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1.  Surgical treatment for medically refractory myasthenic blepharoptosis 
Currently, only a few reports have recommended surgery as a suitable treatment for blepharoptosis associated with myasthenia gravis. The present study aims to introduce our surgical criteria, surgical options, outcomes, and precautions for medically refractory myasthenic blepharoptosis.
Patients and methods
Eight patients who failed to respond to at least 2 years of medical treatment and who underwent blepharoptosis surgery, from January 2008 to December 2011, were enrolled in this study. Medical records, photographs, and questionnaire results regarding postoperative status were evaluated. Of the eleven procedures performed, four involved frontal suspension, four involved external levator advancement, one involved nonincisional transconjunctival levator advancement, and two involved subbrow blepharoplasty with orbicularis oculi muscle tucking. The margin reflex distance improved postoperatively in seven patients.
Seven patients had very minimal scarring, and one had minimal scarring. Five patients showed no eyelid asymmetry, one had subtle asymmetry, and two had obvious asymmetry. Seven patients were very satisfied, and one patient was satisfied with the overall result. Postoperative complications included mild lid lag with incomplete eyelid closure, prolonged scar redness, and worsened heterophoria. No patient experienced postoperative exposure keratitis or recurrent blepharoptosis during the study period.
Our results indicate that blepharoptosis surgery is effective for patients with myasthenia gravis, especially those with residual blepharoptosis despite multiple sessions of medical treatments. We recommend that neurologists and surgeons collaborate more systematically and discuss comprehensive treatment plans to increase the quality of life for patients with myasthenia gravis.
PMCID: PMC4179829  PMID: 25278744
ptosis; myasthenia gravis; ocular myasthenia; blepharoplasty
2.  The relationship between insight and subjective experience in schizophrenia 
To examine the relationship between level of insight and various subjective experiences for patients with schizophrenia.
Materials and methods
Seventy-four patients with schizophrenia who were discharged from our hospital were evaluated. The level of insight into their illness and various subjective experiences were evaluated at discharge. We used the Scale to Assess Unawareness of Mental Disorder (SUMD) for evaluation of insight. In addition, five different rating scales were used to evaluate subjective experiences: Subjective Experience of Deficits in Schizophrenia (SEDS), Subjective Well-being under Neuroleptic drug treatment Short form (SWNS), Schizophrenia Quality of Life Scale (SQLS), Beck Depression Inventory (BDI), and the Drug Attitude Inventory (DAI)-30.
The SWNS and the scores for awareness of mental disorder and awareness of the social consequences of mental disorder on SUMD showed a weak positive correlation. The DAI-30 showed a significant negative correlation with most general items on SUMD and a negative correlation between the subscale scores for the awareness and attribution of past symptoms. SEDS, SWNS, SQLS, and the BDI significantly correlated with the subscale scores for awareness of current symptoms on SUMD, and weakly correlated with the subscale scores for attribution of current negative symptoms.
Awareness of subjective distress was related to awareness of having a mental disorder. Feeling subjective distress was related to awareness of current symptoms, as well as to the ability to attribute current negative symptoms to a mental disorder. Positive attitudes toward medication correlated with better general insight into the illness.
PMCID: PMC4122548  PMID: 25114533
schizophrenia; insight; subjective experiences; subjective deficit; subjective well-being; subjective quality of life
3.  The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder 
The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior.
We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs) of major depressive disorder (MDD).
The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups – without suicide risk group (n=15), and with suicide risk group (n=15) – based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15). All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II), the Beck Hopelessness Scale (BHS), Rosenberg’s Self-Esteem Scale (RSES), and SF-36v2™ (The Medical Outcomes Study 36-item short-form health survey version 2), and they were all administered a battery of neuropsychological tests.
The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group.
The individual’s self-esteem and social functioning may play an important role in suicide risk among young adults with MDEs of MDD.
