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Biomedical subjects

A Hayakawa

Publications and source records attributed to A Hayakawa.

At least 55 records · Page 3Linked to original sources

Alteration of redox state of human serum albumin in patients under anesthesia and invasive surgery.

Human serum albumin is a mixture of mercapt- (HMA, reduced form) and nonmercaptalbumin (HNA, oxidized form). We studied the mercapt<-->nonmercapt conversion of human serum albumin, which reflects the redox state of the extracellular fluids, in cardiac and other common surgical_ patients using high-performance liquid chromatography. Mean values of [(HMA)/(HMA+HNA)]+/-standard deviation, fHMA+/-sigma], for patients who received common surgery (group 1) and cardiac surgery (group 2) at the start of anesthesia were 0.636+/-0.050 (n = 83) and 0.615+/-0.062 (n = 14), respectively. fHMA values were markedly lower than those for healthy male adults of 0.750+/-0.028 (n = 28). fHMA values increased at 24 h after the start of anesthesia and decreased on the 4th postoperative day in most of the patients. These postoperative changes were prominent in cardiac surgical patients. Although fHMA values after the 7th postoperative day recovered to those at the start of anesthesia in almost all of common surgical patients, those in cardiac surgical patients never recovered even on the 21st postoperative day.

Adult↗

alpha-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation.

Antibodies to an alpha-galactosyl saccharide structure are mainly responsible for hyperacute rejection after pig-to-primate xenotransplantation. The beneficial effect of alpha-galactosyl oligosaccharides has been shown on the inhibition of anti-pig natural antibodies. We synthesized polyethylene glycol (PEG)-conjugates of alpha-galactosyl disaccharide (Di) and trisaccharide (Tri) as potential inhibitors of the rejection reaction. The half lives of Di, Tri, PEG-conjugated Di (Di-PEG) and PEG-conjugated Tri (Tri-PEG) were 18.1 +/- 2.3 min, 20.2 +/- 0.9 min, 38.7 +/- 2.8 min and 35.8 +/- 1.6 min, respectively. Furthermore, Di-PEG and Tri-PEG showed biphasic clearance, and their half lives at the second phase were longer than 10 hours. PEG-conjugated oligosaccharides (Di-PEG, Tri-PEG) markedly inhibited cytotoxic action of human sera to pig kidney cell line (PK15) compared to unconjugated oligosaccharides (Di, Tri). The binding of IgM antibodies to PK15 cells, however, was more strongly blocked by unconjugated oligosaccharides than PEG-conjugated oligosaccharides. This phenomenon can be explained by the finding that PEG has anti-complement activity and masks antigenic sites of oligosaccharides. In conclusion, conjugation of PEG to oligosaccharides provided two beneficial effects; prolonged intravascular retention time and anti-complement activity, upon systemic application of the oligosaccharides. The present findings opened a new approach to treatment of hyperacute rejection after xenotransplantation.

Animals↗

Fas antigen expression of hepatocytes and its modification by immunosuppressants.

Active cell death induced by ligation of the Fas antigen (Fas-Ag) with its antibody, Fas ligand (Fas-L), has been known to play a major role in cell killing via apoptosis by cytotoxic T lymphocytes (CTL). Thus, in liver transplantation, Fas-Ag expression of hepatocytes and its modification by immunosuppressive agents such as FK 506 or CsA can theoretically influence allograft survival. Mouse hepatocytes (BALB/c) were isolated and cultured with or without FK 506 or CsA, and Fas-Ag expression was determined by flow cytometry. Fas-Ag expression in the control was 17.2 +/- 2.5% after 24 hr of culture. When FK 506 or CsA was added, Fas-Ag expression with FK 506 at a concentration of 0.01-0.1 microg/ml was significantly lower than that with CsA (P < 0.05). When the cells were incubated with apoptosis-inducing anti-Fas-Ag monoclonal antibody, agarose gel electrophoresis of the control cells yielded a typical pattern of DNA fragmentations. The cells with FK 506 at 0.01 microg/ml yielded the least DNA fragmentation. These findings suggested that in the in vivo setting, the hepatocytes of the allograft would have a lower chance of being attacked by CTL in the host treated with FK 506.

Animals↗

Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice.

Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and to determine how such abnormal activation might affect other cell lineages. Elevated levels of IgG, IgE and autoantibodies in IL-2R beta-/- mice were found to be associated with activated CD4+ T cells which secreted elevated levels of IL-4. Thymocytes in IL-2R beta-/- mice showed normal negative and positive selection patterns when analyzed in transgenic mice bearing a TCR specific for HY antigen, suggesting that neither IL-2 nor IL-15 is essential for thymic selection. Peripheral T cells in IL-2R beta-deficient mice underwent normal programmed cell death in response to staphylococcal enterotoxin B superantigen, in contrast to cells from mice deficient for either IL-2 or IL-2R alpha. Activated T cells in IL-2R beta-deficient mice expressed normal levels of Fas antigen and underwent normal apoptosis in response to induction with anti-Fas mAb. Thus, the accumulation of activated T cells in IL-2R beta-/- mice does not appear to be derived from abnormalities in either thymic selection or Fas-mediated apoptosis.

Animals↗

Freeze-fracture cytochemistry of membrane cholesterol in Blastocystis hominis.

Membrane cholesterol in Blastocystis hominis was detected by freeze-fracture methods using a polyene antibiotic, filipin. Since the intramembrane particles (IMP) were distributed heterogeneously on both plasma and vacuole membranes, many IMP-free areas were observed. Even in filipin-treated cells, filipin-cholesterol complexes were not detected in IMP-free areas on the plasma membrane, whereas on the central vacuole membrane the complexes were mainly observed in IMP-free regions. These results indicate the different organization of the membrane cholesterol between the plasma membrane and central vacuole membrane. Most of the granules in the central vacuole were densely labeled with filipin, indicating the accumulation of cholesterol in the vacuole.

Animals↗

[Intraoperative acute myocardial infarction during total gastrectomy under general anesthesia combined with thoracic epidural anesthesia].

A 61-year-old, 54-kg man with gastric cancer was scheduled for total gastrectomy under general anesthesia combined with thoracic epidural anesthesia. Approximately 20 minutes after the start of the operation, the patient developed sudden hypotension and ventricular fibrillation. The cardiac rhythm returned to normal after 38 minutes of cardiopulmonary resuscitation. The operation was discontinued and the patient was transferred to an intensive care unit. A 12-lead electrocardiogram (ECG) revealed complete right bundle branch block and elevation of the ST-segment from leads II, III, aVF, V1, and V2 which indicated an inferior myocardial infarction. Laboratory data showed elevated levels of enzymes such as glutamic oxaloacetic transaminase (495 IU.l-1), lactic dehydrogenase (1781 IU.l-1), and creatine kinase-MB (112 IU.l-1). The mildly elevated levels of the enzymes decreased around 10 hours after the termination of the operation, but they increased markedly again without any change in ECG on the second postoperative day. Elevation in serum myoglobin and glutamic pyruvic transaminase and decline in arterial ketone body ratio were also detected. Furthermore, renal failure developed with increase in blood urea nitrogen and creatinine. Because of hepatic failure and renal failure which might have been caused by rhabdomyolysis, the patient needed inotropic support with dopamine, dobutamine, and epinephrine to maintain the circulation. The patient died of reinfarction of the 20th postoperative day despite intensive care such as intraaortic balloon pumping, hemodiafiltration, and continuous intravenous infusion of prostaglandin E1.

Acute Kidney Injury↗

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation.

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2 +/- 1.5 pg/ml) was significantly higher (P < 0.05) than in pretransplantation samples (3.2 +/- 0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8 +/- 5.9 mg/dl, which was significantly higher than before transplantation (6.4 +/- 2.2 mg/dl). There was a positive correlation between the serum BUN and ET-1 (r = 0.62, P < 0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9 +/- 32.4%) than with those obtained before transplantation (18.3 +/- 9.2%) when compared to a standard contractility rate of 100% with 40 mM KCI. Moreover, these contractility response rates were significantly reduced (32.8 +/- 21.0%) with the addition of the ET-1 receptor antagonist FR139317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.

Animals↗

Influence of free residual chlorine on cultured human epidermal keratinocytes from normal skin and hypertrophic scars.

