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Biomedical subjects

K Yamaguchi

Publications and source records attributed to K Yamaguchi.

At least 127 records · Page 7Linked to original sources

Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation.

We have established an orthotopic implantation model that is highly metastatic to the liver. A human gastric carcinoma cell line, AZ521, with low capacity for liver metastasis was implanted as a single-cell suspension in the stomach of nude mice. The tumor cells derived from a few liver metastatic foci were subsequently implanted orthotopically, and we established a cell line, AZH5G, by repeating the in vivo stepwise selection method. This metastasizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521 developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric analysis demonstrated that the expression of alpha 6-integrin significantly decreased in AZH5G (4.9% +/- 4.1%) compared to in AZ521 (17.7% +/- 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fibronectin was clearly higher than that of AZ521 cells. These findings suggested that changes in the expression of integrins on the cell surface might play an important role in metastatic ability. This well characterized line and its in vivo experimental model should be useful to investigate the mechanisms of liver metastasis and to develop a new therapeutic approach for human gastric cancer.

Adenocarcinoma↗

Stereospecific antitumor activity of radicicol oxime derivatives.

PURPOSE: Radicicol is a novel hsp90 antagonist, distinct from the chemically unrelated benzoquinone ansamycin compounds, geldanamycin and herbimycin. Both geldanamycin and radicicol bind in the aminoterminal nucleotide-binding pocket of hsp90, destabilizing the hsp90 client proteins, many of which are essential for tumor cell growth. We describe here antitumor activity of a novel oxime derivative of radicicol, KF58333. We also investigated the mechanism of antitumor activity of KF58333 in comparison with its oxime isomer KF58332. METHODS: Antiproliferative activities were determined in a panel of breast cancer cell lines in vitro. We also examined inhibition of hsp90 function and apoptosis induction in erbB2-overexpressing human breast carcinoma KPL-4 cells in vitro. Direct binding activity to hsp90 was assessed by hsp90-binding assays using geldanamycin or radicicol beads. In animal studies, we investigated plasma concentrations of these compounds after i.v. injection in BALB/c mice and antitumor activity against KPL-4 cells transplanted into nude mice. Inhibition of hsp90 function and induction of apoptosis in vivo were investigated using tumor specimens from drug-treated animals. RESULTS: KF58333 showed potent antiproliferative activity against all breast cancer cell lines tested in vitro, and was more potent than its stereoisomer KF58332. These results are consistent with the ability of KF58333 to deplete hsp90 client proteins and the induction of apoptosis in KPL-4 cells in vitro. Interestingly, KF58333, but not KF58332, showed significant in vivo antitumor activity accompanied by induction of apoptosis in KPL-4 human breast cancer xenografts. Although the plasma concentrations of these compounds were equivalent, KF58333, but not KF58332, depleted hsp90 client proteins such as erbB2, raf-1 and Akt in the tumor specimen recovered from nude mice. CONCLUSIONS: These results suggest that inhibition of hsp90 function, which causes depletion of hsp90 client proteins in tumor, contributes to the antitumor activity of KF58333, and that the stereochemistry of the oxime moiety is important for the biological activity of radicicol oxime derivatives.

Animals↗

Sequence analysis on the mitochondrial orfB locus in normal and Ogura male-sterile cytoplasms from wild and cultivated radishes.

In order to gain a better understanding of the origin and evolution of Ogura male-sterile cytoplasm in radish, sequence analysis was conducted for the mitochondrial locus, orfB, using wild and cultivated radishes. The nucleotide sequence of the entire coding and flanking regions of orfB (approximately 1 kb) was determined for six radishes with normal and Ogura cytoplasm and they were classified into three types (types 1-3). The sequence of the 5' flanking region of orfB was further analyzed in 40 additional plants. Irrespective of the category of radish, plants with Ogura male-sterile cytoplasm contained only the type 1 sequence, whereas plants with normal cytoplasm had either type 2 or type 3. The results suggested that the mutational event, which led to the association of orfB with the male-sterile gene orf138, had occurred only once in the history of radishes.

