Complex gangliosides are essential in spermatogenesis of mice: possible roles in the transport of testosterone

Mice, homozygous for disrupted ganglioside GM2/GD2 synthase (EC 2.4. 1.94) gene and lacking all complex gangliosides, do not display any major neurologic abnormalities. Further examination of these mutant mice, however, revealed that the males were sterile and aspermatogenic. In the seminiferous tubules of the mutant mice, a number of multinuclear giant cells and vacuolated Sertoli cells were observed. The levels of testosterone in the serum of these mice were very low, although testosterone production equaled that produced in wild-type mice. Testosterone was found to be accumulated in interstitial Leydig cells, and intratesticularly injected testosterone was poorly drained in seminiferous fluid in the mutant mice. These results suggested that complex gangliosides are essential in the transport of testosterone to the seminiferous tubules and bloodstream from Leydig cells. Our results provide insights into roles of gangliosides in vivo.     

Consideration on safety research strategy toward commercialization of FBRs

The situation of FBR enters upon development stage expecting to commercialize upto 2030's and has not yet established the concept of commercialized FBR plant. The primary subject is remarkable improvement of economy which can be accomplished through higher performance of plant systems, reduction of the amount of materials of the plant due to simplification of the plant systems and maximization of plant availability. This subject can be solved by development of foresighted plant design through full utilization of the inherent safety characteristics of FBR's. The secondary subject is acquirement of public confidence of FBR safety. If recriticality accident can be eliminated from the safety analysis for licensing of future FBRs with firm experimental evidences, then safety logic for the FBRs will more simple and thus friendly to the public. Then the public will be quite confident of safety securement of the FBR system and will be free from any anxiety. Discrepancy of the confidence level of FBR safety between the experts and the public will be significantly improved by showing experimental evidence of elimination of recriticality accidents. In addition, an optimized plant design for further reduction of the plant construction cost can be accomplished by elimination of recriticality accidents in an FBR plant design. In order to realize the above experiments and clarify these phenomena with a subassembly scale, development of new in-pile experimental facility using real materials in an FBR core is essential. Considering requirements of prototypicality or objectives for demonstration, it is concluded that the new in-pile experimental facility should be built early in the next century. The tertiary subject is reinforcement of FBR safety and reliability technologies in a more broad sense developed by the industry's voluntary safe-ensuring activities. These requirements have been realized through lessons learned from the sodium leak incident in the secondary heat transport system of Monju occurred on December 8th, 1995. For acquirement of social confidence on FBR safety by the public, significant amount of sodium leakage should be precluded, even if spilled sodium is non-radioactive and thus gives no radiological consequence to the public. Countermeasures for prevention and mitigation against such sodium leakage should be reinforced not as regulation-based activities but as the voluntary safe-ensuring activities by the utilities/development organizations. It thus appears that development of rules, standards and guidelines made by the industries in addition to reinforcement of wide range of sodium-related fundamental technology are essential for the future commercialization of FBRs.

In order to solve the above-mentioned subjects, it is essential to optimize and clarify the roles between the government and industries, to execute safety researches based on the well-organized long-term plan and to make the most use of international cooperation.     

Nitric oxide derived from sympathetic nerves regulates airway responsiveness to histamine in guinea pigs

Nitric oxide (NO), which can be derived from the nervous system or the epithelium of the airway, may modulate airway responsiveness. We investigated how NO derived from the airway nervous system would affect the airway responsiveness to histamine and acetylcholine in mechanically ventilated guinea pigs. An NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mmol/kg i.p.) significantly enhanced airway responsiveness to histamine but not to acetylcholine. Its enantiomer D-NAME (1 mmol/kg i.p.), in contrast, had no effect. The L-NAME-induced airway hyperresponsiveness was still observed in animals pretreated with propranolol (1 mg/kg i.v.) and atropine (1 mg/kg i.v.). Pretreatment with the ganglionic blocker hexamethonium (2 mg/kg i.v.) completely abolished enhancing effect of L-NAME on airway responsiveness. Bilateral cervical vagotomy did not alter the L-NAME-induced airway hyperresponsiveness, whereas sympathetic stellatectomy completely abolished it. Results suggest that NO that was presumably derived from the sympathetic nervous system regulates airway responsiveness to histamine in guinea pigs.     

Apoptosis and proliferation of growth plate chondrocytes in rabbits

The growth plates of the femoral head of Japanese white rabbits aged 5, 10, 15 and 20 weeks were stained for apoptotic and proliferating chondrocytes using the TUNEL and PCNA antibody staining techniques. Both TUNEL- and PCNA-positive chondrocytes were detected in all of the specimens. The positive ratios of both stainings were calculated for the whole plate and for the resting, proliferating and hypertrophic zones. The highest ratios in both stainings occurred in the hypertrophic zone in all age groups. With growth, the TUNEL-positive ratio increased whereas the proliferating ratio decreased. We suggest that the increase in chondrocytic death by apoptosis and the decrease in cell proliferation potential led to closure of the growth plate.     

