-kit mRNA increased at each time point. Our results suggest that in vivo transfer of the HGF gene into liver accelerates proliferation of hepatic oval cells in the Solt-Farber model in rats.

2-Acetylaminofluorene↗
PubMed2000

Preoperative treatment with tegafur suppositories enhances apoptosis and reduces the intratumoral microvessel density of human colorectal carcinoma.

BACKGROUND: This study examined the effect of tegafur, a depot of 5-fluorouracil, in human colorectal carcinomas in terms of apoptosis, cell proliferation, and expression of p53 gene and angiogenesis-related molecules. METHODS: A total of 32 patients with colorectal carcinoma were divided into 2 groups; 20 patients received tegafur suppositories (TS) at 1 g/day for 14 days before surgery, and 12 patients did not receive any chemotherapy. Surgically removed specimens were examined immunohistochemically for Ki-67, CD34, p53, p21, Bax, vascular endothelial growth factor (VEGF), and thymidine phosphorylase (dThdPase). Apoptotic tumor cells were visualized by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL) procedure. RESULTS: The mean percentage of apoptotic index (AI) was 6.9 +/- 1.2 in the 20 TS-treated tumors and 4.4 +/- 1.0 in the 12 nontreated tumors (P < 0.001). In contrast, the mean percentage of Ki-67 labeling index (KI) became significantly lower in the former group (P < 0.05). The frequency of p21 expression was significantly higher in the TS-treated group than in the nontreated group (P < 0.05), whereas no difference was detected in p53 and Bax expression between the two groups. The mean intratumoral microvessel density was 47.8 +/- 19.8 in the TS-treated tumors and 66.8 +/- 16.5 in the nontreated tumors (P < 0.01). The frequency of dThdPase expression, but not of VEGF expression, became significantly lower with the TS treatment. p53 expression did not correlate with AI, KI, IMV density, or the expression of VEGF, p21, or Bax, except for dThdPase, which was significantly higher in the 18 p53 positive tumors (P < 0.05). CONCLUSIONS: Preoperative TS treatment enhances apoptosis and suppresses angiogenesis of colorectal carcinomas in a p53-independent manner.

Aged↗
PubMed2000

Thymidine phosphorylase expression results in a decrease in apoptosis and increase in intratumoral microvessel density in human gastric carcinomas.

Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor (PD-ECGF) is expressed at higher levels in a variety of human carcinomas than in adjacent normal tissue. The higher expression is associated with an increase in intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. This study examined the role of dThdPase in apoptosis, IMVD and p53 expression in human gastric carcinomas, dThdPase expression was noted in 12 (35.3%) of 34 early carcinomas, and in 20 (55.6%) of 36 advanced carcinomas. At least 10 areas consisting of carcinoma cells with diffuse dThdPase expression from the 32 dThdPase-positive tumors (category I), and 10 areas without dThdPase expression from the 38 negative tumors (category II) were selected from each case. For early gastric carcinoma, the mean IMVD was 88.8+/-19.4 in category I and 61.4+/-17.3 in category II carcinomas, while for advanced gastric carcinoma, the mean IMVD was 98.8+/-21.0 in category I and 76.0+/-27.1 in category II carcinomas. The mean IMVD was significantly higher in category I than in category II tumors (P<0.05). The mean apoptotic index (AI: percentage of apoptotic cells) was 1.95+/-1.30 in category I, and 3.76+/-1.49 in category II carcinomas for early gastric carcinoma, and 1.51+/-0.98 in category I and 2.14+/-0.66 in category II carcinomas for advanced gastric carcinoma, the value of the mean AI being significantly (P<0.05) higher in dThdPase-negative tumors (category II) than in the positive tumors (category I), regardless of tumor stage or histological type. There was a significant inverse correlation (P<0.001) between AI and IMVD. These results indicate that dThdPase expression is associated with both an increase in intratumoral microvessels and a decrease in apoptosis in human gastric carcinomas.

Adenocarcinoma↗
PubMed2000

Elastofibroma of the sigmoid colon.

A case of elastofibroma occurring in the sigmoid colon of a 69 year-old woman is reported. The woman presented for survey of her gastrointestinal tract. Colonoscopy disclosed two polyps in the sigmoid colon, one of which was clinically considered to be recurrent adenoma. Histologically, the lesion had characteristic eosinophilic fibers and globules, termed elastofibroma fibers with hematoxylin and eosin stain. In addition, these elastinophilic materials were digested by elastase. Histological evaluation confirmed the diagnosis of elastofibroma. Our case might suggest that it is the result of long-term fibrosis after previous endoscopic resection of a sigmoid colonic adenoma.