5' Flanking Region↗

Hyaluronic acid secretion during carbon dioxide pneumoperitoneum and its association with port-site metastasis in a murine model.

BACKGROUND: The mechanism of port-site metastasis after laparoscopic cancer surgery is unclear. This study aimed to determine whether carbon dioxide (CO2) pneumoperitoneum caused an increase in hyaluronic acid, which is secreted from mesothelial cells of the peritoneal cavity, and to assess the risk for port-site metastasis using a murine pneumoperitoneal model. METHODS: Sandwich-binding protein assay was used to measure the concentration of hyaluronic acid in the peritoneal cavity at 6, 12, 18, 24, 48, and 72 h after CO2 pneumoperitoneum or laparotomy for 30 min. The concentrations of hyaluronic acid during pneumoperitoneum were compared among different gases (CO2, helium, air), intervals (5, 30, 60 min), and pressures (0-2, 4-6, 8-10 mmHg). To investigate the effects of exogenous hyaluronic acid, the development of port-site metastasis was examined using mouse adenocarcinoma cell-line colon 26 cells. RESULTS: The intraperitoneal concentration of hyaluronic acid after CO2 pneumoperitoneum had increased already at 6 h, had reached the maximum level at 24 h, and had begun to decrease at 72 h. The concentration of hyaluronic acid at 24 h and 48 h in the CO2 pneumoperitoneum group was higher than that in the laparotomy group. This increase in hyaluronic acid also was found during helium and air pneumoperitoneum, and the concentration of hyaluronic acid in the peritoneal cavity was at its maximum when CO2 pneumoperitoneum lasted 30 min at 4 to 6 mmHg. The frequency of port-site metastasis was the highest when hyaluronic acid was injected during CO2 pneumoperitoneum (100%). CONCLUSIONS: In a murine model, the intraperitoneal concentration of hyaluronic acid was significantly increased after CO2 pneumoperitoneum, and the increase was more evident than that after laparotomy. Increased hyaluronic acid during pneumoperitoneum may be associated with port-site metastasis after laparoscopic cancer surgery.

Adenocarcinoma↗

Surgical bypass versus metallic stent for unresectable pancreatic cancer.

With the development of interventional radiology and endoscopy, the practice of inserting expandable metallic stents for malignant jaundice has become widespread. Many studies have compared surgical bypass with polyethylene stents, or metallic stents with polyethylene stents. However, few data are available on the comparison of surgical bypass and metallic stents. The aim of this study was to compare the patient's postprocedure course and the cost performance of surgical bypass and metallic stents in patients with unresectable pancreatic cancer. The parameters analyzed were the rates of procedural and therapeutic success, duration of hospital stay, prevalence of early and late complications, cost performance, and prognosis. The rates of procedural and therapeutic success were excellent with both palliative treatments. With surgical bypass, there was a low prevalence of late complications, but duodenal obstruction sometimes occurred in patients without gastric bypass. With metallic stents, there was shorter hospitalization and lower cost, but a higher prevalence of late complications. Stent occlusion tended to occur in patients with uncovered metallic stents. There was no difference in the prognosis between the two palliative treatments. Thus, in consideration of the poor prognosis of pancreatic cancer, in patients with unresectable pancreatic cancer, insertion of covered metallic stents would be preferable to surgical bypass, because of the subsequent short hospitalization and the low cost. On the other hand, in patients with a relatively long expected prognosis, or in those with existing duodenal obstruction, biliary bypass with gastrojejunostomy may provide an advantage.

Adult↗

Periampullary choledochoduodenal fistula in ampullary carcinoma.

