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Biomedical subjects

B Sato

Publications and source records attributed to B Sato.

At least 55 records · Page 3Linked to original sources
PubMed1994

Living related liver transplantation across ABO blood groups.

We performed 13 pediatric liver transplants from ABO-incompatible living related maternal or paternal donors using a combination of preoperative removal of isohemagglutinin and postoperative immunosuppressive therapy with FK506 and prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The data obtained indicated that the preoperative removal of isohemagglutinin prevented hyperacute humoral rejection with hemorrhagic infiltration in the sinusoids in 10 successful cases. The incidence of acute rejection was not significantly different among ABO-identical, -compatible, and -incompatible groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

ABO Blood-Group System↗
PubMed1994

Mapping of a transcription element critical for expression of the fibroblast growth factor receptor 1 gene.

The fibroblast growth factor receptor 1 (FGFR1) gene has no TATA or CCAAT-elements. To examine its mechanism of expression, we characterized the transcription element of this gene. The basal promoter element was mapped to the 5'-flanking region from -89 to -43. The DNase I protection assay and gel shift analysis revealed that a nuclear protein extracted from FGFR1-expressing cells (NIH3T3 and SC-3), but not from FGFR1-nonexpressing cells (P3U1), could bind to the nucleotide sequence from -62 to -42. The molecular weight of this protein was approximately 100 kDa by Southwestern analysis. In addition, both the promoter activity and the nuclear protein binding activity were markedly impaired by the substitution of two bases within this footprint site. Interestingly, this footprint site appeared to lack the consensus sequence of the currently reported transcription factors. These results indicate that the 5'-flanking region from -62 to -42 plays a pivotal role in FGFR1 gene expression.

3T3 Cells↗
PubMed1994

Thyroid hormone inhibits androgen-enhanced DNA synthesis in Shionogi carcinoma 115 cells without affecting autocrine growth factor mRNA expression.

The growth of the mouse mammary Shionogi carcinoma 115 (SC 115)-derived cell line (SC-3) is markedly stimulated by androgen through induction of a heparin-binding growth factor termed androgen-induced growth factor (AIGF). This androgen-induced growth is partly blocked by thyroid hormone(s) such as triiodothyronine (T3). Transforming growth factor beta 1 (TGF beta 1) also inhibits the growth of SC-3 cells. Thus, we have investigated the possibility that T3 exerts its inhibitory effects on SC-3 cell growth through an alteration in AIGF or TGF beta 1 mRNA expression. Unexpectedly, T3 failed to modulate the expression of AIGF mRNA. T3 was also unable to significantly affect TGF beta 1 mRNA levels in androgen-stimulated SC-3 cells. More importantly, a neutralizing antibody against TGF beta 1 could not block T3-dependent inhibition of androgen-induced SC-3 cell growth. However, the inhibitory ability of T3 was potentiated by TGF beta 1. In addition, T3 treatment resulted in a significant inhibition of AIGF-induced DNA synthesis. Thus, T3 treatment renders SC-3 cells somehow refractory to AIGF. The signal pathway for T3 to reduce AIGF responsiveness may be shared by TGF beta 1.

Animals↗
PubMed1994

Facilitation of autonomous phenotype acquisition in androgen-dependent Shionogi carcinoma 115 cells by transfection of androgen-induced growth factor expression vector.

Androgen-induced growth factor (AIGF) is an autocrine growth factor for androgen-dependent SC-3 cells, which is induced by androgen stimuli. To elucidate the mechanism of the progression from hormone-dependent to -independent tumor, we transfected an expression vector of cDNA encoding AIGF into SC-3 cells and established a stable transfectant (A1) expressing AIGF. A1 cells showed enhanced DNA synthesis. This enhanced DNA synthesis was blocked by exposing the cells to AIGF antisense oligonucleotides, heparin, or suramin, indicating that enforced AIGF expression is responsible for the increase in DNA synthesis. However, A1 cells did not grow in serum-free medium unless stimulated with androgen. Recloning from A1 cells in semi-solid agar supplemented with fetal calf serum but without androgen quickly generated an autonomous subline that was able to grow rapidly in the serum-free medium irrespective of androgen stimulus. Mock-transfected SC-3 cells failed to form any colony under identical conditions. These results suggest that stable expression of AIGF alone is not sufficient for, but facilitates the conversion of SC-3 cells from androgen-dependent to -independent phenotype.

Androgens↗
PubMed1994

Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas.

