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Y Adachi

Publications and source records attributed to Y Adachi.

At least 271 records · Page 15Linked to original sources
PubMed1999

Thrombin in the airways of asthmatic patients.

The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that, in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor were measured in the sputum of all subjects. The concentrations of thrombin (p = 0. 007), TAT (p = 0.01), and tissue factor (p = 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that sputum from asthmatic patients (p = 0. 01) and thrombin (p = 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the sputum concentrations of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether these findings are also observed in other airway diseases.

Antithrombin III↗
PubMed1999

Clinicopathologic study of gastric cancer based on Dukes' classification.

Dukes' classification is a useful staging system in patients with colorectal cancer. The aim of this study was to present clinicopathologic characteristics and survival of patients with gastric cancer based on Dukes' classification. A total of 273 patients with gastric cancer curatively treated by radical gastrectomy and lymph node dissection (D2, D3) were studied. With the modified Dukes' classification, A includes tumors limited to the mucosa, submucosa, or muscularis propria; B includes tumors extending into the subserosa or serosa; Ca includes tumors with one to six positive lymph nodes; and Cb includes tumors with seven or more positive lymph nodes. Dukes' classification modified by the number of positive lymph nodes well correlated with the tumor size (p < 0.01), depth of wall invasion (p < 0.01), level of lymph node metastasis (p < 0.01), and degree of lymphatic permeation (p < 0.01) and venous permeation (p< 0.01). The 5-year survival rate was significantly different among Dukes' A (98%), Dukes' B (90%), Dukes' Ca (75%), and Dukes' Cb (44%) cases. The results indicate that Dukes' classification modified by the number of positive lymph nodes (Dukes' A, B, Ca, an Cb) significantly correlates with tumor progression and patient survival; and it may be a simple and useful staging system for gastric cancer.

Adenocarcinoma↗
PubMed1999

Histopathologic criteria for local excision of colorectal cancer: multivariate analysis.

BACKGROUND: Local treatment of colorectal cancer, including endoscopic removal of colonic polyps and transanal resection of rectal tumors, has become widely accepted. However, risk factors predicting the presence of lymph node metastasis have not been fully investigated. To determine the criteria for local excision of colorectal cancer, histopathologic factors independently predicting the lymph node metastasis were investigated. METHODS: We performed a retrospective histopathologic study on 335 patients who underwent resection of colorectal cancer and dissection of regional lymph nodes between 1982 and 1996. Features of node-positive tumors (n = 150) were compared with those of node-negative tumors (n = 185), with special reference to the histopathologic findings of the resected tumor. Multivariate analysis was done using the stepwise logistic regression test. RESULTS: Node-positive tumors, when compared with node-negative tumors, were characterized by tumor larger than 6 cm (42% vs. 22%), serosal invasion (88% vs. 56%), lymphatic invasion (32% vs. 5%), venous invasion (9% vs. 2%), and histology other than well-differentiated (66% vs. 29%). Multivariate analysis showed that factors independently associated with lymph node metastasis were serosal invasion, lymphatic invasion, and histologic type. When these three risk factors were negative, lymph node metastasis was rare (5%). When one, two, or three factors were positive, the frequency of lymph node metastasis was 38%, 66%, and 85%, respectively. CONCLUSIONS: In colorectal cancer, factors independently associated with lymph node metastasis are serosal invasion, lymphatic invasion, and histologic type. When these three parameters are favorable, local treatment of colorectal cancer does not require additional lymph node dissection.

Colorectal Neoplasms↗
PubMed1999

Inflammatory and immunopharmacological activities of meta-periodate oxidized zymosan.

Zymosan (ZYM), a strong complement-activating yeast cell preparation composed mainly of mannan and beta-glucan moieties, is a potent inflammatory substance with immunopharmacological activity. We previously analyzed the metabolism of ZYM in mice and found that it was deposited in liver and spleen for at least several months and then gradually oxidatively degraded. In this paper, we prepared oxidized ZYM by sodium metaperiodate oxidation (NaIO4) and borohydride reduction (I/B-ZYM) and/or limited hydrolysis of oxidized moieties (I/B/H-ZYM). Activities of the resulting products were assessed by (i) vascular permeability in mice, (ii) H2O2 synthesis by macrophages, (iii) TNF-alpha synthesis by macrophages, and (iv) reactivity to anti-ZYM sera. As a general trend, NaIO4, oxidation products exhibited reduced, but still significant, activity. Interestingly, the H2O2 production induced by I/B/H-ZYM was significantly reduced after extensive sonication. Antagonist(s) for H2O2 synthesis were concomitantly solubilized by sonication of I/B/H-ZYM. On the contrary, TNF-alpha production induced by I/B/H-ZYM was comparable with that of ZYM. These facts strongly suggest that highly branched 1,3-beta- and 1,6-beta-glucosidic linkages resistant to NaIO4 oxidation are important for biological activity of ZYM. Further, the minimal structure in ZYM necessary for biological activity may depend on the activity tested.