Most patients with ampullary carcinoma have obstructive jaundice without cholangitis. We experienced a patient with ampullary carcinoma who presented with obstructive jaundice and cholangitis, probably because of an accompanying periampullary choledochoduodenal fistula. A 77-year-old Japanese man had jaundice, high fever, and upper abdominal pain and was diagnosed, at another hospital, with obstructive cholangitis. On admission to our hospital, his symptoms and signs had subsided spontaneously. Abdominal ultrasonography showed cholecystolithiasis and dilatation of the common bile duct. Duodenoscopy showed an ulcerating tumor at the oral prominence of the ampulla of Vater and a periampullary choledochoduodenal fistula at the bottom of the ulcer. Biopsy from the fistula showed well differentiated adenocarcinoma. With a diagnosis of ampullary carcinoma with fistula formation, the patient underwent pylorus-preserving pancreatoduodenectomy. The diagnosis was confirmed by histology. This communication presents a unique case of ampullary carcinoma that caused obstructive jaundice, which subsided spontaneously but was associated with cholangitis caused by the divergent effects of the periampullary choledochoduodenal fistula formed by the carcinoma.

Aged↗

Cronkhite-Canada syndrome associated with advanced rectal cancer treated by a subtotal colectomy: report of a case.

A 41-year-old man with Cronkhite-Canada syndrome presented with multiple juvenile polyps with hyperplastic and adenomatous changes throughout his stomach and entire colorectum. Dysgeusia was recognized and the degree of hypoproteinemia was remarkable. A barium enema study and colonofiberscopy also revealed an advanced cancer in the rectum. Chronic hepatitis B and membranous glomerulonephritis were also present. It was difficult to design a conservative protocol using steroids for the treatment of protein-loosing enteropathy because the patient was a hepatitis B virus carrier. As a result, a subtotal colectomy while preserving the cecum with cecorectal anastomosis was performed. Pathologically, the ulcerated rectal tumor was a moderately differentiated adenocarcinoma with invasion into the muscularis propria. Most polyps showed cystically dilated glands without dysplasia or edematous stroma with inflammatory cell infiltration. A few polyps were juvenile-type polyps with adenoma components. Although no remarkable improvement was observed in the hypoproteinemia postoperatively, an alpha1-antitrypsin clearance test showed a significant decrease in protein loss from the gastrointestinal tract, which was only about one third of the loss seen preoperatively. These findings lead us to conclude that when improvement using conservative treatment can be neither obtained nor is expected, then the use of surgery should be considered when treating patients with Cronkhite-Canada syndrome.

Adenocarcinoma↗

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↗

A study of quality assessment in clinical microbiology performance of independent laboratories in Tokyo: 18-year participation in the Tokyo Metropolitan Government External Quality Assessment Program.

We evaluated the performance of independent microbiology laboratories in Tokyo over an 18-year period of participation in the external quality assessment (EQA) program, and we estimated the impact of the EQA program. The study design was a longitudinal retrospective analysis of performance, including isolation, identification, and antimicrobial susceptibility testing of bacteria from simulated patients' samples, in "open" surveys compared with "blind" surveys. Independent microbiology laboratories, licensed by the Tokyo Metropolitan Government, have been subject to mandatory evaluation by the EQA program since 1982. Survey reports, correspondence, annual guidance meetings, and inspections are used as quality improvement strategies. The performance for identification in "blind" surveys was significantly worse than that in "open" surveys (P < 0.001). Poorly performing laboratories had common features, including inadequate supervision by physicians and lack of familiarity with the impact of variations on the use of the standards. However, there were improvements in the performance of identification of some pathogens. The performance of susceptibility testing has not yet reached the relatively high level seen for identification. Some of the smaller laboratories have been gradually acquired by commercial chains operating outside Tokyo. The EQA program has established a role both in regard to laboratory improvement and as an educational tool. However, the program lags behind these of other developed countries in regard to the practical sciences. The main problems in regard to laboratory improvements are a shortage of human resources in clinical microbiology, lack of standardization of laboratory methods, and the pressures of financial constraints in the Japanese medical insurance system.

Data Collection↗

Pattern of lymph node micrometastasis and prognosis of patients with colorectal cancer.

BACKGROUND: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer. METHODS: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes' B colorectal cancer. Five serial 6-microm sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups. RESULTS: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01). CONCLUSIONS: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes' B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.

Aged↗

Quality of life after pylorus-preserving pancreatoduodenectomy.