Adenoma↗
PubMed2000

Histopathology of a human allografted kidney with clinically sufficient function.

To clarify the clinico-pathological significance of protocol biopsy and clinically silent rejection in the management of renal graft recipients, we selected a total of 139 (23%) from 604 biopsy specimens according to the following criteria: 1) less than 1.4 mg/dL of serum creatinine and 2) more than 1,500 mL/d of urine volume at time of biopsy. Clinical indications for the biopsy were classified into five categories: i) protocol biopsy (73 specimens), including 69 cases at discharge post-transplantation; ii) slight increase in serum creatinine (32); iii) proteinuria (20); iv) evaluation of pulse-therapy (13); and v) fever elevation (1). Except for the last category, the specimens were histopathologically diagnosed as being normal in 50 (68%), 6 (17%), 1 (5%), and 5 (38%) specimens, respectively. Even borderline changes, and mild acute rejection, as well as drug-induced nephropathy were included, implying the existence of clinically silent rejection or drug-induced nephropathy. Obvious diversity in the histopathological diagnosis was noted in category iii) showing proteinuria, which was mainly caused by chronic rejection, drug-induced nephropathy and glomerulonephritis. The graft survival rate was no different among the four categories, except for category v). These results indicate that biopsies obtained from functionally sufficient renal grafts could provide useful information in the management of the recipients. The clinical significance of protocol biopsy awaits further clarification by the analysis of a large number of cases.

Biopsy↗
PubMed1999

Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma.

BACKGROUND: Nuclear profiles have been reported to be useful prognostic predictors in various cancers. Data from computerized morphometry are objective and are quickly obtained by conventional microscopic analysis. However, this image analysis of nuclear features has been only rarely applied to investigations of colorectal adenocarcinoma. The aim of this study was to evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in cases of colorectal adenocarcinoma. METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 343 patients with colorectal carcinoma and in 57 patients with colorectal adenoma. In each case, 300 nuclei of carcinoma or adenoma cells were analyzed on routine hematoxylin and eosin stained slides by means of a computer-assisted image analysis system that involved tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patients' survival, clinicopathologic status, and DNA ploidy pattern of tumors. RESULTS: The mean nuclear area (NA) enlarged from normal colorectal mucosa to adenoma and carcinoma (normal mucosa: n = 343, mean NA = 19 micrometer(2); adenoma: n = 57, mean NA = 34 micrometer(2); mucosal carcinoma: n = 15, mean NA = 45 micrometer(2); P < 0.001). In 343 colorectal carcinomas, NAs of cancer cells in tumors with lymphatic invasion, venous invasion, lymph node metastasis, or hepatic metastasis were significantly larger than those of cancer cells in tumors without such factors. The mean NA of DNA aneuploid tumors was larger than that of DNA diploid tumors (P < 0.001). The nuclear area of cancer cells was determined to be one of the independent prognostic factors in multivariate analysis (P < 0.001). Moreover, the large nuclear area of cancer cells was recognized as one of the risk factors of metachronous hematogenic metastasis in patients after curative surgery. CONCLUSIONS: Data from computerized morphometry are objective and can be obtained rapidly by conventional microscopic analysis. The nuclear area of cancer cells appears to predict 1) the ability of cancer cells to invade the microvessels in the colorectal wall and 2) the ability of cancer cells to metastasize to the lymph nodes or liver. Therefore, nuclear morphometry is beneficial in mass screening to select patients who are at risk of hematogenic or lymph node metastatic recurrence after curative surgery for colorectal carcinoma.

Adenocarcinoma↗
PubMed1999

Thymidine phosphorylase expression in human colorectal mucosa, adenoma and carcinoma: role of p53 expression.

