Showing papers by "Hiroshi Maeda published in 1996"

Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals

Abstract: The role of nitric oxide (NO) in the pathogenesis of influenza virus-induced pneumonia in mice was investigated Experimental influenza virus pneumonia was produced with influenza virus A/Kumamoto/Y5/67(H2N2) Both the enzyme activity of NO synthase (NOS) and mRNA expression of the inducible NOS were greatly increased in the mouse lungs; increases were mediated by interferon gamma Excessive production of NO in the virus-infected lung was studied further by using electron spin resonance (ESR) spectroscopy In vivo spin trapping with dithiocarbamate-iron complexes indicated that a significant amount of NO was generated in the virus-infected lung Furthermore, an NO-hemoglobin ESR signal appeared in the virus-infected lung, and formation of NO-hemoglobin was significantly increased by treatment with superoxide dismutase and was inhibited by N(omega)-monomethyl-L-arginine (L-NMMA) administration Immunohistochemistry with a specific anti-nitrotyrosine antibody showed intense staining of alveolar phagocytic cells such as macrophages and neutrophils and of intraalveolar exudate in the virus-infected lung These results strongly suggest formation of peroxynitrite in the lung through the reaction of NO with O2-, which is generated by alveolar phagocytic cells and xanthine oxidase In addition, administration of L-NMMA resulted in significant improvement in the survival rate of virus-infected mice without appreciable suppression of their antiviral defenses On the basis of these data, we conclude that NO together with O2- which forms more reactive peroxynitrite may be the most important pathogenic factors in influenza virus-induced pneumonia in mice

Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth

Abstract: BACKGROUND. Rapid tumor growth is caused by angiogenesis factors, growth factors, etc. We previously reported a possible connection between nitric oxide (NO) and enhanced vascular permeability in solid tumor. In the present experiment, the role of NO in solid tumor pathology was further investigated in animal tumor. METHODS. To identify NO formed in solid tumor (AH136B) implanted in the feet of rats, electron paramagnetic resonance (EPR) spectroscopy was performed directly on the frozen tumor tissue at 110K by measuring endogenous nitrosyl iron-sulfur complexes, and by using exogenously added NO capturing agents, i.e., diethyldithiocarbamate (DETC)-Fe 2+ and N-(dithiocarboxy)sarcosine (DTCS)-Fe 2+ complexes. Induction of inducible isoform of nosymthase iNOS mRNA was examined with reverse transcriptase-polymerase chain reaction (RT-PCR) combined with Southern blot analysis. In addition, vascular permeability was assessed by measuring extravasation of 51 Cr-labeled bovine serum albumin in solid tumor. RESULTS. Strong EPR signals from NO adducts of DETC-Fe 2+ and DTCS-Fe 2+ as well as strong signals from NO-hemoglobin and dinitrosyl iron sulfur complex were generated by tumor. The signal height of NO-(DTCS) 2 -Fe 2+ observed in AH136B solid tumor was increased as the tumor gained up to 1.75 g. Induction of iNOS mRNA expression was confirmed by the above methods. Enhanced vascular permeability was suppressed by NOS inhibitors N ω -monomethyl-L-arginine or S-methylisothiourea sulfate and augmented with administration of L-arginine. CONCLUSIONS. Excessive NO production by iNOS in solid tumor was identified unequivocally by EPR spectroscopy. NO formed in solid tumor can be involved in enhanced vascular permeability and increased blood flow, and hence sustain tumor growth.

Role of microbial proteases in pathogenesis.

Abstract: The manifestation of microbial pathogenesis is dependent on complex events and processes in the infected hosts. Even with the advent of the development of antibiotics, the importance of understanding disease processes has never decreased. Diseases attributed to bacterial toxins are rather specific to each toxin in the manifestation of respective diseases, whereas most of disease states attributed to the microbial proteases are nonspecific and very complex. Therefore, microbial proteases have received less attention compared to toxins in the manifestation of the microbial virulence. Microbes, whether bacteria or fungi, produce wide varieties of

Pathogenic mechanisms induced by microbial proteases in microbial infections.

