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Two MdERFs (ethylene-response factors) were isolated from ripening apple (Malusxdomestica Borkh. cv. Golden Delicious) fruit. The features of their conserved motifs indicated that MdERF1 and MdERF2 belong to group VII and group IX categories in Arabidopsis, respectively. MdERF1 was expressed predominantly in ripening fruit, although a small degree of expression was also observed in non-fruit tissues, whereas MdERF2 was expressed exclusively in ripening fruit. The increased expression in ripening fruit was repressed by treatment with 1-methylcyclopropene (1-MCP: a potent antagonist of ethylene receptors), indicating that transcription is regulated positively by the ethylene signalling system. Indeed, it was a tendency for cultivars with low ethylene production to show lower MdERFs expression than those with high ethylene production. On the basis of concomitant analyses of the expression of some genes related to ripening, the functions of MdERFs and the role of ethylene in the ripening process are discussed.

GABAergic interneurons of the spinal cord substantia gelatinosa regulate the transmission of nociceptive information. Hydrogen peroxide (H2O2) is likely a diffusible messenger contributing to the development of long-lasting pathological pain states after nerve injury. In this study, we examined the presynaptic effects of H2O2 on the inhibitory interneurons of mouse substantia gelatinosa (SG) using whole-cell patch-clamp recordings from spinal cord slices. H2O2 increased the frequency of GABAergic miniature inhibitory postsynaptic current (mIPSC) in a concentration-dependent (10-1000 microM) manner. The profound increase in mIPSC frequency was diminished by thapsigargin or cyclopiazonic acid suggesting that the intracellular stored pool was the source of presynaptic calcium. Further examination revealed the 2-aminoethoxydiphenil borate blockable inositol-(1,4,5) trisphosphate receptor (IP3R) regulated pool of stored calcium as the likely source. The phospholipase C (PLC) blocker, 1-(6-[([17beta]-3-methoxyestra-1,3,5[10]-trien-17-yl)-amino]hexyl)-1H-pyrrole-2,5-dione (U73122), did not block the frequency increase, which suggested that the site of action of H2O2 lies downstream in the IP3 signalling pathway, and nifedipine-sensitivity of the frequency increase indicated a possible role of calcium-induced calcium-release. However, a direct examination of L-type voltage-gated calcium channels (VGCC) demonstrated that H2O2 did not increase the calcium influx through these channels. The H2O2 effect on mIPSC frequency was markedly reduced in the opisthotonus (Opt) mutant mice with a known deletion in the IP3R1 gene. We demonstrated that H2O2 increased presynaptic activity in the GABAergic interneurons by the release of calcium from the IP3R-regulated intracellular pool. The presynaptic IP3R could emerge as a novel target for preventing H2O2-induced synaptic plasticity in substantia gelatinosa leading to pathological pain states.

To investigate the functional and morphologic prognoses of eyes with subfoveal hemorrhage from acute branch retinal vein occlusion (BRVO), and to examine the effect of intravitreal ranibizumab injection (IVR) on these prognoses, we assessed 81 eyes with acute BRVO, of which 38 did not receive IVR [IVR(-) group], and 43 were treated with IVR [IVR(+) group] for macular edema. The foveal morphologic changes were examined via optical coherence tomography (OCT). At initial examination, 63 eyes exhibited subfoveal hemorrhage. At final examination, the defect lengths in the foveal external limiting membrane (ELM) and ellipsoid lines in these eyes were longer, and final VA was significantly poorer, compared with eyes without subfoveal hemorrhage. In comparisons between the final measurements in eyes with subfoveal hemorrhage in the IVR(-) and IVR(+) groups, while there were no differences in initial ocular conditions, final VA was significantly better in the IVR(+) group. The defects in the ELM and ellipsoid lines in the IVR(+) group were shorter than those of the IVR(-) group (p = 0.002 in both). Final VA was correlated with the defect lengths of foveal ELM and ellipsoid lines in both the IVR(-) and IVR(+) groups (both p < 0.001). In addition, the defect lengths of foveal ELM and ellipsoid lines were closely correlated with the duration of subfoveal hemorrhage (both p < 0.001). BRVO-associated subfoveal hemorrhage caused damage to the foveal photoreceptors, and visual dysfunction. However, IVR improved these prognoses, by accelerating the absorption of the subfoveal hemorrhage.

Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10−5) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10−14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10−3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies.

Since diabetes mellitus (DM) is the most common cause of heart failure (HF), it is critically important to clarify whether incretin hormones including glucagon-like peptide-1 (GLP-1), which play an important role in blood glucose control, mediate cardioprotection. There are many lines of basic research evidence indicating that GLP-1 improves the pathophysiology of HF: In murine and canine HF models, either GLP-1 analogues or DPP-IV inhibitors improved cardiac functions. The first question that arises is how either GLP-1 analogues or DPP-IV inhibitors mediate cardioprotection. Cardiovascular diseases are tightly linked to impaired glucose tolerance (IGT): IGT is not only one of the causes of cardiovascular events but also the result of HF. Indeed, the treatment of IGT improved HF, showing that one of the mechanisms attributable to DPP-IV inhibitors is related to the improvement of IGT. Intriguingly, either DPP-IV inhibitors or GLP-1 analogues mediate cardioprotection even without IGT, suggesting two possible explanations: One is that GLP-1 analogues directly activate the prosurvival kinases, such as Akt and Erk1/2, and another is that DPP-IV inhibition increases cardioprotective peptides such as BNP and SDF-1α. The next question is whether cardioprotection is translated to clinical medicine. Small scale clinical trials proved their cardioprotective effects; however, several large scale clinical trials have not proved the beneficial effects of DPP-IV inhibitors. Taken together, GLP-1 analogues or DPP-IV inhibitors can mediate cardioprotection, however, what needs to be clarified is who mainly receives their benefits among the patients with cardiovascular diseases and/or DM.

Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of 99mTc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P

The rho1 subunit of the ionotropic GABA receptors is thought to contribute to the formation of the GABA(C) receptors with pharmacological and physiological properties distinct from those of GABA(A) receptors. Previous characterization of this subunit expressed in the Xenopus oocytes revealed an ion channel with slow activation and deactivation and no desensitization, quite different from the properties of GABA(C) receptors observed in native cells. We expressed the human rho1 subunit in human embryonic kidney (HEK) 293 cells and quantitatively characterized the kinetic properties of these receptors using a rapid drug application device. The rho1 subunit expressed in HEK293 cells exhibited pharmacological and kinetic properties qualitatively identical to those described when rho1 was expressed in the oocytes. An apparent desensitizing current observed during a constant GABA application was determined to be secondary to an E(Cl) shift. Detailed kinetic analyses and parameter estimation for a five-state kinetic model revealed that the channel is best described by a set of rate constants with a notably faster GABA unbinding K(off) rate compared to the parameters proposed for the same subunit expressed in the oocytes. The same subunit expressed in hippocampal neurons showed activation and deactivation kinetics identical to the current characterized in HEK293 cells. The kinetic properties of rho1 subunit expressed in a nonoocyte model system may be better described quantitatively by the rate constants presented here.

女子学生を対照に、安静時代謝測定、身体計測、生活時間調査を行い、その安静時エネルギー消費量と体組成の関係、1日の消費エネルギー量と体組成の関係について検討を行なった。なお生活時間調査は、平日の時間的ゆとりのある日、多忙な日、休日の3パターンを設定して観察した。実験Iの空腹時換気量(VE)は6.5±1.46l/minで、実験IIの随時換気量(VE)は7.5±1.51l/minであり有意差が見られた(p

女子学生を対象に、5年間の身体計測及びダイエットと体型意識に関するアンケート調査を行った。1.BMIによる分類では「低体重」者が年々増加し、1999年8.5%から2003年は17.2%であった。2.BMIと体脂肪率は強い相関を示すが、BMI低体重群の91.0%が体脂肪率判定では「普通」に属した。3.女子学生の理想身長は160.9±3.4cm、理想体重48.1±4.3kg、理想BMIは18.6±1.5であり、「やせ気味」体型を理想としている。4.体型の自己評価は、2003年結果で58.4%が「太っている」と評価し、部位別では「お腹」(腹部)に対し、「やや不満」「大変不満」の回答が91.9%であった。また78.0%が改善を希望している。5.ダイエットは6割が経験者で、体重減少を目標とし、目標体重への到達を成功と捉え、リバウンドすることを失敗とする回答が最多であった。6.ダイエット方法は「運動」「食事」単独の方法に比べて「運動+食事」法が効果的で、その体重減少量は平均-4.5～-5.9kgであった。, The results of 5-year questionnaire surveys on physical measurements, perception of body shape and dieting in female students were summarized. In analysis of BMI (Body Mass Index), the percentage of students with low-body weight has increased each year, from 8.5% in 1999 to 17.2% in 2003. While there was a strong correlation between BMI and percent body fat, 91.0% of the students with lowbody weight according to BMI were classified as having average percent body fat. The ideal body shape of female students was as follows: height 160.9±3.4cm, body weight 48.1±4.3kg and BMI 18.6±1.5. These members show that female students tend to believe that a slightly thin body shape is ideal. In 2003, a survey on self-assessment of body shape showed that 58.4% of the respondents felt that they were overweight, especially in the abdomen. In other words, 91.9% of the students stated that they were slightly or very unhappy about their abdomen, and 78.0% of the students wished to have a better abdomen. About 60% of the students surveyed had tried diets to lower their body weight. The most common answer was that a diet is a success if a target body weight is achieved and a failure if the body weight rebounds. When comparing dieting and exercise, dieting combined with exercise was more effective, with the amount of body weight reduction ranging from 4.5 to 5.9kg.

To determine the persistence and spread of antibiotic-resistant strains in Gunma University Hospital, 83 Pseudomonas putida strains (each from a different patient) were isolated from January 1997 through December 2001. Of the 83 strains isolated, 27 were resistant to carbapenems. All 27 produced metallo-β-lactamase and were found to be PCR positive for the bla IMP gene. Most (22 strains) were primarily isolated from the wards (W7 [9 strains] and W4 [8 strains]). Another five bla IMP -positive P. putida strains from wards W7 and W4 were obtained by swabbing around the water pipes. A total of 32 bla IMP -positive P. putida strains were assessed by pulsed-field gel electrophoresis (PFGE) and testing of drug susceptibility to 10 chemotherapeutic agents. Both PFGE and MIC patterns revealed that there were long-term resident strains among inpatients and hospital environments. The bla IMP genes of 22 of 32 strains were all transferable to a recipient strain of Pseudomonas aeruginosa by conjugation or transformation and conferred resistance to carbapenems and cephems. The bla IMP plasmids were conjugally transmissible among P. aeruginosa strains and mediated resistance to amikacin as well as β-lactams. Ten of the 22 plasmids mediated additional resistance to gentamicin and tobramycin. Plasmids with identical DNA and drug resistance patterns were found in P. putida strains with identical PFGE patterns and with different PFGE patterns. We presumed that P. putida was one of the resident species in inpatients and especially in hospital environments, spreading drug resistance genes via plasmids among P. putida strains and supplying them to more pathogenically important species, such as P. aeruginosa .

