[Feed back mechanism of cortisol].
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17-Hydroxycorticosteroids↗
Biomedical subjects
Y Takemoto
Publications and source records attributed to Y Takemoto.
Production and activation of hepatocyte growth factor in acute renal failure.
Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). HGF is produced as a single-chain precursor by cells of mesenchymal origin and is converted to a biologically active, heterodimeric molecule by proteolytic processing. We studied HGF mRNA and protein levels in systemic organs of glycerol-induced ARF rats, a model of crush syndrome. HGF protein concentration of tissue homogenate was measured by ELISA. Both mRNA and protein levels were increased in liver and spleen at 24 hours after the glycerol injection whereas HGF protein level was decreased in the injured kidney. Expression of HGF receptor/c-met mRNA was elevated only in the kidney. These results suggest that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF. Next, we measured serum HGF concentration by ELISA in 8 ARF patients caused by crush syndrome and the molecular size of serum HGF was determined by immunoblotting. Although serum HGF levels elevated in all patients, the HGF levels did not associate with their prognoses. While a single-chain molecule was predominantly observed in sera from chronic renal failure patients and healthy subjects, the majority of serum HGF was a heterodimeric form in 7 ARF patients. In one patient who developed disseminated intravascular coagulation syndrome and had a poor prognosis, a single-chain molecule was predominant although the serum HGF concentration was equivalent. These data suggest that the activity of proteolytic processing may be also an important factor for the expression of the biological function of HGF.
Acute Kidney Injury↗
Development of a novel biocompatibility test method based on intracellular calcium ion mobilization.
This paper presents a novel evaluation method for determining platelet/material interaction at the transmembrane level by incorporation of a Ca-sensitive fluorophore (Fura-2) into platelets. The transmembrane stimulation of platelets which are eluted from commercially available artificial dialyzers was quantitatively measured as the elevation of intracellular free calcium ion concentration. This method clearly differentiated platelet response to hydrophilic (ethylene vinyl alcohol copolymer and cellulose) vs. hydrophobic (polyacrylonitrile and cellulose acetate) membranes, and offers a versatile means to understanding platelet/material interaction.
Biocompatible Materials↗
Molecular understanding of cellular adhesion on artificial surfaces.
This study was conducted to clarify cellular adhesion mechanisms of blood cells (platelets [PLT] and white blood cells [WBC]) and vascular endothelial cells at the molecular level. This study indicated that the adhesion of three cellular systems to proteins such as fibronectin and fibrinogen proceeds via the RGD (Arg-Gly-Asp) ligand-receptor interaction, in which the RGD tripeptidyl sequence is the minimal amino acid sequence common to adhesive proteins. This was evident from the dose-dependent inhibitory effect of RGD-containing peptide on cellular adhesion. Additional supporting evidence was the presence of PLT and WBC receptors, which molecularly recognize RGD, verified by fluorescein-labelled RGD-containing peptide. The adhesion of vascular endothelial cells was also predominantly controlled by the ligand-receptor mechanism, and participation of complement activation on WBC adhesion was demonstrated as well. The adhesion of WBCs on surface hydroxyl group-bearing polymers proceeded via the CR3 receptor-C3b ligand interaction, in which activated complement factor C3b is chemically fixed upon complement activation. Thus, the molecular understanding of cellular adhesion mechanisms provide the basis of biocompatibility for implantation and extracorporeal circulation, as well as molecular design of artificial and bioartificial organs.
Animals↗
Japanese patients not seeking kidney transplants.
In Japan, the number of patients seeking kidney transplants has declined in recent years. To investigate the reasons for this decline, a questionnaire was given to 73 haemodialysis patients treated at the Tokiwa-Tatsumi Clinic. The resulting data showed the percentage of patients seeking transplants declined from 61% in 1992 to 19.2% in 1999. The reasons given for not seeking transplants were the improvements of physical condition and resultant quality of life (QOL) due to progress in dialysis therapy, upgraded social welfare support, uncertainties of transplant medicine, loss of expectations due to limited availability of transplant kidneys and aging of patients. Meanwhile, the number of patients on dialysis continues to increase by approximately 10,000 a year, and the mean age of patients rises. To reduce this number, greater effort must be directed toward preventive medical care as well as educating the public regarding transplant medicine.
Adult↗
Scrotal ulcer occurring in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.