Abstract: Most bacterial and fungal proteases excreted into infected hosts exhibit a wide range of pathogenic potentials ranging from pain, edema or even shock to translocation of bacteria from the site of infection into systemic circulation, thus resulting in septicemia. The basic mechanism or principle common to all these phenomena is explained by kinin generation, either directly from high- and/or low-molecular weight kininogens or indirectly via activation of the bradykinin generating cascade: i.e. Hageman factor-->activated Hageman factor-->prekallikrein-->kallikrein-->high-molecular weight kininogen-->bradykinin. Some bacterial proteases are also involved in activation of other host protease zymogens such as plasminogen, procollagenase (matrix metallo proteases) and proenzymes of the clotting system. Furthermore, most bacterial proteases are not only resistant to plasma protease inhibitors of the hosts, most of which belong to a group of serine protease inhibitors called serpins (serine protease inhibitors), but they also quickly inactivate serpins. Some bacterial proteases may also activate bacterial toxins thus rendering toxigenic pathogenesis. They are also capable of degrading immunoglobulins and components of the complement system and facilitate propagation of micro organisms. All in all, microbial proteases are very critical in enhancing pathogenesis of severe diseases. It is also noteworthy that bacterial cell wall components themselves, i.e. endotoxin (or lipopolysaccharide) of gram negative bacteria and teichoic/lipoteichoic acid of gram positive bacteria, are also able to activate the bradykinin generating cascade-involving activation of Hageman factor as mentioned above.

Potentiation of nitric oxide-mediated vasorelaxation by xanthine oxidase inhibitors

Abstract: Nitric oxide (NO), now almost synonymous with endothelium-derived relax- ing factor (EDRF), reacts with superoxide anion radical (O,-) and forms a potentially toxic molecular species, peroxynitrite (ONOO-). Because xanthine oxidase (XO) seems to be a major 0,--producing enzyme in the vascular system, it is important to clarify the mechanism of XO regulation of NO/EDRF. We first characterized the inhi- bition of XO in vitro by three types of pyrazolopyrimidine derivatives. Kinetic studies indicated that 4-amino-6-hydroxypyrazolo(3,4-d)pyrimidine (AHPP) and allopurinol competitively inhibited the conversion of xanthine to uric acid catalyzed by XO, with apparent K, values of 0.17 f 0.02 and 0.50 f 0.03 pM, respectively; alloxanthine inhibited this conversion in a noncompetitive manner with an apparent K, value of 3.54 2 1.12 pM. 0,- generation in the xanthine/XO system assayed by lucigenin- dependent chemiluminescence was suppressed most strongly by AHPP in a dose- dependent fashion; allopurinol itself appears to reduce the enzyme by transfer of an electron to 02, thus generating 0,-. AHPP significantly augmented EDRF-mediated relaxation of aortic rings from both rabbits and spontaneously hypertensive rats (SHR) in a dose-dependent manner, whereas allopurinol did not affect the relaxation and only marginal potentiation of the vasorelaxation was observed with alloxanthine. Finally, iv injection of AHPP (50.4 mglkg; 100 pmo1/300 g rat) reduced the blood pressure of SHR rats to 70% of the initial pressure; this pressure is al- most the blood pressure of normal rats. Allopurinol (100 pmo1/300 g rat; iv) showed transient decrease in blood pressure and moderate reduction of hypertension of SHR (10%) was observed with iv injection of alloxanthine (100 pmo1/300 g rat). On the basis of these results, it seems that XO regulates EDRFINO via production of 0,-. (P.S.E.B.M. 1996, Vol 21 11

Expression of inducible nitric oxide synthase and its involvement in pulmonary granulomatous inflammation in rats

