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Biomedical subjects

M Hatano

Publications and source records attributed to M Hatano.

At least 109 records · Page 6Linked to original sources
PubMed1991

Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia.

Molecular cloning of the t(10;14)(q24;q11) recurrent breakpoint of T cell acute lymphoblastic leukemia has demonstrated a transcript for the candidate gene TCL3. Characterization of this gene from chromosome segment 10q24 revealed it to be a new homeobox, HOX11. The HOX11 homeodomain is most similar to that of the murine gene Hlx and possesses a markedly glycine-rich variable region and an acidic carboxyl terminus. HOX11, while expressed in liver, was not detected in normal thymus or T cells. This lineage-restricted homeobox gene is deregulated upon translocation into the T cell receptor locus where it may act as an oncogene.

Amino Acid Sequence↗
PubMed1991

CO binding studies of engineered cytochrome P-450ds: effects of mutations at putative distal sites in the presence of polycyclic hydrocarbons.

The kinetic parameters of CO binding to genetically engineered cytochrome P-450d (P-450d) and two putative distal mutants, Glu318Asp and Thr322Ala, have been evaluated in the presence and absence of polycyclic hydrocarbons. The dissociation constant (Kd) of CO from wild-type P-450d was decreased by half (from 1.8 microM to approximately 0.9 microM) in the presence of phenanthrene or anthracene but was increased to 11 microM in the presence of 1,2:3,4-dibenzanthracene or 7,8-benzoflavone. These changed Kd values were not altered markedly by mutations at the putative distal site. In contrast, the recombination rate constants (kon) of CO to the Glu318Asp mutant in the presence of phenanthrene (15.5 X 10(5) M-1 s-1) and 7,8-benzoflavone (0.75 X 10(5) M-1 s-1) were much larger than those for the wild type. Similar but smaller increases of the kon values were observed for the Thr322Ala mutant. It was suggested that phenanthrene and anthracene distort the Fe-C-O bond and/or affect the access of CO to wild-type P-450d in an opposite way from 1,2:3,4-dibenzanthracene and 7,8-benzoflavone. Glu318 and Thr322 may be located so close to a CO binding channel in ferrous P-450d that mutations of these residues can open the sterically hindered CO channel caused by the hydrocarbons.

Animals↗
PubMed1991

Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase.

To identify amino acids of cytochrome P450d (P450d) which participate in the interaction with NADPH-cytochrome P450 reductase, we changed conserved ionic amino acids of P450d to others by site-directed mutagenesis. Turnover numbers (0.032-0.008 min-1) of purified mutants Lys94-Glu, Lys99-Glu, Lys105-Glu, Lys440-Glu, Lys453-Glu, Arg455-Glu, and Lys463-Glu toward 7-ethoxycoumarin were much lower than that (0.380 min-1) of the wild type at 25 degrees C. Reduction rates (less than 0.054 s-1) of the heme of all mutants (0.1 microM) in the presence of NADPH and the reductase (0.3 microM) were much lower than that (5.9 s-1) of the wild type. Furthermore, a turnover number (0.042 min-1) of a microsomal triple mutant (Arg135-Leu + Arg136-Leu + Arg137-Leu) of a conserved Arg cluster was much lower than that (0.674 min-1) of the wild type at 37 degrees C. Thus, we suggest that Lys94, Lys99, Lys105, Lys440, Lys453, Arg455, Lys463, and perhaps the Arg cluster Arg135-Arg136-Arg137 of P450d will participate in the intermolecular electron transfer process by forming ionic bridges between the two proteins and/or by orienting appropriate geometry for electron transfer on the interfacial surface between the two proteins.

Amino Acid Sequence↗
PubMed1991

Transforming growth factor beta 1 differentially regulates alpha-fetoprotein and albumin in HuH-7 human hepatoma cells.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit hepatocyte growth in vitro and in vivo. In this study, we analyzed the effect of TGF-beta 1 on alpha-fetoprotein (AFP) and albumin gene expression in HuH-7 human hepatoma cells. TGF-beta 1 inhibited cell growth in a dose dependent manner. The cellular secretion rate of AFP but not albumin was suppressed significantly by TGF-beta 1. TGF-beta 1 caused a significant reduction in the level of AFP mRNA. In contrast, the levels of albumin mRNA or beta-actin mRNA were not changed by TGF-beta 1. In transient transfection experiments, TGF-beta 1 resulted in selective repression of AFP promoter activity. These results suggest that TGF-beta 1 is one of the key factors involved in the differential regulation of the AFP gene and the albumin gene.

