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M Morikawa

Publications and source records attributed to M Morikawa.

At least 127 records · Page 7Linked to original sources

Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs.

BACKGROUND: Histamine N-methyltransferase (HMT) modulates histamine- and antigen-induced bronchoconstriction. However, it is unclear whether vascular permeability evoked by an allergic reaction can be exaggerated by inhibition of HMT activity. METHODS: We studied the effects of intravenously injected SKF 91488, a specific HMT inhibitor, on increases in plasma extravasation induced by intravenously injected histamine in unsensitized guinea pigs and by intravenously injected ovalbumin antigen in guinea pigs sensitized to ovalbumin in vivo with Evans blue dye as a marker. RESULTS: Pretreatment with SKF 91488 shifted, in a dose-dependent fashion, the dose-response curves of the leakage of dye to histamine to lower concentrations in the trachea, main bronchi, and nasal mucosa. Likewise, pretreatment with SKF 91488 (20 mg/kg intravenously) significantly increased the leakage of dye induced by ovalbumin antigen (200 micrograms/kg intravenously) in three parts of the airway (p < 0.05). In contrast to SKF 91488, intravenously injected aminoguanidine, a specific inhibitor of diamine oxidase (16 mg/kg intravenously), did not alter the leakage of dye induced by histamine (from 0.001 microgram/kg to 10 micrograms/kg intravenously) (p < 0.20). HMT activities were observed in the nasal mucosa, as well as in the trachea and main bronchi, as shown in a previous study. CONCLUSION: These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine induced by antigen challenge on plasma extravasation in the airway in guinea pigs in vivo.

Amine Oxidase (Copper-Containing)↗

Phosphorylation of HS1, GAP-associated p190 and a novel GAP-associated p60 protein by cross-linking of Fc gamma RIIIA.

Human Fc gamma receptor IIIA (hFc gamma RIIIA) cDNA was introduced into mouse macrophage/monocyte cell line P388D1, and several stable cell clones expressing hFc gamma RIIIA were isolated. This facilitated the study of the biological function of Fc gamma RIIIA in monocytes/macrophages. The cloned cells showed the high phagocytic activity mediated by hFc gamma-RIIIA, while the original P388D1 cells did not. In order to examine the phosphorylation of proteins involved in hFc gamma RIIIA signal transduction, these receptors were stimulated by cross-linking. The cross-linking of hFc gamma RIIIA induced a rapid increase in tyrosine phosphorylation of several proteins, including PLC-gamma 1, Syk, HS1, and p21rasGAP-associated p190 and p60 proteins. Immunoblotting with a polyclonal antibody specific for the GAP-associated p62 protein, which was originally found in fibroblasts and is homologous with an RNA-binding protein, revealed that the p60 phosphorylated after cross-linking of hFc gamma RIIIA seemed to represent a novel GAP-associated protein unrelated to the known GAP-associated p62 protein, which was also present in the P388D1 cells.

Adaptor Proteins, Signal Transducing↗

Potentiating effect of nicorandil, an antianginal agent, on relaxation induced by isoproterenol in isolated rat aorta: involvement of cyclic GMP-inhibitable cyclic AMP phosphodiesterase.

In rat aortic rings, isoproterenol (ISO) 10(-9)-3 x 10(-6)M relaxed the contraction induced by phenylephrine (PE) 3 x 10(-7)M. Pretreatment with nicorandil 3 x 10(-7) and 3 x 10(-6) M potentiated the relaxation induced by ISO. Nicorandil 3 x 10(-6) M also potentiated the relaxations induced by forskolin 3 x 10(-9) - 10(-6) M and dibutylyl-cyclic AMP 3 x 10(-6) - 3 x 10(-4) M. Nitroglycerin (NTG) 10(-8) M, but not cromakalim 3 x 10(-8) M, also potentiated the ISO relaxation. Pretreatment with glyburide 10(-6) M or apamin 10(-6) M did not affect the potentiating action of nicorandil 3 x 10(-6) M. Pretreatment with methylene blue (MB) 10(-6) M, but not with NG-monomethyl-L-arginine (NMMA), however, markedly inhibited the potentiating effect of nicorandil. Removal of endothelium impaired the relaxation induced by ISO but did not inhibit the potentiating effect of nicorandil. In addition, in the presence of MCl-154 (10(-7) M), which itself potentiated ISO-induced relaxation, nicorandil 3 x 10(-6) M did not further potentiate the relaxing response to ISO. Furthermore, nicorandil 3 x 10(-6) M potentiated the increase in the tissue level of cyclic AMP caused by ISO 3 x 10(-7) M, whereas the nicorandil-induced increase in cyclic GMP levels were not affected by ISO. These results suggest that the potentiating effect of nicorandil on the relaxation induced by ISO is most likely due to inhibition of phosphodiesterase III (PDE III) by increased cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗

Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes.

