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Biomedical subjects

Y Saitoh

Publications and source records attributed to Y Saitoh.

At least 217 records · Page 12Linked to original sources
PubMed1997

Influences of dietary omega-3 polyunsaturated fatty acids on the recovery of cardiac and renal functions after preservation in hyperlipidemic rats.

BACKGROUND: The effects of a soybean oil diet and a high-cholesterol oil (HC) diet, and an HC diet with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) supplementation, on basal and postpreservative cardiac function of the hearts and on postpreservative renal function of the kidneys from older rats were examined. METHODS: Groups 1 through 4 of 100-week-old rats were fed either soybean oil, HC, HC with EPA, or HC with DHA, respectively, for 12 weeks. Blood was collected for analysis of plasma fatty acids, and the heart and left kidney were removed from the rat. In experiment 1, the heart was perfused on a Langendorff apparatus. After evaluation of the cardiac function of each rat, the heart was stored in histidine-tryptophan-ketoglutarate solution for 8 hr at 4 degrees C. The heart was reperfused and the recovery of cardiac function was evaluated. The coronary perfusate during reperfusion was collected to measure 6-keto prostaglandin F1alpha and thromboxane B2. Coronary flow (CF) perfused with Krebs-Henseleit bicarbonate (KHB) solution containing 5-hydroxytryptamine (5-HT) and nitroglycerin were evaluated in the Langendorff mode with atrial pacing (330 beats/min). In experiment 2, the excised left kidney was immediately flushed and preserved with University of Wisconsin solution for 8 hr at 4 degrees C. The kidney was then reperfused with KHB solution and renal function was evaluated. RESULTS: The plasma and cardiac EPA levels in group 3 were significantly higher than the levels found in the other groups. The plasma and cardiac ratios of EPA to arachidonic acid were significantly higher in groups 3 and 4 than in groups 1 and 2. There were no significant differences in basal cardiac function among any of the diet-fed rats. The percentage values of the recovery of aortic flow, cardiac output (CO), and left ventricular max dp/dt in group 3 and CO in group 4 were significantly higher than in group 2. In addition, the recovery of CF in group 3 tended to be higher than in group 2 (P=0.07). The percentage values of the recovery of aortic flow, CF, CO, and left ventricular max dp/dt in group 1 were significantly lower than in the other dietary groups. CF reperfused with KHB solution containing 5-HT was significantly higher in group 3 than in groups 1 and 2. CF reperfused with KHB solution containing 5-HT was significantly higher in group 4 than in group 1. CF reperfused with KHB solution containing nitroglycerin in group 3 tended to be higher than in groups 1 and 2 (P=0.07). The thromboxame B2 concentrations in the coronary perfusate during reperfusion in groups 3 and 4 were significantly lower than in groups 1 and 2. Fractional sodium reabsorption in group 3 was significantly higher than in group 2. Inulin clearance in groups 3 and 4 was significantly higher than in group 1. The postpreservative urinary flow in group 3 was significantly higher than in groups 1 and 2. The urinary flow was significantly higher in group 4 than in group 1. CONCLUSIONS: These results suggest that EPA administration may attenuate preservation and reperfusion injury and improve the recovery of cardiac and renal functions in hyperlipidemic and older rats. DHA administration may also show beneficial effects on kidney preservation in hyperlipidemic rats.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis.

We have isolated a novel cDNA, vesl, that was induced during convulsive seizure in the rat hippocampus. The vesl gene encodes a protein of 186 amino acids that has significant homology to the EVH1 domain of the VASP/Ena family of proteins implicated in the control of microfilament dynamics. The expression of vesl mRNA was induced in the granule cell layer during persistent long-term potentiation (LTP) of the dentate gyrus in an NMDA receptor-dependent manner. Furthermore, vesl mRNA was expressed at a high level during hippocampal synaptogenesis. We suggest that the Vesl protein may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development.

Amino Acid Sequence↗
PubMed1997

Relationship between the phenotypes of circulating erythrocytes and cultured erythroblasts in paroxysmal nocturnal hemoglobinuria.

