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Biomedical subjects

S Kasai

Publications and source records attributed to S Kasai.

At least 55 records · Page 3Linked to original sources
PubMed1999

Histopathological assessment of multidrug resistance in gastric cancer: expression of P-glycoprotein, multidrug resistance-associated protein, and lung-resistance protein.

Because local recurrence is common after a curative resection for advanced gastric cancer, there has been significant interest in adjuvant chemotherapy. However, the overall effect of chemotherapy remains debatable regarding patients with advanced gastric adenocarcinoma. Multidrug resistance is thought to be a major cause of failure in cancer chemotherapy, and thus the expression of P-glycoprotein (P-Gp), multidrug resistance-associated protein (MRP), and lung-resistance protein (LRP) in tumor cells was evaluated by immunohistochemistry. In 20 gastric adenocarcinomas, 11 (55%), 2 (10%), and 0 (0%) were positive for MRP, LRP, and P-Gp. In malignant lymphomas, only 3 out of 10 cases were positive for MRP (30%). The positive rate of MRP staining was significantly higher in well and moderately differentiated adenocarcinomas (80%) than in poorly differentiated adenocarcinomas (20%). With regard to the degree of MRP expression and histological cell type, higher grades (grade 2-3) were observed only in well and moderately differentiated adenocarcinomas. In terms of the positive-stained cells and staining intensity, heterogeneity was observed in the staining profile of MRP. The proliferative cell nuclear antigen labeling index (PCNA LI) of MRP-positive and MRP-negative cases was 49.3% +/- 11.6% and 49.4 +/- 6.9%, respectively. No correlation was observed between the MRP expression and PCNA LI. In conclusion, the incidence of MRP expression in gastric cancer was the highest in three different multidrug resistance-related epitopes. An evaluation of the MRP expression thus seemed to be beneficial for determining the optimal strategy of chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain.

The whole genome scan for quantitative trait loci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, an established murine model of senile osteoporosis, exhibiting a significantly lower peak bone mass, and SAMP2, exhibiting a higher peak bone mass. Cortical thickness index (CTI), a parameter of bone mass of femurs, was measured in 488 F2 progeny at 4 months of age, when the animals attained peak bone mass by microphotodensitometry. Genetic markers were typed at 90 loci spanning all chromosomes except the Y. By interval mapping of 246 male F2 mice, two loci were identified with significant linkage to peak bone mass, one on Chromosome (Chr) 11 and another on Chr 13, with a maximum lod score of 10.8 (22.2% of the total variance) and 5.8 (10.0%), respectively. Another locus on the X Chr was suggestive of a QTL associated oppositely with a low peak bone mass to the SAMP2 allele. This association was consistent with the distribution of peak bone mass in the F1 and F2. These findings should be useful to elucidate the genetics of osteoporosis.

Animals↗
PubMed1999

Mucin-producing tumors of the pancreas: clinicopathological features, surgical treatment, and outcome.

Mucin-producing tumors (MPTs) of the pancreas are increasingly being recognized. To evaluate the appropriate surgical treatment and predict the prognosis of MPTs, we performed a retrospective clinicopathological study in 51 patients, 27 with benign tumors and 24 with borderline/malignant tumors. Three of the malignant tumors showed stromal invasion and lymph node metastasis on histological examination. Of the 24 patients with borderline/malignant tumors, 2 died of MPTs and 4 died of other diseases. At the last follow-up, 35 patients were alive and well. The 5-year postoperative survival rate was 90% for patients with benign tumors, and 78% of these with borderline/malignant tumors. Five of the patients with borderline/malignant tumors had multicentric tumors. Three of these patients underwent resection of the rest of the pancreas, 5, 6, and 8 years, respectively, after the first operation. Extended radical resection is required for malignant MPT with invasion of the pancreatic stroma. We prefer to perform pancreatogastrostomy or Imanaga's procedure to allow examination of the body and tail of the pancreas by endoscopic retrograde pancreatography after resection of the pancreatic head. Careful follow-up for a long period may be the most prudent approach for detecting multiple MPTs in the residual pancreas after surgical treatment.

Adenocarcinoma, Mucinous↗
PubMed1999

Papillary adenoma of the distal common bile duct.