1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+ concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a biphasic concentration-dependent effect on O2- generation induced by f-methionyl-leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40 microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2- generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation. 5. Addition of a high concentration of NO (40 microM) decreased authentic O2- formation by pyrogallol in a cell-free system, but a low concentration of NO (400 nM) had no effect on this. On the other hand, addition of SNP in the concentration-ranges used had no effect on authentic O2- formation by pyrogallol. 6. In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The results suggest that the enhancement observed with SNP and NO at low concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP pathway. The suppressive effect of SNP and NO at higher concentrations is mediated by the NO-induced O2--scavenging effect and activation of the guanylate cyclase-cyclic GMP pathway.

Calcium↗

Oxidants affect permeability and repair of the cultured human tracheal epithelium.

To examine the effects of oxidants on the airway epithelial barrier functions, human tracheal epithelial cells were cultured on porous filter membrane. Glucose oxidase (GO; 10 U/ml), hydrogen peroxide (H2O2; 4 x 10(-3) M), and xanthine (5 x 10(-4) M) plus xanthine oxidase (20 mU/ml) (X-XO) significantly increased electrical conductance across epithelial membrane (G), short-circuit current (Isc) measured with Ussing's chamber methods, and [3H]mannitol flux through the cultured epithelium. Increases in G and Isc induced by oxidants were significantly inhibited by catalase (1,000 U/ml) and the protein kinase C inhibitor staurosporine (10(-7) M), but superoxide dismutase (SOD; 100 U/ml) was without effect. GO, H2O2, and X-XO inhibited the epithelial cell growth, [3H]thymidine incorporation by the cells, and epithelial repair of artificially produced focal epithelial defects (1-2 mm diam) on plastic vessels. Catalase also inhibited effects induced by oxidants on cell growth and proliferation. These results suggest that oxidants reduce tracheal epithelial barrier functions by damaging tight junctions and inhibiting cell proliferation, and these effects of oxidants on epithelial cells may be mediated by H2O2 rather than superoxide anion and by activation of protein kinase C.

Catalase↗

Activity of artificial mutant variants of human growth hormone changes in charged residues around 62-67.

Our previous work has shown that the amino acid residues around 62-67 located in the connecting loop between helix I and II of human growth hormone (hGH) are important in eliciting the differentiation of preadipose 3T3-F442A cells to adipocytes. In this study, we evaluated the role of the charged residues around 62-67 in receptor binding and biological activity. Eight artificial mutant variants of hGH were prepared in Escherichia coli by site-directed mutagenesis. Replacement of Arg64 with Tyr (R64Y variant) resulted in a significant loss of binding to the somatogenic receptors on 3T3-F442A cells, but retained full adipose conversion activity on these cells. Replacement of Arg64 with Glu (R64E) produced a considerable loss in receptor binding and a significant loss in biological activity. hGH variants in which either Glu65 or Glu66 was replaced with Asp (E65D and E66D) and with Gln (E65Q and E66Q) showed a slight loss in binding activity and retained almost a full adipogenic activity. An E65P variant (replacement of Glu65 with Pro) possessed the same binding activity as hGH, although it failed to induce full biological activity. The insertion of Ala between Asn63 and Arg64 (63NAR) caused a marked loss in both activities. These results indicate that the positively charged Arg64 is important for receptor binding and thereby in eliciting the biological activity of hGH, while negatively charged Glu65 and Glu66 are less important. In addition, our findings confirm that the conformation and size of the loop region around Arg64 is important for the adipose conversion activity of hGH.

Adipose Tissue↗

Quantitative assessment of daily physical activity levels in patients with chronic heart failure by measuring energy expenditure--effects of converting enzyme inhibitor therapy.