健常時の体温を知る目的で、健康な女子学生423名(体調不良の57名を除く)に対して、実験室で注意事項を遵守させて行った体温測定と、自己申告による体温に関するアンケート調査(480名)を行い、その結果を解析した。測定時間は午前10時30分～12時、午後は14時～16時であり、いずれも食後1時間以上を経過後測定した。水銀体温計による平衡温測定は、腋窩の平衡時間14.5±3.0分、36.91±0.33℃、口腔は11.6±3.7分、37.07±0.28℃であった。腋窩温と口腔温の平衡温差は、前者よりも後者の方が0.16±0.22℃高く、平衡温に達するまでの時間は前者が3.0±4.4分多く要した。電子体温計による腋窩温測定は、予測36.77±0.36℃、実測36.75±0.33℃で予測時と実測時の温度間に有意差は見られない。水銀体温計腋窩温と比較すると、電子体温計腋窩温が有意に低い値であった。耳式体温計による耳内温は36.83±0.38℃であった。この値は、口腔温よりも0.20℃低く、水銀体温計の腋窩温とほぼ等しく、電子体温計腋窩温よりも高い値であり、耳内温が高いということはなかった。また、測定時刻午前と午後の比較では、午後測定の体温が有意に高いことを確認した。家庭での水銀体温計による体温測定は腋窩・口腔共に5分位で、平衡温に達する前に測定を終了していた。また、被験者は各自の「平熱」を76.3%が把握しており、平均値は36.06±0.34℃であった。水銀体温計腋窩温と比較して0.85℃低かったことからも、測定時間不足により正確な体温より低い値を平熱と認識している現状が観察される。以上の結果より、体温測定は正しい方法で行うことが大切であることは勿論、病態時のみでなく健常時に体温を測定し、各自の「平熱」を知り健康管理に役立てることが大切であると考える。

近年,生活習慣病の深刻化に伴い,管理栄養士に高度な専門知識や技能が求められるようになった。対象者の食行動の変容を目的とした栄養教育の過程で,栄養状態や食習慣の十分な把握は重要であり,実際に個人または集団レベルでの食物および栄養摂取量評価のために食事調査が行われている。その方法は多種類あるが,我々は個人および集団を対象とし,簡便かつ調査者および被調査者の負担が軽く,より正確な摂取状況を把握する方法としてサービングサイズを用いた簡易食物摂取量調査法を開発するために,20歳代女子大生に見合った簡易記録法(以下,簡易法)I,IIを作成し,段階的調査を行った。簡易法の摂取栄養量の算出のため,食品群別荷重平均成分表(以下,荷重平均成分表)を作成し,24時間秤量法(以下,秤量法)との整合性をはかり,精度を高める検討をした。秤量法と簡易法の一回目の検討の結果,食品群では調味料類を除いて有意な差は認められなかったが,食品摂取量の間に相違がみられた。栄養素では,ナトリウム(以下,Na)を除いて有意な差は認められなかった。両調査法間の相関関係は,全ての食品群で有意な正の相関がみられた。栄養素では,レチノール当量を除いて有意な正の相関が認められた。しかし,簡易法の摂取量と秤量法のそれとの間の近似をはかるために,1日の目標量を訂正し,両調査法の二度目の検討を行った。調査IIの結果,食品群では嗜好飲料類を除いて有意な差は認めらなかった。両調査法による食品摂取量は,目標量に対する充足率80&acd;120%を示し,近似値が認められた。栄養素では,鉄(以下,Fe),レチノール当量,ビタミンC(以下,VC)を除いて有意な差は認められなかった。両調査法間の相関関係は,嗜好飲料類を除く全ての食品群で有意であった。また,全ての栄養素で有意な正の相関が認められた。

Gary Snyder has been a cultural bridge between East and West since the late icso's.1 Together with Allen Ginsberg who was widely known as a "Beat" poet, read "Howl" at Six Gallery in 1955, and who was deeply affected by Eastern philosophy and the Buddhist poet Phillip Wheren Snyder turned to Eastern Philosophy for his poetic inspiration. His poetry and essays examine various critical concerns, and recently many studies have been done, from critical and anthropological angles, as well as from the view of "an ecological consciousness." Consequently, Gary Snyder is being placed in the tradition of Robert Bly and Ezra Pound, and he has attracted the attention of comparatists in China, who are interested in the influences of Zen, Taoism, Hua-yen Buddhism and Cathay's upon his work. Snyder's poetic identification of the mind with things, as we read in the poem "Riprap" and others, may derive from his interest in Hua-yen Buddhism. According to this philosophy, the metaphor for the interconnectedness of nature is "the jeweled net of Indra" and is mirrored in ecological images. Robert Kern has shown Hua-yen Buddhism, especially Avatamsaka and "the jeweled net," has a prominent place in Snyder's ecological consciousness.2 Avatamsaka, as Snyder uses it, means "Flower Wreath" a flower crown or flower earrings. It is the original name of Huayen Buddhism, according to "Hua-yen" a Tibetan translation of Hua-yen Buddhism, and it is symbolized literally by Hua-yen (^PJlxX Likewise, the "jeweled net of Indra" that Snyder sometimes uses comes from the Huayen idea, H vummW^iE^r Pi , and it represents infinitely crossing relationships and the interconnectedness of all things. There is also a similarity between Snyder's principle and the Hua-yen Buddhist view, " 29 ttife J?*." In