Animals↗
PubMed1999

Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells.

The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP-470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA-MB-231, T-47D, MCF-7, KPL-1, and MKL-F). In all five cell lines, EPA and TNP-470 alone both showed tumor growth inhibition in a time- and dose-dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP-470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bcl-xS, the apoptosis-enhancing proteins, was more up-regulated and that of Bcl-2 and Bcl-xL, the apoptosis-suppressing proteins, was more down-regulated compared to the use of EPA or TNP-470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.

Apoptosis↗
PubMed1999

IL-4 and IL-13 stimulate human bronchial epithelial cells to release IL-8.

Cytokine networks are important in regulating the traffic of inflammatory cells in the airways. Interleukin-8 (IL-8) released by human bronchial epithelial cells (HBECs) is thought to be of particular importance in attracting neutrophils and monocytes to sites of inflammation. Increased release of IL-8 by HBECs in response to Th-1 cytokines such as TNF alpha and IL-1 beta may be an important pathophysiologic pathway. The present study was designed to explore the role of the Th2 cytokine IL-4 and the functionally related interleukins IL-10, and IL-13 on the regulation of IL-8 release by HBECs. HBECs (passage 4-6) were cultured in LHC9/RPMI and when confluent cells were stimulated in unsupplemented medium LHCD/RPMI by IL-4, IL-10, and IL-13 at 10 ng/ml concentration for all cytokines. TNF alpha stimulation was used as a positive control. After 24 hours supernatants were collected and tested for IL-8 by a sandwich ELISA. Unstimulated HBECs spontaneously released limited amounts of IL-8 (11 +/-1 pM) and significantly increased cytokine production in response to IL-4 (42 +/- 1 pM), IL-13 (30 +/- 1 pM) and TNF (128 +/- 11 pM). Stimulation with IL-10 (11 +/- pM) did not change basal production of IL-8. When HBECs were co-stimulated with IL-4 plus TNF, the production of IL-8 was further increased (204 +/- 5 pM). In contrast, IL-10 attenuated the effect of TNF during co-stimulation (82 +/- 5 pM). IL-13 did not affect the release of IL-8 induced by TNF (111 +/- 9 pM). Northern blot analysis of IL-8 mRNA levels showed the highest induction of IL-8 mRNA in HBECs co-stimulated with TNF and IL-4. We conclude from our study that IL-4 directly induces IL-8 release from HBECs and amplifies the release of IL-8 in response to TNF alpha. IL-13 is less active and IL-10 has an inhibitory effect. Airway epithelial cells are able to interact, therefore, with products of both Th1 and Th2 cells with respect to modulating release of IL-8.

Bronchi↗
PubMed1999

Indication for and outcome of laparoscopy-assisted Billroth I gastrectomy.

BACKGROUND: Since 1991, laparoscopy-assisted Billroth I gastrectomy has been used for patients with early gastric cancer. The aim of this study was to clarify the outcome of 40 patients who underwent this operation and to examine the indications based on a retrospective histological study of 248 resected cases of early gastric cancer. METHODS: Operating time, blood loss, length of skin incision, and postoperative hospital stay and complications were examined using the operation records and medical charts. The presence or absence of lymph node metastasis, tumour size, site, gross type, histological type, depth of invasion, presence or absence of ulceration, and status of lymph node metastasis were investigated in 248 early gastric cancers. RESULTS: The mean operating time was 3 h and 48 min and the mean length of skin incision was 5.8 cm. Although one patient who had suffered from chronic bronchitis developed pneumonia and wound dehiscence, no other patients had a postoperative complication. The mean hospital stay after operation was 16 days and all patients were alive without recurrence at a median follow-up of 21 months. The incidence of lymph node metastasis in early gastric cancer was 2 per cent (three of 130) in mucosal cancers and 14 per cent (17 of 118) in submucosal cancers. These lesions could have been completely resected by laparoscopy-assisted gastrectomy. CONCLUSION: All 40 patients were treated successfully by laparoscopy-assisted Billroth I gastrectomy without significant complications and with no recurrences to date. Pathological study of conventionally resected stomach and lymph nodes confirmed that laparoscopy-assisted Billroth I gastrectomy would be a safe and useful operation for most early gastric cancers.

Adult↗
PubMed1999

Molecular aspects of organic compound transport across the plasma membrane of hepatocytes.

