Neuroinflammation such as reactive gliosis and microglial activations are important pathological findings of ALS. We present a first autopsy case of ALS in Korea related with neuroinflammatory change. A 67-year-old ALS patient suddenly expired due to accidental head trauma. Gross autopsy finding showed marked atrophic change in spinal cord. Pathological finding include a marked loss of motor neurons, reactive gliosis and microglial infiltrations. These findings suggest neuroinflammation may play a role in pathogenesis of ALS.
Aged ; Amyotrophic Lateral Sclerosis ; Autopsy ; Craniocerebral Trauma ; Gliosis ; Humans ; Korea ; Motor Neurons ; Spinal Cord

To investigate a specific mechanism of apoptosis induced by sonication, we applied 20 kHz ultrasound to leukemia cell line HL-60 with different intensities (0-60 W/cm2) and time durations (0-100 sec). In accordance with previous reports, ultrasound treatment in HL-60 cells induced immediate cell death and delayed cell death which are associated with cell lysis and apoptosis, respectively. Delayed cell death of HL-60 was also detected 5 hours after sonication in our experiment. Detection of caspase activation by Western blot and sub-G1 accumulation by flow cytometry confirmed that apoptosis plays a role in delayed cell death induced by sonication in HL-60 cells. In addition, we found that decrease in lysosomes of HL-60 cells after sonication suggesting lysosomal rupture is involved in the mechanism of cell death induced by sonication.
Apoptosis* ; Blotting, Western ; Cell Death ; Cell Line ; Flow Cytometry ; HL-60 Cells* ; Humans ; Leukemia ; Lysosomes ; Rupture ; Sonication* ; Ultrasonic Therapy ; Ultrasonography

Medication adherence is generally defined as the extent of voluntary cooperation of a patient in taking medicine as prescribed. Adherence to long-term treatment with chronic disease is essential for reducing disease comorbidity and mortality. However, medication non-adherence in chronic disease averages 50%. This study was conducted a genome-wide association study to identify the genetic basis of medication adherence. A total of 235 medication non-adherents and 1,067 medication adherents with hypertension or diabetes were used from the Korean Association Resource project data according to the self-reported treatment status of each chronic disease, respectively. We identified four single nucleotide polymorphisms with suggestive genome-wide association. The most significant single nucleotide polymorphism was rs6978712 (chromosome 7, p = 4.87 x 10-7), which is located proximal to the GCC1 gene, which was previously implicated in decision-making capability in drug abusers. Two suggestive single nucleotide polymorphisms were in strong linkage disequilibrium (r2 > 0.8) with rs6978712. Thus, in the aspect of decision-making in adherence behavior, the association between medication adherence and three loci proximal to the GCC1 gene seems worthy of further research. However, to overcome a few limitations in this study, defining the standardized phenotype criteria for self-reported adherence should be performed before replicating association studies.
Chronic Disease* ; Comorbidity ; Drug Users ; Genome-Wide Association Study* ; Humans ; Hypertension ; Linkage Disequilibrium ; Medication Adherence* ; Mortality ; Phenotype ; Polymorphism, Single Nucleotide

Progressive multifocal leukoencephalopathy (PML) is a fatal disease that is characterized by progressive demyelination of the cerebral white matter due to JC viral infection. We report serial magnetic resonance spectroscopy (MRS) and tractography changes in a patient with PML. After a three-cycle treatment with cidofovir and cytarabine, the patient exhibited remarkable improvements in motor and cognitive functions. Follow-up MRS and tractography revealed regeneration of the white-matter fibers. This is the first consecutive neuroimaging study showing improvements in neurological symptoms using MRS and tractography.
Cytarabine ; Cytosine ; Demyelinating Diseases ; Follow-Up Studies ; Humans ; Leukoencephalopathy, Progressive Multifocal ; Magnetic Resonance Spectroscopy ; Neuroimaging ; Organophosphonates ; Regeneration

