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Biomedical subjects

K Aoyagi

Publications and source records attributed to K Aoyagi.

At least 55 records · Page 3Linked to original sources

Hemodialysis does not influence the peroxidative state already present in uremia.

Hemodialysis (HD) patients are exposed to high oxidative stress, however, the nature of this stress is still unclear. In this study, we employed a specific lipid peroxidative product, phosphatidylcholine hydroperoxide (PCOOH), and evaluated the peroxidative effect of end stage renal disease by measuring thiobarbituric acid reactive substances (TBARS) and PCOOH in both plasma and erythrocyte membrane. We also surveyed plasma TBARS and PCOOH before and after HD sessions thereby assessing oxidative stress by a single HD procedure. The plasma TBARS level of healthy controls was 2.9 +/- 0.4 nmol/ml. Those of HD patients before and after HD session were 5.1 +/- 1.4 and 3.1 +/- 0.5 nmol/ml, respectively, and the pre-HD plasma TBARS levels were significantly higher than those of controls and after HD. The plasma PCOOH concentration of patients before HD was 119.7 +/- 58.4 pmol/ml and was significantly higher than that of controls which was 88.6 +/- 14.3 pmol/ml. After HD, the plasma PCOOH level decreased to 103.2 +/- 36.0 pmol/ml, which was still significantly higher than that of controls. In erythrocytes, the PCOOH level of patients was 259.3 +/- 105.4 nmol/g RBC and was significantly higher than that of controls with 88.6 +/- 32.0 nmol/g RBC. Analyzed with respect to the cause of renal disease, the polycystic kidney disease patients showed significantly lower plasma PCOOH levels than the others. These results suggest that there is an increase of lipid peroxidation in both plasma and erythrocytes of HD patients, though this oxidative stress was not brought about by HD.

Erythrocyte Membrane↗

Unresectable advanced gastric cancer effectively treated by combined chemo-immunotherapy: a report of two cases.

We have experienced two cases of unresectable advanced gastric cancer effectively treated by chemo-immunotherapy. One case was of a 68-year-old male patient diagnosed as having inoperable advanced gastric cancer with liver and lung metastasis. This patient was treated by combined chemo-immunotherapy of MMC 10 mg/M, 5'-DFUR 800 mg/day and OK-432 5 KE/2W. At 6 months later, a computed tomography (CT) scan and upper gastrointestinal (GI) series revealed that the metastatic liver tumors and stomach lesion were remarkably decreased in size, and endoscopic biopsy confirmed no cancer cells in the stomach lesion. Moreover, the metastatic lung tumor had disappeared on chest X-ray. The other case was of a 68-year-old female patient with unresectable advanced gastric cancer treated by combined administration of MMC 10 mg/M, 5-FU 200 mg/day and OK-432 5 KE/2W. At 2 months after commencing the treatment, there was a reduction in the serum carcinoembryonal antigen (CEA) level. At 6 months later, the CEA had decreased to normal, the primary and metastatic sites had completely disappeared on CT, and endoscopic biopsy confirmed no cancer cells in the stomach lesion. This patient has survived to date for 5 years and 6 months after commencing the treatment. These results suggested that combined chemo-immunotherapy of MMC, antimetabolite, and OK-432 was an effective treatment for unresectable advanced gastric cancer.

Aged↗

Immunohistochemical study on the expression of cyclin D1 and E in gastric cancer.

Cyclin D1 and E have been found to be deregulated and overexpressed in various types of cancers. In order to study the cell cycle regulatory mechanisms in gastric cancer, we have analyzed the protein expression of cyclin D1 and cyclin E in 76 tumor specimens from patients with primary gastric cancer, using immunohistochemistry. Overexpression of cyclin D1 was observed in 38 cases (50.0%). Overexpression of cyclin E was observed in 40 cases (52.6%). There was no significant difference between the expression of cyclin D1 and any clinicopathological factor. Cyclin E overexpression was correlated with a high incidence of lymph node metastasis, a low incidence of T1, and with Stage I. There was no significant difference in survival curves between cyclin D1 (+) and cyclin D1 (-). The survival curves of cyclin E (-) were significantly higher than those of cyclin E (+). These results suggested that in gastric carcinoma, cyclin E overexpression was useful as a prognostic indicator, but cyclin D1 was not.

Cyclin D1↗

Two cases of cancer in the remnant stomach derived from gastritis cystica polyposa.

