High rate capability by sulfur-doping into LiFePO4 matrix.

Enhanced electrochemical performance of LiFePO4 for Li-ion batteries has been anticipated by anion doping at the O-site rather than cation doping at the Fe-site. We report on the electrochemical performance of S-doped LiFePO4 nanoparticles synthesized by a solvothermal method using thioacetamide as a sulfur source. S-doping into the LiFePO4 matrix expands the lattice due to the larger ionic radius of S2- than that of O2-. The lattice parameters a and b increase by around 0.2% with sulfur content, while that of c remains almost unchanged with only 0.03% increase. The S-doping also contributes to the suppression of antisite defects (Fe occupying Li sites), which facilitates the easy migration of Li in the diffusion channels without blockage. Owing to these effects of S-doping, the S-doped LiFePO4 nanoparticles show enhanced electrochemical properties with a high discharge capacity of ∼113 mA h g-1 even at a high rate of 10C.

Computational modeling of 137Cs contaminant transfer associated with sediment transport in Abukuma River.

A numerical model capable of simulating the transfer of (137)Cs in rivers associated with transport of fine sediment is presented. The accident at Fukushima Dai-ichi Nuclear Power Plant (FDNPP) released radionuclides into the atmosphere, and after fallout several radionuclides in them, such as radiocesium ((134)Cs, (137)Cs) and radioiodine ((131)I) were adsorbed on surface soil particles around FDNPP and transported by surface water. To understand the transport and deposition of the radioactive contaminant along with surface soil particles and its flux to the ocean, we modeled the transport of the (137)Cs contaminant by computing the water flow and the associated washload and suspended load transport. We have developed a two-dimensional model to simulate the plane flow structure, sediment transport and associated (137)Cs contaminant transport in rivers by combining a shallow water flow model and an advection-diffusion equation for the transport of sediment. The proposed model has been applied to the lower reach of Abukuma River, which is the main river in the highly contaminated area around FDNPP. The numerical results indicate that most (137)Cs supplied from the upstream river reach with washload would directly reach to Pacific Ocean. In contrast, washload-oriented (137)Cs supplied from the upstream river basin has a limited role in the radioactive contamination in the river. The results also suggest that the proposed framework of computational model can be a potential tool for understanding the sediment-oriented (137)Cs behavior in rivers.

Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice.

AIMS/HYPOTHESIS: Orexin/hypocretin is a hypothalamic neuropeptide that regulates motivated behaviours, such as feeding and arousal, and, importantly, is also involved in energy homeostasis. The aim of this study was to reveal the role of orexin in the regulation of insulin sensitivity for glucose metabolism. METHODS: Orexin knockout mice fasted overnight underwent oral glucose tolerance testing and insulin tolerance testing. The impact of orexin deficiency on insulin signalling was studied by Western blotting to measure levels of Akt phosphorylation and its upstream and downstream molecules in the hypothalamus, muscle and liver in orexin knockout mice. RESULTS: We found that orexin deficiency caused the age-related development of impaired glucose tolerance and insulin resistance in both male mice without obesity and female mice with mild obesity, fed a normal chow diet. When maintained on a high-fat diet, these abnormalities became more pronounced exclusively in female orexin knockout mice that developed severe obesity. Insulin signalling through Akt was disrupted in peripheral tissues of middle-aged (9-month-old) but not young adult (2-to-3-month-old) orexin knockout mice fed a normal chow diet. Moreover, basal levels of hypothalamic Akt phosphorylation were abnormally elevated in orexin knockout mice at every age studied, and insulin stimulation failed to increase the level of phosphorylation. Similar abnormalities were observed with respect to GSK3beta phosphorylation in the hypothalamus and peripheral tissues of middle-aged orexin knockout mice. CONCLUSIONS/INTERPRETATION: Our results demonstrate a novel role for orexin in hypothalamic insulin signalling, which is likely to be responsible for preventing the development of peripheral insulin resistance with age.

Mechanical stress induces expression of cytokines in human periodontal ligament cells.