Thermoelectric properties for P-type (Bi2Te3)0.2(Sb2Te3)0.8 alloys fabricated by shear extrusion

P-type (Bi₂Te₃)_0.2(Sb₂Te₃)_0.8 compounds were synthesized via bulk mechanical alloying (BMA), and subsequently prepared by a shear extrusion process in order to create the developed texture. The shear extrusion process improved the preferred orientation factor of the anisotropic crystallographic structure. It was found by an electron backscattered diffraction pattern (EBSP) analysis that approximately 90% of the crystallographic orientations for shear-extruded sample are aligned in the range deviated from 60° to 90° from the c-axis. The electric resistivity is well controlled at 1.008×10⁻⁵Ωm, which is nearly equal to that of the unidirectionally grown sample. The maximum figure of merit for the (Bi₂Te₃)_0.2(Sb₂Te₃)_0.8 alloy was found to be z=3.03×10⁻³K⁻¹. The bending strength of the material produced is also improved to 120 MPa, six times larger than that of the unidirectionally grown sample.     

Procainamide induced change of the width of the zone of entrainment and its relation to the inducibility of reentrant ventricular tachycardia

Procainamide depresses conduction velocity and prolongs refractoriness in myocardium responsible for reentrant VT, but the mechanism by which the induction of VT is suppressed after procainamide administration remains to be determined. In the present study, the relationship between electrophysiological parameters and the noninducibility of VT was assessed during procainamide therapy with a special reference to the change of an excitable gap. Clinically documented monomorphic sustained VT was induced in 30 patients and, utilizing the phenomenon of transient entrainment, the zone of entrainment was measured as the difference between the cycle length of VT and the longest paced cycle length interrupting VT (block cycle length) which was determined as the paced cycle length decreased in steps of 10 ms, and used as an index of the excitable gap. The effective refractory period was measured at the pacing site and the paced QRS duration was used as an index of the global conduction time in the ventricle. The cycle length of VT, the block cycle length, and the width of the zone of entrainment were determined and compared between the responders and nonresponders. In 15 patients, these parameters were determined at the intermediate dose and related to subsequent noninducibility at the final dose. At the final doses of procainamide, VT was suppressed in 8 (26.7%) of 30 patients. However, the cycle length of VT, the block cycle length, and the width of the zone of entrainment were unable to predict the drug efficacy, i.e., noninducibility. The change in the effective refractory period at the pacing site or the width of the paced QRS duration was not different between the responders and nonresponders. Among the variables, only the width of the zone of entrainment showed a significant narrowing in the responders at the intermediate dose of procainamide, and it was smaller than that of the nonresponders. The significant narrowing of the width of the zone of entrainment was associated with the subsequent noninducibility of VT at the final dose. The present study showed that the baseline cycle length of VT, the block cycle length, the drug induced change of the effective refractory period, or the paced QRS duration was not a predictor of the noninducibility after procainamide administration. However, a significant narrowing of the width of the zone of entrainment at the intermediate dose was associated with the noninducibility of VT at the final dose.     

Molecular interfacing for protein molecular devices andneurodevices

Several protein-based molecular biodevices have been made possible by the molecular interfacing technology that enables proteins to electronically communicate with the conventional electronic materials, such as metals or semiconductors. The molecular interfacing technology, however, should be extensively improved to allow for precise designs at the single-molecule level. The molecular-scale design of protein-based molecular biodevices may be accomplished by further innovation in molecular interfacing technology. It is also important to pursue the possibility of utilizing the self-organization of biomolecules for information processing, and to make it possible to create a molecular network-based biodevice without any preprogrammed wiring among its molecules. Major advances have recently been made in basic technology. Yet, it will take some time to construct a prototype neurodevice in which neurons are utilized as components. Further investigations should focus on the development of molecular interfaces that offer bilateral communication between neurons and conventional electronic materials     

Selective planting of cationized, haptenized ovalbumin on the rat tubular basement membrane

We developed an experimental protocol for planting exogenous antigens with different molecular weights and charges on the constituents of the renal tubulointerstitium. The cationized antigens were injected selectively into the left renal arteries of Wistar rats. Antigen localization was documented by immunohistochemistry on frozen sections. Cationized bovine serum albumin (BSA; 68 kDa, isoelectric point = 9.5) localized almost exclusively along the glomerular capillary wall. After application of highly cationic polyethyleneimine, cationized BSA given subsequently was found in a linear distribution along the glomerular capillary wall and along the peritubular capillaries. The fate of highly cationized ovalbumin conjugated with trinitrophenol (TNP-OA), subjected to gel filtration to obtain monomers (42 kDa, isoelectric point > 10) differed; it was deposited in a linear pattern on the tubular basement membrane (TBM) and Bowman's capsule, and remained up to 36 h after injection. Noncationized, monomeric TNP-OA (42 kDa, isolectnic point = 4.6) showed fine granular deposition in the tubular epithelium exclusively. These findings indicate that the barrier of the glomerular BM acts selectively on antigens with different molecular weights. They either settle on the peritubular capillaries, after passing the glomerular, or reach the urinary space, after which they are reabsorbed by the tubular epithelial cells to reach the TBM.