Inhibition of skeletal muscle sarcoplasmic reticulum Ca2+-ATPase by nitric oxide

The effects of nitric oxide on the activities of thapsigargin-sensitive sarcoplasmic reticulum Ca2+-ATPase (SERCA) and Ca2+ uptake by sarcoplasmic reticulum (SR) membranes prepared from white skeletal muscle of rabbit femoral muscle were studied. Pretreatment of the SR preparations with nitric oxide at concentrations of up to 250 microM for 1 min decreased the SERCA activity concentration dependently, and also decreased their Ca2+ uptake. Both these effects of nitric oxide were reversible. Inhibitors of guanylyl cyclase and protein kinase G (PKG) had no significant effect on the nitric oxide-induced inhibitions of SERCA and Ca2+ uptake. Moreover, dithiothreitol did not reverse the inhibitory effects of nitric oxide on SERCA and Ca2+ uptake. These findings suggest that nitric oxide inhibits SERCA, mainly SERCA 1, of rabbit femoral skeletal muscle by an action independent of the cyclic GMP-PKG system or oxidation of thiols, and probably by a direct action on SERCA protein.     

Identification of alternative splicing form of Stat2

Three cases of pulmonary leiomyosarcoma were presented. The characteristic clinical features were described with review of literature. In comparison with bronchogenic carcinoma, the leiomyosarcoma has some characteristics: 1) On chest X-ray, it usually appears as a sharply demarcated, even density round mass, growing rapidly within the lung, it rarely accompanies with hilar or mediastinal lymph node metastasis. 2) The preoperative cytological or pathological diagnosis is difficult either by sputum smear or by bronchoscopic biopsy or by fine needle percutaneous aspiration biopsy. 3) Pathological differential diagnosis of leiomyosarcoma of lung from anaplastic lung cancer is difficult. In conclusion, the primary pulmonary leiomyosarcoma is a rare malignant tumor, detecting the present illness seriously, paying attention to the chest X-ray films characterize, early surgical resection is the only way to get diagnosis and effective treatment method.     

Lattice corneal dystrophy type II associated with familial amyloid polyneuropathy type IV

BACKGROUND: Finnish-type familial amyloidosis (FAP-IV) is an autosomal, dominantly inherited disorder characterized by progressive polyneuropathy and lattice corneal dystrophy type II. The vast majority of families with this disorder originated from Finland. Only two families, in neighboring districts, have been reported in Japan previously. METHODS: The authors report two additional Japanese patients with FAF-IV. The proband, a 70-year-old man, had decreased perspiration and abnormal facial muscle movement. Results of neurologic examination showed bilateral facial and hypoglossal nerve palsies, and an autonomic disturbance, including orthostatic hypotension and dysfunction of perspiration. Histochemical, immunohistological, and DNA studies confirmed the diagnosis of FAP-IV. RESULTS: Results of ophthalmologic examination showed asymptomatic lattice corneal dystrophy of both eyes, but the appearance of the cornea was different from that described in the patients from Finland. Lattice lines in the authors' patient were very fine, short, and glassy and could be observed with indirect retroillumination, but might be missed with direct illumination by the slit-lamp microscope. The proband's younger half-sister, a 68-year-old woman, showed clinical findings and laboratory data similar to those of the proband. CONCLUSION: The authors report two Japanese patients with lattice corneal dystrophy type II related to FAP-IV. This is the third Japanese family with this disorder, and there is no familial relationship to the two previously reported families in Japan.     

Pharmacokinetic re-evaluation and phase I study of high dose epirubicin in advanced non-small cell lung cancer

We performed a phase I trial to evaluate the toxicity and the maximum tolerated dose of high dose epirubicin on a three-consecutive-day schedule on Japanese patients with advanced non-small cell lung cancer. Fourteen patients were entered in the study. At least three patients were assigned to each different dose level. Epirubicin was given intravenously daily for three day by bolus injection. The dose was started at 60 mg/m2/course and escalated by 30 mg/m2/course. Granulocytopenia was found to be the dose limiting toxicity with a maximum tolerated dose of 150 mg/m2/course. Thrombocytopenia and non-hematological toxicities were mild and well tolerated. The maximum tolerated dose was lower than that in Europe and Canada. Partial responses were observed in two out of five patients on 150 mg/m2/course. The recommended phase II dose for high dose epirubicin was demonstrated to be 120 mg/m2/course. A further dose-escalating study of epirubicin in conjunction with the administration of granulocyte colony stimulating factor is scheduled for the determination of its antitumor activity in non-small cell lung cancer.     

Morphology and rotation twin in ZnSe on GaAs (111)

ZnSe crystals were grown by a vapour transport method on a GaAs substrate with a (111) A or (¯1¯1¯1) B surface. Crystals obtained on the (111) A surface of the substrate were fine crystals and hexagonal plates. Whereas crystals grown on the (¯1¯1¯1) B were uniform thin films on which trigonal hills and trigonal pyramids developed. These crystallites had a complicated morphology. In addition, the hill and pyramid grown on the (¯1¯1¯1) B surface contained rotation twins around a polar axis parallel to the growth direction or around the other polar axes.     