OBJECTIVE: Periodontal tissue has a unique structure in that the human periodontal ligament (hPDL) lies between the hard tissues of cementum and alveolar bone. Although the role of cytokines in hPDL function is not clearly understood, we investigated the effect of mechanical stress as hydrostatic pressure (HP) on cytokine expression in hPDL cells. MATERIALS AND METHODS: The hPDL cells were obtained from a healthy maxillary third molar. After the third to fourth passage, the cells were exposed to HP ranging from 1 to 6 MPa as previously described. Total RNA was extracted and the expression of cytokine mRNA was determined by RT-PCR. RESULTS: The exposure to 6 MPa of HP caused no morphological changes of hPDL cells, and did not affect the cellular viability. No expression of IL-1beta, IL-6, IL-8, TNF-alpha, receptor activator of NF-lambdaB (RANK), receptor activator of NF-lambdaB ligand (RANKL), or osteoprotegerin mRNA was observed in the control cells under atmospheric pressure, whereas, in hPDL cells treated with HP, a pressure-dependent enhancement of IL-6, IL-8, RANKL, and OPG mRNA expression was observed between 10 and 60 min after the exposure to HP. CONCLUSION: These results suggest that hPDL cells may play a role in the production of cytokines in response to mechanical stress in vivo.

Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers.

AIM: To compare the interocular and intraocular differences of capillary perfusion, and the intraocular regional differences of retinal blood flow in the macular area of healthy volunteers. METHODS: Tissue blood flow in the macula was examined in both eyes of 20 healthy volunteers with the Heidelberg retinal flowmeter. Blood flow measurements were made in a 10 degrees x 2.5 degrees area superior and inferior to the macula. The mean blood flow (MBF) was calculated by an automatic full field perfusion image analyser program. The MBF in the right and left eyes and in the superior and inferior macular areas of the same eye were compared. RESULTS: The ratios of the MBF in the right eye to the left eye in the macular areas were 1.00, and 1.03, respectively. The ratio of the MBF in the superior macular area to the inferior area was 1.01 for the right eyes and 1.04 for the left eyes. CONCLUSIONS: Because no significant differences were found in the MBF between the two eyes and between the superior and inferior macular areas in the same eye, interocular (for example, affected eye versus fellow eye) and intraocular (superior versus inferior macular areas) comparisons of MBF can be made to determine if changes in retinal perfusion have occurred.

Formant interaction as a cue to vowel perception: a case report.

Accumulating evidence indicates that cerebral processing of consonants and vowels is separable. It has been shown that disordered temporal acuity leads to disturbed consonant perception in cases with pure word deafness. In contrast, there has been no clear explanation of how vowel perception is impaired. We examined a patient with auditory agnosia, who showed a differential ability to identify the five Japanese vowels after bilateral cerebral lesions. He correctly identified the vowel [a] in more than 70% of auditory presentations, whereas he identified [i] in only about 30% of presentations. The difference between the first and second formant frequencies "F2-F1" and an artificially defined value "F1-(F2-F1)" for each vowel correlated significantly with the percentage of correct identifications. These findings support the hypothesis that vowel perception is based on formant interactions.

[Early phase II clinical trial of amrubicin hydrochloride in patients with malignant lymphoma].

An early phase II multi-center collaborative study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted for malignant lymphoma at 12 institutions nationwide. A total of 41 patients were enrolled in this study between January 1988 and October 1990. Of these, 36 patients, six patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL), were eligible for the study. The starting dose of amrubicin hydrochloride was 100 mg/m2 (body surface area) and it was administered once every three weeks, in principle. The efficacy was assessed for 34 patients, excluding two patients: one who has not been followed up adequately and the other violated the dosing schedule (once per week). The overall response rates (CR + PR) were 50.0% (3/6) for HD and 42.9% (12/28) for NHL. Furthermore, a relatively high response rate was noted in 8 (36.4%) of 22 NHL patients who had been treated with other anthracycline derivatives prior to the trial. The safety of amrubicin hydrochloride was assessed for 36 eligible patients. Leukopenia (grade 3 or higher) and thrombocytopenia were noted in 21 patients (58.3%) and 10 patients (27.8%), respectively. Anorexia, nausea/vomiting, fever, alopecia, decrease in hemoglobin and elevations of GOT and GPT levels were observed with a relatively high frequency. Other than myelosuppression, the following adverse reactions (grade 3 or higher) occurred during the course of the trial: diarrhea (two patients), alopecia (two patients), stomatitis (one patient), anorexia (one patient), nausea/vomiting (one patient) and fever (one patient). In conclusion, these results indicate that amrubicin hydrochloride is effective in the treatment of patients with malignant lymphoma.