Abstract: Two types of pulmonary granulomatosis were produced in rats by intratracheal instillation of zymosan or silica. In both models, immunostaining with anti-rat monoclonal antibody for inducible nitric oxide synthase (iNOS), ANOS11, showed that the intensity of iNOS immunoreactivity in the inflammatory lesions peaked at 3 days and declined thereafter. Immunohistochemical double staining and in situ hybridization demonstrated the expression of iNOS in neutrophils, monocyte-derived macrophages, and bronchiolar epithelial cells in the pulmonary lesions. Electron spin resonance spectroscopy revealed the production of an excessive amount of nitric oxide (NO) in the pulmonary lesions. Immunostaining with a polyclonal antibody against nitrotyrosine indicated the formation of nitrotyrosine residues in the granulomatous lesions, particularly in the periphery of the lesions, providing indirect evidence for the generation of peroxynitrite anion in the zymosan- or silica-instilled lungs. Administration of N omega-nitro-L-arginine methyl ester or S-methylisothiourea sulfate, which significantly suppressed NO production, resulted in marked reduction of monocyte/macrophage infiltration as well as in inhibition of induction of monocyte chemoattractant protein-1 in the lesions. These data indicate that NO and its more reactive product peroxynitrite anion may be important mediators of granuloma formation in the lung.

Bradykinin generation triggered by Pseudomonas proteases facilitates invasion of the systemic circulation by Pseudomonas aeruginosa

Abstract: To elucidate the mechanism of bacterial exoprotease in promotion of the intravascular dissemination of Pseudomonas aeruginosa, we examined the possible involvement of bradykinin (whose generation is induced by pseudomonal proteases in septic foci) in the invasion by bacteria, and in access of bacterial toxins to systemic blood circulation. P. aeruginosa 621 (PA 621), which produces very little protease, was injected intraperitoneally into mice together with pseudomonal exoproteases (elastase/alkaline protease). Dissemination of bacteria from the peritoneal septic foci to the blood was assessed by counting viable bacteria in the blood and spleen by use of the colony-forming assay. The results showed that pseudomonal proteases markedly enhanced (10- to 100-fold) intravascular dissemination of bacteria in mice. This enhancement was induced not only by pseudomonal proteases but also by bradykinin. More importantly, the increased spread of PA 621 induced by pseudomonal protease and bradykinin was significantly augmented by the addition of kininase inhibitors, indicating the direct involvement of bradykinin in bacterial dissemination. Similarly, bradykinin caused effective dissemination of pseudomonal toxins such as endotoxin (lipopolysaccharide) and exotoxin A when the toxins were injected into the peritoneal cavity with bradykinin. Furthermore, the lethality of the infection with PA 621 was strongly enhanced by pseudomonal proteases given i.p. simultaneously with PA 621. On the basis of these results, it is strongly suggested that pseudomonal proteases as well as bradykinin generated in infectious foci are involved in facilitation of bacterial dissemination in vivo.

A beta-adrenoceptor agonist evokes a nitric oxide-cGMP relaxation mechanism modulated by adenylyl cyclase in rat aorta. Halothane does not inhibit this mechanism.

Abstract: Background : The objective of this study was to characterize the effects of halothane on the agonist-induced nitric oxide-cyclic GMP (NO-cGMP) mechanisms by comparing the intracellular signal transduction mediating isoproterenol- and acetylcholine-induced nitric oxide formation. Metbods : Isoproterenol-induced relaxations of rat aortic rings with and without endothelia were examined in the absence and presence of halothane. Studies were also done in the presence of inhibitors of nitric oxide-synthase, adenylyl cyclase, calmodulin, protein kinase A, and intracellular Ca 2+ release mechanism. The relaxations under some of these conditions were compared with those induced by acetylcholine. Cyclic nucleotide contents of the rings were also measured. Results : Isoproterenol relaxed aortic rings via the endothelium-dependent nitric oxide-cyclic GMP mechanism. Inhibition of adenylyl cyclase or of protein kinase A attenuated the isoproterenol-induced relaxations significantly but did not affect those induced by acetylcholine. Inhibition of intracellular Ca 2+ release abolished the acetylcholine-induced relaxations but did not affect those induced by isoproterenol. Calmodulin inhibition attenuated both agonist-induced relaxations significantly. Unlike acetylcholine-induced relaxation, that induced by isoproterenol was not affected by halothane. Isoproterenol increased both the cyclic adenosine monophosphate and cGMP contents of rings significantly when endothelia were intact. Inhibition of nitric oxide synthase attenuated the isoproterenol-induced cGMP content increases significantly but did not affect the cyclic adenosine monophosphate content increases. Halothane (2%) did not affect isoproterenol-induced increases in nucleotide content. Conclusions : Isoproterenol-induced nitric oxide formation requires the activation of constitutive nitric oxide synthase, but the Ca 2+ release mechanism is not involved in activating this enzyme. Halothane can inhibit the nitric oxide-cyclic GMP mechanism only when Ca 2+ release is greatly involved in the activation of constitutive nitric oxide synthase.