A 73-year-old man with a papillary adenoma located in the distal common bile duct is reported. He underwent pylorus-preserving pancreatoduodenectomy. The lesion in the common bile duct featured papillary proliferation of the epithelium and fibrous elements with diffuse infiltration by inflammatory cells. Positive staining for MIB-1 (Ki-67) and p53 was identified in the nuclei of the proliferative epithelium. These findings suggested the malignant potential of this lesion. Further progress in imaging diagnostic techniques should increase the frequency with which such lesions are discovered. Even now, if mural irregularities and defects are found in the extrahepatic biliary system, especially the distal common bile duct, the possibility of such borderline biliary adenoma should be taken into consideration when making a diagnosis.

Adenoma, Bile Duct↗
PubMed1999

Prevalence and symptomatology of comorbid obsessive-compulsive disorder among bulimic patients.

This study sought to assess the prevalence and symptomatology of comorbid obsessive-compulsive disorder (OCD) among Japanese subjects who met the DSM-III-R criteria for bulimia nervosa (BN). The Structured Clinical Interview for DSM-III-R Patient Version was used to distinguish 26 BN patients with concurrent OCD from 52 BN patients without OCD. Obsessive-compulsive symptoms in BN subjects with concurrent OCD were evaluated using the Japanese version of the Yale-Brown Obsessive-Compulsive Scale. There were no differences in the prevalence of concurrent OCD between BN subjects with and without a lifetime history of anorexia nervosa. Among BN subjects with concurrent OCD, symptoms related to symmetry and order were most frequently identified, followed by contamination and aggressive obsessions, and checking and cleaning/washing compulsions. Bulimia nervosa subjects with concurrent OCD were more likely than subjects without OCD to have more severe mood and core eating disorder psychopathology. Comorbid OCD is a common phenomenon in Japanese bulimics (33%) similar to that suggested in BN subjects in the Western countries. Obsessive-compulsive symptoms related to symmetry and order were most frequently observed in BN subjects with concurrent OCD, which was a similar finding to that reported among restricting anorexic subjects.

Adult↗
PubMed1999

Occurrence of P-flavin binding protein in Vibrio fischeri and properties of the protein.

In previous studies involving Photobacterium species we proposed that (i) P-flavin is the product of luciferase, (ii) the physiological function of the lux operon is not to produce light but to produce FP(390) (luxF protein), including its prosthetic group, P-flavin, and (iii) FP(390) reactivates oxidatively inactivated cobalamin-dependent methionine synthase similar to flavodoxin but at relatively high ionic strength. It seems difficult to extend this idea to all luminous bacteria because the luxF gene is not present in the lux operon in Vibrio or Xenorhabdus. But we predicted that a luciferase fragment which binds P-flavin should function like FP(390) in these species. In this study, we isolated P-flavin binding protein from Vibrio fischeri ATCC 7744. The obtained protein was a modified luciferase as expected, in which the beta-subunit was intact but about 25 amino acid residues at the C-terminus of the alpha-subunit were deleted and the prosthetic group was the fully reduced P-flavin. These results strongly support that the physiological function of the lux operon is as described above even in luminous bacteria other than Photobacterium species. We propose that chromophore B reported by Tu and Hastings [Tu, S.-C. and Hastings, J.W. (1975) Biochemistry 14, 1975-1980] is the reduced P-flavin.

Amino Acid Sequence↗
PubMed1999

Prolonged function of hepatocytes transplanted into the spleens of Nagase analbuminemic rats.

Hepatocytes isolated from F344 rats were transplanted into the spleens of congenic Nagase analbuminemic rats (NARs). The morphology and function of the transplanted hepatocytes were investigated after 18 months. The hepatocytes had formed nodules that occupied approximately 35% of the area of the splenic parenchyma on microscopic examination. Ultrastructural examination demonstrated that the organelles of the transplanted cells were indistinguishable from those of normal hepatocytes. The serum albumin level in NARs at 18 months after intrasplenic transplantation (HCTx) was about 3.6% of that in normal rats. We confirmed that the hepatocytes in the spleen produced albumin and increased the serum albumin level in NARs with HCTx. The NAR model demonstrates the effect of HCTx and prolonged changes in the morphology of the hepatized spleen.

Animals↗
PubMed1999

Angiolipoma of the colon with right lower quadrant abdominal pain.

BACKGROUND/AIM: An angiolipoma is a common benign neoplasm with a characteristic vascular component that occurs in the subcutaneous tissue and rarely in the gastrointestinal tract. We report on a 69-year-old man with a submucosal angiolipoma in the cecum. METHODS: This patient was treated with a laparoscopy-assisted ileocecostomy, and a side-to-side anastomosis was performed extracorporeally. RESULTS: A light microscopic study supported the diagnosis of an angiolipoma of the colon. After 5 years of follow-up, the patient has no symptoms or signs of recurrence. CONCLUSION: The colonic angiolipoma was successfully removed using a minimally invasive laparoscopic technique.