To investigate erythropoiesis in paroxysmal nocturnal hemoglobinuria (PNH), we studied the expression of glycosylphosphatidylinositol (GPI)-anchored membrane proteins on circulating erythrocytes and erythroblasts obtained by erythropoietic cell culture in nine patients with this disease. One-color and two-color flow cytometric analyses were performed using monoclonal antibodies for decay-accelerating factor (DAF) and/or CD59/membrane attack complex-inhibitory factor (MACIF). In addition, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) analysis was performed to assess apoptosis of erythroblasts from six patients. On flow cytometric analysis, cases 1 to 6 had positive and negative erythrocyte populations, case 7 intermediate and negative populations, case 8 positive, intermediate, and negative populations, and case 9 a single double-negative population. In addition, cases 1 to 6 and 8 had positive, intermediate, and negative erythroblast populations, while cases 7 and 9 had intermediate and negative populations. The percentage of double-negative erythrocytes showed a significant correlation with that of double-negative erythroblasts (r = .741, P < .05). In seven of nine patients, more erythroblasts than erythrocytes were negative for the two membrane proteins. Also, some patients with an intermediate population of erythrocytes did not necessarily show an increase of PNH II erythroblasts. Apoptosis of PNH erythroblasts was also detected, but the percentage of apoptotic cells in PNH patients showed no difference from that in healthy volunteers. These findings suggest that the final phenotype of mature erythrocytes in PNH is determined during maturation from erythroblasts to erythrocytes by the disappearance or persistence of PNH II erythroblasts. In addition, PNH erythroblasts in vitro may be partly lost by apoptosis, but apoptosis does not play an important role in determining GPI-linked protein expression.

Adult↗
PubMed1997

Analysis of the Rb gene and cyclin-dependent kinase 4 inhibitor genes (p16INK4 and p15INK4B) in human ovarian carcinoma cell lines.

In the present study, we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular biology techniques. For the Rb gene, in all six cell lines (PA-1, Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), Rb gene abnormality was not detected using Southern blotting. In the Caov-3 cell line transcripts were not detectable by either Northern blot or polymerase chain reaction. Sequence analysis of the entire coding region of the Rb gene revealed point mutations (AAC to GAC) resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell line. In the PA-1 cell line both wild-type Rb and mutant-type Rb (codon 798: CGG to TGG) were expressed, and in the OVCAR-3 cell line both wild-type Rb and mutant-type Rb (codon 704: ATG to GTG) were expressed. In four of six human ovarian carcinoma cell lines Rb gene abnormality was detected. For the p16INK4 and p15INK4B genes, only the SK-OV-3 cell line had abnormalities. There was a gene rearrangement or minor deletion of the p16INK4 gene in the SK-OV-3 cell line, while the p15INK4B gene was deleted in this cell line. In the SK-OV-3 cell line no mRNAs of p16INK4 and p15INK4B were expressed. At the point of Rb gene inactivation, we can explain five cell lines of six: four cell lines had abnormalities in the Rb gene itself, which is another mechanism by which the Rb gene is inactivated, while one cell line (SK-OV-3) had abnormalities in CDK4 inhibitor genes, another of the inactivation mechanisms of the Rb gene. These data suggest that abnormalities of Rb and CDK4 inhibitor genes (p16INK4, p15INK4B) may be involved in human ovarian carcinogenesis.

Carcinoma↗
PubMed1997

Nocturnal 5-fluorouracil infusion to patients with breast cancer prior to surgery: appearance of 5-fluorouracil-induced AgNORs aggregation (FAA).

Between 1994 and 1995, 1 day nocturnal infusion of 5-fluorouracil (5-FU) was performed prior to surgery in 13 primary breast cancer patients; 300 mg/m2 of 5-FU was infused constantly from 2100 h to 0700 h via peripheral vein with a volumetric pump. 5-FU concentration in tissues was measured within surgical specimens by HPLC. The concentrations of 5-FU in tumor tissues ranged from 6 to 49 ng/g (average +/- SEM 25.0 +/- 4.1 ng/g), while in normal breast tissues and adipose tissues 5-FU was below the detection limit (<3 ng/g). The 5-FU concentration was lower in estrogen-receptor-positive tumors (14.4 +/- 4.5 ng/g) than in estrogen-receptor-negative tumors (31.8 +/- 5.0 ng/g). Typical FAA was observed in the tumor tissues of three patients. In these three cases, AgNORs were aggregated to one large spheroidal figure in more than 39% of tumor cells. Appearance of FAA could not be predicted by other clinical features. Nocturnal 5-FU infusion caused FAA changes in certain types of primary breast cancer.

Aged↗
PubMed1997

Expression of urokinase-type plasminogen activator receptor in hepatocellular carcinoma.

