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Biomedical subjects

A Yoshimura

Publications and source records attributed to A Yoshimura.

At least 199 records · Page 11Linked to original sources
PubMed1994

GD2 ganglioside-specific monoclonal antibody reacts with murine cytotoxic T lymphocytes reactive with FBL-3N erythroleukaemia.

Ganglioside expression on cytotoxic T lymphocytes induced against the mouse erythroleukaemia line FBL-3N, was analysed, compared with that of naive T lymphocytes in the thymus, lymph nodes and spleen. Although normal uncultured and cultured T lymphocytes expressed no GD2, GD3 or GM2 gangliosides, cytotoxic T cells with CD4+CD8-, CD4-CD8+, and CD4-CD8- phenotypes reacted with anti-GD2 monoclonal antibody with various intensities. The reactivity with anti-GD2 was associated with the intensity of cytotoxic activity as analysed using cytotoxic T lymphocyte (CTL) clones established from the bulk CTLs of each phenotype. An increase of the mRNA expression of GM2/GD2 synthase gene was demonstrated by Northern blot hybridization using RNA extracted from thymocytes, spleen cells, Con A-treated spleen cells and various types of CTL cells. These results indicated that GD2 ganglioside expression might be associated with the functional differentiation of murine T lymphocytes.

Animals↗
PubMed1994

Immunochemical study of epidermal growth factor in rats with mercuric chloride-induced acute renal failure.

Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 +/- 0.15 versus 3.78 +/- 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 +/- 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 +/- 2.12 versus 4.84 +/- 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 +/- 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues in ARF.

Acute Kidney Injury↗
PubMed1993

Progesterone and its metabolites: the potent inhibitors of the transporting activity of P-glycoprotein in the adrenal gland.

P-glycoprotein (P-gp) is a transmembrane glycoprotein responsible for the multidrug resistant (MDR) phenotype in various cancer cells. It has been shown that P-gp transports various kinds of anti-cancer agents as well as hydrophobic chemicals. Although P-gp is also expressed in normal human tissues, such as liver, kidney, and adrenal gland, its function and transporting substrates in these tissues are still unknown. In previous work, we demonstrated that some compounds in human plasma modulate the transporting activity of P-gp. We also found that P-gp is expressed at a high level in the bovine adrenal gland and that this tissue contains large amount of compounds which inhibit the transporting activity of P-gp. We purified such compounds from the adrenal gland by monitoring the ability to enhance the accumulation of [3H]vincristine in MDR cells. Two major compounds were purified and identified as progesterone and pregnenolone by nuclear magnetic resonance (NMR) analysis. Progesterone was the most potent and abundant compound that inhibited the transporting activity of P-gp among the compounds extracted from bovine adrenal gland with methanol. We also found that six authentic progesterone metabolites in the 5 beta-metabolic pathway but none in the 5 alpha-metabolic pathway were able to enhance the accumulation of [3H]vincristine in MDR cells and to inhibit [3H]azidopine photolabeling of P-gp in the adrenal gland. These results indicate that some progesterone metabolites can interact with P-gp and that stereoisomerism around carbon 5 of the progesterone metabolites is important for them to be recognized by P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas.

BACKGROUND: Renal cell carcinomas (RCC) respond poorly to anthracyclines, Vinca alkaloids, and other agents. P-glycoprotein is overproduced in multidrug-resistant cells and thought to function as an energy-dependent drug efflux pump. The authors thus examined the expression level of P-glycoprotein in RCC and transitional cell carcinomas (TCC). METHODS: P-glycoprotein was detected using immunoblotting with a monoclonal antibody against it, C219. RESULTS: Thirty-three of 38 patients with RCC and 3 of 17 patients with TCC had P-glycoprotein positive tumors. The expression level of P-glycoprotein in most of RCC was lower than that in the normal kidney tissues and that of P-glycoprotein in the TCC was very low. The size of P-glycoprotein in 14 RCC and 3 TCC was 5-10 kilodaltons smaller than in the normal renal tissues. The variation of P-glycoprotein size in the RCC was attributed to differential N-linked glycosylation. P-glycoprotein in a RCC was photolabeled by tritiated azidopine, and the labeling was inhibited by some organic agents. P-glycoprotein distributed on the apical or marginal cell surface of the RCC. CONCLUSIONS: These data show that P-glycoprotein was expressed in many RCC, and its expression level, glycosylation, and distribution were altered. These data also suggest that the P-glycoprotein in RCC had similar drug binding site(s) to that in multidrug-resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Rejection of an IA+ variant line of FBL-3 leukemia by cytotoxic T lymphocytes with CD4+ and CD4-CD8- T cell receptor-alpha beta phenotypes generated in CD8-depleted C57BL/6 mice.