PURPOSE To report on high-penetrating swept source optical coherence tomography (SS-OCT) imaging and enhanced depth imaging in an eye with presumed retinal pigment epithelial hamartoma . METHODS AND PATIENTS A 60-year-old man with presumed retinal pigment epithelial hamartoma underwent complete ophthalmologic examination, including fluorescein angiography, indocyanine green angiography, enhanced depth imaging OCT, and SS-OCT. RESULTS In the left eye, there were six darkly pigmented, nodular, circumscribed lesions in the macular area. The margins were well defined and were not associated with changes such as edema, exudation, or hemorrhage. Fluorescein angiography revealed a minimally dilated feeding artery and draining vein in each lesion. Spectral domain OCT demonstrated an elevation of the retina at the site of the lesions with greatly enhanced optical reflectivity of the inner surface and complete shadowing of optical transmission with crisp vertical margins. However, enhanced depth imaging OCT and SS-OCT revealed deeper retinal layer structures in the pigmented lesions. Intraretinal lesions showed superficial involvement and preretinal extension with or without superficial hyporeflective regions. CONCLUSION Enhanced depth imaging OCT and SS-OCT revealed deeper retinal layer structures in the pigmented lesions in a case with presumed retinal pigment epithelial hamartoma. Enhanced depth imaging OCT and SS-OCT are useful for visualization of intraretinal structures in these lesions, leading to further investigation of the origin and development of retinal pigment epithelial hamartoma.

Purpose To investigate the efficacy of periodic injection of aflibercept in each subtype of age-related macular degeneration (AMD) and to explore the predictive factors for visual outcome in clinical settings. Design Prospective nonrandomized interventional case series. Methods Patients with AMD were recruited and were administered aflibercept injections once a month for 3 months followed by once every 2 months for 8 months. The logarithm of the minimal angle of resolution (logMAR) at 12 months and improvement of vision from baseline were compared among polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. Regression rate of polypoidal lesions was assessed. We also performed regression analysis with logMAR at 12 months as the dependent variable. Results The study sample consisted of 98 patients: 46 had typical AMD, 42 had PCV, and 10 had RAP. Mean logMAR improved from 0.36 to 0.21 in 12 months. While there was no difference in visual improvement between typical AMD and PCV, final logMAR was better in PCV (0.32 ± 0.09 vs 0.08 ± 0.04, P = .016). Thirty-nine PCV patients underwent follow-up angiography, and regression of polyps was observed in 27 cases (69.2%). Multiple regression analysis showed that the presence of external limiting membrane (ELM), smaller greatest linear dimension, and the presence of polypoidal lesion were associated with better visual outcome (R2 = 0.53, P = 2.73 × 10−14). Conclusions Periodic injection of aflibercept is effective for PCV as well as for typical AMD. The statuses of ELM, greatest linear dimension, and polypoidal lesion are predictive for visual outcome.

To evaluate visual and anatomic outcomes in response to the conversion of treatment in patients with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to previous treatment. We also investigated the effect of genetic factors. We recruited patients with AMD or PCV refractory to ranibizumab and initiated aflibercept treatment. Changes in the logarithm of minimum angle of resolution (logMAR) and central retinal thickness (CRT) measured using optical coherence tomography (OCT) 6 months after the conversion were compared between the AMD and PCV groups. We also genotyped each patient for the ARMS2 A69S, CFH Y402H, and I62V alleles, and investigated the association between genotype and treatment response. Mean age of the participants was 75.6 ± 8.0 years. There were 15 patients with AMD and 26 patients with PCV. While PCV patients gained about 1 line of vision (0.40 ± 0.37 to 0.31 ± 0.40, P = 0.003), AMD patients did not show significant improvement (0.41 ± 0.37 to 0.42 ± 0.39, P = 0.699) despite the decrease in CRT (202.1 ± 113.7 to 131.2 ± 55.7 μm, P = 0.003). The prevalence of dry retina after treatment was higher among PCV patients (80.8 vs 46.7 %, P = 0.024). There was no significant difference between patients with risk and non-risk alleles for ARMS2 A69S, CFH Y402H, and I62V. In AMD or PCV patients refractory to ranibizumab, switching to aflibercept is generally effective regardless of patient genotype. PCV patients may benefit more significantly than AMD patients.

Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Soy isoflavones, a subgroup of flavonoids, are abundantly found in the soy germ. They are thought to exert a number of effects by specifically binding to estrogen receptors due to their structural similarity to estrogen. Recently, soy isoflavones have been found to exert antioxidant effects, ameliorating disorders caused by reactive oxygen/free radicals. Based on these observations, the effects of soybean isoflavones on impaired salivary secretion were studied in patients with dry mouth. Soy isoflavone aglycones were administered at 25 mg per day to 15 subjects with an average age of 67.9 ± 8.0 years for 2 months, and salivary secretion was analyzed. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.

Purpose: Recently, indocyanine green angiography (IA) was used to examine chorioretinal circulation in posterior uveitis in humans, and abnormal IA findings were reported. However, choroidal pathologic examination in conjunction with these abnormal IA findings has rarely been done. Experimental autoimmune uveoretinitis (EAU) is a model for posterior uveitis in humans. The purpose of this study was to correlate abnormal IA findings in Lewis rats with EAU with pathologic findings. Methods: Eleven male Lewis rats were immunized with bovine S-antigen in complete Freund's adjuvant with Bordetella pertussis. After immunization, IA was performed by using a scanning laser ophthalmoscope. Eyes with abnormal IA findings were enucleated and examined histopathologically. Results: Demonstrated leakage from retinal vessels at the initial stage of disease; a decrease of background fluorescence and of the number of moderate and large vessels of the choroid, and leakage from choroidal vessels at the progressive stage; and hypofluorescent areas at the late stage. Histopathologic examination at the initial, progressive, and late stages revealed inflammation of the inner layers of the retina, a large number of inflammatory cells in the thickened retina and choroid, and impaired choroidal capillaries, respectively. Conclusion: Since a correlation between pathologic findings and IA findings was demonstrated in Lewis rats with EAU, IA may be useful for evaluating the severity of uveitis in humans.