It is well known that a urokinase-type plasminogen activator receptor (uPAR) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various cancer cells. To assess the expression of uPAR in hepatocellular carcinoma (HCC), we analyzed the expression of uPAR messenger RNA (mRNA) and the protein in 31 pair-samples of solitary HCC and nontumorous liver tissues from the same patients. Fifteen samples exhibited no histological potential of recurrence, such as portal involvement or intrahepatic metastasis (group A), and 16 samples exhibited such histological features (group B). Seventy-one percent of the cases showed uPAR signals, and these signals were mainly localized at the cytoplasm of the tumor cells and tended to be at the front of invasive foci. 87.5% of the cases in group B showed uPAR signals against 53.3% of the cases in group A (P < .05). The rate of recurrence in the uPAR positive/negative cases in group A was 75.0% and 14.3%, respectively (P < .05). In non-neoplastic cases, e.g., chronic active hepatitis and cirrhosis, weak uPAR mRNA and protein signals were detected in hepatocytes neighboring the portal tracts, suggesting that this protein plays some role in such cases. The present study indicates that uPAR plays an important role at least in its initial stage in invasion and metastasis of HCC, and that uPAR expression can be a candidate predictor of these factors.

Antigens, Neoplasm↗
PubMed1997

Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6.

Serum levels of hepatocyte growth factor (HGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were determined at the time of admission in 38 patients with acute pancreatitis. The clinical utility of HGF for the detection of severe pancreatitis and for predicting prognosis, bacterial infection (infected pancreatic necrosis or sepsis), and organ dysfunction (liver, kidney, and lung) during the clinical course of acute pancreatitis was compared with the clinical utility of CRP and IL-6 by analysis of receiver operator characteristic (ROC) curves. The optimum cutoff levels of HGF for severity, prognosis, infection, hepatic dysfunction, renal dysfunction, and respiratory dysfunction were 0.9, 1.1, 1.0, 1.1, 1.1, and 1.0 ng/ml, respectively. HGF was as useful as CRP and more useful than IL-6 for detection of severe pancreatitis and for predicting hepatic dysfunction. Moreover, HGF was more useful than CRP or IL-6 for predicting prognosis, renal dysfunction, and respiratory dysfunction. However, for predicting infection, CRP was more useful than HGF. These results suggest that serum HGF levels on admission may be a useful new clinical parameter for determining the prognosis of acute pancreatitis and that HGF may be closely related to the organ dysfunction of acute pancreatitis.

Acute Disease↗
PubMed1997

Splenic hamartoma associated with thrombocytopenia.

A case of splenic hamartoma associated with thrombocytopenia is reported. A 70-year-old man was referred to our hospital because of carcinoma of the body of the pancreas. Hematological examination disclosed thrombocytopenia and elevated serum CA19-9 and Span-1 levels. In addition to typical findings of pancreatic carcinoma, a solid mass was observed in the spleen by imaging procedures. On ultrasonography, the splenic mass was well demarcated and slightly hypoechoic. Computed tomography demonstrated a homogeneous low-density mass 5 cm in diameter. On T1- and T2-weighted magnetic resonance images, the splenic mass was demonstrated as low intensity and high intensity, respectively. On selective angiography, the tumor was hypervascular. Distal pancreatectomy plus splenectomy was performed. Microscopically, the splenic tumor consisted of red pulp tissue and was diagnosed as splenic hamartoma.

Aged↗
PubMed1997

Absence of apoptosis in somatotropinomas treated with octreotide.

Octreotide is a potent agonist of somatostatin that lowers the serum level of growth hormone (GH), and reduces the size of somatotropinomas. However, the detailed mechanism of shrinkage of this tumour is not known. We, therefore, evaluated 11 patients with somatotropinomas who were treated with octreotide 300 micrograms/day for 2-5 weeks to observe the morphological changes in the tumour using electron microscopy and the immunocytochemical study of apoptosis using polyclonal anti-single stranded DNA. Findings were compared with those obtained with bromocriptine treatment (10 mg/day, 2 weeks) of 5 patients with somatotropinomas, and 11 patients who received no preoperative treatment (control group). The octreotide group showed neither increase in stromal tissue nor cell death. The size of tumour cells appeared to be slightly reduced. No typical apoptotic bodies were seen on the electron micrographs. The apoptotic index in the octreotide group (0.40 +/- 0.60%; mean +/- SD) resembled that in the control group (0.81 +/- 0.79%). In contrast, the bromocriptine group showed some cell death and an increase in stromal tissue. The bromocriptine group also showed the apoptotic index which (20.1 +/- 14.8%) was significantly higher than that of the control group (0.81 +/- 0.79%). Thus, octreotide did not induce apoptosis in somatotropinomas despite the presence of tumour shrinkage. Because of the lack of fibrosis observed in the octreotide-treated tumours, the preoperative administration of octreotide may help to improve the outcome of the transsphenoidal operation.