Many organic compounds are taken up from the blood by membrane transporters, taken across the sinosuidal membrane of hepatocytes and then excreted into bile via the bile canalicular membrane. The hepatic uptake of conjugated bile acids is mediated by the sodium taurocholate cotransporting polypeptide. Many organic anions and bulky organic cations are incorporated into hepatocytes by the organic anion transporting polypeptide, while small organic cations are transported by the organic cation transporter. At the canalicular membrane, organic compounds are excreted into bile by ATP-binding cassette transporters which hydrolyse ATP to ADP. Excretion of monovalent bile acids is mediated by the canalicular bile salt transporter and that of organic anions, including divalent bile acid, conjugates, are mediated by the multi-drug resistance-associated protein 2, also termed canalicular multi-specific organic anion transporter. Organic cations are excreted into bile by the multi-drug resistance gene product (MDR) 1 and phospholipids are excreted by MDR3 (mdr2 in mice and rats). The clinical syndromes associated with alterations of these transporters are also discussed.

Animals↗
PubMed1999

Codon 54 polymorphism of the fatty acid binding protein gene and insulin resistance in the Japanese population.

AIM: To determine the relationship of the polymorphism at codon 54 of the intestinal fatty acid binding protein gene (FABP2) with insulin resistance and susceptibility to Type 2 diabetes mellitus (DM) in the Japanese population. METHODS: We evaluated the polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 150 Type 2 DM patients and 147 healthy control subjects. The frequency of alleles encoding threonine (Thr54) and alanine (Ala54) at codon 54 of FABP2 in Type 2 DM patients was compared with that of healthy controls. Insulin sensitivity was assessed by the hyperinsulinaemic euglycaemic clamp in Type 2 DM patients with Ala54 homozygotes, Ala54/Thr54 heterozygotes and Thr54 homozygotes and by homeostasis model assessment (HOMA) in the nondiabetic group. RESULTS: The frequency of alleles encoding Ala54 and Thr54 was 0.59 and 0.41 in Type 2 DM patients, respectively, similar to that observed in nondiabetic controls (0.64 for Ala54 and 0.36 for Thr54). Insulin sensitivity was not significantly different between subjects with and without Thr54 allele either within the DM group or healthy controls. CONCLUSIONS: The allele encoding threonine in the FABP2 does not predispose to Type 2 DM or insulin resistance in the Japanese population.

Carrier Proteins↗
PubMed1999

Positive association between an estrogen receptor gene polymorphism and Parkinson's disease with dementia.

Parkinson's disease (PD) is a common cause of dementia in the elderly. Dementia in Alzheimer's disease (AD) and PD share common biologic and clinical features. The estrogen receptor (ER) gene is one of the susceptibility genes for AD. In order to test the hypothesis that the overlap between AD and PD may have a genetic basis, we determined ER gene polymorphisms in 13 PD patients with dementia (PDD) (age +/- SD; 71.9 +/- 5.5 years), 71 PD patients without dementia (PDND) (68.4 +/- 7.5 years), 86 AD patients (76.8 +/- 8.0 years) and 51 control subjects (CTL) (74.9 +/- 6.9 years). ER genotypes were classified as a P or p allele on the basis of a Pvu II-RFLP, and X and x on the basis of a Xba I-RFLP. The frequency of the P allele in the PDD group as well as the AD group was higher than that in CTL. There was no significant difference in the distribution of the P allele between CTL and PDND. There were no significant differences in the distribution of the X allele among the PDD, PDND and CTL groups, whereas a higher incidence was found in AD. We conclude that the ER gene may be a common susceptibility gene for dementia in PD as well as AD.

Aged↗
PubMed1999

Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome.

Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia. Previous studies of the defects in the human canalicular multispecific organic anion transporter gene (MRP2/cMOAT) in patients with DJS have suggested that the gene defects are responsible for DJS. In this study, we determined the exon/intron structure of the human MRP2/cMOAT gene and further characterized mutations in patients with DJS. The human MRP2/cMOAT gene contains 32 exons, and it has a structure that is highly conserved with that of another ATP-binding-cassette gene, that for a multidrug resistance-associated protein. We then identified three mutations, including two novel ones. All mutations identified to date are in the cytoplasmic domain, which includes the two ATP-binding cassettes and the linker region, or adjacent putative transmembrane domain. Our results confirm that MRP2/cMOAT is the gene responsible for DJS. The finding that mutations are concentrated in the first ATP-binding-cassette domain strongly suggests that a disruption of this region is a critical route to loss of function.