Aspirin and salicylate enhances the induction of inducible nitric oxide synthase in cultured rat smooth muscle cells

Aspirin and sodium salicylate enhance to a similar extent the production of nitric oxide (NO) in cultured smooth muscle cells following stimulation by interleukin-1beta (IL-1beta). The similar potencies of aspirin and sodium salicylate indicate that acetylation of cellular macromolecules is not essential for the enhancement of NO production. The failure of added prostaglandin E2 (PGE2) or Thromboxane A2 (TXA2) to overcome the effects of aspirin or sodium salicylate indicates that these effects are not simply the result of inhibition of prostaglandin synthesis. The enhancement of NO production occurs dependent of the effects of these agents on induction of inducible nitric oxide synthase (iNOS) expression by IL-1beta. Aspirin and sodium salicylate enhance the induction of iNOS expression by IL-1beta. We previously reported that pretreatment of vascular smooth muscle cells (VSMCs) with high glucose decreased the response of the cells by IL-1beta, that is, the induction of iNOS expression and NO production. We investigated the effect of aspirin and sodium salicylate on the response by IL-1beta of VSMCs pretreated with high glucose (25 mM). Aspirin and sodium salicylate ameliorate the down-regulation of iNOS expression and the decrease of NO production caused by pretreatment with high glucose (25 mM). These results suggest a possible therapeutic role in atherosclerotic disease and diabetes mellitus for aspirin and sodium salicylate by enhancing the level of iNOS expression and NO production.     

Structure-activity relationships of spontaneous nitric oxide releasers, FK409 and its derivatives

(+/-)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) shows both potent in vitro vasorelaxant and antiplatelet activities via nitric oxide (NO) generated spontaneously from the compound. In this study, we measured spontaneous NO-releasing rates of a series of FK409 derivatives, of which chain lengths or substituents were systematically modified, in sodium-phosphate buffer solution at pH 7.4. Furthermore, we studied their in vitro antiplatelet and vasorelaxant effects to evaluate relationships between spontaneous NO-releasing activities of FK409 analogs and their biological activities. FK409 derivatives were found to possess different spontaneous NO-releasing rates and biological activities according to their structural modification. In addition, these studies revealed a close correlation between NO-releasing rates of FK409 derivatives and their in vitro antiplatelet activities in human platelet-rich plasma, whereas the in vitro vasorelaxant activities of these compounds in isolated rat aorta did not correlate with the rates of NO liberation. The vasorelaxant effects were supposed to be affected by the structural properties of FK409 derivatives as well as their NO-releasing abilities.     

Materials evaluation of diffusion bonded steel bar and its impact characteristics

When we apply non-destructive test for evaluating the soundness of weld joints it is necessary to know the mechanical properties of the joints by destructive test. In this paper we tried to obtain the correlation between the data by ultrasonic C-scope method and the absorbed energy by Charpy impact test for diffusion bonded steel bars. The surface roughness of specimens (materials: S25C, mild steel) used for the diffusion bonding was changed into several steps by machining and the diffusion bonding was performed on five kinds of combinations of the surface roughness. Through this process we obtained the diffusion bonds whose ratio of non-bonded area was different. In the ultrasonic test we used the frequency of 10 MHz and a transducer of 12.7 mm in diameter. The ratio of non-bonded area is obtained by using C-scope method by immersion testing, and this depended on the threshold echo level when we binarized the images of C-scope presentation and the surface roughness of the specimen. The lower the threshold echo level, the larger the ratio of non-bonded area. The absorbed energy depended on the ratio of non-bonded area. It is made clear that the proper threshold echo level should be selected for evaluating the soundness of diffusion bonds by ultrasonic test. Moreover, when the transition liquid phase diffusion bonding was performed on SD345 (deformed reinforcing steel bar) using Ni amorphous foil as an insert metal the absorbed energy also decreased with the increase in the ratio of flaw area obtained by ultrasonic test, though no change in the tensile strength was observed.     

Simultaneous measurement of surface tension and kinematic viscosity using thermal fluctuations

We have developed a surface laser-light scattering apparatus to measure simultaneously surface tension and kinematic viscosity. In this method, we can obtain the surface properties by the laser heterodyne detection of light scattered from thermally excited capillary waves (called ripplon), which are typically of low amplitude (1 nm) and a characteristic wavelength (100m). Two gratings (d=100 and 200m) were employed to select the wave number of the capillary waves and to produce a reference beam for heterodyne detection. It was found through an experimental study on water that this contact-free method has considerable potential for application to measurements under extreme conditions such as high temperatures and high pressures.Paper presented at the Twelfth Symposium on Thermophysical Properties, June 19–24, 1994, Boulder, Colorado, U.S.A.