Acinetobacter baumannii strains resistant to both imipenem (IPM) and ceftazidime (CAZ) were isolated from 1994 through 1996 at Gunma University Hospital. Nine isolates from different inpatients were examined for carbapenem-hydrolyzing activity and for the carbapemase gene bla IMP by the PCR method. All nine isolates were carbapenemase-producing strains that hydrolyzed IPM and that harbored bla IMP . The bla IMP gene was transmissible by conjugation to an IPM-susceptible recipient strain of A. baumannii and conferred resistance to IPM, CAZ, cefotaxime (CTX), ampicillin (AMP), and piperacillin (PIP). Either intermediate or high-level resistance to amikacin (AMK) was transferred from two and five strains, respectively, concomitantly with bla IMP , and gentamicin (GEN) resistance was also transferred in one instance of high-level AMK resistance. Comparative examination of clinical isolates for resistance patterns to nine drugs, IPM, CAZ, CTX, aztreonam, AMP, PIP, AMK, GEN, and norfloxacin, in addition to pulsed-field gel electrophoresis patterns with Not I-digested genomic DNA, confirmed nosocomial transmission of infections involving carbapenemase-producing A. baumannii strains.

Equilibrium constants for the formation of 1 : 1 inclusioncomplexes of α-cyclodextrin (α-CD) with neutral and anionic phenol derivatives (3- and 4-cyanophenols and 3- and 4-nitrophenols) have been evaluated at 5, 12, 25, and 35 °C by means of spectrophotometry. Similarly, the equilibrium constants have been determined for the inclusion complexes ofβ-cyclodextrin (β-CD) with the phenols. Enthalpy and entropy changes for the formationof the inclusion complexes have been estimated from the temperature dependences of theequilibrium constants. With α-CD, the enthalpy andentropy changes for the anionic species have been found to be more negative than those for the neutral ones, except for 4-cyanophenol, suggesting that the inclusion complexes of the anionic species are more rigid than those of the neutral species. From analyses of chemical shift differences in 13C NMR spectra of 3- and 4-cyanophenolsand 3- and 4-nitrophenols in aqueous solutions with and without CDs, a nitro ora cyano group has been found to be first bound to the α- and β-CD cavities.

ATP感受性Kチャネル (以下KATPチャネル) は, 近年の精力的な研究の結果, Kir6.xとSUR (sulfonylureareoeptor) の2つの異なるサブユニットが細胞膜で4量体を形成して機能することが発見された.我々は, KATPチャネルが, 虚血に際して心筋保護的に働くことから, ラット心筋梗塞モデルを用いて虚血刺激がKATPチャネルに与える影響を, その構成サブユニットことに検討した.60分以上の虚血刺激によりKATPチャネルのチャネル孔を形成するKir6.1分子のupregulationが特異的に観察された.ついで, CDS7細胞を用いた再構築系を用いて, このKir6.1の増力口の意義を明らかとするため4量体を作るKチャネル分子の中にKir6.1が入り込むことによりSUR2A/Kir6.2チャネルの性質を変え, ひいてはATPに対する感受性の変化を起こす可能性を検討した.

Reactions of isoselenocyanate with methyl aminoacetate hydrochlorides in the presence of triethylamine afforded selenohydantoins, 2-selenoxoimidazolidin-4-ones, in high yields.

Luteophanols B (1) and C (2), new polyhydroxyl linear carbon-chain compounds, have been isolated from the cultured marine dinoflagellate Amphidinium sp. The structures of 1 and 2 were elucidated by detailed analyses of two-dimensional NMR data containing HMBC, HMQC-RELAY, CH2-selected E-HSQC, and CH2-selected E-HSQC-TOCSY.

Seventeen strains of Streptococcus pyogenes were isolated from 17 patients in the Dermatological Ward of Gunma University Hospital in Japan between June 1994 and March 1995. Of these 17 strains, 14 were isolated from the pus of skin infections, two from blood, and one from ascitic fluid. The strains showed the same minimum inhibitory concentrations; 4 mg/L of minomycin, 4 mg/L of ofloxacin and 16 mg/L of fosfomycin. T-antigen typing of the strains indicated they were T11 type. The restriction endonuclease digestion patterns of chromosomal DNA from the 17 strains were all identical. The vinyl sheet covering the bed on which the patients were treated was found to be contaminated with S. pyogenes. This strain showed identical characteristics to the strains derived from the patients. These results suggest that S. pyogenes was transmitted to patients in the Dermatological Ward from the surface of the vinyl sheet covering the bed.

A 20-year-old man with congestive heart failure (CHF) and hypertension (HT) was admitted to hospital. Ultrasonic echocardiography showed that he had aortic stenosis caused by a bicuspid aortic valve. The plasma renin concentration was slightly elevated, and enhanced magnetic resonance imaging and renography revealed a hypoplastic kidney that had almost lost its normal function. It is postulated that the increased afterload and preload of the left ventricle induced by both of these abnormalities contributed to the onset of CHF and HT. Pharmacological therapy alone failed to control the CHF and HT, but surgical removal of the hypoplastic kidney was effective in reducing the plasma renin concentration and treating the CHF and HT.