Carcinoma, Hepatocellular↗
PubMed1991

Ligand binding studies of engineered cytochrome P-450d wild type, proximal mutants, and distal mutants.

Interactions of various axial ligands with cytochrome P-450d wild type, proximal mutants (Lys453Glu, Ile460Ser), and putative distal mutants (Glu318Asp, Thr319Ala, Thr322Ala) expressed in yeast were studied with optical absorption spectroscopy. P-450d wild type and all five mutants were purified essentially as the high-spin form, but the putative distal mutants contained about 5% low-spin form. Bindings of metyrapone and 4-phenylimidazole to the wild type and all mutants formed nitrogen-bound low-spin forms. In contrast, binding of 2-phenylimidazole to the wild type and most of mutants formed oxygen-bond low-spin forms except for the mutant Glu318Asp in which the nitrogen-bound low-spin form was formed. By analogy with the distal structure of P-450cam, it was thus suggested that Glu318 of P-450d, which corresponds with Asp251 of P-450cam, somehow interacts with 2-phenylimidazole over the heme plane. Addition of 1-butanol and acetanilide, a substrate of P-450d, to the wild type and mutants caused the spin change to the low-spin form. The order of dissociation constants of these oxygen ligands to P-450d was wild type greater than proximal mutants greater than putative distal mutants. Spectral analyses showed that the binding of acetanilide is the same as that of another substrate, 7-ethoxycoumarin, in the putative distal mutants but is not the same in the wild type and proximal mutants. From these findings together with other spectral data, it was suggested that the region from Glu318 to Thr322 is located at the distal region of the heme in membrane-bound P-450d as suggested from the X-ray crystal structure of water-soluble P-450cam and amino acid alignments of P-450s.

Amino Acid Sequence↗
PubMed1991

Distribution of carotenoids in the eggs from four species of salmonids.

1. The distribution of carotenoids in unfertilized ovulated eggs from chum salmon, kokanee (natural and cultured), masu salmon and cultured rainbow trout was examined from the comparative biochemical point of view. 2. The carotenoid contents in the eggs from cultured salmons such as kokanee and rainbow trout were low, whereas those from natural salmons were high. 3. The carotenoids were distributed in both chylomicra particles with high levels of triglyceride and lipovitellin. The carotenoids in the eggs of cultured kokanee and masu salmon were mostly distributed in lipovitellin, whereas those of the other salmons were equally contained in both chylomicra particles and lipovitellin. 4. Comparison of carotenoid distribution in the eggs from immature and mature chum salmon indicated that the carotenoids were bound to lipovitellin, as well as to chylomicra particles, during vitellogenesis.

Animals↗
PubMed1991

IgG response is impaired in H2-c-fos transgenic mice.

Transgenic mice carrying the proto-oncogene c-fos under the control of H-2Kb promoter (c-fos mice) were generated from (C57BL/6 x SJL)F2 mice. One line was backcrossed with C57BL/6 mice for 10 generations. These semi-congenic c-fos mice express exogenous c-fos RNA in their hematopoietic tissues. The following immunological states are apparent. (i) Titers of serum IgM, IgG, and IgA of naive c-fos were within the control range. (ii) These mice could not produce primary IgG antibody specific for immunized antigen. (iii) Production of primary IgM and IgA antibody to the antigen was within the control range. (iv) There were no IgG memory B cells generated in the spleens of c-fos mice. (v) Activities of antigen-presenting cells and carrier-specific helper T cells from c-fos mice were normal. These findings strongly suggest that the immune abnormality of c-fos mice is in limiting B cell function to the production of IgG to immunized antigens.

Animals↗
PubMed1991

Soluble immune complexes stimulate production of interleukin-1 by cultured rat glomerular mesangial cells.

