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Biomedical subjects

M Onda

Publications and source records attributed to M Onda.

At least 55 records · Page 3Linked to original sources
PubMed2001

Celiac artery aneurysm: a case evaluated preoperatively with three-dimensional computed tomographic angiography.

In a 63-year-old woman computed tomography (CT) incidentally detected a celiac artery aneurysm approximately 3 cm in diameter. While conventional angiography suggested that the splenic artery and common hepatic artery arose from the celiac artery aneurysm, three-dimensional CT angiography indicated that the aneurysm involved only the mid portion of the celiac artery. Considering the risk of eventual aneurysm rupture, surgery was performed. Aneurysmectomy and devascularization of hepatic, splenic, and celiac arteries were carried out following complete cross-clamping of the celiac artery. The distal segment of the celiac artery was directly anastomosed to the proximal segment in an end-to-end fashion. Histologically, the aneurysm wall showed atheromatous changes. Contrast-enhanced abdominal CT confirmed complete removal of the celiac artery aneurysm, and postoperative angiography confirmed good arterial flow. The patient recovered uneventfully after surgery, with normalization of transiently abnormal hepatic function parameters. In this case of celiac artery aneurysm, three-dimensional CT angiography was found to be valuable in determining the relationships of the aneurysms to important arterial branches.

Aneurysm↗
PubMed2001

Liver cell adenoma in a 26-year-old man.

This is a report of a case of liver cell adenoma (LCA) in a 26-year-old man with no prior history of liver disease or glycogen storage disease and no record of hormonal therapy. He was found to have an asymptomatic hepatic mass during a routine medical examination. The physical findings were unremarkable, and the results of routine laboratory studies were all within normal limits. Selective hepatic arteriography showed a hypervascular mass within the right lobe of the liver. Despite the radiological examination, the nature of the mass was unknown, and preoperative biopsy was unadvisable because of the risk of bleeding. Because of the difficulty of determining the malignancy of the hepatic tumor preoperatively, elective laparotomy for diagnosis and hepatectomy as treatment appeared to be the best available approach. Pathological examination of the surgical specimen resulted in a diagnosis of LCA. A review of the literature revealed that LCA unassociated with the use of oral contraceptives is rare.

Adenoma, Liver Cell↗
PubMed2001

Spontaneous disappearance of a hepatic cyst.

The spontaneous disappearance of a hepatic cyst is described. A 62-year-old woman presented with symptoms of general fatigue in August 1992. Her past medical history was significant for chronic hepatitis, which was diagnosed in 1990 but not treated. Initial laboratory tests revealed mild liver dysfunction with a positive serologic test for hepatitis C. In August 1992, ultrasonography and computed tomography disclosed a cystic lesion along the middle hepatic vein in the right anterior segment of the liver, which was 40 mm in diameter. Repeat radiologic studies in June 1994 demonstrated that the size of the cyst was unchanged. In May 1995, the cyst was only 25 mm in diameter, and it continued to decrease in size thereafter, to 10 mm in September 1995 and 7 mm in September 1996. No hepatic cyst was visualized in December 1996, though the region in which the cyst existed was hyperechoic. Laboratory data were essentially unchanged from August 1992 to December 1996. Clinically the patient remained asymptomatic.

Cysts↗
PubMed2001

[Gastric cancer--novel strategy of gene therapy for gastric cancer].

Recently stage-oriented treatment for gastric cancer has been done in Japan. Endoscopic mucosal resection for intramucosal cancer and wedge resection under laparoscopy for minimal invasive cancer in the stomach have been performed. For advanced gastric cancer, extended lymph node dissection(D2) has been applied as standard treatment in Japan. However, new strategy has been required for advanced gastric cancer with distant lymph node metastasis and/or peritoneal dissemination. It is well known that gene therapy for cancer has limitation of efficacy, but we believe the new strategy will be available in post-genome era for gastric cancer treatment using 1. developing novel adenovirus, 2. usage of drug delivery system and 3. effective treatment for adverse effect.

Adenoviridae↗
PubMed2001

[Functional characteristics of pharmacy services related to home care in a certain suburban area].