ATP-Binding Cassette Transporters↗
PubMed1999

Messenger RNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human hepatocellular carcinoma.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma is relatively poor because of the high rate of intrahepatic recurrences. We have previously demonstrated an association between enhanced secretion of active matrix metalloproteinases (MMPs; gelatinase A and matrilysin) and early recurrence in hepatocellular carcinoma. The aim of this study was to examine further the relationship between messenger RNA levels of metalloproteinases and their inhibitors and behavior of this carcinoma. METHODS: Messenger RNA expression of gelatinase A, gelatinase B, matrilysin and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 were analyzed in 30 patients with hepatocellular carcinoma by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results were contrasted with the clinicopathological data of the patients. RESULTS: Enhanced mRNA expression of gelatinase A, gelatinase B and matrilysin in tumor was observed in 20, 22 and 19 of 30 patients, respectively. Enhanced mRNA expression of gelatinase A or gelatinase B and of matrilysin showed trends toward presence of capsular invasion (P = 0.078) and intrahepatic metastasis (P = 0.064), respectively. Concomitant overexpression of gelatinase A and matrilysin was associated with portal invasion, intrahepatic metastasis and recurrence within the first postoperative year (P < 0.05). A modest increase of mRNA expression of TIMP-1 and TIMP-2 in tumor was observed in half of the patients, but did not correlate with any clinicopathological features. CONCLUSION: Our results suggest that semiquantitative RT-PCR analysis of MMPs may be helpful in disease management of patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1999

Quality of life after laparoscopy-assisted Billroth I gastrectomy.

OBJECTIVE: To evaluate the quality of life of patients who had undergone laparoscopy-assisted Billroth I gastrectomy (LAG) for cure of cancer. SUMMARY BACKGROUND DATA: In 1994, the authors reported the first case of LAG for early gastric cancer, and this approach quickly has been adopted by Japanese surgeons. However, little is known about the subjective clinical results of this less invasive surgery. METHODS: Quality of life was estimated using the 24-item questionnaire with a scoring system of 1, 2, and 3 and was compared between 41 consecutive patients with LAG and 35 with conventional open gastrectomy. All patients underwent Billroth I gastrectomy for early gastric cancer from January 1993 to July 1997 and were alive without recurrence. RESULTS: Patients who had undergone LAG were taking a normal diet (100%) with >66% of volume at each meal (90%), showed no decreased performance status (90%), and were satisfied with their surgical results (88%). Patients with LAG, when compared with open gastrectomy, showed significantly better results with regard to weight loss, difficulty in swallowing, heartburn and belch, early dumping syndrome, and total score. LAG was better accepted by the patients. CONCLUSIONS: Quality of life after Billroth I gastrectomy was significantly better in patients in whom a laparoscopic technique was used than in those who underwent a conventional method. LAG is less invasive and better accepted by patients and is the procedure of choice for the treatment of early gastric cancer.

Aged↗
PubMed1999

Induction of apoptotic cell death in human hepatocellular carcinoma SK-HEP-1 cells by a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone).

The antitumor effects of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on the human hepatocellular carcinoma SK-HEP-1 cell line have been investigated. The growth of these cultured hepatocellular carcinoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed, and morphological changes due to programmed cell death (apoptosis) were observed in these MGBCP-treated hepatocellular carcinoma cells. These results suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in this human hepatocellular carcinoma cell line.

Antineoplastic Agents↗
PubMed1999

Clinical results and prognostic factors of radiologically node-positive gastric carcinoma.

Lymph node metastasis determined by histologic examination is an important prognostic indicator in gastric carcinoma. However, prognostic value of lymph node metastasis detected by computed tomography (CT) is unknown. The aim of this study was to evaluate clinical results and prognostic factors of patients with radiologically node-positive gastric carcinoma. The study included 78 patients with primary gastric carcinoma and lymph node metastasis confirmed by CT. The level of lymph node metastasis was simply graded as follows: level I included perigastric nodes; level II included intermediate nodes along the left gastric, common hepatic, and celiac arteries; and level III included distant nodes along the hepatoduodenal ligament, pancreas, spleen, and abdominal aorta. Sixty patients (79%) had stage IV tumors showing one or more of the following: level III lymph node metastasis in 37, pancreatic invasion in 27, peritoneal dissemination in 23, and liver metastasis in 19. Overall 1- and 5-year survival rates were 29% and 6%, respectively, and the 1-year survival rate was significantly influenced by the level of lymph node metastasis on CT (55% for level I, 27% for level II, 7% for level III, P < 0.01). In patients with gastrectomy, prognostic factors were tumor size (<10 cm versus >10 cm, P < 0.01), gross type (localized versus infiltrative, P < 0.01), histologic type (well differentiated versus poorly differentiated, P < 0.01), and curability of the disease (curative versus noncurative, P < 0.01). Our study indicates that prognosis of patients with radiologically node-positive gastric carcinoma is poor because of high frequency of extensive tumor spreads. Patients having only positive level I nodes on CT are candidates for curative gastrectomy, which may offer long-term survival.

Adenocarcinoma↗