Interleukin-1 (IL-1) is a pleiotropic factor, eliciting a broad set of immunologic and inflammatory events. We have previously shown that IL-1 is present in inflamed glomeruli. To evaluate factors that might regulate of IL-1 production, we tested the effects of substances accessible to mesangial cells (MC): immune complexes (IC) are known to modulate MC function. We have attempted to assess the ability of soluble IC derived from rat glomerular basement membrane to induce the production of IL-1. When isolated MC were incubated with the soluble IC, substantial amount of IL-1 could be detected in the supernatants as measured by the mouse thymocyte assay. To block the effect of prostaglandins on the IL-1 assay, we cultured the MC with the addition of indomethacin and assayed IL-1 activity in the culture supernatants. The use of indomethacin resulted in a further increase in IL-1 production. These biological activities were neutralized by a specific antibody to IL-1. In the present report, we show that IC represent important sources of stimulation of MC for the production of IL-1. We speculate that IC could augment local inflammatory responses in the kidney partly due to their capacity to induce the production of IL-1.

Animals↗
PubMed1991

Renal tubular epithelial antigen-containing immune complexes stimulate interleukin-1 production by cultured rat glomerular mesangial cells.

The ability of immune complexes (IC) derived from rat renal tubular epithelial (RTE) antigen to trigger the production of interleukin-1 (IL-1) was investigated. When cultured rat mesangial cells (MC) were activated by the IC, substantial amounts of IL-1 could be detected in the culture supernatants as measured by the mouse thymocyte assay. To avoid the effect of prostaglandins on the IL-1 assay, we cultured the MC with addition of indomethacin and assayed IL-1 activity in the culture supernatants. This cyclooxygenase inhibitor augmented IC-induced IL-1 production. These biological activities were neutralized by a specific antibody to IL-1. These findings suggest that IC may participate in local inflammatory responses in the kidney partly due to their capacity to induce the synthesis of MC IL-1.

Animals↗
PubMed1991

Sudden appearance of coronary thrombus observed by angiography--a case report.

A sudden coronary thrombus formation was documented by chance during cardiac catheterization in a patient with postinfarction angina. The thrombus was successfully treated with intravenous urokinase and heparin infusions, and thereafter, coronary angioplasty was performed without any complication.

Angina, Unstable↗
PubMed1991

Low doses of endothelin-3 elicit endothelium dependent vasodilation which accompanies with elevation of cyclic GMP.

Low doses (10(-16)-10(-10) M) of endothelin-3 (ET-3) elicited continuous vasodilations of mesenteric arteries preconstricted with norepinephrine (NE) but not with KCl. In arteries perfused with Ca2+ free solution, ET-3 did not affect the perfusion pressure. In endothelium-denuded arteries preconstricted with NE, ET-3 significantly elevated the perfusion pressure in a dose-related manner. The levels of cyclic GMP and cyclic AMP from the intact arteries were significantly elevated by ET-3; the cyclic GMP elevasion disappeared with methylene blue. Following endothelium-denudation, cyclic GMP elevation was abolished, but cyclic AMP elevation was unaffected. Levels of 6-Keto-PGF1 alpha in the arteries were not changed appreciably by ET-3. These data indicate that the vasodilating effects of ET-3 depend on the presence of extracellular Ca2+ and the existence of endothelium. They are accompanied by elevations of cyclic nucleotides and the elevation of cyclic GMP depends on the endothelium. It is possible that the vasodilating effects of low doses of ET-3 are associated with endothelium-derived relaxing factor.

Animals↗
PubMed1991

Cyclic GMP formation of resistance vessel in the development of hypertension in spontaneously hypertensive rats.

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the mesenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to infusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated release of EDRF is not associated with the development of hypertension.

Acetylcholine↗
PubMed1991

Effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine on the vasoactive effects of endothelin-3.