BACKGROUND: With increasing numbers of long-term survivors after pylorus-preserving pancreatoduodenectomy (PPPD), postoperative quality of life (QOL) has become a great concern. However, few reports are available on data of the postoperative changes in QOL after PPPD. METHODS: A total of 20 patients were studied regarding QOL before and at short term (within 2 months), intermediate term (6 months), and long term (1 year) after PPPD, using a questionnaire. The questionnaire consisted of 13 physical and 10 psychosocial items. The medical records were also reviewed to evaluate objective nutritional status. Factors predicting delayed recovery of QOL were examined at intermediate term by univariate and multivariate analyses. RESULTS: Overall and physical QOL scores returned to the preoperative level at intermediate term after PPPD, showing parallel changes with the objective nutritional status. However, the scores of psychosocial condition, which reflected the patient's mental health, remained low even at long term. QOL scores at intermediate term in patients with pancreatic carcinoma were significantly lower than those with other diseases. Univariate analysis showed that preoperative body weight loss, impaired preoperative pancreatic exocrine function, long operative time, intraoperative radiotherapy, pancreatic carcinoma, and postoperative diarrhea were factors predicting the delayed recovery of QOL. Multivariate analysis revealed that preoperative pancreatic exocrine function significantly affected the delayed recovery of QOL. CONCLUSIONS: Preoperative supplement of pancreatic enzymes together with perioperative mental care would improve QOL at long term after PPPD.

Adult↗

Postoperative pancreatic exocrine function influences body weight maintenance after pylorus-preserving pancreatoduodenectomy.

BACKGROUND: Most patients who undergo pylorus-preserving pancreatoduodenectomy (PPPD) are able to gain their weight postoperatively. However, sometimes patients experience a lack of weight gain even at long term after PPPD. The aim of this study was to examine factors influencing a body weight change after PPPD. METHODS: In 34 Japanese patients with PPPD, 28 clinical parameters were assessed as possible factors affecting body weight maintenance at long term (1 year) after the operation by univariate and multivariate analyses. RESULTS: Univariate analysis showed that long operation time (P = 0.02), extended retroperitoneal lymph node dissection (P = 0.0005), intraoperative radiotherapy (P = 0.02), adjuvant postoperative chemotherapy (P = 0.02), histopathological diagnosis of pancreatic cancer (P = 0.02), postoperative ulceration (P = 0.007), and insufficient postoperative pancreatic exocrine function (P = 0.002) were significantly related with the lack of weight gain at long term after PPPD. Multivariate analysis regarding the seven profound factors revealed that the insufficient postoperative pancreatic exocrine function significantly affected the lack of weight gain after PPPD. The use of ordinary amount of pancreatic exocrine enzymes did not influence the weight gain after PPPD (P = 0.23). CONCLUSIONS: In patients refractory to an ordinary amount of medicine, a large dosage of enzymes may be necessary to gain weight after PPPD.

Adult↗

Is peripapillary choledochoduodenal fistula an indication for endoscopic sphincterotomy?

BACKGROUND: Most patients with a peripapillary choledochoduodenal fistula undergo fistulotomy by endoscopic sphincterotomy for the treatment of bile duct stones. However, whether sphincterotomy should be performed in patients with the fistula but without stones is controversial. METHODS: Among 165 patients in whom a benign peripapillary choledochoduodenal fistula was diagnosed at ERCP, the clinical outcome was retrospectively analyzed and compared between those who underwent fistulotomy by endoscopic sphincterotomy (group 1) and those whose fistula was left untreated (group 2). All patients with hepatolithiasis, residual stones, biliary diversion, or transduodenal papilloplasty were excluded (32, leaving 133). Fistulas were divided into types I and II according to the location of the fistula (Ikeda classification). RESULTS: Follow-up data collected during a median period of 124 months were available for 127 of 133 patients (95%), 76 in group 1 and 53 in group 2. Late complications were bile duct stone recurrence (17 patients), acute cholangitis (7 patients), and biliary carcinoma (2 patients). The incidence of stone recurrence was not significantly different between the 2 groups (p = 0.1). In group 2, 4 patients (8%) with an untreated type II fistula had 1 to 3 episodes of presumed reflux cholangitis, which resolved quickly with conservative treatment. CONCLUSIONS: Endoscopic sphincterotomy is not always necessary for peripapillary choledochoduodenal fistulas if bile duct stones are absent because reflux cholangitis is a relatively rare complication that can be easily managed.

