Biomedical subjects

Y Adachi

Publications and source records attributed to Y Adachi.

At least 343 records · Page 19Linked to original sources

PubMed1998

Bone mineral density in patients taking H2-receptor antagonist.

Osteoporosis after gastrectomy is a common clinical disorder. In gastrectomized patients, decreased gastric acidity may be associated with impaired calcium absorption. This study was undertaken to determine whether patients with chronic use of H2-receptor antagonists (HRA) had demonstrable decreases in bone mineral density (BMD). Thirty-three patients taking cimetidine, ranitidine, or famotidine for more than 2 years were analyzed. We measured BMD of L2-L4 using dual energy X-ray absorptiometry (DXA). Osteoporosis (BMD less than 0.70 g/cm2) was found only in three patients (9%). As compared with healthy controls, age- and sex-matched BMD ranged from 74.4% to 132.9%, with a mean of 97.0%, and was not influenced by the period of HRA use (<5 years versus >5 years or more). Although the age- and sex-matched BMD was different among the kinds of HRA (98.6% for cimetidine, 101.3% for ranitidine, and 85.5% for famotidine), the relationship between the BMD and type of drug was not significant by multivariate analysis. These results indicate that chronic use of HRA has little influence on the degree of BMD, and suggest that decreased gastric acidity is not always associated with osteoporosis after gastrectomy.

Adult↗

PubMed1998

Hepatic cirrhosis: magnetisation transfer contrast in the globus pallidus.

The magnetisation transfer ratio (MTR), a quantitative tissue characteristic, and the pallidal index were measured in the globus pallidus of 37 patients with hepatic cirrhosis and 37 control subjects. The MTR decreased with severity of the disease, as indicated by the serum total bililubin, indocyanine green 15-min retention rate, and plasma ammonia. The pallidal index correlated significantly with haematological parameters, although the correlation coefficients tended to be lower than those between MTR and haematological parameters. This change in MTR corresponded to the results of the manganese chloride experiments. T1 shortening in the pallidum of patients with cirrhosis is presumably caused by paramagnetic effects, and possibly attributed to manganese deposition.

Case-Control Studies↗

PubMed1998

Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II.

Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase activity. Recently, there has been progress in mutation analysis of patients with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from five unrelated families. The mutations found in this study were classified into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These mutations, which were detected in five patients from three unrelated families, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Trp) in exon 1. The third type, which was detected in one patient and was a new type of mutation combination, was composed of a homozygous insertion mutation of the TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1. Although the first and the second type of mutations are recessive, the third type appears to be dominant with incomplete penetrance, since the allele frequency of the insertion mutation of the TATAA element is very high (40%).

Adult↗

PubMed1998

Fibronectin production by cultured human lung fibroblasts in three-dimensional collagen gel culture.

In vivo, fibroblasts are distributed in a three-dimensional (3-D) connective tissue matrix. Fibronectin is a major product of fibroblasts in routine cell culture and is thought to regulate many aspects of fibroblast biology. In this context, we sought to determine if the interaction of fibroblasts with a 3-D matrix might affect fibronectin production. To examine this hypothesis, fibronectin production by fibroblasts cultured in a 3-D collagen gel or on plastic dishes was measured by ELISA. Fibroblasts in 3-D gel culture produced more fibronectin than those in monolayer culture. Fibroblasts in 3-D culture produced increasing amounts of fibronectin when the collagen concentration of the gel was increased. The 3-D nature of the matrix appeared to be crucial because plating the fibroblasts on the surface of a plastic dish underneath a collagen gel was not different from plating them on a plastic dish in the absence of collagen. In addition to increased fibronectin production, the distribution of the fibronectin produced in 3-D culture was different from that of monolayer culture. In monolayer culture, more than half of the fibronectin was released into the culture medium. In 3-D culture, however, approximately two-thirds remained in the collagen gel. In summary, the presence of a 3-D collagen matrix increases fibroblast fibronectin production and results in greater retention of fibronectin in the vicinity of the producing cells.

