Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.     

The investigation of surgical procedures for post infarcted ventricular septal defects: a comparison between Daggett and David method

Post infarcted ventricular septal perforations (VSP) has diverse clinical and pathological manifestations and the surgical results in severe cases have not yet been satisfactory. In the past we had performed the procedure of Daggett. However since 1992 we have also introduced the procedure of infarction exclusion technique proposed by David which involves plastering the ventricular cavity in a large patch without infarcted myotomy. We reported 5 cases treated with David method, 5 cases with Daggett method, and their results were compared. There were four mortality cases in Daggett method and three in David method. No significant difference was observed regarding the surgical mortality. However, there were different post-operative features between the two groups. In Daggett method patients had prolonged heart failure and LOS. In David method patients, had no severe LOS, but residual shunt were recognized in two cases. We think that the emergence of residual shunt in David method was probably due to suturing without prior removal of the damaged fragile infarcted myocardium. In Daggett method there were death cases caused by LOS and postoperative heart failure but without residual shunts. Despite its recent growing popularity for treating VSP, our experience suggests that residual shunt is an important issue remains to be solved in David method.     

Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes

Attention is drawn to the high incidence of varus angulation in the lower femur in Ollier's disease; eight of a total of 14 patients with this condition have this deformity. There may be retardation or arrest of the medial portion of the lower femoral growth plate. One case demonstrates a bone bridge, a condition not previously described in Ollier's disease. The limb-length inequality and varus angulation require concurrent management by a variety of techniques, which are described. Three of the eight patients have reached skeletal maturity; the remainder provide useful information on the condition and are a stimulus for discussion of future management.     

The Importance of Hydration Thermodynamics in Fragment‐to‐Lead Optimization

Using a computational approach to assess changes in solvation thermodynamics upon ligand binding, we investigated the effects of water molecules on the binding energetics of over 20 fragment hits and their corresponding optimized lead compounds. Binding activity and X‐ray crystallographic data of published fragment‐to‐lead optimization studies from various therapeutically relevant targets were studied. The analysis reveals a distinct difference between the thermodynamic profile of water molecules displaced by fragment hits and those displaced by the corresponding optimized lead compounds. Specifically, fragment hits tend to displace water molecules with notably unfavorable excess entropies—configurationally constrained water molecules—relative to those displaced by the newly added moieties of the lead compound during the course of fragment‐to‐lead optimization. Herein we describe the details of this analysis with the goal of providing practical guidelines for exploiting thermodynamic signatures of binding site water molecules in the context of fragment‐to‐lead optimization.     

Theoretical analysis of mass and depth resolutions of cyclotron Rutherford backscattering spectrometry system

Cyclotron Rutherford backscattering spectrometry (CRBS), which utilizes the cyclotron motions of scattered ions in a uniform magnetic field, enables us to perform elemental depth profile measurements with an acceptance angle of larger than 10 msr and a relative energy resolution of better than 1%. CRBS thus allows precise measurements with less radiation damage in addition to the features of conventional RBS, i.e., nondestructive and quantitative measurements. In the present paper, the mass and depth resolutions of CRBS are theoretically examined. It is shown that CRBS can provide better mass resolution and a larger acceptance angle than conventional RBS or high-resolution RBS with a reasonably high depth resolution; hence, the CRBS system is a promising tool for thin film analysis.     

Layer‐by‐Layer Fabrication and Characterization of Gold‐Nanoparticle/Myoglobin Nanocomposite Films

Multilayer thin films of ～ 7 nm diameter gold nanoparticles (GNPs) linked with horse heart myoglobin (Mb) are fabricated, for the first time, by layer‐by‐layer (LbL) assembly on glass slides, and silicon and plastic substrates. The GNP/Mb nanocomposite films show sharp surface plasmon resonance (SPR) absorption bands that are used to follow the LbL growth of the film and to determine the kinetics of GNP adsorption on the Mb‐modified surface. The GNP/Mb nanocomposite films are characterized using atomic force microscopy, transmission electron microscopy, polarized UV‐vis spectroscopy, and spectroscopic ellipsometry. The GNPs in the multilayer films are spatially separated from one another, and interparticle interactions remain in the film, making it optically anisotropic. The GNP/Mb nanocomposite films are stable in air at temperatures up to 100 °C, and can withstand successive immersions in strongly acidic and basic solutions. The SPR absorption band of the GNP/Mb nanocomposite film in air exhibits a red‐shift in the wavelength maximum and an increase in the maximum absorbance relative to that in water. This result, which is in contrast to that observed with a GNP monolayer on an aminosilane‐functionalized substrate, suggests the shrinkage in air and swelling in water of Mb molecules embedded in the nanocomposite film.     

Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.     

Recent progress on analytical chemistry and biochemistry of D-amino acids

Recent findings that D-amino acids, especially D-aspartic acid and D-serine, exist in vivo in the mammalian tissues (brain and peripheries), prompted us now to investigate their biological and pathological roles in mammals. In this review, the overview of the progress of analytical chemistry and biochemistry of D-amino acids is described.     

The effects of using a leukocyte removal filter during cold blood cardioplegia

During myocardial ischemia, neutrophils and platelets exert negative effects on the myocardium. In this study, we used a leukocyte removal filter during cardioplegia, and investigated its effect on myocardial damage during reperfusion by measuring the plasma levels of granulocyte components, platelet components, and cardiac enzymes [creatinine phosphokinase (CK) and creatinine phosphokinase myocardial band (CK-MB)] in 24 patients who underwent cardiopulmonary bypass. The patients were divided into two groups of 12 according to whether or not a filter was placed in the cardioplegic route. Blood samples were drawn directly from the coronary sinus before aortic cross clamping, and at 1, 5, and 15 min after declamping. Group F, which had the filter, showed better cardiac enzyme and lipid peroxidation results than group N, which did not. The results of this study suggest that the application of a filter during cold blood cardioplegia may reduce myocardial damage.