OBJECTIVES: This study was performed to investigate the effect of drink containing sodium benzoate on the change of urinary hippuric acid (UHA) and methyl hippuric acid (UMHA) excretion among workers coexposed to low toluene and xylene. METHODS: Study subjects were 55 male shipbuilders who were divided into 3 groups; nonexposed group (n=10, who were not exposed to organic solvent and had drunk sodium benzoate), exposed A group (n=24, who were coexposed to toluene and xylene, and had drunk sodium benzoate), and exposed B group (n=21, who were coexposed to toluene and xylene, and had not drunk sodium benzoate). The study methodology consisted of questionnaire survey, urinary analysis for metabolites of toluene and xylene before and after drinking with or without sodium benzoate, and personal air sampling of toluene and xylene. RESULTS: Before drinking, there was no significant difference in UHA or UMHA between the exposed A and B groups. After 1.5 hour of drinking, UHA of the exposed A group was significantly higher than that of the exposed B group. After 3 hours, however, UHA of the exposed A group was decreased to the level of the exposed B group, regardless of the ambient toluene level. UMHA exhibited no significant difference between the exposed A and B groups regardless of time and ambient toluene level. The regression model showed that drinking of sodium benzoate was positively correlated with UHA after 1.5 hours of drinking, but not after 3 hours. In addition, sodium benzoate didn't affect UMHA. CONCLUSIONS: This study showed that sodium benzoate initially increased UHA temporally but that its effect disappeared after 3 hours. In the medical examination of toluene exposure workers, the ingestion of drink containing sodium benzoate should be forbidden during the 3 hours prior to urinary sampling.
Drinking ; Eating ; Humans ; Male ; Questionnaires ; Sodium Benzoate* ; Sodium* ; Toluene* ; Xylenes*

Gastric cancer is the third most common cancer and the third most frequent cause of cancer mortality in Asia. It is predicted that gastric cancer will remain an important cause of death at least during the next half century because of the increasing number of new cases in an aging population. However, little has been revealed about the role of gastric microbes and their reaction to gastric cancer. In this study, we identified differences in the microbial communities between gastric cancer and normal gastric mucosa by comparing the microbiomes of tissues from the same patients. The clustering analysis results showed different bacterial communities between normal gastric mucosa and gastric cancer. A comparison of bacterial communities at the species level revealed that Helicobacter pylori was significantly reduced in cancer tissue compared to that in normal gastric mucosa in the same patient. A comparison at the genus level showed that Propionibacterium spp., Staphylococcus spp., and Corynebacterium spp. had significantly reduced populations in cancer tissue, whereas Clostridium spp. and Prevotella spp. had significantly increased populations in cancer tissue.
Aging ; Asia ; Cause of Death ; Clostridium ; Corynebacterium ; Gastric Mucosa ; Helicobacter pylori ; Humans ; Microbiota ; Mortality ; Mucous Membrane* ; Prevotella ; Propionibacterium ; Staphylococcus ; Stomach Neoplasms ; Stomach*

HL-60 cells (human promyelocytic leukemia cells) differentiate into the monocyte/macrophage like cells that die spontaneously by apoptosis when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). It is known that inhibitors of apoptosis proteins (IAP) bind to and inhibit caspase 3, 7, 9 activity and the induction of apoptosis. In this study, we examined the expression of IAP genes during TPA induced differentiation of HL-60 cells. During the differentiation, HIAP-1, HIAP-2, and XIAP expressions were decreased in protein levels. The pan-caspase inhibitor z-VAD-fmk blocked the decrease of HIAP-1 and HIAP-2, which indicates HIAP-1 and HIAP-2 could be caspase substrates. These findings suggest that the decrease of IAP proteins is related to the induction of apoptosis that is associated with TPA- induced HL-60 cell differentiation.
Apoptosis ; Caspase 3 ; HL-60 Cells* ; Humans ; Leukemia