In order to clarify functional characteristics of pharmacy services related to home care in a suburban area, a questionnaire survey regarding home-care services was conducted for all 75 pharmacies belonged to T-City Pharmaceutical Association. The following services were investigated; A) prescription (medication guidance for patients and their families, provision of drug information to patients, management of the patient's drug history, dispensing, advice to physicians, inquiries, management of prescriptions for home infusion services); B) supply (sales of items such as over-the-counter [OTC] drugs [commercially available drugs that do not require a physician's prescription], display and catalogue sales of nursing items); C) consultation (consultation on home care, holding events such as health education programs); D) management (guidance for drug management by home visit); and E) information exchange (information exchange with other medical professionals and social workers). The results of the present study were as follows. (1) The following services were considered important and therefore regularly performed; A) prescription: medication guidance for patients and their families, provision drug information to patients, management of the patient's drug history, dispensing, advice to physicians, inquiries; and B) supply: sales of items such as OTC drugs. (2) The following services were considered important, but not sufficiently regularly performed; B) supply: display and catalogue sales of nursing items; C) consultation: consultation on home care, holding events such as health education programs; D) management: guidance for drug management by home visits; and E) information exchange. (3) On factor analysis, among home care-related pharmacy services, display and catalogue sales of nursing items as well as consultation on home care were present in the same factor group as contained sales of items such as OTC drugs, which showed a high accomplishment rate. Guidance for drug management by home visits and information exchange with other social workers were present in the same factor group as contained information exchange with other medical professionals, which showed a relatively low accomplishment rate. In summary, home care-related pharmacy services were found to be associated with information exchange and supply/consultation functions. This suggests that to improve home care-related services in pharmacies, information exchange among health, medical practices, and social welfare-associated professionals, not previously promoted, should be stimulated and supported.

Adult↗
PubMed2001

Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels.

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluorouracil (5-FU) catabolism. We measured DPD activities represented as DPD protein levels (units/mg protein) and the associated mRNA levels in tumorous and normal tissues from 40 colorectal cancer patients, and we studied the relation to 5-FU concentrations in the same samples after treatment with doxifluridine, a prodrug of 5-FU. DPD mRNA levels were also measured in biopsy samples before treatment for comparison with those in surgical samples. 5-FU concentrations in tumors were higher than those in normal tissues (P < 0.05) and were inversely associated with DPD protein levels (r = -0.463; P < 0.05). DPD activities in tumorous and normal tissues showed a significant correlation (r = 0.527; P < 0.01). DPD protein levels correlated with their mRNA levels detected by semiquantitative reverse transcription-PCR in tumor tissues (r = 0.740; P < 0.01). DPD mRNA levels in tumor biopsy specimens correlated with those in surgical specimens (r = 0.366; P < 0.05). These results suggest DPD activities in tumors to be predictive of 5-FU levels in colorectal cancer tissues and are reflected by DPD mRNA levels as measured by reverse transcription-PCR.

Antimetabolites, Antineoplastic↗
PubMed2001

[Possibility and future problems of gene therapy for gastric cancer].

Recently, stage-oriented surgery has been performed for gastric cancer, but a new strategy is necessary for stage IV gastric cancer. The first target of gene therapy for gastric cancer was for stage IV patients with-widespread lymph node metastases and/or peritoneal dissemination. We reported on suicide gene therapy in experimental gastric cancer induced by ENNG in the dog, and the results showed that in situ gene transfer of a suicide gene (Ad. CAGHSV-TK) followed by prodrug (GCV) treatment may be applicable not only to the primary gastric tumor, but also to lymph node metastasis. Next, we assessed the efficacy of in situ gene therapy with Ad. CAGHSV-TK/GCV in gastric cancer induced by MNNG in rats, and followed the histopathological changes in the gastric cancer and HSV-TK gene in peripheral blood for 30 days. The results showed that: 1) apoptosis preceded tissue degeneration; 2) histopathological efficacy requires 30 days after suicide gene therapy; and 3) the HSV-TK gene persisted for 30 days. Based on these studies, we speculated that combination treatment with endoscopy is possible for all early gastric cancer, i.e., endoscopic mucosal resection of the primary tumor plus suicide gene therapy for sentinel lymph node metastasis. New possible strategies for peritoneal dissemination are: 1) tumor dormancy therapy with adeno-associated virus (AAV); and 2) combination gene therapy with suicide genes plus gene transfer to provide immunotherapy.

Adenoviridae↗
PubMed2001

Microsatellite instability in thyroid cancer: hot spots, clinicopathological implications, and prognostic significance.