To clarify the mechanisms underlying the vasoactive effects of endothelin-3 (ET-3), we examined the effects of indomethacin, endothelium-denudation, methylene blue and L-NG-monomethyl arginine (L-NMMA) on the perfusion pressures of isolated rat mesenteric arteries infused with ET-3. ET-3 at 10(-15)-10(-8) M elicited significant vasodilations in a dose-related manner, in which 10(-9) and 10(-8) M ET-3 caused biphasic pressure changes involving a transient dilation and subsequent vasoconstriction. Five micromolar indomethacin did not affect the vasodilations and vasoconstrictions induced by ET-3. In endothelium-denuded arteries, 10(-13)-10(-8) M ET-3 elicited significant vasoconstriction in a dose-related manner without any vasodilation. In the presence of 30 microM methylene blue, the vasodilations induced by ET-3 disappeared. In the presence of 100 microM L-NMMA, 10(-15)-10(-8) M ET-3 elicited significant vasoconstrictions in a dose-related manner, and the vasodilation by ET-3 existed only at 10(-8) M ET-3. These data suggest that the vasodilating effects of low doses of ET-3 through the endothelium overcome the vasoconstricting effects, and that the vasodilating effects of ET-3 are associated with an endothelium-derived relaxing factor as an endothelium-derived nitric oxide.

Animals↗
PubMed1991

Effect of endothelin-3 (ET-3) on renal function in rat perfused kidney.

We examined the effect of endothelin-3 (ET-3) at a high dose (pressor dose) and a low dose (non-pressor dose) in rat perfused kidney (PK), since ET-3 has recently been reported to exert a vasodilator action especially at a low dose. Kidneys were perfused with Krebs-Henseleit buffer at a fixed flow rate (6 ml/min) in situ. After collection of the renal venous effluent and urine for 20 min, vehicle (saline; n = 6), 10(-13)M ET-3 (low dose; n = 6) or 10(-8) M ET-3 (high dose; n = 6) was added to the perfusate, and sample collection was performed for the same period with each. The high dose of ET-3 significantly increased the perfusion pressure, fractional sodium excretion and synthesis of prostaglandins (PGs) consistently with a significant reduction in the glomerular filtration rate (GFR). On the other hand, the low dose of ET-3 significantly increased the GFR, urine volume and free-water clearance with no change in the perfusion pressure or synthesis of PGs. These findings suggest that a low dose of ET-3 can increase the glomerular capillary ultrafiltration coefficient and that ET-3 exerts an influence on sodium and water handing in the rat PK.

Animals↗
PubMed1991

An approach to optimal dialysis using urea kinetic modeling.

Urea kinetic modeling (UKM) was carried out to evaluate the water control in patients undergoing long-term hemodialysis. In 21 patients on chronic dialysis, the results of two different determinations of the total body water, i.e. by the deuterium oxide (D2O) method and by UKM, were compared. A correlation was observed with Y = 0.98X + 5.9 (P less than 0.01, r = 0.91) for males and Y = 0.97X + 6.2 (P less than 0.01, r = 0.90) for females, indicating that UKM is useful for determining the total body water. In addition, the 21 patients were classified into two groups based on their ECG findings, and UKM was performed in the two groups for comparison. The values of the total body water were 68.5 +/- 4.0% and 68.6 +/- 6.2% of body weight, respectively, with no significant difference between them. However, the CTR was 50.2 +/- 2.8% and 46.2 +/- 4.4%, respectively. Thus, not only X-ray examinations but also UKM should be carried out to determine the standard weight (SW-DW) in the presence of cardiac dysfunction. Instructions for water control were given when the total body water exceeded 73% during the UKM measurements over 5 years, which allowed an optimal total body water to be maintained thereafter. The possible influence of erythropoietin (EPO) was also examined by performing UKM in 8 cases receiving EPO and 7 cases without EPO. No noticeable difference was observed between the two groups. 17 patients using a polyacrylonitrile (PAN) membrane were further divided into those with and those without EPO to evaluate the possible influence of the PAN membrane-EPO combination. As a result, no significant difference was demonstrated, suggesting that UKM can be satisfactorily performed under such conditions. In 11 patients on chronic dialysis, the levels of alpha-human atrial natriuretic peptide (alpha-hANP) were measured pre- and post-dialysis to examine the relationship between the change in alpha-hANP and rate of weight loss (%). A significant correlation was observed with Y = 12.8X + 5.1 (P less than 0.05, r = 0.68). In conclusion, UKM was found to be useful for evaluating the water control and for assessing the optimal dialysis in patients receiving long-term hemodialysis.

Acrylic Resins↗