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Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 199 records · Page 11Linked to original sources
PubMed1998

Time-dependent cyclosporine A-induced nephrotoxicity in rats.

1. We investigated the toxicity of cyclosporine A (CsA) with reference to the timing of its administration in rats. 2. To elucidate the time-dependent effects of CsA on renal function and survival rate, CsA (75 mg/kg per day) or vehicle was orally administered once daily at four different times (3, 9, 15 and 21 h after lights on; HALO) over a period of 21 days to male Wistar rats (n = 56) kept in rooms with a 12 h light-dark cycle. 3. On the 7th day after treatment, creatinine clearances (Ccr) of groups dosed at 3 and 9 HALO (inactive period) were not reduced in comparison with clearances of time-matched control rats, whereas Ccr significantly decreased in rats dosed at 15 and 21 HALO (active period). Cyclosporine A markedly increased urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in all dosed groups at the 7th day after treatment, except for rats dosed at 3 HALO. In rats dosed at 3 HALO, Ccr decreased progressively; however, it did not decrease progressively in rats dosed at 9 HALO. In surviving rats treated during the inactive period, urine NAG subsequently returned to control levels. Survival rates were greater in animals dosed during inactive periods than those in groups dosed during active periods. 4. Significant differences in CsA-induced toxicity were obvious as a result of the timing of its administration. A different time course between Ccr and urine NAG excretion was observed during repeated CsA administration. Degenerative changes in proximal tubules were demonstrated after chronic administration of CsA, suggesting that severe and persistent tubular damage cannot be assessed by urinary NAG excretion.

Acetylglucosaminidase↗
PubMed1998

Effect of fibrin glue on small and large bowel anastomoses in the rat.

Fibrin glue has been used as a hemostatic and adhesive agent for many years, but its efficacy in digestive surgery is still controversial. In this study, we evaluated the effect of fibrin glue on the healing of the small and large bowel anastomotic portions by measurement of the anastomotic bursting pressure. Further, the efficacy of fibrin glue in preventing intra-abdominal adhesion formation was assessed. Our results indicated that fibrin glue enhanced the resistance towards an elevation of intraluminal pressure in small bowel, but not in large bowel. Concomitantly, the glue did not significantly attenuate postoperative adhesion formation. A sealing action of fibrin glue might protect against bleeding and microleakage, resulting in beneficial effects on small bowel anastomosis.

Anastomosis, Surgical↗
PubMed1998

Serial magnetic resonance imaging of acute spontaneous thrombosis of a giant intracranial aneurysm--case report.

A 46-year-old female presented with decreased bilateral visual acuity due to an unruptured non-thrombosed giant aneurysm arising from the left internal carotid artery. After admission, acute thrombosis of the aneurysm occurred spontaneously. Her consciousness and visual acuity temporarily worsened. Serial T2-weighted magnetic resonance (MR) imaging showed the size of the low intensity area near the orifice increased, and the aneurysm ruptured thereafter. Trapping of the aneurysm with a high-flow bypass was performed. Serial MR imaging findings clearly demonstrated the intraluminal structure of the thrombosed giant aneurysm. The aneurysm grew in size after thrombosis. The enlarging signal-void area on T2-weighted MR images were indicative of aneurysmal rupture. MR imaging is quite helpful to evaluate the changes of intraluminal thrombosis and size in giant aneurysms.

Acute Disease↗
PubMed1998

[Graft-versus-host disease after organ transplantation: donor and host factors].

Graft-versus-host disease (GVHD) induced by organ transplantation is dependent on both the quality and quantity of lymphocytes included in the graft. Changes in the host immune function after surgery are also important factors in the development of this disease. Based on our experimental data, GVHD after organ transplantation is reviewed To test the reactivity of graft lymphocytes in in vivo, small bowel, liver pancreas/spleen, and heart/lung transplantations were performed using a rat in parent-to-F 1 hybrid combination. All of the lymphoid organ transplants induced lethal GVHD, while liver graft did not accelerated the disease after the transplantation procedure. Lymphocytes in liver grafts had a unique population and showed a low response against alloantigens in vivo. Surgical treatments also increased the susceptibility to GVHD, especially the ischemic-reperfusion procedure; Endogenous endotoxemia triggered by reperfusion promoted the development of lethal GVHD.

Animals↗
PubMed1997

Lead levels in 24-h urine in Japanese adults.