PURPOSE: To determine whether microsatellite instability (MSI) in particular loci has clinicopathological significance in thyroid cancer. EXPERIMENTAL DESIGN: Seventy-six cases of surgically resected thyroid cancer were screened for MSI at nine microsatellites: THRA1, TSHR, D2S123, D11S912, D2S115, D2S399, p53, RET, or BAT-26. Multivariate analysis was performed to test for links between MSI and the clinical parameters of gender, age, histology, stage, nodal involvement, and prognosis. RESULTS: THRA1, residing in the thyroid hormone receptor alpha gene, displayed the highest levels of MSI at 36.5%. MSI in TSHR, located within the thyroid-stimulating hormone receptor gene, was found to be linked to cancer in the elderly (>70 years of age) and with high-grade (N 3, 4) nodal involvement. In follicular cancer, MSI in D2S123 occurred at a frequency of 100% (7/7) with no (0%) occurrence of MSI at the nearby D2S115, D2S399, or BAT-26 loci. Regarding prognosis, patients with MSI-positive cancer showed better long-term survival. BAT-26, which is an important marker in colorectal cancer, displayed the lowest frequency of MSI in our panel of thyroid tumors. CONCLUSION: Whereas patients with MSI-positive cancer showed better long-term survival, as is the case for colorectal cancer, our finding of the low frequency of MSI in BAT-26 suggests that the biochemical defects governing the spectrum of MSI in thyroid and colorectal cancer are different. MSI in THRA1, TSHR, and D2S123 appears to be an integral part of thyroid carcinogenesis, as evidenced by the high frequency of MSI and significant correlation to clinical data.

Adult↗
PubMed2001

Establishment and characterization of a human rectal neuroendocrine cell carcinoma in vitro.

Human colorectal neuroendocrine cell carcinoma ( NECC ) is uncommon. Treatment of the disease has not yet been established, and NECC of the colon and rectum behave clinically more aggressively than their exocrine counterparts, so the prognosis is generally worse. One reason for the lack of established treatment is that there are no model systems of this disease. There have been a few reports on cell lines from neuroendocrine tumors, because these tumors are difficult to culture, and there are even fewer reports on colorectal carcinoma cell lines with neuroendocrine features. We therefore attempted to establish a permanent cell line in order to investigate the biological behavior and treatment of NECC. The cell line we succeeded in culturing is called N-TAK1. Gastrin promotes the growth of gastrointestinal epithelial cells and also stimulates the growth of gastrointestinal cancers. Hormone-receptor antagonists restrict the growth of hormone-dependent tumors. The growth of colon cancer was promoted by the application of gastrin, whereas it was restricted by proglumide, which is known to be a gastrin receptor antagonist. We demonstrated that gastrin has a stimulatory effect on the growth of N-TAK1 cells and that it could be detected by immunohistochemistry in the cells. We also showed that proglumide inhibited the growth effect of gastrin.

Animals↗
PubMed2000

Inhibition of TNF-alpha produced by Kupffer cells protects against the nonspecific liver toxicity of immunotoxin anti-Tac(Fv)-PE38, LMB-2.

LMB-2 (anti-Tac(Fv)-PE38) is a recombinant immunotoxin composed of the Fv fragment of the anti-Tac Ab fused to a 38-kDa form of Pseudomonas: exotoxin A. Recent clinical trials showed that LMB-2 is a promising agent for the treatment of patients with Tac-positive leukemia or lymphoma. One major side effect that needs to be overcome is nonspecific liver toxicity. In the current study, we have analyzed the mechanism of this toxicity using a mouse model. Mice that were injected with a lethal dose of LMB-2 showed severe hepatic necrosis. Immunohistochemistry revealed that LMB-2 accumulated in Kupffer cells in the liver, suggesting that the damage to the hepatocytes was indirect. When we examined the effects of LMB-2 on peritoneal macrophages, cells in the same lineage as Kupffer cells, we found that LMB-2 induced the production of TNF-alpha by these cells. Following LMB-2 administration to mice, the levels of TNF-alpha in the liver increased to very high levels, whereas the rise in serum levels was modest. In addition, the LMB-2-induced liver toxicity was blocked by a specific TNF binding protein (TNFsRp55). Liver toxicity was also blocked by indomethacin, which also blocked the rise of TNF-alpha in the liver. Both TNFsRp55 and indomethacin treatment protected mice against a lethal dose of LMB-2. These data indicate that TNF-alpha produced in the liver by Kupffer cells has an important causal role in the nonspecific liver toxicity of LMB-2. These findings have important clinical implications for the use of immunotoxins in the therapy of patients with cancer.

Animals↗
PubMed2000

Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity.