OBJECTIVE: Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized in human pituitaries. In addition, altered or insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non-tumorous and tumorous human pituitaries should be examined. DESIGN: Total RNAs were extracted from non-tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression. SAMPLES: Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non-functioning adenomas were obtained at surgery. Two non-tumorous pituitaries were also included in this study. MEASUREMENTS: The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products. RESULTS: PC2 and PC3 mRNAs in non-tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT-PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas. CONCLUSION: The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.

Adenoma↗
PubMed1994

Living-related liver transplantation for fulminant hepatic failure in children.

Liver transplantation is increasingly accepted as a choice of treatment for fulminant hepatic failure (FHF) since it has been proved to significantly improve the survival rate in these patients compared with other therapeutic modalities. We have successfully performed a total of 76 living related liver transplantations (LRLT) three of which were for FHF. The first case was an 11-year-old boy with FHF due to an unidentified cause. He had required plasmapheresis a total of 24 times and haemofiltration to save his life before LRLT. He was transplanted with a left lobe (420 g) graft, calculated as 1.05% of his weight (40 kg). He recovered hepatic function uneventfully and was discharged from hospital after 7 weeks. The second case was a 13-year-old girl who developed FHF with grade III encephalopathy due to acute Wilson's disease, and was referred to us. She underwent LRLT with a left lobe graft (440 g), estimated as 0.95% of her weight (47 kg), which functioned well after surgery. The third case was a 13-year-old girl with grade II encephalopathy due to acute Wilson's disease. She was 27% obese with a body weight of 58 kg. She underwent LRLT with ABO blood group incompatibility with a left lobe (352 g), estimated as 0.80% of her weight (modified 44 kg). She was discharged with sensorimotor neuropathy due to vitamin B deficiency. The present results suggest that LRLT is feasible for FHF both clinically and ethically, and that a partial liver graft weighing around 1% of the recipient's weight can maintain the recipient's life. We limit the diagnostic indication for LRLT to chronic liver disease, since an urgent situation may affect a voluntary decision for the patient's parents to donate the partial liver. However, LRLT is thought to be an acceptable choice of treatment provided it is requested by the patient and family. Furthermore, it is a potential option for resolving the graft shortage in paediatric liver transplantation, being independent of cadaver donor availability.

Adolescent↗
PubMed1994

Interrelationship of oxygen supply by hepatic artery and portal vein: rapid analysis of ischemia-reflow-induced changes in hepatic oxygenation in experimental and clinical subjects by tissue near-infrared spectroscopy.

The rapid changes in extracellular oxygenation and intracellular oxidation during ischemia and reflow were measured in deep liver tissue by a novel method combining tissue near-infrared spectroscopy with multicomponent curve-fitting analysis. This method enabled us to make real-time measurements of oxygen saturation (SO2) and amount (THB) of hemoglobin in the liver sinusoid as parameters of extracellular oxygenation state and of redox transition of cytochrome aa3 as intracellular oxidation state. Clamping of the hepatic artery in rabbit decreased the THB with a transient fall of SO2. Clamping of the portal vein decreased both SO2 and THB. The decreases of SO2 and THB caused by Pringle's maneuver were larger than the sum of decreases by hepatic artery and portal vein. These changes in SO2 were correlated with intramitochondrial oxidation state as measured by cytochrome aa3. These results indicate the presence of an interrelationship of oxygen supply by hepatic artery and portal vein. This method was clinically applied during and after clamping of hepatic artery and portal vein in 19 cases of hepatic resection with or without chronic hepatic diseases. The decrease in SO2 values before and after clamping (SO2D) and the slope of SO2 recovery (SO2R) after release were calculated. SO2D and SO2R values of the portal vein in cirrhotics were significantly higher and lower, respectively, than those in the normal liver. These data indicate that the present method provides a rapid and reliable method of quantifying hepatic oxygenation during liver surgery and its perioperative management.

Animals↗
PubMed1994

Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor.

Intracranial germ cell tumors are known to be frequently associated with anterior pituitary hypofunction and diabetes insipidus. In general, these manifestations are not ameliorated even after successful radiotherapy. Since platinum based chemotherapy is introduced as a therapeutic approach to these tumors, its effectiveness is compared with the outcome obtained by radiotherapy in terms of tumor regression and endocrine functions. In this study, six patients received conventional radiotherapy and one received chemotherapy as an initial treatment. In all patients, complete remission was achieved irrespective of the therapeutic method. Their diabetes insipidus was not improved. Many patients treated with radiotherapy did not show the complete improvement of pre-existing hypofunction of the anterior pituitaries. In contrast, chemotherapy achieved almost complete hormonal remission. These clinical observations suggest that chemotherapy is quite effective in oncological as well as endocrinological aspects in treating intracranial germ cell tumors.

