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Biomedical subjects

H Saito

Publications and source records attributed to H Saito.

At least 163 records · Page 9Linked to original sources
PubMed2001

KAI1, CAR, and Smad4 expression in the progression of colorectal tumor.

PURPOSE: The abnormal expression of several genes is involved in the development of colorectal tumors. The aim of this study was to examine the expression of KAI1, CAR, and Smad4, which has been associated with the progression of other cancers. METHODS: We examined 12 adenomas, 38 primary carcinomas, 10 liver metastases, and 7 adenocarcinoma cell lines, by fluorescent multiplex reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: KAI1 expression was higher in adenomas (2.55 +/- 0.61; P < 0.05) and primary carcinomas (3.30 +/- 0.42; P < 0.005) than in normal mucosa, but it was not correlated with tumor stage. CAR expression was lower in Dukes' B (1.28 +/- 0.53) than in Dukes' A (2.38 +/- 0.48) (P < 0.05), but increased with tumor progression; Dukes' C (1.45 +/- 0.25), Dukes' D (1.53 +/- 0.14), and metastases (2.09 +/- 0.39) (P < 0.05). Smad4 expression increased in adenomas (2.30 +/- 0.46; P < 0.05), but decreased with tumor progression; Dukes' A (2.14 +/- 0.37), Dukes' B (1.65 +/- 0.41), Dukes' C (1.57 +/- 0.25), Dukes' D (1.08 +/- 0.18), and metastases (0.82 +/- 0.21) (P < 0.05). CONCLUSIONS: These results suggest that the upregulation of CAR and down-regulation of Smad4 are associated with the progression of colorectal tumors, while the upregulation of these genes and of KAI1 seems to be involved in the early stage.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2001

Multicentric occurrence of esophageal cancer after gastrectomy: a preliminary report.

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated, focusing on its multicentric occurrence. We retrospectively evaluated 28 patients who underwent subtotal esophagectomy for intrathoracic esophageal cancer between 1985 and 1999. They were divided into two groups according to whether or not they had previously undergone a gastrectomy: group 1, comprising 7 patients who had undergone gastrectomy and group 2, comprising 21 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer than in those who had undergone gastrectomy for a peptic ulcer, and also in the patients for whom anastomosis had been performed by Billroth I compared with Billroth II. The patients in group 1 were significantly younger than those in group 2. The multiple occurrence of esophageal cancer was found in 4 of 5 patients (80%) in group 1, and in 2 of 18 patients (11%) in group 2, with significantly higher frequency being seen in group 1. More than two coexisting cancer lesions apart from the primary tumor were detected in all four patients. Histological examination of all the coexisting cancer lesions showed well-differentiated squamous cell carcinoma confined within the superficial mucosal layer. No significant differences were noted in the location of the coexisting lesions between the oral and anal side of the primary tumors. Squamous dysplasia was randomly observed, especially around the cancer lesions. These findings suggest that gastrectomy precipitated subsequent chronic gastroesophageal reflux which in turn induced the development of squamous dysplasia and carcinoma at multiple locations in the esophagus.

Aged↗
PubMed2001

Hepatocellular carcinoma with a sarcomatous appearance: report of a case.

A 59-year-old man was admitted with general fatigue, an epigastric mass, and remittent fever. Radiological examinations disclosed a huge solid-to-cystic mass in the right lobe of the liver, and the mass severely compressed the right diaphragm, the inferior vena cava, and the right atrium. In addition, the patient suffered from chronic hepatitis; however, the serum alpha-fetoprotein, carcinoembryonic antigen, and PIVKA II levels were all within the normal ranges. The serum C-reactive protein level was 7.71mg/dl. With a clinical diagnosis of a malignant hepatic tumor invading the right diaphragm, surgery was performed. The tumor originated from segments IV and VII of the liver, was well defined, and grew extrahepatically. The tumor was resected using an ultrasonic cavitational aspirator together with the infiltrated right diaphragm. The resected tumor measured 23 x 13 x 23cm in size and weighed 3,700 g. Histologically, the tumor was found to consist of hepatocellular carcinomatous component and sarcomatous component. In the sarcomatous component, spindle-shaped cells which were positive for the immunohistochemical localization of vimentin, alpha-smooth muscle actin, and keratin were identified. The postoperative course was uneventful. The value of the serum C-reactive protein returned to within the normal range, and the patient became afebrile. The patient received a postoperative combination chemotherapy (etoposide, epirubicin, and cisplatin), and remains well with no signs of recurrence 12 months after the operation.

Carcinoma, Hepatocellular↗
PubMed2001

Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions.

The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan. Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity.

Asia↗
PubMed2001

Combined resection of invaded organs in patients with T4 gastric carcinoma.