Adult↗

Treatment of the athlete with multidirectional shoulder instability.

Treatment of multidirectional instability in the athlete continues to be a challenging problem. Nonoperative treatment remains the initial treatment of choice in most athletes. However, some patients will fail nonoperative treatment and might require operative intervention. An open capsular shift procedure is indicated in nonoverhead athletes, most contact athletes and in most revision situations. However, the advances in thermal treatment of the capsule have made arthroscopic electrothermal capsulorrhaphy increasingly attractive as an alternative to the open approach for the primary treatment of multidirectional instability. Longer follow-ups will be necessary before definitive statements can be made regarding the arthroscopic techniques.

Arthrography↗

Increase in number of functional release sites by cyclic AMP-dependent protein kinase in cultured neurons isolated from hippocampal dentate gyrus.

The enhancement of synaptic exocytosis is one form of long-term potentiation (LTP) of synaptic transmission. As possible mechanisms underlying this enhancement, increases in the release probability and/or the number of release sites are suggested. To obtain direct evidence for the increase in the number of functional release sites induced by protein kinase A (PKA) cascade, we attempted to visualize functional release sites using styryl dyes, FM4-64 and FM1-43, and investigated the effects of PKA on the release sites. A PKA activator FSK increased the number of active release sites by approximately 20-30%. A direct PKA activator, Sp-cAMPS, showed the same effect, which was blocked by a PKA inhibitor, KT5720, suggesting that this effect was mediated by PKA. This PKA-dependent increase in the number of release sites requires Ca(2+) in the bath solution, and Sr(2+) can not be a substitute for Ca(2+). Since the number of functional release sites is approximately half the total number of synaptophysin-immunoreactive sites, the PKA dependent activation of silent release sites of DG neuron terminals is suggested.

Animals↗

Virtual MR microscopy for unruptured aneurysm.

PURPOSE: This study was performed to evaluate the usefulness of virtual magnetic resonance microscopy (VMRM) for the diagnosis of cerebral aneurysms. MATERIALS AND METHODS: We reviewed 11 patients with unruptured aneurysms confirmed by angiography or surgical therapy. We evaluated the ability of VMRM to represent aneurysms and the findings of the form and neck of the aneurysms. RESULTS: VMRM revealed 17 aneurysms, one of which was not detected by MR angiography (MRA). One suspected aneurysm by MRA was denied by VMRM. Although VMRM did not clearly demonstrate either one giant aneurysm or distal middle cerebral artery, two aneurysms in the cavernous sinus were clearly visualized by VMRM. VMRM seems to be almost equivalent to computed tomography angiography when detecting aneurysms without additional radiation exposure. CONCLUSION: VMRM is found valuable not only to plan the microscopic surgical therapy, but to visualize aneurysms.

Aged↗

Alleviation of sleep disturbance and repetitive behavior by a selective serotonin re-uptake inhibitor in a boy with Asperger's syndrome.

An 8 year-old boy with Asperger's syndrome had difficulties in communicating with his teachers and classmates. He occasionally stole out of the classroom. He could not sleep at night recalling his awful experience and kept crying every night and refused to go to school. The treatment with fluvoxamine was started at the dose of 25 mg daily. Four weeks after the treatment, his repetitive behavior and hyperactivity decreased and night crying diminished. Although he still has difficulties in communicating with others, he is now able to attend extra-curricular classes in a private school. Fluvoxamine, a selective serotonin re-uptake inhibitor that has been mainly used for patients with depression and obsessive-compulsive disorder, might be effective for compulsive symptoms and sleep disturbance of patients with pervasive developmental disorders.

Asperger Syndrome↗