The enzyme, thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), which acts as a potent angiogenic factor. The present study immunohistochemically examined the expression of dThdPase in human colorectal mucosa, adenomas and carcinomas, as well as six cultured colorectal carcinoma cell lines, in terms of intratumoral microvessel density (IMVD) and P53 expression. Thymidine phosphorylase was observed in lymphocytes, fibroblasts and macrophages, as well as smooth muscle cells and Schwann cells in the peripheral nerve fibers. The dThdPase-positive stromal cells apparently outnumbered the normal epithelial cells, adenoma and carcinoma cells with dThdPase. Weak but obvious cytoplasmic immunoreactivity was noted in a few normal colonic epithelia, predominantly the upper surface area, while a few adenoma cells showed weak nuclear immunostaining for dThdPase in six (24%) of the 25 colonic adenomas. Expression of dThdPase was noted in 33 (73.3%) of the 45 Dukes A and B, 14 (51.9%) of the 27 Dukes C and 14 (56.0%) of the 25 Dukes D carcinomas. The mean IMVD was 84.0 +/- 26.2 in the 36 dThdPase-negative carcinomas and 97.9 +/- 31.6 in the 61 dThdPase-positive carcinomas, the value being significantly higher in the latter group (P < 0.05). The frequency of dThdPase expression was significantly lower in the P53-negative carcinomas than in the positive carcinomas (P < 0.05). Western blot analysis showed the highest expression of dThdPase in LoVo carrying the wild-type p53 gene, followed by Colo201, Colo320, DLD-11 and WiDr carrying the mutated gene. These results indicate that: (i) the main source of dThdPase is stromal cells, including lymphocytes and macrophages in both colorectal normal and carcinoma tissues; (ii) dThdPase may take part in the induction of intratumoral microvessels, regardless of tumor stage; and (iii) expression might be modulated by not only P53 but also other molecules.

Adenoma↗
PubMed1999

Wild-type p53 gene transfer resulted in cell cycle arrest, but not apoptosis of newly established human malignant fibrous histiocytoma cell line.

We established a human malignant fibrous histiocytoma (MFH) cell line, MFH-ToE, from a tumor originally developed in the right thigh of a 78-year-old woman. The original tumor histologically consisted of histiocytic, fibroblastic and giant cells. The tumor cells showed immunoreactivity for vimentin and alpha-1-antichymotrypsin, and were positive for acid phosphatase and non-specific esterase, being compatible with MFH. Although the histology of the heterotransplanted tumor into nude mice was similar to that of the primary MFH, the population of giant cells gradually decreased along with the culture passages. Cytogenetic analysis revealed a highly aneuploid nature with varying numbers of chromosomes from 71 to 140. Chromosome 17 showed monosomy and exon 6 to 8 of p53 gene was not amplified by PCR, implying absence of p53 function. Adenovirus vector-mediated wild-type p53 gene was successfully transfected into the MFH-ToE, which showed up-regulation of P53 and P21, as well as gradual up-regulation of Bcl-2 protein. The transfection resulted in cell cycle arrest, but not apoptosis of the MFH-ToE cells. These results revealed unique properties of the MFH-ToE, which might be useful in further studies analyzing pathological and biological characteristics of MFH.

Aged↗
PubMed1997

Intragastric distribution of nonsteroidal anti-inflammatory drug-related ulcers in patients without collagen diseases.

During the long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs), approximately 3% of patients have gastric ulcers develop in each year. Although much is known about the endoscopic characteristics of NSAID-induced gastric ulcers in patients with rheumatoid arthritis (RA), it is not clear where in the stomach NSAIDs induce ulcers in patients without RA. We looked at that question. During the 1-year study period, 29 patients with gastric ulcer, who had been taking NSAIDs regularly for more than 4 weeks mainly for osteoarthritis, were identified. Seventy-five patients with gastric ulcers who had not taken NSAID also were found. The sites of gastric ulcers of these two groups were quite different. The NSAID-induced ulcers mainly were found in the gastric antrum, whereas the majority of NSAID-unrelated ulcers were in the gastric corpus. We conclude that NSAID-induced ulcers in non-RA patients mainly are formed in the gastric antrum.

Adult↗
PubMed1986

Measurement of active phagocytosis by polymorphonuclear leukocytes by fluorescence liberation from phagocytized microspheres.