Although a major goal in the treatment of chronic heart failure is to improve daily physical activity levels, this has not been assessed quantitatively. An increased daily activity level may be reflected by an increase in daily energy expenditure. In the present study, measurements of energy expenditure with a commercially available ambulatory calorimeter were first validated using cardio-pulmonary exercise tests in 5 normal volunteers. The energy expenditure measured by the calorimeter correlated well with that estimated from oxygen uptake (r = 0.89). Subsequently, the daily energy expenditure was serially measured with the calorimeter during long-term administration of the converting enzyme inhibitor ramipril for 24 weeks in 8 patients with chronic heart failure. Changes in echocardiographic parameters and exercise capacity were also studied. Peak oxygen uptake and anaerobic threshold assessed with symptom-limited maximal bicycle exercise were significantly increased 12 weeks or more after the initiation of treatment (P < 0.01 and P < 0.01, respectively). Left ventricular fractional shortening substantially, but not significantly, increased during this period (P < 0.1). These results strongly suggest that an overall improvement in heart failure was achieved after long-term ramipril therapy. The energy expenditure during daily activities was also significantly increased after ramipril therapy for 24 weeks (P < 0.01). Thus, the daily energy expenditure increased with improvement of heart failure, probably reflecting an increase in daily activity levels. We conclude that calorimetric measurement of daily energy expenditure is a novel and simple technique for quantitative evaluation of the effect of therapy on daily physical activity levels in patients with chronic heart failure.

Activities of Daily Living↗

Acute or chronic exercise alters angiotensin II-induced contraction of rat aorta.

Chronic exercise substantially shifted the dose-response curve for angiotensin II (ANG II)-induced contractions to the right with increases in the EC50 value in both endothelium-intact and endothelium-denuded aortae. An acute endurance exercise also caused a 3-fold increase in the EC50 value in both endothelium-intact and endothelium-denuded aortae from sedentary control rats. Whereas, no substantial increase in the EC50 value was observed in trained rats after an acute endurance exercise. Thus, chronic exercise attenuates ANG II receptor-mediated contraction of rat aortae. An acute exercise also caused the reduced responses to ANG II in sedentary control rats but not in chronically exercise-trained rats.

Angiotensin II↗

CT finding of transient focal increased attenuation of the liver adjacent to the gallbladder in acute cholecystitis.

OBJECTIVE: The purpose of this article is to report the finding of transient focal increased attenuation of the liver adjacent to the gallbladder on enhanced CT scans in patients with acute cholecystitis. This finding should not be confused with primary liver abnormalities. MATERIALS AND METHODS: Five patients with acute cholecystitis were studied. Because a thickened gallbladder wall was seen on sonography, all patients were examined preoperatively with incremental dynamic helical CT to exclude carcinoma of the gallbladder. CT findings were compared with results of sonography for five patients, MR imaging for two patients, and surgery for five patients. RESULTS: Transient focal increased attenuation of the liver adjacent to the gallbladder was seen in the early phase of incremental dynamic CT in five patients and extended into the medial segment anterior to the porta hepatis. The areas showing increased attenuation adjacent to the gallbladder had a curvilinear shape around the gallbladder. No hepatic masses were seen on sonograms, on MR images, or at surgery. CONCLUSION: Transient focal increased attenuation of the liver may occur on CT scans in patients with acute cholecystitis. The increased attenuation associated with acute cholecystitis has a typical location and pattern. This finding is probably attributable to hepatic arterial hyperemia and to early venous drainage caused by the adjacent inflamed gallbladder. This finding should be differentiated from hypervascular hepatic tumors.

Acute Disease↗

[A case of psychological non-neuropathic bladder successfully diagnosed by continuous monitoring of detrusor pressure].

We report a case of psychological non-neuropathic bladder difficult to diagnose and treat. A 44-year-old woman was admitted to the Department of Urology of the Asahikawa Medical College Hospital with complaints of difficulty in micturition and urinary incontinence. Urodynamic studies revealed underactive function of the detrusor and incompetent urethra. She was instructed in self intermittent catheterization for difficulty in micturition. Drug therapy, electrical stimulation and vesicourethral suspension were not effective to control urinary incontinence. Since uninhibited detrusor contraction was elicited by psychogenic stress during continuous monitoring of the detrusor function, she was diagnosed as psychological non-neuropathic bladder closely related to psychogenic factor. She had a careful counselling and medical treatment designed by her psychiatrist, urinary incontinence was remitted in about one year and a half.

Adult↗

Posterior fossa glioblastoma multiforme: MR findings.