Abdominal Pain↗
PubMed1999

[Peripheral 5-FU blood concentration after high-dose injection into the hepatic artery: potential preventive effect on extrahepatic metastatic foci].

To clarify the effect of high-dose 5-FU injection into the hepatic artery (1,000 mg/m2 weekly) on liver metastases of colorectal cancer, the peripheral venous 5-FU concentration was measured in two groups of patients, one which had undergone hepatectomy and the other which had not. The area under the concentration-time curve (AUC) was calculated and the preventive effect of 5-FU on extrahepatic lesions was examined. The peripheral venous 5-FU concentration and AUC were higher in patients who received the drug via the hepatic artery after hepatectomy, and 5-FU was effective for the prevention of extrahepatic lesions as well as against recurrence in the residual liver.

Adult↗
PubMed1998

TX-1877: design, synthesis, and biological activities as a BRM-functional hypoxic cell radiosensitizer.

PURPOSE: 2-Nitroimidazole acetamide TX-1877 and its derivatives (TX-1877 analogs) were designed, synthesized, and evaluated by their in vitro and in vivo radiosensitization, tumor growth control, suppression of lung metastasis, and immunopotentiation, as biological response modifier (BRM)-functional hypoxic cell radiosensitizers. MATERIALS AND METHODS: TX-1877 analogs were designed and synthesized in our laboratory. In vitro radiosensitizing ability was estimated using EMT6/KU cells under hypoxic conditions. In vivo radiosensitization, antimetastasis, and immunopotentiation were evaluated using female C3H/He mice bearing the SCCVII tumor. Days (15 or 10) after the inoculation of 10(5) SCCVII tumor cells into the hinder thigh, a drug (0.4 mg/g) was administered i.p. and local irradiation of 30 Gy was given at 30 min after its administration. Tumor growth was observed for 20 days and mice were euthanized to count the number of metastatic nodules on the surface of the lungs. Tumor tissues were extirpated and stained by the ABC method at 1, 2, and 3 weeks after treatment for immunological evaluation. RESULTS: Novel types of bifunctional radiosensitizers, TX-1877 and its analogs possessing BRM-functions (i.e., antimetastatic and immunopotentiation effects) were developed. In vitro radiosensitizing abilities of TX-1877 and its analogs, with their partition coefficient values of more than 0.050, were comparable to misonidazole (MISO) at their doses of 1 mM. Tumor regrowth was suppressed evidently 20 days after the treatment in the irradiated group with TX-1877 (TX-1877 plus R) and with KIN-806 (KIN-806 plus R). The former group reduced markedly the mean number of metastatic lung nodules regardless of radiation therapy. TX-1877 and KIN-806 plus R induced helper T lymphocytes. The TX-1877, TX-1877 plus R, KIN-806, and KIN-806 plus R enhanced macrophage infiltration for 3 weeks after treatment. CONCLUSION: TX-1877 is an excellent BRM-functional hypoxic cell radiosensitizer, expected to be useful for clinical use.

Animals↗
PubMed1998

Fatty acid omega and (omega-1)-oxidation within intrasplenically transplanted fetal hepatocytes.

BACKGROUND: The expression and enzymatic activity of the cytochrome P450 LAomega within intrasplenically transplanted hepatocytes was investigated. METHODS: Fetal hepatocytes were harvested from spontaneously hypertensive rats and transplanted into recipient adult spontaneously hypertensive rat spleens. RESULTS: Microscopic examination revealed masses of hepatocytes in the red pulp. Immunochemical studies detected cytochrome P450 LAomega in transplanted hepatocytes by 6 and 10 weeks after transplantation. Cytochrome P450 LAomega mRNA accumulates at 6 weeks after transplantation. Cytochrome P450-arachidonic acid omega/omega-1 hydroxylase activity (formation of 20/19-hydroxyeicosatetraenoic acid) was detected at 10 weeks after transplantation. CONCLUSION: These results demonstrated that fetal hepatocytes grow in the spleen and function similarly to adult hepatocytes.

Animals↗
PubMed1998

In vitro metabolism of pyriproxyfen by microsomes from susceptible and resistant housefly larvae.