Adolescent↗
PubMed1994

Transforming activity of a newly cloned androgen-induced growth factor.

Our previous study demonstrated that androgen-dependent growth of mouse mammary carcinoma cells (SC-3) was mediated through an induction of heparin-binding growth factor, termed as androgen-induced growth factor (AIGF). Here, we report that NIH3T3 cells stably transfected with AIGF expression vector exhibit the abilities of tumor formation in nude mice, focus formation in monolayer culture and colony formation in soft agar. Thus, this newly cloned growth factor can be categorized as an oncogene. In addition, androgen-induced enhancement of DNA synthesis in SC-3 cells can be blocked by simultaneous incubation with AIGF antisense oligonucleotides. The possibility is also addressed that AIGF exerts its biological activity through an interaction with fibroblast growth factor (FGF) receptor. Transfection of expression vector encoding a variant form of FGF receptor-1 cloned from SC-3 cells into FGF receptor-negative L6 cells results in AIGF-dependent inhibition of differentiation. These results demonstrate that the ability of androgen to elicit transformed phenotype of SC-3 cells is mediated through AIGF induction and its interaction with FGF receptor-1.

Animals↗
PubMed1993

Expression of receptors for advanced glycosylation end products on renal cell carcinoma cells in vitro.

Proteins that have been modified by long-term expose to glucose accumulate advanced glycosylation end products (AGEs) as a function of protein age. In these studies, we have examined the interaction of AGE-protein with renal cell carcinoma cells (RCC) in vitro, using AGE-modified bovine serum albumin (AGE-BSA) as a probe. AGE-BSA showed tendency to induce in vitro cell growth of RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor. Reverse transcriptase-polymerase chain reaction analysis revealed that RCC cells used here express mRNA for a receptor for AGEs (RAGE). These results suggested that AGEs taken up through RAGE on RCC cells might play a role in promoting the growth of RCC cells.

Adenocarcinoma, Clear Cell↗
PubMed1993

Delayed oxidation of intramitochondrial pyridine nucleotide oxidoreduction state as compared with tissue oxygenation in human liver transplantation.

Intra- and post-operative oxygenation of graft liver and subsequent oxidation of the intramitochondrial oxido-reduction state of pyridine nucleotide were studied in partial liver transplantation from living related donors with the ratio of acetoacetate to beta-hydroxybutyrate in arterial blood (AKBR), the ratio of oxidized flavoprotein to reduced pyridine nucleotide (FP/PN ratio) and oxygen saturation of hemoglobin in liver tissue (hepatic SO2). Decreased hepatic SO2 and its heterogenous distribution after reflow of portal vein and hepatic artery were normalized by the end of operation, while the intramitochondrial oxido-reduction state was still reduced at the end of operation and was normalized only at 24 h after the operation. The observed delay in oxidation of the intramitochondrial oxido-reduction state as compared with tissue oxygenation indicates the transition of the intramitochondrial oxido-reduction state associated with the initiation of metabolic activity from the cold preserved state, and suggests an important role for microcirculation in the normalization of the oxido-reduction state.

3-Hydroxybutyric Acid↗
PubMed1993

Suramin interrupts androgen-inducible autocrine loop involving heparin binding growth factor in mouse mammary cancer (Shionogi carcinoma 115) cells.

The androgen-dependent clonal cell line SC-3, derived from Shionogi carcinoma 115, secretes a fibroblast growth factor (FGF)-like autocrine growth factor in response to androgen, which is able to bind to FGF receptors. In SC-3 cells, FGF receptor expression is upregulated by the SC-3-derived growth factor, providing a means of amplifying an autocrine loop of cell growth. In the present investigations, the effects of the polysulfonated naphthylurea suramin on this autocrine loop and its amplification in SC-3 cells were studied. Suramin inhibited androgen-dependent growth of SC-3 cells in a concentration-dependent fashion: approximately 50% inhibition was observed at 25 microM. [3H]Thymidine incorporation into the cells stimulated with partially purified SC-3-derived growth factor was inhibited by suramin in a similar way. Additionally, suramin inhibited acidic (a) or basic (b) FGF-induced cell proliferation, though relatively high concentrations were necessary to achieve the maximal inhibition. Pretreatment of SC-3 cells with suramin decreased cell surface 125I-bFGF binding without altering dissociation constant (Kd) of the binding sites. When the cells were incubated with 250 microM suramin for 24 h, the maximum binding (Bmax) decreased to almost 50% of the control. Treatment with suramin also decreased the levels of FGF receptor-1 mRNA to a similar extent, whereas it appeared not to affect the levels of beta-actin mRNA. Moreover, suramin completely blocked androgen- or bFGF-induced accumulation of FGF receptor-1 mRNA. The inhibitory effects of suramin on FGF receptor expression were reversed by simultaneous addition of high concentrations of bFGF. These results indicate that suramin exerts its potent antiproliferative action on SC-3 cells through inhibition of an androgen-inducible autocrine loop involving SC-3-derived growth factor and FGF receptor.