In Japan, public health regulations state that the water in rinsing pools used before swimming should contain 50-100 mg/l of chlorine. We examined the influence of chlorination at high concentrations in rinsing pools on the skin using cultured human epidermal keratinocytes from normal skin and hypertrophic scars. Chlorination of cell culture for 15 min with 200 mg/l of free residual chlorine proved cytotoxic to both types of keratinocytes as did 100 mg/l of free residual chlorine for 1 or 3 consecutive days. Keratinocytes from hypertrophic scars, when cultivated in 100 mg/l of free residual chlorine, were more vulnerable to chlorine than those from normal skin. Cell characteristics of cultured keratinocytes from hypertrophic scars may be somewhat different from those of normal skin. The phenomena observed in this experimental model of the skin suggest that people exposed to chlorine in rinsing pools at concentrations in excess of 200 mg/l for about 15 min before swimming are at risk of developing cutaneous disorders, especially at sites of injury, e.g. scars.

Adolescent↗

An evaluation of the biological effects of three different modes of magnetic fields on cultured mammalian cells.

The biological effects of static magnetic fields, and their combined effects with ionizing radiation, were studied using a cultured mammalian cell line (FM3A). The three different modes of magnetic fields evaluated in this report were the 0.3 Tesla (T) field with a gradient of 0.3T/m, the 0.7T field with a gradient of 0.7T/m and the 6.34T field with no gradient. Exposure to the 0.3T and 0.7T fields had no effect on cell survival. Exposure to the 6.34T field decreased cell survival. Survival curves showing the combined effect of the 0.3T and 0.7T fields with radiation had a smaller mean lethal dose (D37) value. The survival curve of the 6.34T field was influenced by the interval between magnetic exposure and ionizing irradiation. When the interval was 6 or 12 h, the survival curve showing the combined effect of the 6.34T field had smaller D37 and quasithreshold dose (Dq) values, indicating the potentiation of the radiation effect. Flow cytometric analysis indicated that exposure to the 0.3T and 0.7T fields showed no change and that exposure to the 6.34T field showed an increase in the percentage of G1 phase cells. Our conclusions were as follows: 1) magnetic fields decreased the colony-forming abilities of cultured mammalian cells; 2) magnetic fields can affect the cell cycle; 3) a stronger magnetic field strength does not always have stronger biological effects and 4) the gradient of a magnetic field may be an important factor when combined with ionizing radiation. Despite the foregoing analysis, the biological effects of magnetic fields on mammalian cells remains a complex phenomena.

Animals↗

Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced hepatocellular carcinoma.

Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose of cis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 microns (diameter) for up to 24 h; the release of 28%-34% of the CDDP and 80%-90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.

Antineoplastic Combined Chemotherapy Protocols↗

Different mode of action of endothelin-1 in parietal and visceral veins.

The mode of contractile effect of endothelin-1 in venous smooth muscles was evaluated using three isolated veins, the jugular vein, the portal vein and the inferior caval vein of dogs. The contractile responses to endothelin-1 were attenuated by atropine and augmented by neostigmine in the inferior caval and portal veins, but were not affected by either agent in the jugular vein. We conclude that the contractile responses of visceral veins to endothelin-1 are partly mediated via endogenously released acetylcholine.

Animals↗

Cloning of a gene required for the alkaliphily of alkaliphilic Bacillus sp. strain C-125.

An alkali-sensitive mutant was obtained from alkaliphilic Bacillus sp. strain C-125. A DNA fragment required for the alkaliphily was cloned from the chromosomal DNA of strain C-125 by using the alkali-sensitive mutant as a host. The nucleotide sequence of the cloned DNA fragment indicated the occurrence of several ORFs. Comparison of these ORFs with sequences in the available databases revealed no closely related sequences.

Bacillus↗

[A case of pulmonary alveolar proteinosis--evaluation of a Swan-Ganz catheter in bilateral lung lavage].

Lung lavage, known to be effective for alveolar proteinosis, brings about significant hypoxemia immediately after evacuation of lavage fluid. Impeding blood flow of even a distal branch of a pulmonary artery by using a Swan-Ganz catheter (SGC) successfully prevented this hypoxemia. And this SGC procedure could be safely carried out to make lavage of each lung successively in one day.

Adult↗