Polymer Conjugation to Cu,Zn-SOD and Suppression of Hydroxyl Radical Generation on Exposure to H2O2: Improved Stability of SOD in Vitro and in Vivo

Abstract: Highly reactive hydroxyl radical (OH) is generated during reaction of Cu,Zn-SOD (SOD)1 with H202, its own enzymatic reaction product (SOD plus 0;-). During inactivation of Cu,Zn-SOD with H202, Cu2+ liberated from the SOD catalyzes the formation of OH from H202. The OH thus generated will react with a,-protease inhibitor (a,-PI) if it is available in the milieu. To circumvent OH generation, we prepared eight different polymer-SOD conjugates and compared their stability against H202 treatment. Furthermore, the effect of each polymer-SOD conjugate on a,-PI in the presence of H202 was tested. Most polymer-SOD conjugates, except poly(styrene-co-maleic acid butylate; SMA)-SOD and poly(ethylene glycol; PEG)-SOD, showed higher stability than native SOD against inactivation by H202. The residual activity of divinylether maleic acid/anhydride copolymer (pyran copolymer)-conjugated SOD was 87% of the initial activity after incubation with 0.1 mM H202 for 2 h, whereas that of native SOD was 49%. Antiprotease activity...

Present status and future plan of the Tsukuba Magnet Laboratories

Abstract: We have been developing and installing several high field magnets, i.e. long pulsed magnets, a 40 T class hybrid magnet, a 21 T superconducting magnet, several high resolution magnets, etc. The 40 T class hybrid magnet is composed of a 15 T superconducting magnet with a room temperature clear bore of 400 mm and a 25 T polyhelix-type water-cooled magnet with a 30 mm bore. The 21 T superconducting magnet with a clear bore of 61 mm, operated at 1.8 K, is now being used. Inside the magnet small Bi-2212 coils have been installed and excited to generate a total field up to 21.8 T in a clear bore of 13 mm. Using the high resolution magnet systems, Fermi surface properties of many materials have been revealed. Furthermore, we have fabricated two types of pulsed magnet coils to generate 73.4 T in a short pulse duration of 5 ms and 64.5 T in a long 100 ms duration, using newly developed Cu-Ag alloy composite wires with high strength and high conductivity.

Generation of magnetic fields over 21 T in a 61 mm clear bore using low copper ratio (Nb,Ti)/sub 3/Sn conductors

Abstract: A 21 T superconducting magnet system has been developed and improved at the National Research Institute for Metals in Japan. As the steady progress of high-T/sub c/ superconducting coils required a larger bore for testing their performance, a new innermost coil has been developed. We increased the available bore from 50 mm to 61 mm. The new coil employed three kinds of rectangular (Nb,Ti)/sub 3/Sn conductors. External copper stabilized these conductors, with a Cu:SC ratio of only 0.25. The new coil operated in a 160 mm diameter clear bore with a background field of 18 T in saturated superfluid helium, generating a central field of 21.5 T without any training behavior. A double walled dewar, the outer diameter of which was 60 mm, was also developed. With this dewar, the new system provides a temperature-variable bore of 50 mm.

Jc property and microstructure of Bi2223 tapes made using AgCu alloy sheaths doped with Ti, Zr or Hf

Abstract: Bi-2223 superconducting tapes were prepared by the powder-in-tube technique using Ag-10 at%Cu alloy sheaths with and without a small amount of doping elements of Ti, Zr or Hf, and repetition of sintering and cold pressing. The doped samples showed a high critical current density, J c of 5–9 × 10 4 A/cm 2 , at 4.2 K and 14 T. Micrograph examinations on these samples revealed a modified Bi-2223 grain structure at the sheath/core interface and also a more dense and aligned microstructure. Furthermore, amorphous, small disc-like regions, less than 5 nm in thickness parallel to the (001) plane, were found to be incorporated in the Bi-2223 lattice only for the doped samples. Critical current properties measured by magnetization and resistive methods were described correlating with the microstructures and the magnetic plux pinning. These amorphous regions are likely to provide the effective flux pinning centers in the Bi-2223 superconductors.