PMCID: PMC4031242  PMID: 24868158
suicide risk; self-esteem; quality of life; young adults
4.  Prevalence of drug resistance and culture-positive rate among microorganisms isolated from patients with ocular infections over a 4-year period 
To investigate the microbial isolates from patients with ocular infections and the trend in the emergence of levofloxacin-resistant strains over the past four years from 2006 to 2009 retrospectively.
Patients and methods
The subjects were 242 patients with ocular infections or traumas treated in our hospital including outpatients, inpatients, and emergency room patients. Most of them needed urgent care presenting with eye complaints, traumas, or decreased vision. Clinical samples were obtained from discharges, corneal, conjunctival tissues or vitreous fluid or aqueous humor, and cultured. Items for assessment included the patient’s age, the diagnosis, the prevalence of isolated bacteria, and the results of susceptibility tests for levofloxacin (LVFX) cefamezin (CEZ), gentamicin (GM) and vancomycin. This information was obtained from the patients’ medical records.
There were 156 male patients and 86 female patients who were aged from 2 months old to 94 years old and mean age was 56.8 ± 24.2 years. Of the 242 patients, 78 (32.2%) had positive cultures. The culture-positive rate was significantly higher in male patients than female in total (P = 0.002) and in patients with corneal perforation (P = 0.005). Corneal perforation was the highest culture-positive rate (60.0%), followed by orbital cellulitis (56.5%), blepharitis (50.0%), dacryoadenitis (45.5%), conjunctivitis (38.2%), infectious corneal ulcer (28.5%) and endophthalmitis (24.7%). LVFX-resistant strains accounted for 40 out of a total of 122 strains (32.8%), and the minimum inhibitory concentration (MIC) was significantly higher in LVFX and GM compared with the other antibiotics. There were no vancomycin-resistant strains.
Attention should be paid to a possible future increase of strains with resistance to LVFX, as commonly prescribed ocular antibiotics bring emergence of resistant bacteria. Although no vancomycin-resistant strains were isolated this drug should be reserved as the last resort, in order to prevent the emergence of vancomycin resistance.
PMCID: PMC3625025  PMID: 23589677
ocular infections; drug resistance; levofloxacin; vancomycin; minimum inhibitory concentration
5.  Syntheses and Characterization of New Nickel Coordination Polymers with 4,4′-Dipyridylsulfide. Dynamic Rearrangements of One-Dimensional Chains Responding to External Stimuli: Temperature Variation and Guest Releases/Re-Inclusions 
Crystal structures and dynamic rearrangements of one-dimensional coordination polymers with 4,4′-dipyridylsulfide (dps) have been studied. Reaction of Ni(NO3)2·6H2O with dps in EtOH yielded [Ni(dps)2(NO3)2] ·EtOH (1), which had channels filled with guest EtOH molecules among the four Ni(dps)2 chains. This coordination polymer reversibly transformed the channel structure responding to temperature variations. Immersion of 1 in m-xylene released guest EtOH molecules to yield a guest-free coordination polymer [Ni(dps)2(NO3)2] (2a), which was also obtained by treatment of Ni(NO3)2·6H2O with dps in MeOH. On the other hand, removal of the guest molecules from 1 upon heating at 130 °C under reduced pressure produced a guest-free coordination polymer [Ni(dps)2(NO3)2] (2b). Although the 2a and 2b guest-free coordination polymers have the same formula, they showed differences in the assembled structures of the one-dimensional chains. Exposure of 2b to EtOH vapor reproduced 1, while 2a did not convert to 1 in a similar reaction. Reaction of Ni(NO3)2·6H2O with dps in acetone provided [Ni(dps)(NO3)2(H2O)] ·Me2CO (4) with no channel structure. When MeOH or acetone was used as a reaction solvent, the [Ni(dps)2(NO3)2] · (guest molecule) type coordination polymer, which was observed in 1, was not formed. Nevertheless, the reaction of Ni(NO3)2·6H2O with dps in MeOH/acetone mixed solution produced [Ni(dps)2(NO3)2]·0.5(MeOH·acetone) (5), which has an isostructural Ni-dps framework to 1.