Blotting, Northern↗

PubMed1998

Bile acid metabolism in analbuminemic rats.

The bile acid concentrations in the serum, liver, bile, intestines, and feces of 3- and 19-mon-old male and female Nagase analbuminemic (NA) rats were compared with those in Sprague-Dawley (SD) rats. There was no significant difference in the bile acid levels between NA and SD rats. However, increased biosynthesis and pool size of cholic acid (CD) derivatives and decreased levels of chenodeoxycholic acid (CDCA) derivatives (increased CA/CDCA ratio) were detected in male NA rats as compared to SD rats. The CA/CDCA ratio in female NA rats was not different from that in their SD counterparts. There were no significant differences between NA and SD rats in the biliary bile flow, bile acid levels in the small and large intestines, fecal bile acid excretion, bile acid concentration in the portal and systemic circulation, and in the pool size of bile acids. The blood lipid concentrations were significantly higher in the NA rats than in the SD rats. The hepatic levels of lipids were not significantly different between the two rat strains. In conclusion, this study showed that metabolism of bile acids in NA rats is not significantly affected, and that the hypercholesterolemia observed in these strains is not related to abnormalities of bile acid metabolism.

Animals↗

PubMed1998

The CD14 molecule participates in regulation of IL-8 and IL-6 release by bronchial epithelial cells.

The soluble form of the leukocyte membrane antigen CD14 is known to increase the sensitivity of endothelial and epithelial cell lines to bacterial lipopolysaccharide (LPS). This molecule also directly induces cytokine production in monocytes. Here, the effect of sCD14 and LPS on the release of IL-6 and IL-8 by human bronchial epithelial cells (HBECs) was studied. Soluble CD14 induced cytokine production both in the presence and absence of LPS. In addition, neither sCD14 nor anti-CD14 monoclonal antibody which blocks the interaction of LPS with CD14 had any effect on the binding of LPS to HBECs. These data suggest that sCD14 may induce the release of IL-6 and IL-8 from HBECs. However, the binding of LPS to bronchial epithelium appears to be mediated by CD14-independent mechanisms.

Bronchi↗

PubMed1998

Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice.

BACKGROUNDS/AIMS: No study has so far been conducted to clarify whether the presence of hyperbilirubinemia is detrimental to liver and renal functions. In the present study, the effects of polyethylene glycol-modified bilirubin oxidase (PEG-BOX) therapy on liver and renal function tests, hepatic energy charge and urinary prostaglandin levels were evaluated in a rat model of obstructive jaundice. METHODS: Sprague-Dawley rats were used in the experimental model of obstructive jaundice. PEG-BOX or an equivalent amount of PEG alone was intravenously injected into the animals and sampling of blood and urine, and liver harvesting were done sequentially after bile duct ligation. RESULTS: Conventional liver function tests showed no difference between PEG-BOX and control groups. However, bilirubin concentrations in the peripheral blood and liver tissue specimens markedly decreased, and the hepatic energy charge significantly increased in the PEG-BOX group as compared to controls. The blood concentration of bile acid was lower, but its urinary excretion was higher in the PEG-BOX group than in the control group. In vitro incubation of PEG-BOX with serum from rats with obstructive jaundice decreased the concentration of bilirubin but not that of bile acid. The urinary levels of prostaglandin E2 and the thromboxane B2/6-keto-prostaglandin Fla ratio were significantly lower in the PEG-BOX group than in the control group. CONCLUSIONS: The systemic reduction of bilirubin concentration may contribute to normalization of the urinary levels of prostaglandins and thromboxane B2, to decrease in serum bile acid levels, and to improvement of the hepatic energy charge in obstructive jaundice. These findings suggest that preoperative improvement of jaundice may be beneficial to patients with obstructive jaundice.

