The first author of the article has duely admitted that he is mainly responsible for the misconduct.

BACKGROUND: Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) may have multiple therapeutic applications for cell based therapy including the treatment of pulmonary artery hypertension (PAH). As low survival rates and potential tumorigenicity of implanted cells could undermine the mesenchymal stem cell (MSC) cell-based therapy, we chose to investigate the use of conditioned medium (CM) from a culture of MSC cells as a feasible alternative. METHODS: CM was prepared by culturing hUCB-MSCs in three-dimensional spheroids. In a rat model of PAH induced by monocrotaline, we infused CM or the control unconditioned culture media via the tail-vein of 6-week-old Sprague-Dawley rats. RESULTS: Compared with the control unconditioned media, CM infusion reduced the ventricular pressure, the right ventricle/(left ventricle+interventricular septum) ratio, and maintained respiratory function in the treated animals. Also, the number of interleukin 1alpha (IL-1alpha), chemokine (C-C motif) ligand 5 (CCL5), and tissue inhibitor of metalloproteinase 1 (TIMP-1)-positive cells increased in lung samples and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL)-positive cells decreased significantly in the CM treated animals. CONCLUSIONS: From our in vivo data in the rat model, the observed decreases in the TUNEL staining suggest a potential therapeutic benefit of the CM in ameliorating PAH-mediated lung tissue damage. Increased IL-1alpha, CCL5, and TIMP-1 levels may play important roles in this regard.
Animals ; Apoptosis ; Culture Media ; Culture Media, Conditioned ; Deoxyuridine ; Fetal Blood* ; Gene Expression ; Humans ; Hypertension* ; In Situ Nick-End Labeling ; Interleukin-1alpha ; Lung ; Mesenchymal Stromal Cells ; Models, Animal ; Monocrotaline ; Pulmonary Artery ; Rats* ; Rats, Sprague-Dawley ; Survival Rate ; Tissue Inhibitor of Metalloproteinase-1 ; Umbilical Cord* ; Ventricular Pressure

OBJECTIVE: The Leksell Gamma Knife(R) (LGK) is based on a single-fraction high dose treatment strategy. Therefore, independent verification of the Leksell GammaPlan(R) (LGP) is important for ensuring patient safety and minimizing the risk of treatment errors. Although several verification techniques have been previously developed and reported, no method has ever been tested statistically on multiple LGK target treatments. The purpose of this study was to perform and to evaluate the accuracy of a verification method (modified variable ellipsoid modeling technique, MVEMT) for multiple target treatments. METHODS: A total of 500 locations in 10 consecutive patients with multiple brain tumor targets were included in this study. We compared the data from an LGP planning system and MVEMT in terms of dose at random points, maximal dose points, and target volumes. All data was analyzed by t-test and the Bland-Altman plot, which are statistical methods used to compare two different measurement techniques. RESULTS: No statistical difference in dose at the 500 random points was observed between LGP and MVEMT. Differences in maximal dose ranged from -2.4% to 6.1%. An average distance of 1.6 mm between the maximal dose points was observed when comparing the two methods. CONCLUSION: Statistical analyses demonstrated that MVEMT was in excellent agreement with LGP when planning for radiosurgery involving multiple target treatments. MVEMT is a useful, independent tool for planning multiple target treatment that provides statistically identical data to that produced by LGP. Findings from the present study indicate that MVEMT can be used as a reference dose verification system for multiple tumors.
Brain ; Brain Neoplasms ; Humans ; Patient Safety ; Radiosurgery

Nitric Oxide (NO) actively participates in the regulation of neuronal intracellular Ca2+ levels by modulating the activity of various channels and receptors. To test the possibility that modulation of Ca2+ buffer protein expression level by NO participates in this regulatory effect, we examined expression of calbindin-D28k, calretinin, and parvalbumin in the cerebellum of neuronal NO synthase knock-out (nNOS(-/-)) mice using immunohistochemistry. We observed that in the cerebellar cortex of the nNOS(-/-) mice, expression of calbindin-D28k and parvalbumin were significantly increased while expression of calretinin was significantly decreased. These results suggest another mechanism by which NO can participate in the regulation of Ca2+ homeostasis.
Animals ; Calcium ; Calcium-Binding Protein, Vitamin D-Dependent ; Calcium-Binding Proteins ; Cerebellar Cortex ; Cerebellum ; Homeostasis ; Immunohistochemistry ; Mice ; Neurons ; Nitric Oxide ; Nitric Oxide Synthase

In the present study, we investigated influences of glycogen synthase kinase (GSK) 3beta on the development and/or progression of amyotrophic lateral sclerosis (ALS). We used transgenic mice expressing a human Cu/Zn superoxide dismutase mutant (SOD1G93A) as an in vivo model of ALS and examined expressional changes of GSK3beta immunohistochemically in the spinal cord, brain stem and cerebellum. With these experiments we demonstrate that the neurons in these regions of symptomatic SOD1G93A transgenic mice showed increased GSK3beta immunoreactivities compared with wild-type SOD1 transgenic mice. In contrast to symptomatic SOD1G93A transgenic mice, few GSK3beta immunoreactivity changes were detected in 8w- and 13w-old presymptomatic SOD1G93A transgenic mice. These data suggest the possibility that GSK3 functions as a modulating factor of apoptosis-related alterations in ALS and that GSK3beta exert differential functions in the development and/or progression of ALS. But the exact functional significances of these changes require further elucidation.
Amyotrophic Lateral Sclerosis ; Animals ; Brain Stem ; Central Nervous System* ; Cerebellum ; Glycogen Synthase Kinases* ; Glycogen Synthase* ; Glycogen* ; Humans ; Mice ; Mice, Transgenic* ; Neurons ; Spinal Cord ; Superoxide Dismutase

Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)100] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immnuocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)18] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome- lysosomal accumulation, from a 'dispersed vacuole (DV)' type into a coalescent 'perinuclear vacuole (PV)' type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome-lysosomal system, and that this contributes to huntingtin proteolysis.
Peptide Hydrolases/metabolism ; Nuclear Proteins/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; NIH 3T3 Cells ; Mice ; Lysosomes/*metabolism ; HSP70 Heat-Shock Proteins/genetics/*metabolism ; Endosomes/*metabolism ; Cytoplasm/metabolism ; Cell Survival ; Animals

We report here on a case of a spinal extradural leiomyoma in a 67-year-old woman, and this tumor was in a very unusual location for a leiomyoma. Because the patient underwent hysterectomy for a uterine leiomyoma 20 years ago, we can speculate that the spinal lesion was a metastatic leiomyoma.
Aged ; Female ; Humans ; Hysterectomy ; Leiomyoma* ; Spinal Cord

BACKGROUNDS: Free radical theory showed that aging might be correlating with the accumulation of oxidative damage into biomolecules of animals. Since the process was also observed in some neurodegenerative disease, the study on the subject could improve our understanding of the aging process. In this regard, our study laid focus on the effect of various anti-oxidants on the cells including mutant Cu/Zn-superoxide dismutase, which was reported to be deficient in various diseases or aging processes. METHODS: We tested retinol, Vitamin C, E and coenzyme Q10 on mutant Cu/Zn-superoxide dismutase(A4V) motor neuron cells using immunocytochemical study and accompanying statistical analysis. RESULTS: During our trial on the hydrogen peroxide treatment on A4V mutant cells, Vitamin A and C did not show any defensive effect on oxidative stress induced A4V cells while Vitamin E and coenzyme Q10 exhibited meaningful inhibitory effect against apoptosis relating protein expression. CONCLUSION: In case of oxidative damages induced by Cu/Zn-superoxide dismutase deficiencies, the protective role of some anti-oxidants like Vitamin E or coenzyme Q10 should be positively considered in forthcoming studies.
Aging ; Amyotrophic Lateral Sclerosis ; Animals ; Apoptosis* ; Ascorbic Acid ; Hydrogen Peroxide ; Immunohistochemistry ; Motor Neurons* ; Neurodegenerative Diseases ; Oxidative Stress ; Vitamin A ; Vitamin E ; Vitamins

OBJECTIVES: This study aims to estimate the prevalence of the DSM-IV psychiatric disorders in Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI). METHODS: Subjects were selected by taking multi-stage, cluster samples of 7,867 adult household residents, 18 to 64 years of age, in ten catchment areas. Total 78 trained interviewers administered the K-CIDI to the selected respondents, from June 1 to November 30, 2001. RESULTS: Total 6,275 respondents completed the interview. Some 33.5% of respondents reported at least one lifetime disorder, 20.6% reported at least one-year disorder, and 16.7% reported at least one-month disorder. The most common lifetime disorders were alcohol abuse/dependence (17.24%), nicotine dependence/withdrawal (11.19%), specific phobia (5.16%), and major depressive disorder (4.25%). The lifetime prevalence of substance abuse/dependence (0.25%) and schizophrenia (0.16%) was very low. Nicotine and alcohol use disorder showed very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among female than male. CONCLUSION: The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in distributions of psychiatric disorders across the areas and times were observed.
Adult ; Anxiety Disorders ; Surveys and Questionnaires ; Depressive Disorder, Major ; Diagnostic and Statistical Manual of Mental Disorders ; Epidemiology ; Family Characteristics ; Female ; Humans ; Male ; Mood Disorders ; Nicotine ; Phobic Disorders ; Prevalence* ; Schizophrenia

BACKGROUND: Mutations in the human Cu, Zn-superoxide dismutase(SOD1) gene have been identified in some cases of familial amyotrophic lateral sclerosis(ALS). The aim of this study is to delineate the effect of the SOD1 mutation on neural differentiation, and to investigate the mechanism of neuronal death. METHODS: We studied motorneuron-neurob-lastoma hybrid cells(VSC 4.1) expressing wild type or mutant SOD1(G93A, A4V) during differentiation by dibutyryl cAMP and aphidicolin. RESULTS: Mutant cells(G93A) revealed a decreased viability compared with the control cells, mainly in the early stage ofdifferentiation. The release of cytochrome c and increased nuclear fragmentation were observed. However, cell death was not protected by nonselective caspase inhibitor(z-VAD-fmk), but by the antioxi-dant( Trolox). CONCLUSIONS: The results suggest that oxidative stress may be the main mechanism of neuronal death, particularly in the early stage of differentiation.
Aphidicolin ; Cell Death ; Cytochromes c ; Humans ; Motor Neurons* ; Neurons ; Oxidative Stress