Adenoma↗
PubMed1997

Train-of-four and double burst stimulation fade at the great toe and thumb.

PURPOSE: We compared probabilities of tactile detection of fade in response to train-of-four (TOF), double burst stimulation3.3 (DBS3.3), and DBS3.2 at the great toe with those at the thumb. METHODS: One hundred and thirty adult patients anaesthetized with nitrous oxide, oxygen, isoflurane, and fentanyl were studied. At varying degrees of neuromuscular block caused by vecuronium, an observer determined the presence or absence of fade in response to TOF DBS3.3, or DBS3.2 at the great toe and that at the thumb. The relationship between T1/T0 or TOF ratio (T4/T1) measured at the great toe and that at the thumb was also examined. RESULTS: When TOF ratios were 0-0.10, 0.11-0.20, 0.21-0.30, 0.31-0.40, 0.41-0.50, 0.51-0.60, 0.61-0.70, and 0.71-1.00, the probabilities of detection of fade in response to TOF at the great toe (thumb) were 77 (100), 66 (100), 58 (96), 52 (77), 39 (38), 26 (23), 2(4), and 0(0)%, respectively (P < 0.05 at TOF ratio 0-0.40). Similarly, the probabilities of detection of fade in response to DBS3.3 at the great toe were lower than at the thumb when TOF ratios were 0.21-0.80, and those in response to DBS3.2 at the great toe were lower than at the thumb when TOF ratios were 0.61-0.80. A dose relationship was observed between T1/T0 or TOF ratio at the great toe and that at the thumb. CONCLUSION: This study suggests that the probability of tactile detection of fade in response to TOF, DBS3.3, or DBS3.2 at the great toe is less than that at the thumb. The present results may be because the flexor hallucis brevis muscle is more resistant to non-depolarizing neuromuscular relaxant than the adductor pollicis muscle and that the ratio of fade in response to neurostimulation at the great toe is higher than at the thumb.

Adult↗
PubMed1997

The effects of transmural pressure on prostacyclin release from porcine endocardial endothelial cells--comparison with vascular endothelial cells.

We assessed the effect of pressure on the release of prostacyclin (PGI2) from cultured endocardial endothelial cells (EECs) and vascular endothelial cells (VECs). EECs were harvested from the right ventricle (RV) and left ventricle (LV) of porcine hearts, and VECs from pulmonary artery (PA), aorta (Ao) and coronary artery (CA). Confluent EECs and VECs were incubated for 30 min under various pressures (0, 50, 100, 150 mmHg) and PGI2 release from each cell was measured. Pressure-induced PGI2 release from LV-EECs was larger than that from RV-EECs. Pressure also increased PGI2 release from both PA- and Ao-VECs, but not from CA-VECs. These findings suggest that endocardium can produce PGI2 in response to pressure and PGI2 released into the coronary blood from the ventricle may play an important role in the prevention of myocardial ischemia.

Animals↗
PubMed1997

Peripancreatic fluid cytology: detection of early rejection versus graft pancreatitis after canine pancreatic transplantation.

