Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied Ca++ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of Ca++, EGTA, Mn++, verapamil, omega-conotoxin GVIA, omega-conotoxin MVIIC and omega-agatoxin IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists (Mn++, verapamil, omega-conotoxin GVIA & omega-agatoxin IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But omega-conotoxin MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about 20 ~ 30 min strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by imtophoretical application of Ca++, verapamil, omega -agatoxin IVA, and omega-conotoxin GVIA but not by omega-conotoxin MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied Ca++, verapamil, omega-conotoxin GVIA and omega-agatoxin IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.
Animals ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Egtazic Acid ; Electric Stimulation ; Formaldehyde ; Hypertension ; Injections, Subcutaneous ; Ions ; Iontophoresis ; Membranes ; Mustard Plant ; Neurotransmitter Agents ; omega-Agatoxin IVA ; omega-Conotoxin GVIA ; omega-Conotoxins ; Posterior Horn Cells* ; Rats* ; Spinal Cord ; Synaptic Transmission ; Verapamil

OBJECTIVES: We review the sleep problems of the alcohol dependence patients. Especially we are interested in the prevalence, the severity of symptoms, anxiety, depression, and sleep quality of restless legs syndrome (RLS) in the alcohol dependence patients. METHODS: We recruit 86 alcohol dependence patients who were admitted from October 6th, 2008 to October 17th, 2008. We interviewed each patient and evaluated sleep questionnaires such as the Sleep Disorder Questionnaire (SDQ), the Pittsburgh Sleep Quality Index (PSQI) and the International Restless Legs Syndrome Study Group (IRLSSG) rating scale. The presence of RLS and its severity were assessed using the IRLSSG diagnostic criteria and the IRLSSG severity scale, respectively. Depression and anxiety were evaluated by the Beck Depression Inventory (BDI) and the Beck anxiety inventory (BAI). RESULTS: Of all 86 patients, 59 patients have insomnia, 33 patients have RLS, 30 patients have Periodic limb movement disorder (PLMD), 29 patients have nightmare. RLS patients have more high score in the BAI (21.70+/-10.36 vs 14.67+/-11.98), and their sleep quality was poor in the PSQI (11.09+/-4.08 vs 7.92+/-3.91) than non-RLS patients. CONCLUSION: This study shows that alcohol dependence patients show many sleep problems such as insomnia and RLS. So we should notice that the sleep problems of alcohol dependence patients are important in clinical approach and treatment.
Alcoholism ; Anxiety ; Depression ; Dreams ; Humans ; Nocturnal Myoclonus Syndrome ; Prevalence ; Surveys and Questionnaires ; Restless Legs Syndrome ; Sleep Wake Disorders ; Sleep Initiation and Maintenance Disorders

PURPOSE: Cancer is a genetic disease caused by alterations in key regulators of cell growth and cell turnover. We investigated apoptotic cell death and cell proliferation in gastric adenomas and adenocarcinomas. MATERIALS AND METHODS: The TdT-mediated dUTP-biotin nick end labelling (TUNEL) method and immunohistochemistry for Ki-67 were performed, using paraffin-embedded tissues of 41 gastric adenomas and 100 gastric adenocarcinomas. These results were compared with histopathologic parameters. RESULTS: The Ki-67 labelling index was higher in adenocarcinomas than in adenomas and the apoptotic index was higher in adenomas than in adenocarcinomas. There were no significant difference between the apoptotic index/Ki-67 labelling index and clinicopathological parameters. CONCLUSION: We propose that cell proliferation is more closely associated with gastric adenocarcinomas than apoptosis is, but that neither has any clinical significance as a prognostic factor in gastric adenocarcinomas.
Adenocarcinoma* ; Adenoma* ; Apoptosis* ; Cell Death ; Cell Proliferation* ; Immunohistochemistry