We have recently encountered two patients with early gastric cancer in the remnant stomach which resulted from gastritis cystica polyposa at the anastomosis site. The remnant stomach, which had been reconstructed with the Billroth II method, contained an elevated sessile lesion at the anastomosis site. One patient was a 73-year-old woman who had undergone gastrectomy for a gastric ulcer at 30 years earlier, cancer type I + IIa of the remnant stomach was diagnosed, and total remnant gastrectomy was performed. The other patient was a 59-year-old man who had undergone gastrectomy for a duodenal ulcer at 31 years earlier, cancer type I + IIa of the remnant stomach was diagnosed, and subtotal remnant gastrectomy was performed. Histological examination in each case showed that moderately differentiated adenocarcinoma had developed from gastritis cystica polyposa. These results suggested that this cancer has a close relationship with gastritis cystica polyposa.

Aged↗

Morphological change in the MNNG-treated rat gastric mucosa.

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of the gastric mucosa from both MNNG-treated and control rats were histologically examined every 2 months, for 10 months. In 40% of the MNNG-treated rats, atrophy in the gastric mucosa was observed after 2 months, and regenerative epithelium was observed after 4 months, followed by adenomatous proliferation and disappearance of the tight junction electron microscopically after 6 months. A small intestinal cancer had developed in 2 rats at 6 months. While gastric cancer had developed in 3 rats at 8 months, and in one of these 3 rats, peritoneal dissemination was observed macroscopically and histologically. These results suggested that adenomatous proliferation and disappearance of the tight junction observed electron microscopically were characteristic pathological features of precancerous lesions in the stomach in MNNG-treated rat.

Animals↗

Advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-FU, MMC and peroral administration of 5-FU: a case report.

We have experienced a case of advanced gastric cancer with liver metastasis effectively treated by intra-hepatic arterial infusion of 5-fluorouracil (5-FU), mitomycin C (MMC) and peroral administration of 5-FU. The patient was a 48-year-old male diagnosed as having advanced gastric cancer with multiple liver metastasis in the bilateral lobes of the liver. This patient was treated by intra-hepatic arterial infusion of 5-FU (250 mg/2 days x 8 doses), MMC (20 mg x 1 dose, 6 mg/2 weeks x 6 doses) and peroral administration of 5-FU (200 mg/day). At 14 weeks later, a CT revealed that the metastatic liver tumors had disappeared. However, at 7 months after the therapy, the patient eventually died of liver and brain metastasis. These results suggested that intra-hepatic arterial infusion of 5-FU and MMC was an effective therapy for metastatic tumors in the liver, but we need to perform intra-hepatic arterial infusion using a new prolonged regimen to treat the liver metastasis.

Administration, Oral↗

Multiple carcinoids in the stomach with hypergastrinemia and type A gastritis: a case report.

We have experienced a case of the stomach with hypergastrinemia and type A gastritis with multiple carcinoids in a 37-year-old woman. An upper gastrointestinal series revealed multiple minute polyps in the upper body of the stomach. All polyps were diagnosed as carcinoid using endoscopic biopsies. She had neither symptom or signs of typical carcinoid disease. The serum gastrin level was as high as 725 pg/ml. Total gastrectomy was performed, and the diagnosis of multiple gastric carcinoids (sm, no) with type A gastritis was histologically confirmed. After the operation, the serum gastrin level returned to normal, and the patient has been doing well and is disease-free to date at 7 years after the operation. This case suggested that multiple gastric carcinoid lesions may be precipitated by chronic atrophic gastritis accompanying hypergastrinemia. In the treatment of multiple gastric carcinoids with type A gastritis, total gastrectomy with lymph node dissection should be standard operative procedure, in order to resect the fundic gland area completely which could be the origin of carcinoids and endocrine cell micronest.

Adult↗

Primary gastric lymphoma: a clinicopathological study.

A retrospective study of 25 patients treated for primary gastric lymphoma was made to investigate a number of problems related to treatments and report the factors influencing prognosis. In the 5-year-survival rate according to Working Formulation classification, either survival rate of low-grade type or intermediate-grade type was higher than that of high-grade type. Both the 5-year-survival rate of cases without lymph node metastasis and that of cases that involved perigastric lymph nodes were higher than that of cases that involved distant gastric lymph nodes. Those surviving five years after perigastric lymph node metastasis had received D3 or D4 dissection and postoperative multicombined chemotherapy. Tumors invading only to the submucosal layer had received D2 dissection and were not treated by postoperative multicombined chemotherapy, and recurrence was not recognized in these cases. Of 9 cases infiltrating into the musclaris propria or serosa without lymph node metastasis, 8 cases were treated by postoperative multicombined chemotherapy and were alive without recurrence, but one case without postoperative multicombined chemotherapy died by recurrence. Therefore, adequate therapy for gastric lymphoma with infiltrating into submucosal layer is gastrectomy with D2 lymph node dissection, and postoperative multicombined chemotherapy is not necessary. The cases with perigastric lymph node metastasis, or the cases with invading from muscularis propria to serosa require D3 or D4 lymph node dissection with postoperative multicombined chemotherapy. But the cases with distant gastric lymph node metastasis or invading adjacent structure or high-grade type histologically (WF classification) require preoperative chemotherapy.