Animals↗

PubMed1998

Effects of administration of monoclonal antibodies (anti-CD4 or anti-CD8) on the development of autoimmune diseases in (NZW x BXSB)F1 mice.

(NZW x BXSB)F1 (W/BF1) mice spontaneously develop autoimmune diseases, characterized by lymphadenopathy, lupus nephritis, and immune thrombocytopenia associated with various autoantibodies such as anti-DNA, anti-platelet and anti-cardiolipin antibodies (Abs). In the present study, we investigate the effects of administration of monoclonal Abs (anti-CD4 or anti-CD8 mAb) on the development of autoimmune diseases in W/BF1 mice. MAb was administered from the age of 7 weeks. Prolongation of survival rate and reduction of severity of autoimmune diseases were observed after treatment with anti-CD4 mAb. However, anti-CD8 mAb treatment accelerated the diseases. Serum levels of IFN-gamma and IL-10 in old W/BF1 mice were significantly high, whereas IL-4 levels were low in comparison with those of young W/BF1 mice; the expression of mRNA of IFN-gamma, IL-4 or IL-10 in CD4+ T cells of old W/BF1 mice was parallel to the serum levels of each cytokine. These observations suggest that CD4+ cells are involved in the development of autoimmune diseases in W/BF1 mice, and that CD8+ cells have a suppressive effect on the development of autoimmune diseases in W/BF1 mice.

Age Factors↗

PubMed1998

Cytokine synthesis of human monocytes stimulated by triple or single helical conformer of an antitumour (1-->3)-beta-D-glucan preparation, sonifilan.

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on it's conformation in mice. In this study, we examined the relationship between the conformation of Schizophyllan (SPG), a high molecular weight (1-->3)-beta-D-glucan, and cytokine productivity in an in vitro human system. Monocyte-like human cell lines, THP-1 and U-937, and peripheral blood mononuclear cells (PBMC) were used. THP-1 and U-937 cells were differentiated by phorbol myristate acetate (PMA) before use. SPG usually has a triple helical conformation in water, but it was modified by treatment with aqueous sodium hydroxide to become a single helical conformer (SPG-OH). SPG or SPG-OH was added to the macrophage cell culture and gene expression and translation of several cytokines was analyzed by RT-PCR, ELISA, or bioassays. Differentiated THP-1 expressed high levels of cytokine genes, such as IL-8, in response to SPG-OH. High levels of IL-12 p70 were detected from THP-1 cells stimulated with SPG-OH. U-937 cells expressed high levels of IL-8 and TNF-alpha after SPG-OH treatment. Furthermore, PBMC isolated from healthy donors also strongly reacted with SPG-OH but not with SPG. High concentrations of TNF-alpha were detected in SPG-OH-stimulated PBMC cultures. These data suggest that the biological activities of SPG are strongly associated with its conformation in humans.

Adjuvants, Immunologic↗

PubMed1998

Relation of matrilysin messenger RNA expression with invasive activity in human gastric cancer.

Matrilysin is a member of the matrix metalloproteinase gene family which is believed to play an important role in tumor progression. Expression of matrilysin mRNA was examined by reverse transcription-polymerase chain reaction combined with Southern blot analysis in 46 human primary gastric cancers. Overexpression of matrilysin was observed in 28 (61%) of gastric cancer tissues. The positive expression ratio of matrilysin was significantly higher in the gastric cancers of subserosa or beyond it than in those within the submucosal layer. Immunohistochemical study with anti-matrilysin monoclonal antibody revealed that matrilysin was mainly expressed on cancer cells but not or very weakly expressed on other cells. In addition, an activated form of matrilysin detected by zymographic analysis was observed in gastric cancer tissues whereas none was detected in non-cancerous tissues, suggesting that matrilysin may directly and powerfully contribute to the invasion step of human gastric cancer. In order to gain more insight into the relationship of this metalloproteinase to invasive activity, we also modulated the expression of matrilysin in gastric cancer cells by DNA transfection using gastric cancer cell lines. Overexpression of matrilysin rendered the gastric cancer cells more invasive in vitro. Concomitant with clinical investigations, matrilysin may be an important metalloproteinase in the progression of gastric cancer.