Locally‐Confined Signet‐Ring Cell Carcinoma of the Prostate: A Case Report of a Long‐Term Survivor

Abstract: It is generally believed that signet-ring cell carcinoma (SRCC) of the prostate is a high-grade neoplasm with a poor prognosis. We report a case of a long-term survivor diagnosed with localized prostatic SRCC (T3N0M0), who has been alive without any clinical evidence of disease for 100 months after combination therapy which consisted of local irradiation and hormone administration. A posttreatment needle biopsy confirmed the pathological complete response.

Pharmacological advantages of conjugation of Cu, Zn-superoxide dismutase with succinylated keratin fragment: improvement of biological properties and resistance to oxidative damage.

Abstract: To improve the in vivo pharmacological potential of Cu, Zn-superoxide dismutase (Cu,Zn-SOD), human recombinant Cu,Zn-SOD was conjugated with succinylated keratin fragment (Suc-ker). Suc-ker-conjugated Cu,Zn-SOD (Suc-ker-SOD) was formed by attachment of about 3.7 mol of Suc-ker to 1 mol of Cu,Zn-SOD and exhibited an apparent mean molecular weight of 107 kDa. Suc-ker-SOD exhibited 74.1% SOD activity on a molar basis. When Suc-ker-SOD was administered i.v. into mice, its plasma half-life was prolonged to 20.5 min compared with 4.7 min for native SOD. After i.v. administration of 51Cr-labeled proteins into mice, native SOD was excreted rapidly into urine and no significant accumulation was observed in organs other than the kidneys. On the other had, Suc-ker-SOD was taken up rapidly by the liver. Furthermore, Suc-ker-SOD exhibited much lower immunogenicity and much better therapeutic effects than native and poly(styrene-co-maleic acid)-conjugated SOD against paraquat toxicity in mice. Moreover, the inactivation rate of Suc-ker-SOD by H2O2 was less than those of native SOD and polyethylene glycol-conjugated SOD. The effect of H2O2 on liganded Cu++ in the active site of Suc-ker-SOD was much less than those of other SOD derivatives. These results indicate that Suc-ker-SOD has advantages over the other SOD derivatives tested.

Changes in cellular components of spleen and lymph node cells and the effector cells responsible for Meth A tumor eradication induced by zinostatin stimalamer.

Abstract: We reported previously that pretreatment with zinostatin stimalamer (ZSS) eradicated Meth A tumors in BALB/c mice. We herein investigated cellular components of spleen and lymph node cells of Meth A-bearing ZSS-pretreated mice by flow cytometry; the antitumor effector cells by in vivo depletion of T cells, NK cells, or macrophages; and host-mediated antitumor activity associated with ZSS treatment after tumor transplantation. ZSS given on day -3 transiently decreased the number of spleen cells. The percentage of T cells increased, but B cells and macrophages decreased. B cells decreased in inguinal lymph nodes in Meth A-bearing ZSS-pretreated mice, but increased in Meth A-bearing control mice. In vivo depletion experiments using antibodies or carrageenan showed that antitumor effector cells for tumor eradication are Thy1.2+/Lyt2.2+ and that at least a part of them are asialo GM1+. Thy1.2+/Lyt2.2+/asialo GM1- cells are important in generation of the antitumor activity of ZSS; however, L3T4+ T cells are also involved in initiation of tumor eradication. The result of ZSS treatment after tumor transplantation suggests that ZSS might exhibit antitumor activity by augmentating host-mediated antitumor resistance, as well as its intrinsic cytocidal activity.