Humans↗

[Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice].

We investigated the effects of UFT and its metabolites, GHB and GBL, on angiogenesis induced by tumor cells in a dorsal air sac (DAS) assay in mice. Five tumor cell lines (murine renal carcinoma; RENCA, human gastric cancer; 4-1ST, human small-cell lung carcinoma; LX-1, and human colon carcinoma; DLD-1, KM-20C) were used in the DAS assay. In this model, UFT demonstrated a significant anti-angiogenic activity in a dose-dependent manner while 5-FU (19 mg/kg/day) and 5'-DFUR (200 mg/kg/day) were less effective. Moreover, tegafur (FT), a component of UFT, and gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL), in vivo metabolites of UFT, inhibited angiogenesis induced by RENCA cells. The inhibitory effects of 5-FU, GHB, and GBL on angiogenesis were increased with administration by continuous infusion, providing a suitable pharmacokinetic profile. These results suggest that GHB and GBL are involved in the expression of anti-angiogenic activity of UFT.

4-Butyrolactone↗

[Work load analysis for oral care in special nursing homes].

The work load analysis for oral care in special nursing homes. Dental hygienists undertook oral care of 100 person who were confined to special nursing homes in Aichi prefecture, Japan. The time required, the physical load, the psychological burden were analysed. The results were summarized as follows; 1) Oral care by dental hygienist was incorporated as one of the 59 care tasks given in special nursing. 2) The working time for required oral care was 25.7 minutes per resident on an average. 3) In general, speaking to the elderly, recording on an assessment card, and observing conditions were undertaken most frequently. In oral care, tooth cleaning, gargling, cleaning of dentures, wiping of the mouth and advising those caring for the elderly, was performed most frequently. 4) In general, time taken for advising those caring for the elderly, report to the home dentistry, advising the elderly, recording, and evaluation was most common. In oral care by a dental hygienist, tooth cleaning, cleaning of the dentures, cleaning the mouth, gargling, prevention of dryness of the mouth were performed most frequently. 5) In physical activity, raising the person, moving him from the wheelchair to the bed and helping him to lie down were most frequent. In oral care by a dental hygienist, wiping the mouth, inserting dentures, tooth cleaning, cleaning the mouth and removing dentures were most common. 6) The psychological burden when lifting the person, moving him from the bed to the wheelchair and helping him to lie down was the greatest. In burden involving oral care by a dental hygienist, tooth cleaning, removing dentures, inserting dentures and cleaning the mouth were the greatest.

Homes for the Aged↗

UFT and its metabolites inhibit cancer-induced angiogenesis. Via a VEGF-related pathway.

Treatment with UFT for spontaneous lung metastasis of murine renal carcinoma (RENCA) after resection of the primary tumor has resulted in significant prolongation of the life span of tumor-bearing animals. UFT inhibited the growth of metastatic nodules in the lung, apparently via decreased density of microvessels in the metastatic foci. Subsequent experiments used dorsal air sac assay to directly trace newly forming microvessels. UFT abrogated the process of angiogenesis, induced by the RENCA cells, in a dose-dependent manner. The inhibitory effect appeared to originate from tegafur, a component of UFT, and from its known metabolites: fluorouracil (5-FU), gamma-hydroxybutyric acid (GHB), and gamma-butyrolactone (GBL). The inhibition of angiogenesis by UFT appeared to be a common phenomenon, also observed in other human cancer cell lines characterized by an excessive production of vascular endothelial growth factor (VEGF)--such as gastric, lung, and colon cancers. In vitro analysis revealed that 5-FU and gamma-hydroxybutyric acid regulated VEGF-dependent responses of human umbilical vein endothelial cells. Dorsal air sac assay revealed that UFT, 5-FU, and gamma-hydroxybutyric acid strongly inhibited the angiogenesis induced by recombinant human VEGF. These data suggest that the antiangiogenic activity of UFT is at least partially associated with an ability of the metabolites of UFT to interfere with VEGF-dependent responses of vascular endothelial cells.