Phagocytosis by polymorphonuclear leukocytes (PMN) was determined by a newly developed technique based on measurement of liberation of a fluorescence substance from PMN phagosomes; 4-methylumbelliferyl-beta-D-glucuronide (4MUGL), which is a substrate of beta-glucuronidase in lysosome, was conjugated with a microsphere, and 4-methylumbelliferone (4MU) liberated from phagocytized 4MUGL-microspheres was measured. The microspheres were composed of glyceryl-methacrylate having a diameter of 2.0 micron. Liberating activity of six kinds of 4MUGL-microspheres containing various amounts of amino and carboxyl groups was compared. Among these six kinds of 4MUGL-microspheres, four kinds showed activity similar to that of morphological phagocytosis. These four kinds of 4MUGL-microspheres liberated 4MU into the extracellular fluid from PMN during phagocytosis. Furthermore, they were recognized as a substrate of purified beta-glucuronidase. 4MUGL-MS610 showed the highest liberating activity among the four kinds of microspheres. Optimal conditions for phagocytosis by PMN were determined using 4MUGL-MS610. Total liberation of 4MU from the microspheres increased almost linearly with incubation time with PMN from 0 to 60 min and was linear with 4MUGL-MS in concentrations up to 4 X 10(8) microspheres/ml. This liberation was parallel to phagocytosis in a dose-dependent fashion. During 10-min incubation 20.4% of 4MU was liberated from 4MUGL-microspheres with phagocytosis. Seventy-five percent of the liberated 4MU was distributed in the extracellular fluid. 4MU distributed in the extracellular fluid was not attributable to hydrolysis of unphagocytized microspheres by beta-glucuronidase extracellularly leaked from PMN by phagocytosis. Also phagocytized 4MUGL-MS610 by PMN was observed by scanning electron microscopy. These results indicate that 4MU was liberated from 4MUGL-MS by hydrolysis due to beta-glucuronidase released into phagosomes with phagocytosis by PMN. Sensitivity of this assay was limited to about 50 pmol/ml, being less than 0.5-1 microsphere phagocytized into one cell.

Cell Membrane Permeability↗
PubMed1985

Effects of nicotine on the functions of human polymorphonuclear leukocytes in vitro.

Effects of nicotine on migration, extracellular release of lysosomal enzymes, and superoxide anion (O-2) production of human polymorphonuclear leukocytes (PMN) were studied. Nicotine (5 X 10(-6) to 5 X 10(-4) M) had no effect on random migration, chemotaxis to fMet-Leu-Phe, nor on chemokinesis induced by fMet-Leu-Phe. Nicotine, however, inhibited both extracellular release of lysosomal enzymes from PMN and O-2 production of PMN, both of which were induced by fMet-Leu-Phe and cytochalasin B. The inhibition of enzyme release and O-2 production by nicotine was not affected by atropine, hexamethonium, or acetyl beta-methylcholine, suggesting a direct action of nicotine on PMN functions. It is presumed that nicotine does not affect PMN migration to inflammatory sites, but inhibits the microbicidal functions of PMN. Exposure to PMN to nicotine introduced into the body by smoking could suppress their functions. This might result in harmful influences on the host defense mechanism, including antitumor function.

Cell Survival↗
PubMed1983

Assay method for myeloperoxidase in human polymorphonuclear leukocytes.

A simple assay method for measuring myeloperoxidase (MPO) has been developed. MPO is found in polymorphonuclear leukocytes and is important as a bactericidal agent in the presence of H2O2 and halide ions. This improved assay method is based on work of Andrews and Krinsky using tetramethylbenzidine (TMB) a noncarcinogenic substrate. By assaying MPO under optimal conditions of TMB at 1.6 mM, H2O2 concentration of 0.3 mM, pH 5.4, and incubation temperature of 37 degrees C, sensitivity of MPO measurements increased eightfold in comparison with the original TMB method. A method has been established to determine absorbance at 655 nm of the reaction mixture by incubation for 3 min and then stopping the reaction by the addition of pH 3.0 buffer. An attempt was also made to raise the sensitivity by using 3,3'-dimethyoxybenzidine (DMB), a carcinogenic substrate. The improved TMB method was 34 times more sensitive than the DMB method.

Benzidines↗
PubMed1983

Age-related decline in lysosomal enzyme release from polymorphonuclear leukocytes after N-formyl-methionyl-leucyl-phenylalanine stimulation.

Aging is assumed to decrease lysosomal enzyme release from polymorphonuclear leukocytes (PMN). A synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) was utilized to stimulate enzyme release of PMN from 45 human subjects, 21 males and 24 females, ranging in age from 22-83 yr old. Results of the studies showed no sex differences in the stimulation of enzyme release for either age group. However, stimulation was found to significantly decline in both males and females over 50 yr old compared to subjects under 50 yr old. The linear formulae for beta-glucuronidase, beta-galactosidase and lysozyme in male subjects were Y = 6.5X + 617.2, Y = -1.9X + 311.5 and Y = -1.9X + 327.3 with correlation coefficient of -0.685, -0.352 and -0.401, respectively. The linear formulae in females were Y = -5.2X + 536.6, Y = -3.0X + 340.6 and Y = -1.7X + 333.6 with correlation coefficient of -0.582, -0.303 and -0.462, respectively. These findings suggest that there was an age-related decline of response to the stimulant, fMet-Leu-Phe.

Adult↗