BACKGROUND AND PURPOSE: Recently published, evidence-based guidelines should alter the management of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). However, the newest recommendations for ALS/MND therapy are not reflected in actual clinical practice. We sought to evaluate the current status of the diagnosis and management of ALS in Korea. METHODS: The Korean ALS/MND research group was organized in 2010, involving more than 50 neurologists from neuromuscular centers in Korea. Participating centers collected data from April to September 2010 on the diagnosis and management of patients with ALS. Data forms from the ALS patient care database, which is a component of the ALS clinical assessment, research, and education program (http://www.outcomes-umassmed.org/ALS/), were modified and used for data collection. RESULTS: In total, 373 sporadic ALS cases from 35 centers were enrolled. The demographic features and clinical findings were similar to those in previous reports from other countries. The mean age at onset was 50-60 years, and a slight male predominance was observed. The enrolled patients predominantly showed focal onset of cervical or lumbosacral symptoms. Only about one-half of the indicated patients (31.4%) received a physician's recommendation for a parenteral gastrostomy, and 18.1% underwent the procedure. Noninvasive ventilation was recommended in 23% of patients, but applied in only 9.5% of them. Tracheostomy was performed in 12.7% of patients. CONCLUSIONS: The demographic and clinical features of the diagnosis and management of ALS in Korea are similar to those reported in other countries; however, supportive management, as recommended in evidence-based guidelines, are not yet widely recommended or performed for patients with ALS in Korea.
Amyotrophic Lateral Sclerosis ; Cross-Sectional Studies ; Gastrostomy ; Humans ; Korea ; Male ; Neurons ; Noninvasive Ventilation ; Palliative Care ; Patient Care ; Tracheostomy

BACKGROUND: No prospective analyses of clinical characteristics and prognostic factors on amyotrophic lateral sclerosis (ALS) have been performed in Korea. METHODS: The prognosis of 227 sporadic ALS patient with El-Escorial-compatible criteria were evaluated using the serial Korean Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (K-ALSFRS-R), and the progression rate of K-ALSFRS-R (DeltaFS=48-ALSFRS-R at the time of diagnosis). Their clinical characteristics and survival times were also analyzed. The endpoint was defined as either time to death or the tracheostomy state. The effects of individual prognostic factors on disease progression were assessed with the Kaplan-Meier life-table method and multivariate Cox proportional regression analysis. The declining ALSFRS-R curve, epidemiological data, and neuropsychological tests were evaluated. RESULTS: Among 331 motor neuron disease (MND) patients, 227 were finally diagnosed as sporadic ALS. The mean age at onset in 227 sporadic ALS patients was 50.7 years (range 19-76 years). Analysis of sequential ALSFRS-R data revealed that a mean DeltaFS of 0.73/month and a high DeltaFS score were related with early death or a tracheostomy state. Neuropsychological testing revealed nonmotor symptoms, and especially cognitive impairment, had developed in half of our patients. CONCLUSIONS: Our data suggest that DeltaFS is valuable parameter for evaluating prognosis and clinical course of ALS patients, and clinical characteristics obtained from this study would be informative data for understanding epidemiology of ALS in Korea.
Amyotrophic Lateral Sclerosis ; Disease Progression ; Humans ; Korea ; Motor Neuron Disease ; Neuropsychological Tests ; Prognosis ; Tracheostomy

Recently developed cDNA microarray or DNA chip technology allows expression monitoring of expression of hundreds and thousands of genes simultaneously and provides a format for identifying genes as well as changes in their activity. In order to search for changes in gene expression after X irradiation in HL60 cells, cDNA microarray technique was done. In this study, expression of 588 human genes (including oncogenes, tumor suppressor genes, cell cycle regulator genes, intracellular signal transduction modulator genes, apoptosis related genes, transcription factor genes, growth factors and receptor genes, cytokine genes, etc) were analyzed. For cDNA microarray analysis mRNAs were extracted from control and 8 Gy-irradiated HL60 cells. As a result the changes in expression of several genes were observed. This alteration of gene expression was confirmed by reverse transcription-polymerase chain reaction. The expression of heat shock 60 KD protein, c-jun, erythroid differentiation factor, CPP32, myeloid cell nuclear differentiation antigen, MAP kinase-activated protein kinase, interleukin-8, monocyte chemotactic peptide 1 and RANTES genes was increased, but the expression of p55CDC gene was decreased after X irradiation.
Apoptosis ; Cell Cycle ; Chemokine CCL5 ; DNA, Complementary* ; Gene Expression ; Genes, Regulator ; Genes, Tumor Suppressor ; HL-60 Cells* ; Hot Temperature ; Humans ; Intercellular Signaling Peptides and Proteins ; Interleukin-8 ; Monocytes ; Myeloid Cells ; Oligonucleotide Array Sequence Analysis* ; Oncogenes ; Protein Kinases ; RNA, Messenger ; Shock ; Signal Transduction ; Transcription Factors