FBL-3N is an MHC class II Ag+ variant line that was obtained spontaneously during maintenance of Friend virus-induced leukemia FBL-3 in an athymic C57BL/6 (B6) mouse. Inocula of FBL-3N, but not the parental FBL-3 tumor, regressed after initial growth in CD8-depleted, syngeneic B6 mice. The cellular mechanisms by which FBL-3N was rejected in these mice were investigated in this study. We demonstrated that CTL with both CD4+ and CD4-CD8-TCR-alpha beta phenotypes were generated in mixed lymphocyte tumor cell culture spleen cells obtained from CD8-depleted B6 mice that had rejected FBL-3N by in vitro stimulation with mitomycin C-treated FBL-3N. After adoptive transfer of these CTL that were generated in vitro into athymic B6 mice, challenge with the FBL-3N tumor resulted in tumor regression after its initial growth. Thus, CD4+ and CD4-CD8-TCR-alpha beta CTL mediated rejection of the FBL-3N tumor in CD8-depleted B6 mice. Furthermore, the findings that depletion of B6 mice of CD4+ cells in addition to CD8+ cells abrogated the rejection of FBL-3N and generation of CTL in mixed lymphocyte tumor cell culture spleen cells suggest that CD4+ cells were required not only as a source of CD4+ CTL, but also as helper cells for generation of CD4-CD8-TCR-alpha beta CTL. Tumor Ag recognition of CD4-CD8-TCR-alpha beta CTL was restricted to Db, like that of classical CD8+ CTL, but the restriction appeared to be less obligatory than that of CD8+ CTL.

Animals↗
PubMed1993

Protective effect of the calcium channel blocker diltiazem on hepatic function following warm ischemia.

The purpose of this study was to investigate the protective effect of a calcium channel blocker diltiazem (DTZ) on hepatic ischemic injury using a canine model. Hepatic ischemia was induced by temporary clamping of hepatic afferent blood vessels for 60 min with establishment of a portojugular bypass. The administration of DTZ at a dose of 70 micrograms/kg bolus i.v. injection before hepatic ischemia and thereafter via the portal vein at a dose of 10 micrograms/kg/min well restored the hepatic blood flow (HBF, 92 +/- 5%; P < 0.01) and arterial ketone body ratio (AKBR, 1.15 +/- 0.16; P < 0.01) 1 hr after interruption compared with untreated controls (HBF, 61 +/- 7%; AKBR, 0.53 +/- 0.09). In addition, the increase of plasma lactate level and the decrease of mean arterial pressure were significantly suppressed after ischemia (P < 0.05). We concluded that DTZ has a protective effect on ischemia-induced hepatic damage and might be useful in the prevention of primary graft failure caused by warm ischemia in liver transplantation.

Animals↗
PubMed1993

Urinary epidermal growth factor levels in patients with acute renal failure.

To investigate the importance of epidermal growth factor (EGF) in patients with renal dysfunction, urinary human EGF (hEGF) levels were determined by radioimmunoassay in 16 patients with acute renal failure (ARF) and in 12 healthy controls. Seven patients with chronic renal failure also were studied. Urinary hEGF levels, corrected for urine creatinine concentrations, were significantly decreased in patients with ARF in the acute phase compared with normal control subjects (0.98 +/- 0.20 v 13.74 +/- 1.18 ng/mg creatinine, P < 0.001), and subsequently increased during the recovery phase (6.10 +/- 0.73 ng/mg creatinine, P < 0.001 v acute phase). A significant positive correlation existed between urinary hEGF levels and creatinine clearance in patients with ARF (r = 0.66, P < 0.001). Serum hEGF levels also were significantly lower in patients with ARF compared with normal control subjects (0.10 +/- 0.01 v 0.30 +/- 0.03 ng/mL, P < 0.001). No significant correlation was found between hEGF concentrations in serum and urine. In conclusion, measurement of urinary hEGF may be useful in the diagnosis of ARF and for following the recovery of the kidney after severe tubular injury.

Acute Kidney Injury↗
PubMed1993

Thymidine phosphorylase activity associated with platelet-derived endothelial cell growth factor.

Partial complementary DNA (cDNA) for thymidine phosphorylase (dThdPase) was cloned by means of a polymerase chain reaction. There was complete sequence identity between the amino acid sequence deduced from the nucleotide sequence of a clone (288 nucleotides) and the residues of platelet-derived endothelial cell growth factor (PD-ECGF). The amino acid sequence of all four peptide fragments from purified human dThdPase could be aligned with that of PD-ECGF. Our data indicate that residues 125-244 of PD-ECGF are identical to the sequence of human dThdPase. The molecular weights of human dThdPase and recombinant PD-ECGF (rPD-ECGF) that lacks 10 amino acids at the amino terminal were 55 and 52 kDa, respectively. Anti-PD-ECGF antibody recognized dThdPase, and anti-dThdPase antibody recognized rPD-ECGF. rPD-ECGF had dThdPase activity and its specific activity was similar to that of purified human dThdPase. dThdPase activity and molecules were detected in COS cells transfected with human PD-ECGF cDNA, but not in nontransfected cells. The sizes of PD-ECGF and dThdPase in the transfected COS cells were identical. These data suggest that human dThdPase is identical to PD-ECGF.