BACKGROUND: To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively. METHODS: The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed. RESULTS: In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively. CONCLUSIONS: Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.

Adenocarcinoma↗
PubMed2001

Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester.

Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.

Apolipoproteins E↗
PubMed2001

Alpha-tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2 (2'-carboxyethyl)-6-hydroxychroman, gamma-tocopherol metabolite, in rats.

In this study, we investigated a change in the excretory content of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol (gamma-Toc) metabolite, in rat urine and bile by using a new high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method. In this determination, CEHC [alpha- and gamma-CEHC, where alpha-CEHC = 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman] in the biological specimens were treated with 3 N methanolic HCl to hydrolyze conjugates and to promote esterification. The methylated samples were extracted by n-hexane/water (1:2). The analyses of the methyl esters of alpha-CEHC and gamma-CEHC were performed by an HPLC-ECD using an ODS-3 column at 35 degrees C. The mobile phase was acetonitrile/water (45:55, vol/vol) containing 50 mM sodium perchlorate. After rat urine and bile samples, respectively, were methylated as described above, methylated biliary metabolites were identified by liquid chromatography-mass spectrometry as methyl esters of gamma-CEHC. Furthermore, we examined the differences in the excretion of gamma-CEHC between rat urine and bile after an oral administration of gamma-Toc or alpha- + gamma-Toc by the above HPLC method. In the gamma-Toc group, each vitamin E-deficient rat was given 0.5 mL of a stripped corn oil preparation containing 10 mg of gamma-Toc. In the alpha- + gamma-Toc group, the rat was given 10 mg of alpha-Toc and 10 mg of gamma-Toc. The content of gamma-CEHC in rat urine from the alpha- + gamma-Toc group was increased more in comparison to the gamma-Toc group at 18-36 h after oral administration. Moreover, the content of gamma-CEHC in rat bile in the alpha- + gamma-Toc group was increased more in comparison to the gamma-Toc group at 6-18 h after oral administration. Therefore, we have suggested that gamma-CEHC was shifted mainly to urinary excretion after gamma-CEHC had been excreted into the bile. Furthermore, we assume that alpha-Toc may affect the metabolism of gamma-Toc to gamma-CEHC in the body.

Animals↗
PubMed2001

Effects of the acyl chain composition of phosphatidylcholines on the stability of freeze-dried small liposomes in the presence of maltose.

The effects of the acyl chain composition of phosphatidylcholines (PCs) on the stability of small unilamellar vesicles during freeze-drying and rehydration in the presence of maltose were studied by monitoring the retention of a trapped marker, calcein, in the internal liposome compartment. In dipalmitoyl PC, beta-oleoyl-gamma-palmitoyl-PC and egg yolk PC liposomes, good or fair retentions (>50%) were observed in the presence of maltose, but maltose was ineffective in preserving retention in the dioleoyl PC (DOPC) liposomes (<10%). The extremely low retention in the DOPC liposome was ascribed to neither a formation of the inverted hexagonal phase of the liposomal membrane nor the fusion/aggregation of the liposomes in the drying-rehydration process. Differential scanning calorimetry measurements suggested that interactions of maltose with PC headgroups were essential to stabilizing the dry liposomes. These interactions were significant in the saturated or mixed chain liposomes but were markedly reduced in the DOPC liposomes.

Calorimetry, Differential Scanning↗
PubMed2001

Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-kappaB binding to its recognition sequence.

Cilostazol is a specific inhibitor of cAMP phosphodiesterase, which is used for treatment of ischemic symptoms of peripheral vascular disease. Although cilostazol has antiplatelet and vasodilator properties, its effect on the expression of adhesion molecules in vascular endothelium is not known. In the present investigation, we examined the effect of cilostazol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured vascular endothelial cells. Cilostazol strongly inhibited tumor necrosis factor (TNF)-alpha-induced expression of VCAM-1 protein and its mRNA. In addition, cilostazol reduced TNF-alpha-induced U937 cell adhesion to the vascular endothelial cells. In transient transfection studies, cilostazol inhibited TNF-alpha-induced transcriptional activation of VCAM-1 promoter. Electrophoretic mobility shift assays revealed that cilostazol repressed TNF-alpha-induced increase in binding of the transcription nuclear factor-kappaB (NF-kappaB) to its recognition site of VCAM-1 promoter. Cilostazol, however, failed to prevent nuclear translocation of the NF-kappaB p65 protein. These data indicate that cilostazol repressed VCAM-1 gene transcription in cultured vascular endothelial cells, via inhibiting NF-kappaB binding to its recognition sequence. Since the expression of the adhesion molecule is one of the earliest events occurred in atherogenic process, cilostazol might have the potential to prevent atherosclerosis at least via inhibition of the expression of the adhesion molecule.