Adenocarcinoma↗

PubMed1998

The protective effects of CP-060S on ischaemia- and reperfusion- induced arrhythmias in anaesthetized rats.

1. CP-060S is a novel sodium and calcium overload inhibitor, and is also characterized as a calcium channel blocker. As these activities have each been shown independently to ameliorate ischaemia damage in the myocardium, the combination may synergistically exert cardioprotection. In this study, therefore, the protective effect of CP-060S against ischaemia- and reperfusion-induced arrhythmia was evaluated in anesthetized rats. 2. Rats were anaesthetized with pentobarbitone, and the left anterior descending coronary artery was occluded for either 5 min with subsequent reperfusion (a reperfusion-induced arrhythmia model) or 30 min without (an ischaemia-induced arrhythmia model). All drugs were intravenously administered 1 min before the onset of occlusion. 3. In the reperfusion-induced arrhythmia model, the animals in the vehicle-treated group exhibited ventricular tachycardia (VT) in 100%, ventricular fibrillation (VF) in 89%, and death caused by sustained VF in 56%. CP-060S (30-300 microg kg(-1)) dose-dependently suppressed the incidences of arrhythmias. Significant decreases occurred at 100 microg kg(-1) in VF (incidence: 42%) and mortality (8%), and at 300 microg kg(-1) in VT (50%), VF (33%) and mortality (8%). This protective effect of CP-060S was 10 times more potent than that of a pure calcium channel blocker, diltiazem (30-1000 microg kg(-1)) we tested, in terms of effective dose ranges. As both drugs decreased myocardial oxygen consumption estimated by rate-pressure product to a similar extent, the calcium channel blocking activity of CP-060S would not seem to be sufficient to explain its potency. 4. In the same model, co-administration of ineffective doses of diltiazem (300 microg kg(-1)) and a sodium and calcium overload inhibitor, R56865 (100 microg kg(-1)), produced significant suppression of VT (incidence: 62%), VF (46%) and mortality (8%). By contrast, co-administration of R56865 at the same dose with CP-060S (300 microg kg(-1)) did not add to the effect of a single treatment of CP-060S. 5. In the ischaemia-induced arrhythmia model, CP-060S (300 microg kg(-1)) significantly decreased the incidence of VF from 75% to 29%, whereas diltiazem (1 mg kg(-1)) was ineffective. 6. These results suggest that CP-060S inhibits both ischaemia- and reperfusion-induced arrhythmia. The combination of the calcium channel blocking effect and the calcium overload inhibition was hypothesized to contribute to these potently protective effects.

Animals↗

PubMed1998

Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene.

KAI1 is a potential metastatic suppressor gene for prostate cancer. We found by Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines exhibited undetectable or very low expression level of KAI1 mRNA. The effects of KAI1 on the adhesion, motility and invasiveness of colon cancer cells was therefore investigated by using two kinds of stable transfectants, i.e., antisense transfectants of BM314 cells whose KAI1 mRNA expression was suppressed by transfer of antisense KAI1 cDNA and sense transfectants of DLD-1 cells with the enhanced KAI1 mRNA by sense cDNA transfer. The following results were obtained: (1) KAI1 gene expression had no significant effect on in vitro cell growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay showed that KAI1 enhanced the Ca++-independent aggregatability of those colon cancer cells; (3) It was revealed by cell motility and invasion assays that KAI1 suppressed both the motility and in vitro invasiveness of those cells and (4) Furthermore, both the binding to fibronectin and the migration on fibronectin-coated plates of those cells were inhibited by KAI1 expression. These suggest that reduced KAI1 gene expression may contribute to the invasiveness and metastatic ability of colon cancer cells.