Levels of cytochrome P450 and b5 were investigated in microsomal enzymes of houseflies from the gut and fat body of the third instar larvae of a pyriproxyfen-resistant strain (YPPF) and two pyriproxyfen-susceptible strains (YS and SRS). In comparison to the YS and SRS strains, YPPF microsomes had higher levels of total cytochrome P450s in both the gut and fat body. Furthermore, microsomes from the gut and fat body of YPPF larvae were found to have a much greater ability to hydroxylate aniline than YS larvae. In vitro metabolism studies of pyriproxyfen indicated that the metabolic rates were much higher in both the gut and fat body of YPPF larvae than of YS and SRS larvae. The major metabolites of pyriproxyfen in houseflies were identified to be 4'-OH-pyriproxyfen and 5"-OH-pyriproxyfen. Cytochrome P450 inhibitors, piperonyl butoxide (PB) and 2-propynyl 2,3,6-trichlorophenyl ether (PTPE), decreased the metabolic rates significantly in all three strains. This study confirmed that microsomal cytochrome P450 monooxygenases play an important role in the pyriproxyfen resistance of the housefly. Furthermore, it suggests that the fat body must be as important as the gut for the metabolism of pyriproxyfen in resistant housefly larvae.

Adipose Tissue↗
PubMed1998

Multiporous cellulose microcarrier for the development of a hybrid artificial liver using isolated hepatocytes.

BACKGROUND: This study was aimed at developing an optimal method for immobilizing isolated hepatocytes in cellulose multiporous microcarriers (MCs) and evaluating the metabolic activity of MC-immobilized hepatocytes. MATERIALS AND METHODS: Hepatocytes isolated from the livers of male Wistar rats were immobilized in collagen-coated MCs by intermittent stirring (30 rpm for 2 min per 15 min) for 180 min or accumulation methods. The accumulation method was performed by pouring aliquots of hepatocyte suspension (8 x 10(5)) and MC suspension (1 mg) in turn onto a nylon mesh (pore size: 100 micron). The metabolic activity of MC-immobilized hepatocytes in floating culture and in a newly developed bioreactor was evaluated. The metabolic activity of MC-immobilized hepatocytes in the bioreactor was also evaluated in in vitro perfusion of a hollow-fiber-based hybrid artificial liver support system. RESULTS: The accumulation method immobilized 20 times more hepatocytes in collagen-coated MCs than the intermittent stirring method (P < 0.01). Morphological observation of hepatocyte-immobilized MCs revealed that many hepatocytes were immobilized deep within the MCs maintaining a spherical shape and normal microvilli on their surface. MC-immobilized hepatocytes in floating culture revealed similar NH3 metabolism and glucose synthesis to monolayer-cultured hepatocytes, and this metabolic activity was maintained during 9h of floating culture. MC-immobilized hepatocytes in a bioreactor also showed similar NH3 metabolism to monolayer-cultured hepatocytes. The NH3 metabolism of MC-immobilized hepatocytes in in vitro perfusion of a hybrid artificial liver support system was 241.5 microg/h/mg protein/m2 membrane surface. CONCLUSIONS: The results of this study indicate that the accumulation method was optimal for immobilizing isolated rat hepatocytes in MCs and that MC-immobilized hepatocytes maintained their metabolic activity for a long period.

Ammonia↗
PubMed1998

Nitric oxide release from the liver surface to the intraabdominal cavity during acute endotoxemia in rats.

Nitric oxide (NO) is produced by the liver during lipopolysaccharide (LPS)-induced endotoxemia. The aim of this study was to examine whether NO, which is produced in the liver, is released from the liver surface to the intraabdominal cavity during endotoxemia. NO was quantitatively determined by chemiluminescence and a newly developed gas purge technique was used to directly measure NO released from the liver surface and the intraabdominal cavity of rats before and after LPS (0.1 mg/kg, intraperitoneally) or saline administration. The expression of inducible NO synthase (iNOS) mRNA in the liver was detected by Northern blot analysis. NO levels from both the liver surface and in the intraabdominal cavity were elevated at 2 h after LPS injection and peaked at 10 h and both the time course of NO level were well correlated with each other. Both NO levels were below the detectable range before LPS and after saline administration. Inducible NOS mRNA in the liver exhibited a sharp increase to a maximum level at 4 h after LPS injection. The present study indicates that the hepatic NO, which might have been produced by iNOS in the liver, is released from the liver surface to the intraabdominal cavity during endotoxemia.

Acute Disease↗