Cell Adhesion↗
PubMed2001

Localization and expression of steroid sulfatase in human fallopian tubes.

Localization of steroid sulfatase, a membrane-bound microsomal enzyme, in human fallopian tubes was immunohistochemically investigated, and expression of RNA was confirmed by competitive RT-PCR. Human fallopian tubes were obtained from 10 patients in follicular and early luteal phases during gynecological laparotomy. An anti-human rabbit polyclonal antibody was prepared against sulfatase protein purified from human placenta. Total RNA was isolated from epithelium of fallopian tubes. A heterologous RNA competitor was designed, and competitive RT-PCR was carried out. Steroid sulfatase was localized to the cytoplasm of epithelial cells. With respect to the positive staining of cells, the number of positive secretory cells was higher than that of ciliated cells. A significantly higher number of positive cells was found in tissue obtained from the early luteal phase than that found in tissue from the follicular phase. An abundant expression of sulfatase mRNA in early luteal phase was also observed. This study demonstrates, for the first time, that steroid sulfatase is localized to human epithelial cells and that steroid sulfatase staining and mRNA expression changes with the menstrual cycle. These results suggest that sulfatase in the fallopian tube may be involved in controlling the local steroid environment, which appears to regulate aspects of the physiological reproductive function of the fallopian tube.

Adult↗
PubMed2001

Embryonic development assay with Daphnia magna: application to toxicity of aniline derivatives.

An assay system using Daphnia magna embryos was applied to investigate the adverse effects of aniline derivatives. The data were compared with our previous data for chlorophenols. This new assay provides useful information to evaluate the toxicity of chemicals and the differences in sensitivity between the life stages. The effects of 15 aniline derivatives on embryonic development of D. magna embryos were determined. At the start of exposure, 2-6-h old eggs (between stages 1 and 2, round in shape, diameter approx. 400 microm), were used. In control and solvent control groups, embryonic development from an egg to a free-swimming animal proceeded completely within 3 days with more than 90% hatchability. Median effective concentrations (EC50s) to reduce the numbers hatched were determined and gross morphological abnormalities of hatched animals recorded. Anilines induced no obvious morphological abnormalities and no developmental delay although premature deaths occurred. However, they affected the number of embryos hatching in a dose-dependent manner. In addition, this embryo assay was more sensitive to aniline derivatives (except for aniline) than acute juveniles immobilization assay. Ratios of 48-h EC50 (juvenile)/3-day EC50 (embryo) for eight anilines were greater than 5.0. Particularly, the ratios of 4-methyl-, 4-ethyl- and 3-methylaniline were 77, 23 and 11, respectively. EC50s for embryos and juveniles were poorly correlated (r = 0.41). This indicated that the sensitivities of the two life stages were different to the effects of anilines. EC50s were poorly correlated (r = -0.097) with the log Kow (1-octanol/water partition coefficient). These results were compared with previous results for phenols.

Aniline Compounds↗
PubMed2001

Sustained phosphorylation of mitogen-activated protein kinase is required for basic fibroblast growth factor-mediated axonal branch formation in cultured rat hippocampal neurons.

Basic fibroblast growth factor (bFGF) has been reported to promote the formation of axonal branches in cultured brain neurons. In the present study, we investigated whether the mitogen-activated protein kinase (MAPK) cascade was involved in this action of bFGF in cultured rat hippocampal neurons. Recombinant human bFGF (0.1-10 ng/ml) induced phosphorylation of p44/42 MAPK in a concentration and time-dependent manner. The phosphorylation of p44/42 MAPK occurred rapidly within 5 min after addition of bFGF, and lasted for 48 h. The bFGF-induced phosphorylation of p44/42 MAPK and axonal branch formation were both blocked by simultaneous addition of U0126 and PD98059, specific inhibitors of MAPK kinases. Furthermore, when U0126 and PD98059 were added 24 h after bFGF, phosphorylation of p44/42 m MAPK was decreased, and axonal branch formation was stopped. These results suggest that sustained activation of the MAPK cascade is required for bFGF-mediated axonal branch formation.

Animals↗
PubMed2001

Clinical features and alterations in the inferior horn sizes in lateral ventricle in Alzheimer's patients with different ApoE genotype in Japanese population.