Air Sacs↗

Specific distribution of TOP-53 to the lung and lung-localized tumor is determined by its interaction with phospholipids.

We have investigated the mechanism of TOP-53 distribution to the lung and lung-localized tumor. In contrast to etoposide (VP-16), TOP-53 contains a basic aminoalkyl group that may predispose it to interact specifically with phospholipids, consequently leading to an increase of drug accumulation in the tissues. Therefore, we have studied its interaction with phospholipids in vitro using an organic solvent-water partition system. TOP-53 appeared to have the most potent binding affinity (Ka = 563 x 10(-2) microM) to phosphatidylserine (PhS), whereas VP-16 showed no interaction with any phospholipid tested. PhS content determined after HPLC separation varied among tested tissues; however, large quantities were found in normal lung and lung cancer tissues far exceeding those present in the liver and kidney. The predicted tissue-to-plasma partition coefficient values, estimated based on PhS content and its binding affinity, resembled those experimentally determined. We concluded that tissue distribution of TOP-53 is determined by PhS content in the tissues and by binding affinity. As a result of specific accumulation in the lung, TOP-53 appeared to show a strong antitumor activity (increase of life span = 171%) against cancer metastasizing to the lung, whereas VP-16 was less effective (increase of life span = 78%). These results suggest that TOP-53 may have an advantage over VP-16 in the treatment of lung cancers in patients.

Animals↗

Specific cell-mediated immunity in fish.

This review describes the fish immune system, focusing on specific cell-mediated immunity. Specific in vivo cell-mediated immune responses have been shown by allograft rejection, graft-versus-host reaction (GVHR) and delayed hypersensitivity reaction (DTH). Recent in vitro studies also showed specific cell-mediated cytotoxicity against allogeneic target cells. These in vivo and in vitro experiments strongly suggest the presence of cytotoxic T cells in fishes. Also described are current studies on shark and trout MHC class I polymorphism and function that demonstrate strong similarities between fish and mammals.

Animals↗

Novel exons located more than 200 kb downstream of the previously described 3' exon of the K-sam gene for generating activated forms of KGF receptor.

The K-sam gene was first identified as an amplified gene in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. We have recently found and reported that the carboxyl-terminal exons of K-sam are frequently deleted in the scirrhous type of gastric cancer. The deletion generates preferential expression of at least six novel K-sam-II mRNAs: K-sam-IIH1, -IIH2 and -IIH3/O4, and K-sam-IIO1, -IIO2, and -IIO3, which encode novel proteins lacking the transformation-inhibitory sequence or activated K-sam proteins. In this study, we investigated expression of the previously described K-sam-IIC1 and -IIC3 mRNAs and the novel six K-sam-II mRNAs in 14 gastric cancer cell lines, 7 breast cancer cell lines, and 20 human normal tissues. All the six novel K-sam-II mRNAs were expressed preferentially in the cell lines derived from the scirrhous type of gastric cancers but not in the 7 breast cancer cell lines and the 20 human normal tissues. We further determined the positional relationship of four exons of H1, O1, O2, and O3 out of the six exons of H1, H2, H3/O4, O1, O2, and O3, and found that these four novel K-sam exons were located more than 200 kb downstream of the previously described carboxyl-terminal exon of the K-sam gene. Expression of K-sam-IIH1, -IIO1, and -IIO2 mRNAs encoding activated K-sam products in the scirrhous type of gastric cancer cell lines HSC39, OCUM2M, HSC59, and HSC60 was not due to the deletion of the C1 exon of K-sam.

Amino Acid Sequence↗

Can quinolones cause hemorrhagic colitis of late onset? Report of three cases.

PURPOSE: This study was undertaken to demonstrate that quinolones may cause acute colitis resembling penicillin-induced hemorrhagic colitis. METHODS: We reviewed the medical records of patients with acute colitis in our institutes. Twenty-eight patients with acute hemorrhagic colitis in which no pathogenic microorganisms were identified were the subjects of this study. Pseudomembranous colitis caused by Clostridium difficile was excluded. Ulcerative colitis, Crohn's disease, and radiation proctocolitis were also excluded. RESULTS: Among these patients, 25 had a history of recent administration of penicillin derivatives. The remaining three patients had never been given any penicillin derivatives, but had ingested quinolones approximately four weeks before the developing colitis had been identified. Klebsiella oxytoca was also isolated in these three patients. CONCLUSIONS: Quinolones may cause acute hemorrhagic colitis. The time interval from antibiotic ingestion to onset of the condition may be much longer in quinolones than in penicillin derivatives.

Acute Disease↗