Although all-trans retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL) compared with chemotherapy alone, various adverse effects have been reported. We report here the development of scrotal ulcer in four patients with APL during ATRA treatment. ATRA 45 mg/m2 was administered orally to four patients with newly diagnosed APL, two of whom also received chemotherapy. Scrotal ulcers appeared in all four patients after a median of 22 days (range: 17-29 days) of ATRA treatment. ATRA was discontinued in only one patient, who was then treated with methylprednisolone pulse therapy. The fever resolved, and scrotal ulcer improved after this treatment. The other three patients were treated with steroid or antibiotic ointment for scrotal ulcers. ATRA was re-administered 2 years later in one patient who had relapse of APL. Ulcers appeared again on the scrotal and lower abdominal skin on day 27 of ATRA treatment. These findings strongly suggest that scrotal ulcer is a potential adverse effect of ATRA.
Abdomen↗
Efficacy of all-trans retinoic acid for molecular relapse of acute promyelocytic leukemia during remission.
We analyzed the efficacy of all-trans retinoic acid (ATRA) as an early treatment for four acute promyelocytic leukemia (APL) patients in remission who were PML/RARalpha-positive by reverse transcription-polymerase chain reaction or fluorescence in situ hybridization. ATRA 45 mg/m2 was administered orally. All became negative for PML/RARalpha transcripts after 3 to 6 months of ATRA treatment. However, the PML/RARalpha transcripts subsequently reverted to positive in three cases. Although retreatment with ATRA failed to prevent hematological relapse in two patients, one case remains in hematological remission. No serious side effects were encountered during ATRA treatment. These findings suggest that early treatment of ATRA for PML/RARalpha-positive APL patients in remission may have a therapeutic benefit and prolong the duration of hematological remission without chemotherapy.
Antineoplastic Agents↗
Unexpected complication resulting from peritoneal dialysis catheter break.
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Adult↗
Interleukin-2 as a modulator of 5-fluorouracil in hepatic arterial immunochemotherapy for liver metastases.
BACKGROUND/AIMS: Hepatic arterial infusion of interleukin-2-based immunochemotherapy has yielded a high response rate (> 75%) in patients with unresectable liver metastases. In order to clarify the mechanisms that underlie the apparent benefit of combination treatment, the role of IL-2 as a modulator of 5-fluorouracil metabolism was investigated. METHODOLOGY: A single dose of 5-fluorouracil (50 mg/kg) with or without IL-2 (3500 Japan Reference Units/kg) was given via the hepatic artery to rats bearing liver metastases. Thirty minutes later samples of liver metastatic foci or surrounding normal liver tissue were removed for the measurement of thymidylate synthase, thymidine kinase and dihydropyrimidine dehydrogenase activity, and 5-fluorouracil content. RESULTS: 5-fluorouracil levels in tumor were significantly higher than in normal liver. Although the addition of IL-2 reduced 5-fluorouracil levels in both tumor and normal liver tissues by the activation of dihydropyrimidine dehydrogenase, the ratio of tumor/normal liver 5-fluorouracil levels was unchanged. Both thymidylate synthase and thymidine kinase activities were significantly inhibited in tumor tissue when the combination of 5-fluorouracil and IL-2 was administered. CONCLUSIONS: IL-2 increases 5-fluorouracil cytotoxicity through the inhibition of thymidylate synthase/thymidine kinase activities in the hepatic arterial infusion.
Adenocarcinoma↗
Endothelial injury during extracorporeal circulation. Role of the complement system.
This study attempted to elucidate in vitro, endothelial cell (EC) injury induced by complement activation in extracorporeal devices. The in vitro injury model using cultured bovine ECs showed the following: 1) a dose-dependent transmembrane injury, determined by monitoring intracellular calcium mobilization, occurred spontaneously upon addition of complement-activated serum. 2) The respiratory rate of adherent ECs, monitored by an oxygen electrode, was reduced with increases in activated complement serum levels, and increased further with time. 3) Whole cell activity, measured by the rate of cellular proliferation, was reduced with an increase in activated serum complement levels. 4) These cellular responses were almost completely absent in the presence of C3 antiserum, strongly indicating that activated C3 fragments are responsible for EC injury. Thus, complement activation during extracorporeal circulation may injure endothelium at the transmembranous, mitochondrial, and/or proliferative levels, depending upon contact time and concentration of activated complement.
Animals↗