Interventional radiology (IVR) is a technique using image guidance such as X-ray fluoroscopy to perform diagnostic and therapeutic procedures. It is widespread, and its use continues to increase. Radiofrequency catheter ablation (RFCA) has a long fluoroscopy time, and ablation procedures may be repeated in a single session. The entrance skin dose may reach several Gy, but information on radiation dose of actual procedures is limited. We conducted a survey on RFCA to acquire general information on how the procedures are performed in local institutions, including patient radiation dose in the Kanto area. 43% (33/77 institutions) of institutions to which we sent written questionnaires returned completed forms. Ablation for atrial fibrillation had the longest average fluoroscopy times (100.8 min) and average procedure times (228 min), and average air kerma at the interventional reference point (1173.6 mGy). Percutaneous coronary intervention and RFCA may cause skin injury, which suggests the continued need for radiation safety management.

To investigate the 2-year outcomes of photodynamic therapy (PDT) combined with intravitreal injections of ranibizumab for polypoidal choroidal vasculopathy (PCV). Ninety-five eyes with subfoveal PCV treated with combined therapy were followed for ≥24 months. The association between visual outcomes and single nucleotide polymorphisms in ARMS2 A69S and CFH I62V genes were examined without adjusting for multiple comparisons. Visual acuity (VA) improvement was observed at month 3 (P = 0.009). The improvement persisted until month 12 (P = 0.003), when VA began the decline back to baseline values at month 24. To investigate the factors associated with VA reduction during the second year, patients were divided into those with and those without a second-year VA reduction. Both patients with and without a second-year VA reduction showed similar VA changes over the first year. The first-year VA improvement was not predictive of the VA decline over the second year. Genetic analyses showed no significant difference in the frequency of the A risk allele of CFH I62V between patients with and without a second-year VA reduction. However, patients with the T risk allele of A69S had a higher rate of recurrence and were more likely to experience a reduction in VA during the second year when compared to patients without (P = 0.020 and P = 0.048, respectively). PDT combined therapy resulted in significant visual recovery in the first year, which was not sustained during the second year. VA reduction in the second year was affected by genetic factors.

To investigate the choroidal thickness/volume of eyes with reticular pseudodrusen using high-penetration swept-source optical coherence tomography (SS-OCT) and to evaluate the choroidal vasculature changes using en face images.Prospective cross-sectional study.Thirty-eight eyes with reticular pseudodrusen and 14 normal eyes were studied with prototype SS-OCT. Eyes with reticular pseudodrusen were classified into 3 subgroups: eyes without late age-related macular degeneration (AMD) (Group1), eyes with neovascular AMD (Group2), and eyes with geographic atrophy (Group3). Mean regional choroidal thickness/volume measurements were obtained by 3-dimensional (3D) raster scanning. The choroidal vascular area was measured using en face images reconstructed from a 3D SS-OCT data set.Mean age and axial length did not differ between eyes with reticular pseudodrusen and normal eyes. The mean choroidal thickness and volume of each sector was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P.020 for all). Mean choroidal thickness and volume of each area showed no significant difference between the 3 groups; however, most of them showed decreased thickness compared with normal eyes. En face images through the choroid revealed narrow and sparse choroidal vessels in eyes with reticular pseudodrusen. The area of choroidal vasculature was significantly reduced in eyes with reticular pseudodrusen compared with normal eyes (P = .037).In eyes with reticular pseudodrusen, macular choroidal thickness/volume was reduced regardless of choroidal neovascularization/geographic atrophy. Thinned vessels in the choroid suggest choroidal involvement in the pathogenesis of reticular pseudodrusen.

[Objective] To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages. [Methods] Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography. [Results] Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region. [Conclusion] Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD.

Purpose To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. Methods This study included nine eyes with treatment-naive pachychoroid neovasculopathy and 21 eyes with treatment-naive nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. Results The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). Conclusions The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

Because of the declining availability of hospital beds due to increasing demand, patients with terminal cancer are entering welfare facilities. A patient in whom relief from sharp pain was difficult to achieve in welfare facilities was referred to our clinic. He was an 87-year-old man who had undergone resection and colostomy for advanced rectal and bladder cancers. Although opioid was used to control carcinomatous sharp pain, the pain control was insufficient at the beginning of treatment. It is unusual for welfare patients to complain of pain, and few nurses in such facilities are experienced in the use of opioid. Information sharing was measured among the staff, and palliative care was found to be substantial. In addition to a family physician, a pharmacist's cooperation is effective for the education of staff in welfare facilities, and interregional association was useful in this regard. By assessing the patient's condition and performing palliative care, we were able to tend to the patient in the welfare facilities in the absence of a full-time physician.

In our hospital, the average duration of training in intubation by the emergency medical technician training intubation was 17.9 days. Compared to other reports, our training period is shorter. Short training period has reduced burden of hospital and fire station. One of the important contributions to the society for anesthesiologists is to increase the number of emergency medical technicians who can intubate. But long training period has been increasing the burden of anesthesiologists and emergency medical technicians. We report a practical method of intubation by emergency medical technician in our hospital.