Amino Acid Sequence↗
PubMed1993

Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the presence of magnesium perchlorate.

We have investigated the photosensitized monomerization of the cis,syn-cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5-deazaflavin derivative as photosensitizer. Although little monomerization of the dimer is induced by photoexcitation of the flavins in the absence of any additives, the flavins can function as an efficient photosensitizer in the presence of magnesium perchlorate. Mechanistic studies involving spectroscopic, quantum-yield and flash-photolysis measurements demonstrated that the photosensitized monomerization exclusively proceeds through electron transfer from the dimer to the triplet flavins complexed with Mg2+. The effects of magnesium perchlorate are compared with those on the chloranil-photosensitized monomerization and also with the effects of HClO4 on the flavin-photosensitized reaction.

Flavins↗
PubMed1993

Plateau pattern of afferent discharge rate from frog muscle spindles.

1. A characteristic plateau pattern was observed in the rate of afferent discharges during ramp-and-hold stretch of spindles isolated from semitendinosus muscles of frogs. The plateau pattern was more frequent in summer frogs (84%) than winter frogs (11%). 2. The plateau pattern consisted of a discharge rate around 120 imp/s at the end of dynamic stretch, followed by second and third steps of plateau rates around 60 and 40 imp/s, respectively. The intervals of impulses in lower steps were approximately n times those of the top step. 3. The plateau pattern was not sensitive to cutting extracapsular myelinated branches or lowering temperature from 23 to 12 degrees C. However, the number of the plateau was reduced in both cases. 4. Application of depolarizing current to the sensory terminal abolished the plateau pattern. In contrast, in spindles that did not show a plateau pattern, hyperpolarizing current induced such a pattern. 5. Calcium channel blockers and protein kinase C inhibitors abolished the plateau pattern. The plateau pattern could be established in quiescent spindles by drugs eliciting Ca2+ entry, raising cytosolic-free Ca2+, and activating protein kinase C. 6. The most striking aspect of the present study is the stability in the discharge rate at each step of the plateau, irrespective of different experimental conditions. This suggests that the spindle sensory terminal possesses a stable intrinsic rhythm generator in excitation, of which maximum frequency is 120 imp/s. The generator seems to be triggered by stretch stimulus and to be regulated by cytoplasmic Ca2+ and protein kinase C.

Afferent Pathways↗
PubMed1993

The distribution of 3H-labeled endotoxin in the kidney of liver cirrhotic rats.

Although the etiology and pathogenesis of progressive renal failure is largely unknown, endotoxin is supposed to be one of the contributory factors. However, the distribution of endotoxin in liver cirrhosis has not been clarified. Therefore we studied the distribution of 3H-labeled endotoxin in the kidney in rats with CCl4-induced liver injury. Daily inhalations of CCl4 on rats for 6 and 10 weeks produced liver fibrosis (LF group, N = 5) and cirrhosis (LC group, N = 5), respectively. At 6 or 10 weeks, animals were sacrificed 24 hours after an intravenous injection of endotoxin labeled with 3H at the galactose moiety (12,000 cpm/1 g body weight). In the liver, 3H-labeled endotoxin was taken up mainly by Kupffer cells as determined by autoradiography. Compared to control rats, in rats of the LC or LF group the measured amount of 3H-labeled endotoxin per gram kidney or ml blood increased, while that of the liver was significantly decreased. A positive correlation of the amount of 3H-labeled endotoxin per weight or volume respectively was shown between kidney and blood, but not between lung or spleen and blood. These results suggest that overflow of endotoxin due to decreased inactivation in the liver causes endotoxemia in liver injury and that the resulting endotoxemia may directly affect the kidney. The resulting endotoxin-induced vasoconstriction may be a contributory factor for the progressive renal failure frequently observed in liver cirrhosis.

Animals↗
PubMed1993

Endotoxin-induced acute tubular necrosis in cirrhotic rats.

In order to clarify the role of endotoxin in acute tubular necrosis in liver cirrhosis, lipopolysaccharide (LPS) was injected to rats with liver injury with exposure to carbon tetrachloride (CCl4) inhalation. Rats showed liver cirrhosis with ascites retention after 10 weeks' CCl4 treatment and liver fibrosis after 6 weeks' CCl4 treatment. Histopathological grading of kidney injuries after LPS treatment was more severe either in cirrhotic rats or in liver fibrotic rats than in normal rats. All cirrhotic rats had severe acute tubular necrosis after either dose of LPS, but only small necrotic foci of tubuli were seen in a few normal and liver fibrotic rats. The results indicate that endotoxin, which overflows due to disturbance of inactivation in the cirrhotic liver, may contribute to acute tubular necrosis. This effect of endotoxin is supposed to be a direct hemodynamic damage.

Animals↗