PURPOSE: To characterize the MR findings of glioblastoma multiforme in the posterior fossa. METHODS: MR studies of nine patients with surgically proved posterior fossa glioblastoma multiforme were retrospectively evaluated. MR characteristics studied included tumor location, signal intensity, enhancement pattern, and presence of intratumoral hemorrhage, as well as presence of secondary hydrocephalus or metastatic spread. RESULTS: The tumors were located in the median portion of the cerebellum or brain stem in eight cases. Six extended into the fourth ventricle. Hydrocephalus was seen in four cases. Six cases demonstrated decreased T1- and increased T2-weighted signal intensities. Three cases demonstrated mixed signal intensities suggesting intratumoral hemorrhage. All of the eight patients who received contrast showed moderate to marked heterogeneous ringlike enhancement suggesting intratumoral necrosis. Multicentric/multifocal lesions or extraaxial metastases were identified in three of the nine cases, and there was extracranial extension into the cervical region in one case. CONCLUSION: Glioblastoma multiforme is a rare tumor in the posterior fossa. Differentiating it from metastatic tumor or malignant astrocytoma was difficult. However, combination of heterogeneous and ringlike enhancement, midline location, poorly defined margin, tumoral hemorrhage, concomitant multicentric/multifocal lesions, and extraaxial or extracranial metastasis may be clues for the prospective diagnosis of glioblastoma multiforme.

Adult↗

A case of primary glucocorticoid resistance.

A 79-year-old woman developed hypokalemia and metabolic alkalosis after breast cancer surgery. She was suspected of having primary glucocorticoid resistance on the basis of high plasma ACTH and serum cortisol levels without the features of Cushing's syndrome. To clarify the end-organ resistance to cortisol, we characterized the glucocorticoid receptors (GR) in cultured skin fibroblasts from the patient. The GRs in whole cell assays decreased binding affinity (Kd = 11.1 +/- 0.6 nM) and the number of binding sites for [3H]dexamethasone (binding capacity was 15,600 +/- 1,255 sites per cell). These results strongly suggest that our patient had primary glucocorticoid resistance caused both by a decreased number of GRs and a reduction in the affinity of GRs to cortisol.

Aged↗

Novel retinoic acid, 9-cis retinoic acid, in combination with all-trans retinoic acid is an effective inducer of differentiation of retinoic acid-resistant HL-60 cells.

Recent studies have shown that a high proportion of patients with acute promyelocytic leukemia (APL) achieve complete remission after treatment with all-trans retinoic acid (RA). Nevertheless, despite an initial good response, most patients that received continuous treatment with all-trans RA relapse and develop RA-resistant disease. The 9-cis RA is a high-affinity ligand for retinoid X receptors (RXRs) and also binds efficiently to retinoic acid receptors (RARs); all-trans RA is a ligand for RARs. Both alone are able to induce differentiation of wild-type HL-60 cells. We found that neither all-trans RA nor 9-cis RA (< 2 x 10(-6) mol/L) induced differentiation of RA-resistant HL-60 cells into either mature granulocytes or monocytes. However, morphologic differentiation of the RA-resistant HL-60 cells was induced by 10(-6) mol/L all-trans RA combined with various concentrations (10(-12) to 10(-6) mol/L) of 9-cis RA. Electron microscopic examination also confirmed that the combination of both retinoids induced RA-resistant HL-60 cells to differentiate to mature granulocytes. Functional analysis of differentiation (NBT reduction activity) confirmed the necessity of both analogs to induce differentiation. Also, expression of myeloid-specific differentiation antigens (CD11b and CD14) as well as migration inhibitory factor-related protein (MRP)-8/14 mRNAs were upregulated only in the presence of both retinoids in a dose-dependent manner. In these conditions 3H-thymidine incorporation was inhibited and numbers of viable cells were decreased, suggesting that all-trans RA with 9-cis RA may inhibit cell growth and induce differentiation of RA-resistant HL-60 cells into mature granulocytes. These studies suggest that 9-cis RA in combination with all-trans RA is an effective inducer of RA-resistant HL-60 cells and may have implications for both the biology of retinoids and clinical treatment of RA-resistant acute myelogenous leukemia, including APL patients.

Antigens, Differentiation↗

Construction of a new host-vector system in Arthrobacter sp. and cloning of the lipase gene.