Chemical modification of proteins with polyethylene glycol (PEGylation) can increase plasma half-lives, stability, and therapeutic potency. To make a PEGylated recombinant immunotoxin with improved therapeutic properties, we prepared a mutant of anti-Tac(Fv)-PE38 (LMB-2), a recombinant immunotoxin composed of a single-chain Fv fragment of the anti-human Tac monoclonal antibody to the IL-2 receptor alpha subunit fused to a 38-kDa fragment of Pseudomonas exotoxin. For site-specific PEGylation of LMB-2, one cysteine residue was introduced into the peptide connector (ASGCGPE) between the Fv and the toxin. This mutant LMB-2 (cys1-LMB-2), which retained full cytotoxic activity, was then site-specifically conjugated with 5 or 20 kDa of polyethylene glycol-maleimide. When compared with unmodified LMB-2, both PEGylated immunotoxins showed similar cytotoxic activities in vitro but superior stability at 37 degrees C in mouse serum, a 5- to 8-fold increase in plasma half-lives in mice, and a 3- to 4-fold increase in antitumor activity. This was accompanied by a substantial decrease in animal toxicity and immunogenicity. Site-specific PEGylation of recombinant immunotoxins may increase their therapeutic potency in humans.

Animals↗
PubMed2000

Instability of X chromosome methylation in aberrant crypt foci of the human colon.

Aberrant crypt foci (ACF) in the colon have long been thought to be precancerous lesions and therefore monoclonal, but this is unresolved. Eleven ACF were isolated from five female patients. From these ACF, 178 individual aberrant crypts (ACs) were obtained and assessed for clonality using a method based on X chromosome inactivation of the polymorphic X-linked human androgen receptor (HUMARA) gene. Ten ACF were found to be mixtures of monoclonal and polyclonal types. The HUMARA analysis indicated that almost all ACF were polyclonal lesions. Simultaneously, we investigated K-ras mutations in each AC. We found that seven of the ACF harbored the K-ras mutation; strikingly, this was concordant for all of the ACs from a single ACF. These results, by contrast to the results of HUMARA analysis indicate that ACF lesions are monoclonal. This discrepancy suggests that ACF are apparently polyclonal because of de novo methylation on the active X chromosome. To confirm this possibility, we investigated the methylation status of the X chromosome in male ACF using a competitive PCR assay. One hundred nineteen individual ACs were isolated from eight ACF derived from four male patients. A total of 47 of 119 (39%) of male ACs showed de novo methylation of the HUMARA gene. We found that six of the eight male ACF harbored the K-ras mutation, and this was concordant for all of the ACs from a single ACF. We conclude that X chromosome methylation is unstable in ACF and that this might be an early event in colon carcinogenesis.

Aged↗
PubMed2000

Loss of heterozygosity at 3p24-p25 as a prognostic factor in breast cancer.

Differences in clinical course and biological characteristics among breast cancers will probably be explained ultimately by variations in the pattern of genetic alterations among the many genes that can play roles in carcinogenesis. Loss of heterozygosity (LOH) of a particular chromosomal region in a tumor, which presumably indicates loss of a growth-regulating 'tumor-suppressor' gene in that region, may represent a useful marker for postoperative prognosis. In earlier work we observed LOH at chromosomal regions 3p14-p21 and/or 3p24-p25 in a large proportion of breast cancers. To examine whether allelic losses in either of those regions might correlate with postoperative survival, we tested tumors from a cohort of 504 breast cancer patients for allelic losses of microsatellite markers in the relevant portions of chromosome 3p. Five years postoperatively, patients whose tumors had undergone LOH at 3p24-p25 were found to have borne significantly higher risks of mortality than women whose tumors retained both alleles at that locus; i.e. the 5-year mortality rate was 22% among patients with losses at 3p24-p25 vs. 9% with retentions of heterozygosity at that locus (P=0.0014). These data indicate that LOH at 3p24-p25 is a significant predictive factor for postoperative survival of patients who have undergone surgery for breast cancer.

Adult↗
PubMed2000

Identification of a 1-Mb common region at 16q24.1-24.2 deleted in hepatocellular carcinoma.

To identify the location of one or more putative tumor suppressor genes that may be involved in hepatocellular carcinoma (HCC), we examined 96 such tumors for their patterns of allelic loss at 21 microsatellite marker loci distributed along chromosome arm 16q. Allelic loss at one or more loci was observed in 58 (60%) of these tumors. Detailed deletion mapping identified a distinct commonly deleted region located within an interval flanked by D16S534 and D16S3091 at 16q24.1-24.2. By constructing a physical map consisting of a YAC contig across the region, the extent of the deleted region was determined to be less than 1 Mb. Among the tumors for which clinical data were available, allelic loss at 16q24.1-24.2 was more frequent in tumors arising from liver cirrhosis compared to HCCs arising from chronic hepatitis (30/42, 71%, vs. 13/33, 39%; P = 0. 0054). Additionally, allelic loss at 16q24.1-24.2 was frequently observed in small tumors and early-stage tumors as well as in tumors of more advanced phenotype.