E4 allele of Apolipoprotein E (ApoE) is considered to be not only a risk factor for Alzheimer's disease (AD) but also a determinant of clinical features in AD. However, it is still controversial whether ApoE e4 allele is related to age at onset, severity of memory impairment or brain morphological changes in AD patients. The present study examined the issue in Japanese population: 1) ApoE genotype on in 38 normal controls and 32 AD patients; 2) association between e4 allele of ApoE and clinical features including Wechsler Memory Scale-Revised in 32 AD patients; and 3) association between e4 allele of ApoE and change in size of inferior horn in lateral ventricle (LV) in 13 out of 32 AD patients. The e4 allele of ApoE frequency was higher in AD patients than in normal controls. There was no significant difference in age at onset or neuropsychological results between AD with and without e4 allele of ApoE. Alteration per month of the inferior horn sizes in LV measured by MRI was similar in the AD patients with and without e4 allele of ApoE. These results suggest that e4 allele of ApoE is a risk factor but not a determinant of clinical features for AD in Japanese population.

Aged↗
PubMed2001

Th1 and Th2 cytokines differentially regulate the transformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation.

To investigate the effects of T-helper cytokines on Kupffer cells (KCs), the effects of interferon-gamma (IFN-gamma; Th1 cytokine) and interleukin-4 (IL-4; Th2 cytokine) on KC morphology and their role in modulating the growth of hepatic stellate cells (HSCs) were examined. Fluorescence microscopic and electron microscopic data demonstrated that IL-4 transforms rat KCs into multinucleated giant cells (MGCs) in vitro. This transformation was inhibited by the addition of anti-ICAM-1 and anti-CD18 monoclonal antibodies. In addition, IL-4-induced KC transformation was suppressed by the presence of IFN-gamma. The formation of mouse hepatic MGCs was also demonstrated in vivo by the intraperitoneal injection of recombinant mouse IL-4. Although the presence of MGCs was found in all five out of five livers from IL-4-treated Th2-dominant BALB/c mice, but it was in only two out of five livers from IL-4-treated Th1-dominant C57BL/6 mice. In addition, fewer MGCs were found in the liver of C57BL/6 mice. In contrast, IFN-gamma treatment did not form hepatic MGCs in mice at all. The growth of HSCs in vitro was significantly increased by the addition of culture supernatant from lipopolysaccharide-stimulated rat KCs. Pretreatment of the KCs with either IFN-gamma or IL-4 further enhanced the growth stimulation. These results suggest that IFN-gamma and IL-4 affect KC morphology differently, but that both Th1 and Th2 cytokines play a similar role in the modulation of HSC growth by Kupffer cells in the presence of lipopolysaccharide.

Journal Article↗
PubMed2001

Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats.

The tissue renin-angiotensin system has recently been demonstrated to reduce fibrogenesis in various organs. However, little has been clarified regarding its role in hepatic fibrosis. The purpose of this study was to investigate the effect of angiotensin-converting enzyme inhibitors on liver fibrogenesis induced in rats by low-dose chronic carbon tetrachloride administration. We used lisinopril that is absorbed in its active form and not metabolized in the liver to avoid any influence by the administration of the chemical. Carbon tetrachloride was administered twice a week i.p. Twelve and 24 weeks after the start of treatment, expanded periportal fibrosis or portal-portal bridgings and severe fat deposition were observed in the rats treated with carbon tetrachloride alone, and these findings were significantly reduced with the simultaneous treatment with lisinopril. The hydroxyproline content of the liver was significantly lower in the lisinopril-treated group. Angiotensin II up-regulated mRNA of pro alpha (I) collagen and transforming growth factor-beta in isolated hepatic stellate cells. These results suggest that the local tissue renin-angiotensin system plays a role in rat hepatic fibrogenesis induced by chronic carbon tetrachloride administration and that hepatic fibrogenesis is significantly reduced by ACE inhibitors.

Journal Article↗
PubMed2001

Impairment of an event-related potential correlate of memory in schizophrenia: effects of immediate and delayed word repetition.

OBJECTIVE: We investigated the nature of the memory impairment in schizophrenia using an event-related potential (ERP). METHODS: Visual ERPs were recorded while 20 schizophrenics and 20 controls performed semantic categorization tasks with incidental word repetitions. Participants responded to occasional target words. Half of the non-target words were repeated immediately after initial presentation (lag 0) or after 5 intervening words (lag 5). RESULTS: In both groups, ERPs to words at lag 0 were more positive than those to non-repeated words, though this positive-going effect was attenuated in the schizophrenics, especially around 400-500 ms. The effect at lag 5 was smaller and shorter than that at lag 0 but was comparable between groups. Attenuation of the N400 peak occurred for word repetition at lag 0 in controls but not in schizophrenics, whereas a peak increment in the late positive component induced by word repetition at both lags was observed in both groups. CONCLUSIONS: Findings indicate that patients with schizophrenia have a deficit in a brain process modulating ERP correlates of memory, when words are repeated immediately. This deficit might be related to an abnormal N400 priming effect in schizophrenia.

Adult↗