The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment.

PEPA (4-[2-(Phenylsulphonylamino)ethylthio]-2,6-difluorophenoxyacetamide) is a recently developed allosteric potentiator of AMPA receptors that preferentially affects flop splice variants. We tested the effects of PEPA on ischemia-induced memory deficit in rats. Permanent unilateral occlusion of the middle cerebral artery induced severe impairment of performance of rats in the Morris water maze test. Repeated intravenous administration of PEPA (1, 3, 10 mg/kg/day for 10 days) improved test performance. In contrast, a corresponding dose of aniracetam, a representative potentiator of AMPA receptor, did not significantly improve test performance. Thus, PEPA is more effective than aniracetam in reversing impaired memory function as assessed by the Morris water maze test; and PEPA may be an effective compound for the treatment of impaired memory.

The 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT) induces hyperglucagonemia in rats.

Effects of the 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)tetralin (8-OH-DPAT) on plasma glucagon levels were investigated. 8-OH-DPAT increased plasma glucose and glucagon levels in rats. Both hyperglycemia and hyperglucagonemia elicited by 8-OH-DPAT were prevented by the 5-HT1A receptor antagonist pindolol and prior adrenodemedullation. These results suggest that increases in plasma glucagon levels induced by 8-OH-DPAT were based on the adrenaline release from the adrenal gland and its effects may contribute to its hyperglycemic effects.

Reduction of incretin-like salivatin in saliva from patients with type 2 diabetes and in parotid glands of streptozotocin-diabetic BALB/c mice.

AIM: Diabetic xerostomia is a typical syndrome in diabetic complication. We have reported that salivatin (salivary peptide P-C) derived from human saliva potentiates glucose-stimulated insulin release and inhibits arginine-stimulated glucagon release. The present study is aimed to gain further evidence on the physiological role by investigating the diabetic state-induced change in the amount of salivatin. METHODS: The amount of salivatin was measured in saliva taken from patients with type 2 diabetes with ELISA and with rabbit antiserum against human salivatin immunocytochemically in sections of parotid glands from streptozotocin-diabetic BALB/c mice. RESULTS: The amount of salivatin after a meal was reduced by diabetes in both human saliva and in the serous secretory granule of mouse parotid gland acinar cells. CONCLUSIONS: The above results suggest that salivatin lowers hyperglycaemia after meal and sustains the normal blood glucose levels by incretin-like mechanisms. The function may be damaged by diabetes, and this in turn might make the diabetes worse.

Lumbar posterolateral fusion alone or with transpedicular instrumentation in L4--L5 degenerative spondylolisthesis.

We retrospectively reviewed 57 patients with L4--L5 degenerative spondylolisthesis (L4--L5 DS) who underwent posterior decompression and posterolateral fusion of L4--L5 without (Group A) or with (Group B) transpedicular screw instrumentation at least 2 years earlier. The clinical results and fusion rate were similar between Groups A and B, that is, a 72.4% satisfactory outcome with a fusion rate of 82.8% in Group A versus 82.1% satisfactory outcome with a 92.8% fusion rate in Group B. Screw instrumentation reduced postoperative low back pain and resulted in a lordotic slip angle of L4--L5. However, in patients with radiologically excessive segmental motion showing a translational motion of 3 mm or more, flexion angulation of -5 degrees or less, and a slip angle of -5 degrees or less at the site of spondylolisthesis (L4--L5), the kyphotic slip angle (L4--L5) tended to increase after surgery. In the future, in patients with radiologically excessive segmental motion, this point should be considered, and surgical techniques should be evaluated. Our results suggest that the validity of the general addition of screw instrumentation to L4--L5 fusion for L4--L5 degenerative spondylolisthesis is low.

Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS: Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.

Immunohistochemical localization of somatostatin receptor type 2A in rat and human tissues.

In this study, we elucidated the cellular localization of somatostatin receptor (SSTR) by immunohistochemistry using an antibody specific for SSTR type 2A (SSTR2A) in various organs of rat and human. SSTR2A expression was basically similar in rat and human, except in the pancreas and adrenal cortex. In the pituitary gland, the posterior lobe and the majority of growth hormone cells and some ACTH and TSH cells expressed SSTR2A. In rat adrenal gland, the zona glomerulosa strongly expressed SSTR2A, whereas zone-specific immunoreactivity was not observed in human. The adrenal medulla moderately expressed SSTR2A in both rat and human. SSTR2A immunoreactivity was observed in islet cells and some ductal cells in human pancreas, and also in acinar cells of rat pancreas. In gastrointestinal (GI) tract, the majority of crypt cells and nerve plexuses strongly expressed SSTR2A. The number of SSTR2A positive cells was much more than that of chromogranin A positive endocrine cells. In the kidney, the glomerular capillaries and collecting tubules, but not proximal tubules, showed immunoreactivity. SSTR2A immunoreactivity was observed not only in endocrine cells but also in non-endocrine cells.

[Objective evaluation of visual field loss in a patient with branch retinal artery occlusion and brain infarction].

PURPOSE: To evaluate visual field loss using multifocal ERG(m-ERG), multifocal VEP(m-VEP), and Heidelberg Retina Flowmeter(HRF) in a patient with branch retinal artery occlusion(BRAO) and brain infarction. CASE: A 38-year-old man noticed inferior-nasal visual field loss in the left eye, and was referred to Keio University Hospital. He suffered from paralysis in the left leg due to brain infarction at the age of 24. However, he had not noticed visual field loss due to the brain infarction. His left fundus showed retinal edema in the area of a superior-temporal retinal artery occulusion. He was diagnosed as having BRAO. The Goldmann and Humphry perimetric examinations revealed homonymous quadrantanopia in the upper left field as well as inferior visual field defect in the left eye. RESULTS: Both m-ERG and m-VEP, especially second-kernel responses, were reduced in the affected retinal area of BRAO. But only m-VEP was affected in the corresponding area of homonymous quadrantanopia in the upper left field. The retinal flow in the area with BRAO evaluated by HRF was decreased in some areas and not in others, suggesting that retinal function was not necessarily consistent with retinal circulation. CONCLUSIONS: m-ERG and m-VEP are useful To differentiate retinal lesions from brain lesions in visual field loss.

New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice.

Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a potent anti-inflammatory agent.

Synaptotagmin I expression in mast cells of normal human tissues, systemic mast cell disease, and a human mast cell leukemia cell line.

Synaptotagmin I (STG I) is a Ca(2+) sensor and one of the synaptic vesicle proteins that mediate exocytosis. To determine the mechanism of release of large granules from mast cells, we studied by immunohistochemistry the presence of STG I in mast cells in normal human tissues simultaneously with the mast cell markers mast cell tryptase (tryptase) and c-kit. The tumor cells of systemic mast cell disease (SMCD) and a human mast cell leukemia cell line (HMC-1) were also examined. Human mast cells in normal tissues and the tumor cells of SMCD expressed STG I as well as mast cell tryptase (tryptase) and c-kit. STG I mRNA and its products in HMC-1 were examined by RT-PCR analysis and immunocytochemistry, respectively. STG I expression in HMC-1 cells was compared with that in cells stimulated and non-stimulated by phorbol 12-myristate 13-acetate and also with that in NB-1 and PC12 cells, known to express STG I. STG I mRNA was detected in both non-stimulated and stimulated HMC-1 cells and in NB-1 and PC12 cells. STG I immunoreactivity was weaker than NB-1 or PC12 immunoreactivity. However, it increased in the stimulated HMC-1 cells. Mast cells expressed STG I in various states. STG I may mediate exocytosis of large granules in mast cells.

Pressure distribution measurement in biting surimi gels with molars using a multiple-point sheet sensor.