Animals↗
PubMed1993

Androgen-induced growth factor and its receptor: demonstration of the androgen-induced autocrine loop in mouse mammary carcinoma cells.

SC-3 cells derived from mouse mammary carcinoma (Shionogi carcinoma 115) exhibit remarkable growth enhancement and cell morphology change in response to androgen stimuli. These events are mediated through an androgen-induced growth factor (AIGF). Amino acid sequence deduced from cDNA reveals that AIGF has 215 amino acids with a signal peptide and scattered regions homologous to fibroblast growth factor (FGF) family proteins. The biological ability of AIGF to stimulate SC-3 cell growth is inhibited by heparin or suramin. More importantly, antisense oligodeoxynucleotide of AIGF can block androgen-induced growth of SC-3 cells. Upon synthesis under the control of androgen, AIGF is immediately secreted into the extracellular space without intracellular accumulation. At the early phase (18-24 h) of androgen stimulation, however, AIGF is mainly associated with the glycosaminoglycan on the cell surface or extracellular matrix. In addition, treatment of SC-3 cells with sulfation blocker (chlorate) or heparitinase results in the abolishment of their ability to respond to androgen or AIGF, indicating that heparan sulfate has important roles for condensing AIGF on or near the cell surface as well as potentiating the biological activity of AIGF. Then, AIGF can bind to the FGF receptor. Northern blot analysis and cDNA cloning indicate that SC-3 cells predominantly express the FGF receptor 1 with some altered amino acid sequences. Transfection of expression vectors of AIGF and this variant form of FGF receptor 1 into FGF receptor-negative myoblast cells (L 6 cells) confirms that a variant form of FGF receptor 1 is a receptor of AIGF. These results clearly demonstrate that an autocrine mechanism is operating in androgen-induced growth of SC-3 cells.

Amino Acid Sequence↗
PubMed1993

Effects of retinoic acid on steroid and vitamin D3 receptors in cultured mouse osteosarcoma cells.

The effect of retinoic acid (RA) on the expression of osteoblast-related genes as well as on steroid/vitamin D3 receptor contents was examined using cultured osteosarcoma cell line (BFO cells). Northern blot analysis revealed that mRNAs encoding osteocalcin, pro-alpha 1 (I) collagen and bone morphogenetic protein 4 (BMP-4) are expressed in BFO cells. Stimulation with RA, however, failed to alter their mRNA content, although the transcripts for retinoic acid receptor (RAR)-alpha and -gamma were present in BFO cells. In addition, alkaline phosphatase activity (AP) was significantly but modestly increased by RA treatment. These results suggest BFO cells have well differentiated osteoblastic properties. In contrast to the effects of RA on osteoblast-related gene regulation, RA was found to increase the quantity of estrogen receptor as well as of 1,25-dihydroxy vitamin D3 receptor (VDR) in BFO cells. The quantities, assessed by ligand binding assays, were approximately 200% more than those of the controls after 24 h stimulation with 10(-9)-10(-8) M RA. These RA effects on ER and VDR seem to be specific, since glucocorticoid receptor quantities were not affected by RA treatment. These results suggest that RA regulates ER and VDR quantities in BFO cells.

Alkaline Phosphatase↗
PubMed1993

A role for heparan sulfate in androgen-induced deoxyribonucleic acid synthesis of mouse mammary carcinoma (Shionogi carcinoma 115)-derived SC-3 cells.