Purpose: The aim of this study was to examine the usefulness of the subtraction technique of non-contrast renal magnetic resonance angiography (MRA) between tagged and non-tagged data collection. Material and Methods: We performed renal MRA on eleven healthy volunteers using a 3T MRI unit. For renal MRA, a three dimensional balanced type steady-state free precession (SSFP) sequence (True FISP, Siemens) was used with diaphragmatic navigator gating. We tried to acquire selective arterial images by subtracting black-blood images (tagged images, on which arterial longitudinal magnetization was nearly zero by selective inversion of upper-stream aortic flow) from bright-blood images (non-tagged images, on which arterial flow is bright due to inflow effect). For analysis, two radiologists independently evaluated the visual quality of the axial and coronal targeted maximum intensity projection images (MIP) of original bright-blood MRA and subtraction MRA. Results: Visualization of the main stem of the renal arteries and their 1st branches were satisfactory on both techniques, and there was no statistically significant difference. The score of 2nd branch appeared superior with the subtraction method, but only the right side showed a statistically significant difference (P

Objective We report a case of perioperative management of a single-ventricle patient with Fontan-associated liver disease undergoing hepatectomy. Case Report A 12-year-old boy with Fontan circulation was scheduled for partial hepatectomy to remove a liver mass in segment 6. He received stent implantation to relieve conduit stenosis 6 months before the operation. The operation was performed under general anesthesia and with a bilateral thoracic paravertebral block (PVB). A continuous paravertebral infusion of levobupivacaine was administered via right and left catheters postoperatively. He was hemodynamically stable throughout the perioperative period, extubated soon after surgery, and had an uncomplicated postoperative course. Conclusions An analgesic regimen including thoracic PVB resulted in a rapid recovery without opioid-related side effects and early reinitiation of anticoagulation therapy. Our case illustrates the effective application of thoracic PVB in congenital heart disease patients for non–cardiac-related surgery.

Heart transplantation provides considerable survival benefits for patients with end-stage heart failure, but it is available for only a small fraction of these patients due to donor shortage. Especially in Japan, domestic legal issues had severely limited the number of heart transplantation until the Revised Organ Transplant Law was launched in 2010. The mean waiting period of Japanese heart transplant candidates after left ventricular assist device (LVAD) surgery had exceeded 2 years and occasionally reached 4 years until recently (Sasaoka T et al., 2010). The long-term LVAD support can result in serious complications such as cerebrovascular accident (CVA), the most common cause of death following LVAD surgery (Rose EA et al., 2001; Holman WL, 2009; Saito S, et al. 2010). CVA is the leading cause of death and the primary reason for elimination from transplant eligibility. In addition, transplant recipients with a history of CVA face tremendous difficulties in being reintegrated into society, often for years after transplant (Nakajima I et al., 2011). Therefore, we investigated factors associated with CVA after LVAD surgery in Japanese patients, as well as we reviewed our treatment strategies for CVA and the outcome of these patients after developing CVA.

Granular cell tumors (GCTs) are uncommon soft tissue tumors that mostly occur in patients between 40 and 60 years of age and can occur at various body sites. Malignant granular cell tumors (MGCTs) comprise less than 2 % of GCTs and are mostly found on the lower extremities, especially the thighs. These tumors grow more rapidly than benign GCTs, and most importantly, they can metastasize. We describe an MGCT that presented as a right breast mass in a 79-year-old Japanese woman. Local excision was performed for the primary tumor, which was diagnosed as an atypical GCT, but 15 months later, the tumor recurred at the same site. Thereafter, right mastectomy with axillary lymph node dissection was performed. Metastatic disease was identified in 2 of 12 lymph nodes. The pathological examination revealed that the tumor had progressed to an MGCT after recurrence. Multiple liver, lung and bone metastases were revealed 4 months after the second surgery, and the patient died 34 months after the primary surgery. Our findings highlighted the difficulty in diagnosing MGCTs using histological features alone and suggested the usefulness of Ki67 values. A tumor with a high level of Ki67 should be treated as malignant, even if the tumor has few pathological features of malignancy.

To evaluate the reliability and reproducibility of automated software to analyze human bulbar hyperemia. We enrolled 89 healthy volunteers in this study. A slit lamp was used to take pictures of the conjunctiva on the temporal side of each subject’s right eye. Photographic conditions were standardized by using a single photographer. Images were transferred to software for automatic pixel value calculation in the green channel of the region of interest (ROI). We investigated optimal ROI size, mean ROI pixel frequency, percentage ROI blood vessel coverage, and data reproducibility. We also used this software to evaluate bimatoprost-induced hyperemia and hyperemia in allergic conjunctival diseases. The optimal ROI was found to be 400 vertical pixels by 300 horizontal pixels. Mean ROI pixel frequency was 5305 and % coverage was 4.4%. We confirmed the reproducibility of the analysis by comparing two images (r 2 = 0.7, P

Cerebrovascular accident (CVA) is a major adverse event following left ventricular assist device (LVAD) surgery. This study investigates pre- and post-operative factors associated with CVA in this population.A total of 118 consecutive patients who underwent LVAD surgery at our institution between April 1994 and April 2009 were retrospectively reviewed. Clinical characteristics, hemodynamic data, and laboratory indexes associated with CVA after LVAD surgery were analyzed. In total, 57 (48.3%) patients developed CVA 133.5 ± 184.7 days after surgery. The combination of baseline heart disease, type of LVAD surgery, mean right atrial pressure (mRA), serum total bilirubin and total protein concentration, and right ventricular end-diastolic dimension (RVEDd) was associated with CVA at any time after LVAD surgery, with a discriminant probability of 718%. With regard to CVA development later than 3 months after surgery, the combination of mRA and RVEDd before surgery [odds ratio (OR), 1.24, 1.20; 95% confidential interval (CI), 1.07-1.42, 1.06-1.34; P = 0.004, P = 0.006, respectively], positive blood culture, and C-reactive protein after surgery (OR, 7.66, 2.19; 95%CI, 1.50-39.0, 1.47-3.25; P = 0.015, P0.0001, respectively) was associated with CVA with a discriminant probability of 85.9%.Patients' general condition including malnutrition, in addition to device selection, contributed to overall CVA development after surgery. In the chronic phase after surgery, pre-LVAD right heart failure and post-LVAD systemic infection were highly associated with CVA development.