Arthrobacter sp. strain MIS38 was transformed with a shuttle vector containing the kanamycin resistant gene kan (derived from Tn5) by an electroporation method. This shuttle vector is from Brevibacterium lactofermentum and Escherichia coli, pULRS8. The following optimal condition of electroporation was determined. A square wave pulse of 1 kV/cm electric field strength for 0.5 ms duration yielded 3 x 10(5) transformants/micrograms plasmid DNA. The number of transformants increased with the amount of DNA over the range 0.01-5 micrograms. This host-vector system was then used successfully to clone and express a lipase gene from Arthrobacter sp. strain MIS38 into both Arthrobacter sp. MIS38 and E. coli JM109.

Amino Acid Sequence↗

Significance of tubuloreticular structures forming in Daudi cells cultured with sera from mothers bearing infants with neonatal lupus erythematosus.

It is known that infants with neonatal lupus erythematosus (NLE) may be born to mothers whose sera are positive for the anti-Ro/SSA antibody. However, women who have this antibody do not always give birth to children with NLE. We have demonstrated tubuloreticular structures in vascular endothelial cells in the skin lesions of infants with NLE. Tubuloreticular structures could no longer be detected at the site of the lesions once the annular erythema had resolved, and the anti-Ro/SSA antibody test had become negative. The probability of a child being born with NLE was assessed by observing whether tubuloreticular structures were formed in Daudi cells cultured with sera from eight mothers who were anti-Ro/SSA antibody positive. Tubuloreticular structures formed in Daudi cells cultured with sera from four mothers who bore infants with NLE, but not in Daudi cells cultured with sera from four other mothers who bore normal infants. These results suggest that women who are positive for the anti-Ro/SSA antibody have a higher risk of bearing infants with NLE if tubuloreticular structures are formed in Daudi cells cultured with sera from these women, whereas this risk is lower if tubuloreticular structures do not develop in Daudi cells.

Adult↗

Isolation and purification of a high molecular weight substance from human urine which inhibits calcium oxalate crystal growth.

A high molecular weight inhibitor of calcium oxalate crystal growth in human urine was investigated. Three inhibitors were isolated by DEAE-Sephacel ion-exchange chromatography and, of these, the substance we named "Peak 3 protein" seemed to be the main inhibitor in human urine. Peak 3 protein and several was purified by fast protein liquid chromatography and polyacrylamide gel electrophoresis. This substance, with a molecular weight of 30 kDa, did not contain uronic acid and its inhibitory activity decreased after digestion with proteinase. The difference between Peak 3 protein and several inhibitors previously reported was investigated but no clear difference could be found. The fact that it was the protein structure which was responsible for the inhibitory activity and the fact that Peak 3 protein probably possessed many side-chains which did not contribute to the inhibitory activity influenced the outcome of the investigation.

Calcium Oxalate↗

Cloning of the aapT gene and characterization of its product, alpha-amylase-pullulanase (AapT), from thermophilic and alkaliphilic Bacillus sp. strain XAL601.

A thermophilic and alkaliphilic Bacillus sp. strain, XAL601, was isolated from soil. It produces a thermostable and alkaline-stable enzyme with both alpha-amylase and pullulanase activities. The alpha-amylase-pullulanase gene (aapT) from this Bacillus strain was cloned, and its nucleotide sequence was determined (GenBank accession number D28467). A very large open reading frame composed of 6,096 bases, which encodes 2,032 amino acid residues with an M(r) of 224,992, was found. The deduced amino acid sequence revealed that the four highly conserved regions that are common among amylolytic enzymes were well conserved. These include an active center and common substrate-binding sites of various amylases. In the C-terminal region, a six-amino-acid sequence (Gly-Ser-Gly-Thr-Thr-Pro) is repeated 12 times. The aapT gene was then subcloned in Escherichia coli and overexpressed under the control of the lac promoter. Purification of AapT from this recombinant E. coli was performed, and it was shown that the aapT gene product exhibits both alpha-amylase and pullulanase activities with one active site. The optimum temperature and pH for enzyme activity were found to be 70 degrees C and pH 9, respectively. Furthermore, AapT was found to strongly adsorb to crystalline cellulose (Avicel) and raw corn starch. Final hydrolyzed products from soluble starch range from maltose (G2) to maltotetraose (G4). Only maltotriose (G3) was produced from pullulan. The enzyme also hydrolyzes raw starch under a broad range of conditions (60 to 70 degrees C and pH 8 to 9).

Amino Acid Sequence↗