The bite force of three surimi gels with molars was measured in the mouth using a multiple-point sheet sensor. A peak force appeared at the breaking point of each sample, and then the force increased again, accompanied by a decrease in the opening between the upper and lower teeth. Low values in the peak force, pressure, and time at the first peak, the time at which the maximum contact area was engaged, impulse, and slope of bite curve were observed in samples with low breaking force and low breaking deformation found by the mechanical measurement of gel strength, and with less toughness in the sensory assessment. The duration of the bite force, the second peak time, and active bite pressure at the second peak did not change with a change in the surimi texture. The active pressure at the breaking point of each gel was affected by gel strength, while that at the second peak was independent of the gel strength.

Microcirculation in the macular area of eyes with an idiopathic epiretinal membrane.

PURPOSE: To measure the microcirculation in the macula area of eyes before and after the removal of an idiopathic epiretinal membrane (ERM) by vitreous surgery. METHODS: Tissue blood flow in the macula was examined with the Heidelberg retina flowmeter in 12 eyes with an ERM before and 3, 6, and 12 months after vitrectomy. Blood flow measurements were performed in a 10 x 5 degree area in the macula that was divided into superior and inferior areas. At least three measurements were obtained, and the mean blood flow (MBF) was calculated by scanning laser Doppler flowmetry. The ratio of the MBF in the affected eye to that in the fellow eye was used for statistical analysis. RESULTS: The ratios of the MBF in the affected to the fellow eye in the superior area before and 1, 3, 6, and 12 months after surgery were 0.73, 0.51, 0.77, 0.88, and 1.01, respectively. The ratios of the MBF in the inferior area for the same periods were 0.70, 0.52, 0.75, 0.83, and 0.98, respectively. CONCLUSIONS: Eyes with an ERM showed abnormal hemodynamics in the macula that gradually improved after vitrectomy to a status comparable with the MBF of the normal fellow eye.

Effect of static magnetic fields on bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli.

Biological effect of static magnetic field was investigated by using ferrite magnets to conduct a magnetic field exposure experiment on three species of bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The effects were evaluated by culturing the bacteria and determining their growth rate, the maximum numbers of bacteria, and [3H]-thymidine incorporation. The results showed that the ferrite magnet caused strength-dependent decreases in the growth rate and growth maximum number of bacteria for S. mutans and S. aureus when cultured under anaerobic conditions, but that their growth was not inhibited under aerobic conditions. In addition, [3H]-thymidine was added after culturing each of the species of bacteria for 18 h. After that, culture was continued until 24 h, and changes in [3H]-thymidine incorporation were investigated. But no effect of the magnetic fields was detected. These findings suggested that oxygen related to growth the cases of S. mutans, S. aureus. However, no growth effects were detected on E. coli cultures.

Vascular endothelial growth factor promotes cell-cycle transition from G0 to G1 phase in subcultured endothelial cells of diabetic rat thoracic aorta.

Vascular endothelial growth factor (VEGF) has been claimed to be a major positive regulator of angiogenesis in diabetic retinopathy and atherosclerosis. Diabetic state-induced alteration of the phenotypes and the influence of 12-h pretreatment with VEGF were examined after a further 12-h treatment with only 1% fetal bovine serum in subcultured endothelial cells (EC) derived from rat thoracic aorta. By flow cytometric cell cycle analysis, VEGF showed quite different transition patterns from those of platelet-derived growth factor (PDGF) in 5-day (at the progression phase) cultured normal rat EC even though VEGF belongs to the PDGF family. VEGF promoted cell cycle transition from the G0 to the G1 phase at 3 ng/ml, but at 30 ng/ml, VEGF weakly inhibited it compared with the effect of PDGF. The streptozotocin-diabetic state promoted cell cycle transition of EC from the G0 to the G1 phase. The promotion by the low concentration of VEGF was observed even at the point of 35-day culture (angiogenic EC at the competence phase in normal state). The diabetic state enhanced EC proliferation rather than tube formation, and the tube formation was scarce. The promotion of cell cycle transition by VEGF may aggravate furthermore diabetic angiopathy due to the leaky constitution of blood vessels.