Antigens, CD↗

PubMed1998

Perigastric lymph node status as a prognostic indicator in patients with gastric cancer.

BACKGROUND: The extent of lymph node dissection and histological examination of dissected lymph nodes varies among countries, which leads to the erroneous nodal stage and different surgical results in gastric cancer (stage migration, 'Will Rogers effect'). The aim of this study was to clarify the prognostic significance of the number of positive perigastric lymph nodes, which could be evaluated simply after D1 gastrectomy. METHODS: A consecutive series of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and lymph node dissection (D2 or D3) was studied. The number of metastatic perigastric nodes (level I, nos 1-6) was examined, and its influence on the survival of patients was analysed. RESULTS: The overall 5-year survival rate was 50.9 per cent; the 5-year survival rate was significantly decreased when positive perigastric nodes exceeded six (62 per cent for one to six nodes versus 23 per cent for seven or more nodes, P< 0.001). Tumours having one to six positive perigastric nodes compared with those having seven or more positive perigastric nodes were more likely to have a size less than 4 cm (29 per cent versus one of 30, P< 0.001), grossly localized type (45 per cent versus seven of 30, P=0.042), absence of serosal invasion (32 per cent versus none of 30, P=0.002) and metastasis limited to the perigastric lymph nodes (70 per cent versus seven of 30, P < 0.001). CONCLUSION: The results indicate that the number of positive perigastric nodes correlates with tumour progression and patient survival. This parameter is a simple and useful prognostic indicator for node-positive gastric cancer, and is available not only for D2 and D3 gastrectomy but also for D1 gastrectomy.

Adult↗

PubMed1998

Apoptosis of colorectal adenocarcinoma (COLO 201) by tumour necrosis factor-alpha (TNF-alpha) and/or interferon-gamma (IFN-gamma), resulting from down-modulation of Bcl-2 expression.

Fas antigen is constitutively expressed in the normal colon epithelium, but considerably diminished in most colorectal carcinomas. In the present study, we examine the relationship between Fas antigen expression and apoptosis using the colorectal carcinoma cell line COLO 201, on which a low grade of Fas antigen is expressed. Anti-Fas antibody had no effect on the induction of apoptosis of COLO 201. However, TNF-alpha and/or IFN-gamma, independently and additively, up-regulated Fas antigen expression on COLO 201 and induced apoptosis in a dose-dependent manner. Both cytokines also increased the COLO 201 sensitivity to anti-Fas antibody, resulting from the down-modulation of Bcl-2 and the up-regulation of Bax. These findings indicate that cytokine(s) plus anti-Fas antibody (which mimics natural Fas ligand) are more effective in inducing apoptosis of COLO 201 than cytokine(s) alone. These findings suggest that immunotherapy in combination with cytokine(s) and lymphokine-activated killer (LAK) cells will become a more effective therapy for cancer than cytokine(s) or LAK cells alone, since the Fas ligand is expressed on activated T cells, natural killer cells and macrophages.

Adenocarcinoma↗

PubMed1998

Aberrant neutrophil trafficking and metabolic oscillations in severe pyoderma gangrenosum.

Having previously associated metabolic oscillations with cell locomotion, we hypothesized that patients with abnormalities in neutrophil trafficking may display aberrant intracellular oscillations. A pyoderma gangrenosum patient exhibiting aberrant leukocyte trafficking in vivo and skin ulceration without infection was identified. This patient's neutrophils constitutively overexpressed and clustered the leukocyte integrins CR3 and CR4 and failed to display appropriate integrin-to-GPI receptor interactions. Increased levels of tyrosine phosphorylation were observed. NAD(P)H oscillations, which are sinusoidal in normals, were chaotic with multiple frequency components in this patient's neutrophils. Normal cell shape and sinusoidal NAD(P)H oscillations were restored by providing a pulsed electric field to drive metabolic oscillations and by temperature reduction. N-acetyl-D-glucosamine disrupted CR3 clusters and sinusoidal NAD(P)H oscillations returned. Anecdotal reports suggest that local hypothermia is clinically useful for this patient. These data define the first metabolic oscillation-associated disease and suggest that pyoderma gangrenosum can be classified as a dynamical disease at the cellular level.