Mesonephric adenocarcinoma arising in the female urethral diverticulum

Abstract: A forty four-year-old house-wife presented with gross hematuria and difficulty on urination of a year and 3 months duration. Transvaginal examination showed a hen egg-sized soft mass on the anterior vaginal wall. Urine cytology revealed many clusters of malignant cells suggestive of adenocarcinoma. Cystourethrography revealed two urethral diverticula, whose orifices were cystoscopically located at the proximal and distal side of urethral sphincter, respectively. By vaginal digital pressing, a soy-bean sized papillary tumor came out of the proximal diverticulum. Histopathological examination of the biopsied tumor suggested poorly differentiated transitional cell carcinoma with inverted growth. Under the diagnosis of carcinoma arising in the urethral diverticulum, anterior pelvic exenteration with formation of Indiana pouch was carried out. The tumor in the proximal diverticulum was histologically composed of a variety of adenocarcinomatous pattern, such as tubular, papillary and cystic structure with a distinctive pattern of tubules lined by a superficial layer of hobnail cells, leading to the diagnosis of mesonephric adenocarcinoma of urethral diverticulum. Postoperative radiation therapy was given because the diverticulum was adherent to the pubic bone, though lymph node metastasis was negative. She has been well with no evidence of the disease for 1 year and 4 months after the operation. Although the histogenesis of female urethral mesonephric adenocarcinoma was still controversial, this case seems to be the forty fourth case in the world literature.

Power supply and control system for 40 T class hybrid magnet system

Abstract: The construction of the 40 T class hybrid magnet system was completed at the Tsukuba Magnet Laboratory of NRIM. Now, the total system test is being performed. This system consists of a hybrid magnet composed of a water cooled magnet and a superconducting magnet, power supplies for these magnets, water cooling system, and control system. The power supply for the water cooled magnet is a low ripple power supply, and it also has a "soft stop circuit" to prevent quenching of the superconducting magnet. In order to confirm the achievement of low current ripple and efficiency of the soft stop circuit we carefully analyzed the behavior of this circuit. As a results, we confirmed that the performance of the power supply satisfies the specifications. Also, we verified efficiency of the soft stop circuit.

Development of (Nb, Ti)3 Sn and Nb-Ti conductors for 15 T superconducting magnet of 40 T class hybrid magnet

Abstract: Tube processed (Nb, Ti)3Sn and NbTi conductors have been developed for a 15 T class superconducting magnet with a 400 mm clear bore of a 40 T class hybrid magnet. Prior to testing the actual conductor, the transverse compressive stress effects on the critical current (Ic) of the (Nb. Ti)3Sn conductors were studied using a 1 7 scale reduced conductor. The Ic of the samples with clearance of gap length of over 0.3 mm between Cu-housings and (Nb,Ti)3Sn monolith reached over 90% of unloaded Ic(Ic0) at 14 T and 60 MPa of the transverse compressive stress. Based on the above-mentioned results, a new structure for full-scale Cu-housing (Nb,Ti)3Sn conductors has been designed and fabricated. Fabricated (Nb, Ti)3Sn conductors flowed more than 3870 A at 15 T and had 300 M Pa of 0.2% proof stress. All these values exceeded the values in the specification with a good margin.

21 T superconducting magnet system at TML

Abstract: A 21 T superconducting magnet system is one of the major high field facilities of the Tsukuba Magnet Laboratories (TM L). Before its installation at the TML, this magnet succeeded in generating fields over 21 T in the fully superconducting state. In the beginning of 1994, the whole system was moved to the TML and combined with a refrigeration system. Regular operations have been performed since May 1994. Continuous improvements have been made to generate higher fields in larger space. In October 1994, this magnet could generate a field of 21.1 T in a 61 mm clear bore. In this paper, the present status of the 21 T superconducting magnet system is reported with our future plans.

Electron Beam Direct Writing Techniques for the Development of Sub-Quarter-Micron Devices

Abstract: Novel techniques for electron beam (EB) direct writing are established for the development of sub-quarter micron devices. These techniques include 1) use of highly stable processes for positive and negative chemical amplification resists, 2) precise pattern size control by way of proximity effect correction using the pattern-area-density method, 3) a practical improvement technique for pattern size error at the exposure-field boundary, and 4) a novel alignment technique for a substrate covered with a heavy metal film. Successful fabrication of sub-quarter-micron test devices indicates that variable-shaped EB direct writing using these techniques is the best tool for research and development of advanced devices.