In response to androgen stimuli, SC-3 cells cloned from mouse mammary carcinoma (Shionogi carcinoma 115) secrete heparin-binding growth factor, which is able to bind to fibroblast growth factor (FGF) receptor, ultimately resulting in SC-3 cell proliferation. A role for glycosaminoglycan in the process of this androgen-induced autocrine loop was examined. When quiescent SC-3 cells were stimulated with testosterone, enhanced DNA synthesis was demonstrated even at the early phase (12-24 h) of stimulation. During this early period, autocrine growth-promoting activity was found to be associated with cell surface and extracellular matrix, but not to be present in the conditioned medium. This bound form of growth-promoting activity was able to be extracted with 2 M NaCl (pH 7.5) and absorbed onto a heparin-Sepharose affinity column, from which it was eluted at a concentration of 1.1-1.3 M NaCl. Extracted growth factor, whose activity was partially blocked by anti-basic FGF antibody, up-regulated the expression of FGF receptor-1 mRNA. These characteristics were similar to those of a soluble form of SC-3-derived growth factor previously reported from our laboratory. Androgen-induced enhancement of DNA synthesis was inhibited by simultaneous treatment of SC-3 cells with 10 mIU/ml heparitinase or 25 mM sodium chlorate (an inhibitor of phosphoadenosine sulfate synthesis). However, chlorate treatment did not affect the synthesis and distribution of androgen-induced growth factor, suggesting that the response of chlorate-treated cells to this growth factor was impaired. These results indicate that heparan sulfate has important roles in concentrating androgen-induced heparin-binding growth factor on or very close to the cell surface and in potentiating its bioactivity.

Animals↗
PubMed1993

[Molecular mechanism of androgen-dependent transformation--analysis using serum-free culture system].

SC-3 cells, derived from androgen-dependent mouse breast cancer Shionogi carcinoma 115, have shown not only androgen-dependent growth stimulation but also morphological changes in serum-free culture. We have demonstrated that this androgen-dependent growth is mediated through an induction of heparin-binding growth factor (termed as androgen-induced growth factor: AIGF). We studied the molecular mechanism of androgen-dependent growth. NIH3T3 cells transfected to express AIGF showed focus-forming activity, anchorage-independent growth and tumor formation in nude mice indicating AIGF is an oncogene. The findings that AIGF inhibited binding of [125I]basic fibroblast growth factor (bFGF) and only FGF receptor (FGFR)-1 mRNA expressed in SC-3 cells suggested that AIGF acts through FGFR-1. Therefore, we cloned FGFR-1 from cDNA library of SC-3 cells, which was found to have three mutations. When this variant FGFR-1 was expressed in FGFR-negative myoblast L6 cells, AIGF-dependent inhibition of the differentiation to myocytes was observed suggesting that variant FGFR-1 is receptor of AIGF. Since expressions of c-myc mRNA as well as AIGF mRNA were induced by testosterone treatment, we studied the role of c-myc in androgen-dependent growth in SC-3 cells using phosphorothioate derived antisense oligonucleotides (antisense) of c-myc or AIGF. Not only AIGF antisense but also c-myc antisense inhibited androgen-dependent growth. c-myc antisense did not affect androgen-induced AIGF mRNA expression. c-myc antisense inhibited AIGF-, but not bFGF-induced DNA synthesis. These results suggest that c-myc has a critical role of AIGF-, but not bFGF-induced growth.

3T3 Cells↗
PubMed1992

Beta-adrenergic regulation of a myocardial actin gene via a cyclic AMP-independent pathway.

The skeletal alpha-actin gene encodes a major component of the embryonic cardiac sarcomere that is strongly and selectively re-induced during beta-adrenoceptor-mediated hypertrophy in neonatal rat cardiac myocytes. We present evidence that beta-adrenergic induction of this gene is mediated, not by cAMP, but by a calcium-dependent pathway involving ryanodine-sensitive calcium stores. Nifedipine-induced blockade of the plasma membrane L-type calcium entry channel prevented induction of skeletal alpha-actin mRNA by isoproterenol. Activation of calcium entry by the dihydropyridine agonist Bay K8644 independently induced skeletal alpha-actin mRNA, as did cholera toxin-mediated activation of Gs. Induction of skeletal alpha-actin mRNA by compounds that directly elevate cAMP was weak relative to their effects on other cAMP-dependent phenomena and required calcium entry. In addition, selective inhibition of protein kinase A with KT5720 did not block beta-adrenergic induction of skeletal alpha-actin. Calcium ionophore A23187 did not induce skeletal actin, but prevented its induction by isoproterenol. Ryanodine had bimodal effects: 10(-10) M ryanodine induced skeletal alpha-actin mRNA, whereas 10(-6) M ryanodine prevented skeletal actin induction by beta-adrenergic stimuli. We postulate that beta-adrenergic stimulation of skeletal alpha-actin mRNA requires G-protein-coupled calcium channel activation and compartmentalized calcium release in a manner independent of the cAMP/protein kinase A signal pathway.

1-Methyl-3-isobutylxanthine↗