Samples of 24-h urine were collected from 278 subjects (159 males and 119 females) in 1985, and 321 subjects (161 males and 160 females) in 1993 in the same factory with no occupational exposure to lead (Pb) in Japan. The age range of the subjects was 20-59 years. The urinary Pb concentrations were analyzed by flameless atomic absorption spectrophotometry after wet digestion followed by solvent extraction. The Pb levels in 24-h urine were distributed log-normally with geometric means (geometric S.D.) of 4.74 (1.46) and 2.67 (1.98) micrograms/day for males; and 3.22 (1.42) and 2.14 (2.05) micrograms/day for females in 1985 and 1993, respectively. No age-related changes in Pb levels in 24-h urine in either sex from 20 to 59 years were apparent. Pb levels in 24-h urine were significantly higher in males than in females (P < 0.01). Analysis of male smokers together with age-matched non-smokers failed to show an elevation of Pb levels in 24-h urine as related to smoking habits. Comparison of the Pb levels in 24-h urine in 1985 and 1993 disclosed that the Pb levels in 24-h urine were significantly lower in 1993 than in 1985 in both sexes (P < 0.01).

Adult↗
PubMed1997

Heparan sulfate-binding peptide promotes the deposition of proteoglycans in the extracellular matrix.

A synthetic peptide, which was shown to bind extracellular matrix heparan sulfate chains with a high degree of affinity and specificity [Colburn et al. (1996): Arch Biochem Biophys 325:129-138], has now been found to promote the transfer and the deposition of endothelial cell surface proteoglycans in the extracellular matrix. The peptide also induces preferential binding of extracellular matrix heparan sulfate proteoglycans, which have been added to the supernatant growth medium, and the requirement for its presence is stringent in that only a negligible amount of proteoglycans are bound to the cell layer in the absence of the peptide. In addition, antibodies directed against the peptide detect the accumulation of the peptide in the matrix compartment where the peptide is found associated with the proteoglycans transferred from the cell surface. The sequence of events induced by the peptide appears to be an extension of a naturally occurring process since proteoglycans with properties similar to those of the species ordinarily present in the extracellular matrix have been observed to transfer from the cell surface to the matrix during a pulse-chase experiment. We suggest that formation of the complex peptide-proteoglycan with consequent displacement of the proteoglycan from its anchorage on the cell initiates the process of transfer of the heparan sulfate-bound peptide from the cell surface to the extracellular matrix.

Animals↗
PubMed1997

Introduction of DNA into rat liver with a hand-held gene gun: distribution of the expressed enzyme, [32P]DNA, and Ca2+ flux.

DNA-coated Au particles were accelerated by pressurized He gas to supersonic velocities for introduction of a gene into cells. Experimental and theoretical analyses both revealed a heterogeneous distribution of the particles per shot (1 mg Au = 2.4 x 10(7) particles with 2 microg [32P] DNA = 2.5 x 10(11) moles). For introduction of genes into the liver of living rats, the best results were obtained with a newly developed hand-held gene delivery system. The beta-galactosidase gene introduced into rat liver with Au particles by He at 250 psi was expressed (1.2 microunits/microg protein) in a limited area of the liver surface (8 x 8 mm, depth 0.5 mm). When the same gene gun was used on a monolayer of cultured COS7 cells (about 5 microm thick), cells were lost in the central area of heavy bombardment. Cell death caused by influx of Ca2+ was prevented by the use of the cytosol-type culture medium.

Animals↗
PubMed1997

The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis.

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing cinnamoyl groups.

A series of N-cinnamates of the A-ring pyrrole compound of duocarmycin were synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. The 4'-methoxy- and 4'-BocNH-cinnamates exhibited strong in vitro anticellular activity among the synthesized compounds. The ortho substitution of the 4'-methoxycinnamate did not affect the anticellular activity and contributed to an enhancement of water solubility. Most of the 8-O-(N,N-dialkylcarbamoyl) derivatives of the 4'-methoxycinnamate displayed remarkably superior in vivo antitumor activity to duocarmycin A or B2. Moreover, it is noteworthy that these 8-O-(N,N-dialkylcarbamoyl) derivatives exhibited significant antitumor activity at wider range of doses as compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment B.

Animals↗
PubMed1997

Interleukin-6 and a delay of neutrophil apoptosis after major surgery.

Surgical treatments affect host immune systems. Apoptosis of the circulatory lymphocytes and an elevation of the number of neutrophils are induced by surgery. These alterations are not dependent only on the stress hormone. The course of neutrophilia and the serum concentration of interleukin-6 are given after various surgical treatments. Neutrophil-mediated lung injury is discussed.

Apoptosis↗
PubMed1997

Prevention of graft rejection and graft-versus-host reaction by a novel immunosuppressant, FTY720, in rat small bowel transplantation.