Use of 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine for the manufacture of an antihypertensive agent

Abstract: of EP0759298Antihypertensive agent containing as its active ingredient 4-amino-6-hydroxypyrazoloA3,4-dUpyrimidine (AHPP) or its derivatives represented by the general formula (I) where R is hydrogen atom, alkyl group, alkoxy group or aryl group. The antihypertensive agents of the present invention show a mild and reliable blood pressure lowering activity and have a different mode of action over the currently available antihypertensive agents.

Superconducting Properties of V3Si Multifilamentary Conductor

Abstract: A flattened V3Si multifilamentary conductor was prepared by cold-rolling a wire-composite, and then changes in morphology and configuration of the superconductor — normal metal (S-N) interface and grain boundaries were induced. Correlation between microstructure and the angular dependence of Jc with respect to the transverse field direction indicates clearly the existence of two kinds of pinning centers. The S-N interface acts as a dominant pinning center for parallel fields and becomes important in low magnetic fields, in particular for composites with fine V filaments. The element pinning force of the S-N interface was estimated from Fp vs (V3Si layer thickness)-1 relationship.

Method for treating hypertension using pyrazolopyrimidine derivatives

Abstract: Antihypertensive agents containing as its active ingredient the 4-amino-6-hydroxypyrazolo 3,4-d!pyrimidine(AHPP) or its derivatives represented by the general formula (I) below. ##STR1## where R is hydrogen atom, alkyl group or aryl group. AHPP can be chemically synthesized by a reaction of 3-amino-4-cyanopyrazole and urea. The antihypertensive agents of the present invention show a mild and reliable blood pressure lowering activity, and have a different mode of action from currently available antihypertensive agents.

Conjugation of Succinylated Gelatin to Soybean Trypsin Inhibitor

Abstract: Kunitz-type soybean trypsin inhibitor (SBTI) and succinylated gelatin fragment (Suc-gel) were conjugated by using water-soluble carbodiimide, and physicochemical and biopharmaceutical properties of the conjugate (Suc-gel-SBTI) were characterized. The conjugate contains about 2.5 mol of Suc-gel with a mean molecular weight of 32,000 per mole of SBTI, based on the content of hydroxyproline. After iv injection of the radiolabeled conjugate or native SBTI into mice, it was found that native SBTI showed rapid elimination from plasma (t½α = 2 min), whereas Suc-gel-SBTI was slowly (t½α = 2 min) eliminated. Organ distribution of the two agents at 30 min after iv injection was different: Suc-gel-SBTI accumulated to a large extent in both the liver and the spleen, about 23.4 and 6.9%, respectively which was more than the native SBTI. Native SBTI was taken up more rapidly by the kidney (~ 45%) and excreted into the urine (~34%) before it accumulated in other organs and tissues. In addition, we evaluated the pharmaco...

Antihypertensive agents containing pyrazolopyrimidine derivatives

Abstract: Antihypertensive agents containing as its active ingredient the 4-amino-6-hydroxypyrazolo [3,4-d]pyrimidine(AHPP) or its derivatives represented by the general formula (I) below. (see Formula I) where R is hydrogen atom, alkyl group, alkoxyl group or aryl group. AHPP can be chemically synthesized by reaction of 3-amino-4-cyanopyrazole and urea. The antihypertensive agents of the present invention show a mild and reliable blood pressure lowering activity, and have different mode of action from the currently available antihypertensive agents.

40 T class hybrid magnet system

Abstract: We have already completed the fabrication, installation, cabling, and the piping of a 40 T class hybrid magnet system including a 15 MW DC power supply (430 V × 35 kA), 15 MW water-cooling system (inlet temperatures below 10°C, flow rates up to 800 t/h) helium liquefier/refrigerator, and a hybrid magnet composed of an outer superconducting magnet and an inner resistive magnet. Their test operations are progressing now. Except for the hybrid-mode test operations for the hybrid magnet system we have nearly completed all the other test operations. In this article we describe mainly the specifications of the hybrid magnet, the DC power supplies, total control system, water-cooling system, and the present situation of the test operation.