Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 271 records · Page 15Linked to original sources

PubMed1998

Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation.

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.

Adipose Tissue↗

PubMed1998

Hepatic venous hemoglobin oxygen saturation predicts regenerative status of remnant liver after partial hepatectomy in rats.

This study was designed to evaluate the use of hepatic venous hemoglobin oxygen saturation (ShVO2) as an indicator of hepatic oxygen supply-demand relation and also regenerative status of the liver after partial hepatectomy in rats. We assessed the ShVO2 levels for 7 days, as well as hepatic hemodynamics, oxygen consumption, DNA synthesis and energy charge of the remnant liver for 3 days after 50% hepatectomy or sham operation. Total hepatic oxygen consumption (HVO2) per liver weight, hepatic oxygen extraction ratio (HO2ER), and DNA synthesis were significantly elevated at days 1 and 3 after hepatectomy, compared with the preoperative levels. Meanwhile, significantly decreased ShVO2 levels were observed at days 1 and 3, and the ShVO2 levels were significantly correlated with the HVO2. Furthermore, the decreased ShVO2 levels were synchronized with the increased DNA synthesis in the remnant liver. Energy charge levels were also significantly decreased at day 1 after hepatectomy. These results suggest that the regenerating liver demands an increased amount of oxygen for mitochondrial oxidative phosphorylation to restore hepatic energy charge. In conclusion, the ShVO2 after hepatectomy may reflect oxygen metabolic status in the remnant liver and could be useful for estimating liver regeneration.

Animals↗

PubMed1998

[Changes of serum cytokine levels after thoracoscopic esophagectomy].

We introduced thoracoscopic esophagectomy with extended lymphadenectomy for reduction of respiratory dysfunction and less surgical intervention in July 1995. In this study, we investigated the changes in serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) levels in 8 patients (TS Group) who underwent thoracoscopic esophagectomy with extended lymphadenectomy and compared them with the changes in patients who underwent conventional thoracotomy (CT Group). The duration of the operation and intrathoracic procedure in the TS group were significantly longer than in the CT group. However, the amount of blood loss and intrathoracic blood loss of the TS group were not significantly higher than in the CT group. The number of dissected lymph nodes was not significantly larger. The serum IL-6 levels reached maximum levels 3 hours from the end of operation. In the TS group, the changes in IL-6 levels were significantly larger (p < 0.05). On the other hand, the changes in CRP levels were also significantly larger (p < 0.01). Significant correlation was observed between the duration of the intrathoracic procedure and the maximum levels of IL-6. On the other hand, serum IL-1ra levels were not significantly. At present, these results suggest that the surgical intervention of thoracoscopic esophagectomy are more larger than that of conventional thoracotomy. We think that the length of intrathoracic procedure of thoracoscopic esophagectomy may make more large surgical stress.

Endoscopy↗

PubMed1998

Establishment of chimerism in donor liver with recipient-type bone marrow cells prior to liver transplantation produces marked suppression of allograft rejection in rats.

In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1-2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.

Animals↗

PubMed1998

Expression of bcl-2 homologue mRNAs in rat liver allograft: rejection-induced cell apoptosis is associated with upregulation of bax and bcl-xs expression.

Apoptosis is considered to play an important role in rejection of organ transplants, although the precise mechanism has not been elucidated. In this study, we screened for the expression of bcl-2 homologues (bcl-2, bax, bcl-xl, and bcl-xs) and Fas ligand (FasL) by RT-PCR method in grafts during acute rejection in rats following liver transplantation. Both bax and bcl-xs (inducers of apoptosis) mRNA levels increased steadily in the allografted group from postoperative day (POD) 2 to 8, while no remarkable changes of bcl-2 and bcl-xl expression (inhibitors of apoptosis) were recognized. Significant induction of FasL gene expression was observed in the allografted group on POD 4 and expression gradually decreased thereafter, although minimal FasL mRNA expression was seen in isografts. Our results indicated, for the first time, that rejection-induced cell apoptosis is closely associated with upregulation of bax and bcl-xs expression besides FasL, but not with down-regulation of bcl-xl.

Animals↗

PubMed1998

TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.

We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.

Animals↗

PubMed1998

Effect of FTY720 on immunoregulation in concordant xenotransplantation.

The present study was designed to analyze the immunosuppressive activity of FTY720 in concordant xenotransplantation. When T and B lymphocytes of human peripheral blood were incubated with FTY720, the number of viable cells decreased in a dose-dependent manner at doses higher than 4 x 10(-5) M. DNA fragmentation was observed at doses higher than 1 x 10(-5) M in T cell-rich fractions and at doses higher than 4 x 10(-5) M in B cell-rich fractions. These data demonstrate that FTY720 is cytotoxic to B lymphocytes as well as T lymphocytes and apoptosis may play an important role in this cytotoxicity. Golden Syrian hamsters were the donors and Lewis rats the recipients of skin grafts. The recipients were divided into the following four groups: (1) untreated recipients, (2) FTY720 (5 mg/kg per day) was administered orally for 8 days (days-1-6), (3) FK506 (1 mg/kg per day) was injected i.m. for 7 days (days 0-6), and (4) FK506 (1 mg/kg per day) was injected i.m. for 7 days (days 0-6) and FTY720 (5 mg/kg per day) was administered orally for 8 days (days-1-6). The mean graft survival times in groups 1-4 were 9.7 +/- 0.52 days (n = 6), 12.0 +/- 0.71 days (n = 6), 13.2 +/- 1.6 days (n = 6), and 37.7 +/- 4.3 days (n = 6), respectively. There was a significant difference in the mean survival time between groups one and four. Combined therapy with FTY720 and FK506 is a useful tool for immunoregulation in xenotransplantation.

Animals↗

PubMed1998

Preeclampsia with fetal death in a patient with schistosomiasis japonica.

A case of preeclampsia with fetal death at 32 weeks' gestation is reported. Liver examination of the patient revealed network patterns on ultrasonography and linear calcifications on unenhanced CT scans in the liver. These findings are typical of those of chronic schistosomal infection. Indeed, liver biopsy specimens showed eggs of schistosoma japonicum. We diagnosed her case as preeclampsia with liver cirrhosis due to chronic schistosomiasis japonica. Schistosomal placentitis may have been present and may have contributed to preeclampsia and fetal death.

Adult↗

PubMed1998

Identification of amplified DNA sequences on double minute chromosomes in a leukemic cell line KY821 by means of spectral karyotyping and comparative genomic hybridization.

Double minute chromosomes (dmin) are cytogenetic hallmarks of amplified genes. Using spectral karyotyping (SKY) and comparative genomic hybridization (CGH), we identified the origin of amplified DNA in a leukemic cell line, KY821, that harbors numerous dmin. The SKY revealed that the DNA sequences of dmin are derived from materials of chromosome 8, and CGH showed a high degree of overrepresentation only at 8q22-24, indicating that in KY821 only chromosomal material of 8q22-24, containing MYC, is amplified in dmin. An approach combining SKY with CGH should facilitate efforts to identify novel chromosomal regions of gene amplification and contribute information about genetic lesions that underly neoplastic tumors.

DNA, Neoplasm↗

PubMed1998