In the present study, we examined the immunosuppressive effect of a new drug, FTY720, on small bowel transplantation (SBT) in rats. Grafts from (LEW x BN) F1-to-LEW rats treated with FTY720 at 0.5 mg/kg from day 0 to 14 post-SBT survived significantly longer than untreated grafts. In addition, the administration of FTY720 combined with cyclosporin (CyA; 5 mg/kg per day) had a synergistic effect on allograft survival. The graft-versus-host reaction (GVHR) that occurred in the LEW-to-F1 rats was markedly reduced after the administration of FTY720. FTY720 combined with a low dose of CyA completely abrogated GVHR without any adverse reaction. FTY720 treatment resulted in a significant decrease in the number of lymphocytes in the peripheral blood and the spleen, but the number of peripheral neutrophils was unchanged. Thus, FTY720 would appear to be an ideal drug to combine with CyA in order to control the immune reaction after SBT.

Animals↗
PubMed1997

Hormone-cytokine response. Pneumoperitoneum vs abdominal wall-lifting in laparoscopic cholecystectomy.

BACKGROUND: Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO2 group) vs those who had abdominal wall-lifting (Air group). METHODS: Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10) were measured. RESULTS: The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO2 group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO2 group. CONCLUSIONS: CO2 insufflation may reduce cytokine production in laparoscopic cholecystectomy.

Abdominal Muscles↗
PubMed1997

Studies on duocarmycin SA and its derivatives.

New duocarmycin SA derivatives have been synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells, and in vivo antitumor activity against murine sarcoma 180 in mice. The results suggested that the N,N-dialkylcarbamoyl derivatives bearing the p-methoxy cinnamoyl group, which was prepared from duocarmycin SA, showed good in vivo antitumor activities superior to native duocarmycin SA.

Animals↗
PubMed1997

Concentration of cadmium in rice and urinary indicators of renal dysfunction.

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas polluted by Cd. (2) To establish the maximum allowable concentration of Cd in rice from these findings. METHODS: The target population consisted of 1703 inhabitants (832 men and 871 women) aged over 50 years who consumed home grown rice and had lived in the same hamlet in areas polluted by Cd in the Kakehashi River basin in Ishikawa Prefecture, Japan for at least 30 years. The correlation coefficients between concentrations of Cd in rice and several urinary substances, the prevalence of abnormalities in urine and sex in hamlets polluted by Cd were calculated. Finally, regression analysis was performed for significant indicators to calculate the maximum allowable concentration of Cd in rice based on values in a control group. CONCLUSIONS: Significant correlations between concentration of Cd in rice and concentrations of urinary beta 2-microglobulin, metallothionein, glucose, and aminonitrogen were established. Similarly, there were significant correlations between concentration of Cd in rice and the prevalence of beta 2-microglobulinuria, metallothioneinuria, glucosuria, proteinuria, proteinuria with glucosuria, and aminonitrogenuria. The highest maximum allowable concentration of Cd in rice calculated for these indicators was 0.34 ppm/l and 0.29 ppm/g creatinine. Both values are lower than 0.4 ppm, the tentative limit prescribed by the Japanese government.

Aged↗
PubMed1997

alpha-Galactosylceramide (AGL-517) treatment protects mice from lethal irradiation.

AGL-517 (AGL) has an alpha-galactosylceramide structure and is a derivative of agelasphin-9b, which in turn is isolated from Agelas mauritianus and has immunomodulating activity. When administered before irradiation, AGL has been found to increase survival rates in lethally irradiated mice. In this study, we found that a single injection of AGL administered within 2 hours of lethal irradiation resulted in the long-term survival of mice without bone marrow transplantation. Peripheral blood hematology showed that AGL administration accelerated the recovery of hematopoietic parameters, including reticulocytes and red and white blood cells. Recovery of platelets was moderate. In addition, AGL significantly increased the number of endogenous colony forming units-spleen (E-CFU-S). AGL itself displayed no colony-stimulating activity, but AGL-stimulated spleen cell-conditioned medium (AGL-SCM) promoted the proliferation and differentiation of bone marrow mononuclear cells from normal mice and Lin marrow cells from 5-fluorouracil (5-FU)-treated mice. Using suitable assay systems, we analyzed cytokines in AGL-SCM and found significant increases in stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6 levels compared with control SCM. Additionally, using immunoenzymetric assays, we assessed serum levels of these factors in AGL-treated mice after lethal irradiation. The serum concentrations of IL-3, GM-CSF, and IL-6 were substantially elevated, the maximum levels being reached within 2 hours of injection. Despite inducing the in vitro increase in SCF, AGL did not elevate serum SCF levels. However, certain levels of SCF (approximately 5 ng/mL) were detected in mouse serum regardless of irradiation or AGL treatment. When irradiated mice were given a cytokine cocktail composed of recombinant murine (rm) IL-3, rmGM-CSF, and recombinant human (rh) IL-6 three times a day for 6 days (1 microg of each factor per mouse per day) starting 2 hours after irradiation, 60% of the mice achieved 50-day survival. The radioprotective effect of AGL can be attributed, in part, to the cooperative effect of the cytokines induced by AGL in vivo. These findings suggest that AGL may be a useful in treating radiation-induced hematopoietic damage.

Animals↗