Reduced left ventricular torsion (LV-tor) has been reported to be associated with acute rejection in heart transplant (HTx) recipients. We investigated the utility of LV-tor analysis derived from 2-dimensional speckle-tracking echocardiography (2D-STE) for detecting allograft rejection.A total of 301 endomyocardial biopsies (EMBs), right heart catheterizations and echocardiograms were performed in 32 HTx recipients. Echocardiography was done within 3 hours from EMB or simultaneously with the procedures. The LV-tor was defined as the difference between apical and basal end-systolic rotations. The LV-tor values with and without cellular rejection were compared. In addition, we investigated whether the change in LV-tor values predicts the change in rejection grade in each patient. The baseline LV-tor value in each patient was defined as a mean value of the first 3 LV-tor measurements obtained when the patient was free from rejection.According to the conventional International Society for Heart and Lung Transplantation criteria, 274 biopsies showed a rejection Grade of 0, 1a or 1b (Group AR(-)), whereas 27 biopsies were Grade 2 or higher (Group AR(+)). LV-tor decreased more in Group AR(+) than in Group AR(-) (9.3 ± 0.7 vs 12.2 ± 0.2 degrees, p0.0001). In the LV-tor measurement for each patient, the 25% reduction in LV-tor value from baseline predicted Grade 2 or higher rejection with a predictive accuracy of 92.9%.LV-tor derived from 2D-STE could be of clinical value for non-invasive monitoring of acute rejection in HTx recipients.

Long-term real-time monitoring of free-ranging Bottlenose dolphins (Tursiops truncatus) in the pool of the aquarium “Izu Mito Sea paradise”, i.e. in the enclosed observatory has been started from 22nd June 2008, and continuously conducted ever since then. The monitoring system consists of 1) a modified 5-hydrophone array system deployed in the pool, 2) a web camera placed overland for visual monitoring of the dolphins, and 3) the land base system to process and transmit the acoustic data from the hydrophones of the array and the video images from the web camera to the servers in real-time via internet. The echo-location characteristics of the Bottlenose dolphins in the pool and their behavioral changes in a long-term span have been initially observed and analyzed. Three echolocation phases (search, approach, terminal) have been observed. It is estimated that the dolphins are echo-locating the surrounding environment and targeting something else such as the array as a target. Solo burst-pulses emitted by one of two dolphins swimming side by side in the pool were also observed. For understanding the Bottlenose dolphins' behavioral changes during the long-term monitoring, the trend of the number of clicks recorded around the pool is applied for the analysis as an index of the dolphin's activities. The results show the trend and difference of the changes of the click number in each section of the pool depending on the time of day. Not only depending on the time, but also depending on natural phenomena, the dolphins' behavioral changes were observed. A definite trend of click number reduction is observed during the occurrence of an earthquake, even when they stayed underwater. Significant behavioral changes of the dolphins are also observed just after the earthquake. This indicates that the Bottlenose dolphins in the pool of the “Izu Mito Sea Paradise” did not actually “predict” the earthquake.

Although various management methods have been developed for heart failure, it is necessary to investigate the diagnostic or therapeutic targets of heart failure. Accordingly, we have developed different approaches for managing heart failure by using conventional microarray analyses. We analyzed gene expression profiles of myocardial samples from 12 patients with heart failure and constructed datasets of heart failure-associated genes using clinical parameters such as pulmonary artery pressure (PAP) and ejection fraction (EF). From these 12 genes, we selected four genes with high expression levels in the heart, and examined their novelty by performing a literature-based search. In addition, we included four G-protein-coupled receptor (GPCR)-encoding genes, three enzyme-encoding genes, and one ion-channel protein-encoding gene to identify a drug target for heart failure using in silico microarray database. After the in vitro functional screening using adenovirus transfections of 12 genes into rat cardiomyocytes, we generated gene-targeting mice of five candidate genes, namely, MYLK3, GPR37L1, GPR35, MMP23, and NBC1. The results revealed that systolic blood pressure differed significantly between GPR35-KO and GPR35-WT mice as well as between GPR37L1-Tg and GPR37L1-KO mice. Further, the heart weight/body weight ratio between MYLK3-Tg and MYLK3-WT mice and between GPR37L1-Tg and GPR37L1-KO mice differed significantly. Hence, microarray analysis combined with clinical parameters can be an effective method to identify novel therapeutic targets for the prevention or management of heart failure.

SummaryBackground and purposeThe majority of heart transplant (HTx) candidates require left ventricular assist device (LVAD) support for more than 2 years before transplantation in Japan. However, the only currently available device is the extracorporeal pulsatile LVAD. The long-term management of extracorporeal LVAD support has improved remarkably over the years. To determine which post-operative management factors are related to the long-term survival of patients on such LVAD, we retrospectively compared the incidence of complications and their management strategies between the initial and recent eras of LVAD use, classified by the year of LVAD surgery.MethodsSixty-nine consecutive patients supported by extracorporeal pulsatile LVAD as a bridge to HTx between 1994 and 2007 were reviewed retrospectively. The patients were assigned according to the time of LVAD surgery to either group A (n=30; between 1994 and 2000) or group B (n=39; between 2001 and 2007).ResultsPatients in group B survived significantly longer on LVAD support than those in group A (674.6 vs. 369.3 days; p