Carcinoma, Hepatocellular↗
PubMed2000

Effect of early postoperative feeding on the healing of colonic anastomoses in the presence of intra-abdominal sepsis in rats.

PURPOSE: Intra-abdominal infection is generally considered a major risk factor for dehiscence of primary colon anastomosis. To elucidate the indications for nutritional support during intra-abdominal sepsis, we investigated the healing of anastomoses in an animal model. METHODS: Twenty male Sprague-Dawley rats (280-320 g) underwent cecal ligation and single puncture. After 24 hours the perforated cecum was removed, and the left colon was transected and anastomosed in a single-layer inverted fashion. Animals were randomly assigned to receive both chow and water (early-fed group; n = 10) or water alone for the first 72 hours and chow thereafter (late-fed group; n = 10). Colon-bursting pressure was measured five days after the anastomosis, at which time the anastomosis was excised. RESULTS: The survival rate after cecal ligation and single puncture was 100 percent, and blood cultures were positive in 20 percent of animals five days after surgery. All data are expressed as means +/- standard error of the mean. Body weight increased more in the early-fed group than in the late-fed group (15.6+/-3 vs. -6.3+/-2.8 g; P < 0.001). Early feeding resulted in increased anastomotic bursting pressure (200+/-11 vs. 161+/-12 mmHg; P < 0.05) and total collagen concentration at the site of anastomosis (2.36+/-0.09 vs. 2.01+/-0.07 microg/mg wet tissue; P < 0.01) compared with the late-fed group. CONCLUSION: Early feeding has a positive effect on anastomotic healing in the presence of intraabdominal sepsis. The mechanism by which early feeding enhances the colonic anastomotic healing is unclear, although preservation of colonic collagen seems to play a significant role.

Anastomosis, Surgical↗
PubMed2000

The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines.

Pancreatic cancer frequently causes extrahepatic cholestasis. To identify the direct effects of bile acids in jaundiced serum on pancreatic cancer, the proliferation of PANC-1 and MIA PaCa-2 cells as well as the ultrastructural alteration of PANC-1 cells cultured in crude bile modified media were studied. The growth of these cells in the RPMI-1640 media with or without 1%, 2%, and 4% of the refined crude bile was assessed after 48 and 96 h of incubation. The ultrastructure of PANC-1 cells was investigated by scanning and transmission electron microscopy after 24 and 48 h of incubation. The proliferation of both cell lines in the bile-treated media was greatly inhibited. The inhibitory rates of bile on PANC-1 ranged from 24.1% +/- 3.3% to 66.9% +/- 6.6% (P < 0.01) and those on MIA PaCa-2 ranged from 16.7% +/- 3.8% to 50.7% +/- 5.5%. (P < 0.01). When the bile-added media were replaced, the cells were able to restore their proliferating ability. The PANC-1 cells incubated in the bile-supplied media indicated that the mirovilli, mitochondria, and other organelles had thus been injured. These results suggest that bile acids appear to inhibit the proliferation of PANC-1 and MIA PaCa-2 cells, and the probable inhibitory mechanism is mainly considered to be due to the cytotoxicity of such bile acids.

Bile Acids and Salts↗
PubMed2000

Reconstruction of the vena cava with the peritoneum.

BACKGROUND: Reconstruction of the vena cava with an autologous vein requires extra incisions. Prosthetic material is associated with an increased risk of infection. We therefore created an animal model of vena cava reconstruction using the peritoneum. METHODS: A 2.5 x 2.5 cm piece of peritoneum was resected from 7 pigs weighing 30 to 40 kg. An oval window (long axis: 1.5 cm) was made in the infrarenal vena cava. This was repaired with the peritoneal patch fixed in alcohol. RESULTS: In 2 animals sacrificed at 5 hours, there was no evidence of thrombosis, but there was fibrin clot on the patches. Two animals sacrificed on day 8 exhibited excellent patency of the vena cava. Complete endothelialization of the patch was noted at day 15. At 6 weeks, the vena cava was healed. No infections or other problems were noted. CONCLUSIONS: The peritoneum is an accessible and safe substitute for reconstruction of the vena cava.

Animals↗