Acetylglucosamine↗

PubMed1998

Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome.

Members of the ATP-binding cassette (ABC) transporter superfamily are mutated to cause diseases that include cystic fibrosis, hyperinsulinemia, adrenoleukodystrophy, Stargardt disease and multidrug resistance. We recently isolated a novel human member of ABC transporter superfamily as the candidate transporter for the glucuronide and glutathione-conjugated antitumor agents, and found it highly homologous to the rat cmoat gene. consistent with recent findings of defects in the homologous cmoat gene in two rat models of hyperbilirubinemia (TR- and Eisai), we report two deletions and a missense mutation in the active transport family signature region in the gene in patients with hyperbilirubinemia II/Dubin-Johnson syndrome (DJS; MIM 237500), respectively. These results strongly implicate the cMOAT gene as responsible for the defects in DJS patients.

Amino Acid Sequence↗

PubMed1998

Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer.

Liver metastasis is the gravest prognostic factor in colorectal cancer. To identify a reliable indicator for liver metastasis, we evaluated macroscopic features and seven established histopathological findings at the cut section containing the deepest penetration using univariate and multivariate analyses in 417 colorectal cancers. Macroscopic features were divided into two types, streak type and non-streak type, according to the presence or absence of white streak(s) at the advancing margin of tumor invasion. Streak type was observed in 109 patients (26%). The frequency of liver metastasis in streak type tumors (56%) was significantly higher than that in non-streak type tumors (13%) (p < 0.001). The white streak corresponded histologically with cancer cells showing focal dedifferentiation with marked stromal and perivascular fibrosis extending towards the serosa or adventitia. In 343 curatively treated patients, univariate analysis showed that recurrent liver metastasis was significantly associated with macroscopic features, venous invasion, focal dedifferentiation and lymph node metastasis. Multivariate analysis disclosed that macroscopic features and lymph node metastasis were independent indicators of liver metastasis. These macroscopic features, corresponding histologically to stromal behavior against invading cancer cells, are a simple and useful indicator of liver metastasis of colorectal cancer.

Colonic Neoplasms↗

PubMed1998

Low-dose cisplatin-5-fluorouracil prevents postoperative suppression of natural killer cell activity in patients with gastrointestinal cancer.

BACKGROUND: The effect of administering low-dose cisplatin (CDDP)-5-fluorouracil (5-FU) postoperatively on the activity of the immune system is not known. To clarify the effect on natural killer (NK) cell activity of treatment with low-dose CDDP-5-FU, we compared NK cell activity after surgery for gastrointestinal cancer in patients treated with low-dose CDDP-5-FU, a bolus dose of mitomycin C (MMC) or no anticancer drug. METHODS: Sixty-two patients consisted of three groups: low-dose CDDP-5-FU (n = 15), MMC (n = 20) and no-drug (n = 27). Chemotherapy was initiated immediately after surgery. NK cell activity was measured on the day before surgery (pre-op) and on postoperative days 7 (POD7) and 21 (POD21). RESULTS: The NK cell activities of the CDDP-5-FU group were 37.7% at pre-op, 36.1% on POD7 and 33.6% on POD21. However, the NK cell activities in the no-drug and MMC groups were significantly decreased on POD7 (from 36.6 to 24.8% and from 31.4 to 16.6%, respectively). The NK cell activity in the MMC group remained depressed on POD21 (18.6%) whereas that in the no-drug group recovered (31.6%). CONCLUSIONS: Consecutive administration of low-dose CDDP-5-FU appears to be useful as postoperative adjuvant chemotherapy because of its preventive effect on NK cell suppression after surgery.

Aged↗