It is particularly difficult to distinguish between early rejection and graft pancreatitis when early rejection produces an elevated serum amylase level. In this study we determined whether peripancreatic fluid cytology (PFC) can differentiate early acute rejection and graft pancreatitis as an alternative diagnostic tool to graft biopsy that has the potential of pancreatic fistula and hemorrhage. Sixty-two dogs received either a segmental pancreas allograft (n = 25) or autograft (n = 37) heterotopically in the neck. This study included five groups: allografts without immunosuppression (group A, n = 12), allografts with immunosuppression (group B, n = 13), autografts without immunosuppression (group C, n = 11), autografts with immunosuppression (group D, n = 12), and autografts treated by 45 minutes of pretransplant warm ischemia to induce acute graft pancreatitis (group E, n = 14). A closed suction drainage catheter was placed next to the graft to collect peripancreatic fluid daily after the transplant. PFC was performed using May-Gruenwald-Giemsa double-staining technique and compared to the corresponding histology through the observation period. In analyses of 50 functioning grafts, PFC performed on day 1 showed similar neutrophil accumulations in all groups. In sharp contrast, on days 3 and 6, group A had dramatically increased mononuclear cell concentrations in PFC, whereas groups B, C, and D showed significantly lower concentrations, the percent of mononuclear cells among total leukocytes being 47.3 +/- 23.4%, 11.8 +/- 4.9%, 4.3 +/- 1.8%, and 6.4 +/- 2.4% (day 3); and 32.7 +/- 9.8%, 10.5 +/- 4.8%, 7.2 +/- 4.2%, and 8.6 +/- 6.4% (day 6) in groups A, B, C, and D, respectively. On the other hand, in group E numerous degenerating neutrophils with a marked to moderate increase in necrotic tissue fragments were observed by PFC on days 3 and 6. In terms of graft histology on days 3 and 6, group A showed interstitial mononuclear cell infiltration indicating an acute rejection process, whereas groups B, C, and D had minimal inflammatory cell infiltration. In group E graft pancreatitis was histologically confirmed on days 3 and 6. These results suggest that PFC after pancreas transplantation could be a safe, simple, useful diagnostic tool for discriminating early graft rejection from graft pancreatitis.

Animals↗
PubMed1997

Pharmacokinetics of adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation.

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n = 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P < 0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P < 0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Animals↗
PubMed1997

Local disturbance of neuronal migration in the S-100beta-retarded mutant mouse.

Homozygotes of a mouse strain with genetic polydactyly (Pdn) show disrupted cortical lamination and a significant decrease of S-100beta-immunoreactive elements in a particular area of the brain. In order to understand the abnormal cortical formation at the cellular level, the migration of cortical neurons and the development of glial cells were studied using bromodeoxyuridine (BrdU), S-100beta, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Homozygous mice (Pdn/Pdn) displayed a variable pattern of abnormalities. Irregular GFAP-positive radial glial cells and disturbance of neuronal migration were found in a circumscribed area of the caudo-dorsal cortex of newborn Pdn mouse. The number of S-100beta-positive cells was reduced in this area. The present results suggest that abnormal cortical lamination closely correlates with disturbance of neuronal migration and abnormalities of glial cells, especially a significant decrease of S-100beta-immunoreactive cells.

Animals↗
PubMed1997

Antithrombotic effects of endocardial endothelial cells-comparison with coronary artery endothelial cells.

The purpose of this study was to assess the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after a brief incubation with cultured EECs. EECs were isolated from the right ventricles of porcine hearts and coronary artery endothelial cells (C-ECs) were also isolated from the same animals. After brief incubations (2-min) of platelet suspensions with cultured EEC and CEC monolayers, platelet aggregation in response to thrombin and 6-keto-PGF1 alpha (a stable metabolite of PGI2) content of platelet suspensions were measured. Platelet aggregation was significantly inhibited by a brief incubation of platelet suspensions with EEC and C-ECs monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 x 10(-5) M) restored platelet activity, but pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME, 5 x 10(-5) M) or hemoglobin (1 x 10(-6) M) did not. Platelet/EEC interactions multiplicatively increased the 6-keto-PGF1 alpha content of platelet suspensions and the 6-keto-PGF1 alpha content of platelet suspensions after incubations with EECs correlated significantly with the inhibition of platelet aggregation. Both the anti-aggregation properties and 6-keto-PGF1 alpha production were significantly greater in EECs than in C-ECs. A brief incubation (2-min) with PDGF (10 ng/ml) or TGF-beta (1 and 10 ng/ml) stimulated 6-keto-PGF1 alpha production in EECs but not in C-ECs, although these growth factors stimulated 6-keto-PGF1 alpha production in C-ECs after a longer incubation time (30 or 60 min). In this study, after a brief incubation (2-min) with platelet suspensions, EECs inhibited platelet aggregation mainly through the release of PGI2 but not EDRF. As this anti-aggregation property was significantly greater in EECs than in C-ECs, it is suggested that endocardial endothelial PGI2 may inhibit both intracardiac and intracoronary artery thrombus formation, contributing to the prevention of myocardial ischemia.

6-Ketoprostaglandin F1 alpha↗