PMCID: PMC2996732  PMID: 21152276
porous coordination networks; phase transition; dynamic structural change; crystal structure
6.  A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1 
The Journal of Cell Biology  2004;167(3):445-456.
In the unfolded protein response, the type I transmembrane protein Ire1 transmits an endoplasmic reticulum (ER) stress signal to the cytoplasm. We previously reported that under nonstressed conditions, the ER chaperone BiP binds and represses Ire1. It is still unclear how this event contributes to the overall regulation of Ire1. The present Ire1 mutation study shows that the luminal domain possesses two subregions that seem indispensable for activity. The BiP-binding site was assigned not to these subregions, but to a region neighboring the transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying deletions in the indispensable subregions suggests these subregions are responsible for multiple events that are prerequisites for activation of the overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high temperature. We conclude that in the ER stress-sensory system BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses.
PMCID: PMC2172501  PMID: 15520230
7.  Genetic Evidence for a Role of BiP/Kar2 That Regulates Ire1 in Response to Accumulation of Unfolded Proteins 
Molecular Biology of the Cell  2003;14(6):2559-2569.
In the unfolded protein response (UPR) signaling pathway, accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a transmembrane kinase/ribonuclease Ire1, which causes the transcriptional induction of ER-resident chaperones, including BiP/Kar2. It was previously hypothesized that BiP/Kar2 plays a direct role in the signaling mechanism. In this model, association of BiP/Kar2 with Ire1 represses the UPR pathway while under conditions of ER stress, BiP/Kar2 dissociation leads to activation. To test this model, we analyzed five temperature-sensitive alleles of the yeast KAR2 gene. When cells carrying a mutation in the Kar2 substrate-binding domain were incubated at the restrictive temperature, association of Kar2 to Ire1 was disrupted, and the UPR pathway was activated even in the absence of extrinsic ER stress. Conversely, cells carrying a mutation in the Kar2 ATPase domain, in which Kar2 poorly dissociated from Ire1 even in the presence of tunicamycin, a potent inducer of ER stress, were unable to activate the pathway. Our findings provide strong evidence in support of BiP/Kar2-dependent Ire1 regulation model and suggest that Ire1 associates with Kar2 as a chaperone substrate. We speculate that recognition of unfolded proteins is based on their competition with Ire1 for binding with BiP/Kar2.
PMCID: PMC194903  PMID: 12808051
8.  Necrotic Death Pathway in FAS Receptor Signaling 
The Journal of Cell Biology  2000;151(6):1247-1256.
A caspase 8–deficient subline (JB6) of human Jurkat cells can be killed by the oligomerization of Fas-associated protein with death domain (FADD). This cell death process is not accompanied by caspase activation, but by necrotic morphological changes. Here, we show that the death effector domain of FADD is responsible for the FADD-mediated necrotic pathway. This process was accompanied by a loss of mitochondrial transmembrane potential (ΔΨm), but not by the release of cytochrome c from mitochondria. Pyrrolidine dithiocarbamate, a metal chelator and antioxidant, efficiently inhibited the FADD-induced reduction of ΔΨm and necrotic cell death. When human Jurkat, or its transformants, expressing mouse Fas were treated with Fas ligand or anti–mouse Fas antibodies, the cells died, showing characteristics of apoptosis. A broad caspase inhibitor (z-VAD–fmk) blocked the apoptotic morphological changes and the release of cytochrome c. However, the cells still died, and this cell death process was accompanied by a strong reduction in ΔΨm, as well as necrotic morphological changes. The presence of z-VAD–fmk and pyrrolidine dithiocarbamate together blocked cell death, suggesting that both apoptotic and necrotic pathways can be activated through the Fas death receptor.
PMCID: PMC2190580  PMID: 11121439
apoptosis; caspase; Fas; mitochondrial membrane potential; necrosis

Results 1-8 (8)