3-Methylcrotonyl-CoA carboxylase(MCC) is a biotin-dependent enzyme involved in the leucine metabolism. We describe a patient with MCC deficiency who manifested with Reye syndrome-like illness with status epilepticus, metabolic acidosis, hypoglycemia, hyperammonemia, elevated liver enzymes and neurologic impairments after a viral gastroenteritis and then suffered from Lennox-Gastaut syndrome. Urinary organic acid analysis revealed increased excretions of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. This patient was managed with a leucine restriction diet and supplementation of biotin and carnitine, which was not so effective. He suffered from neurologic sequelae such as Lennox-Gastaut syndrome, motor and cognitive impairements.
Acidosis ; Biotin ; Carnitine ; Diet ; Gastroenteritis ; Humans ; Hyperammonemia ; Hypoglycemia ; Leucine ; Liver ; Metabolism ; Status Epilepticus

Excitatory amino acid (EAA) and substance P (SP) have been known to be primary candidates for nociceptive neurotransmitter in the spinal cord, and calcium ions are implicated in processing of the sensory informations mediated by EAA and SP in the spinal cord. In this study, we examined how Ca2+ modified the responses of dorsal horn neurons to single or combined iontophoretical application of EAA and SP in the rat. All the LT cells tested responded to kainate, whereas about 55% of low threshold (LT) cells responded to iontophoretically applied NMDA. NMDA and kainate excited almost all wide dynamic range (WDR) cells. These NMDA- and kainate-induced WDR cell responses were augmented by iontophoretically applied EGTA, but suppressed by Ca2+, Mn2+ verapamil and omega-conotoxin GVTA, effect of verapamil being more prominent and well sustained. Ca2+ and Mn2+ antagonized the augmenting effect of EGTA. On the other hand, prolonged spinal application of EGTA suppressed the response of WDR cell to NMDA. SP had triple effects on the spontaneous activity as well as NMDA-induced responses of WDR cells: excitation, inhibition and no change. EGTA augmented, but Ca2+, Mn2+ and verapamil suppressed the increase in the NMDA-induced responses and spontaneous activities of WDR cells following iontophoretical application of SP. These results suggest that in the spinal cord, sensory informations mediated by single or combined action of EAA and SP can be modified by the change in calcium ion concentration.
Animals ; Calcium* ; Egtazic Acid ; Excitatory Amino Acids* ; Hand ; Ions ; Iontophoresis ; Kainic Acid ; N-Methylaspartate ; Neurotransmitter Agents ; omega-Conotoxins ; Posterior Horn Cells* ; Rats* ; Spinal Cord ; Substance P ; Verapamil

BACKGROUND/AIMS: The aim of this study was to investigate the immunohistochemical expression of bcl-2, bcl-xL, bax, and p53 proteins according to the pathological parameters such as grade of dysplasia, histological type, depth of invasion, lymph node metastasis, and TNM stage in the gastric adenoma and gastric adenocarcinoma. METHODS: Immunohistochemical staining using monoclonal bcl-2, bcl-xL, bax, p53 antibodies were performed on paraffin embedded specimens from forty-one gastric adenomas and 100 gastric adenocarcinomas. RESULTS: The expression rate of bcl-2 was higher in adenomas (34.2%), especially in high grade dysplasia (52.4%), than adenocarcinomas (2.0%). The expression rate of bcl-xL was higher in adenocarcinomas (55.0%) than adenomas (22%). The expression rate of the bax was higher in adenocarcinomas (58.0%) than adenomas (14.6%). In the adenocarcinoma, the bax expression was significantly related with the depth of invasion, lymph node metastasis, and TNM stage. The expression rate of p53 was higher in adenocarcinomas (64.0%) than adenomas (14.6%). CONCLUSIONS: Bcl-2 protein would be related with the development of gastric adenoma, especially with high grade dysplasia. Bcl-xL and p53 proteins would be involved in the development of relatively early stage of gastric adenocarcinoma but not in tumor progression. Bax protein would be involved in the development of gastric adenocarcinoma and related with depth of invasion, lymph node metastasis, and TNM stage.
Adenocarcinoma/*metabolism/pathology ; Adenoma/*metabolism/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Stomach Neoplasms/*metabolism/pathology ; Tumor Suppressor Protein p53/*metabolism ; bcl-2-Associated X Protein/*metabolism ; bcl-X Protein/*metabolism

Hairy cell leukemia (HCL) is a chronic B- cell disorder characterized by the presence of typical hairy cells in the peripheral blood and marrow, pancytopenia, and a variable degree of splenomegaly. Identification of typical hairy cells in the peripheral blood and demonstration of tartrate-resistant acid phosphatase (TRAP) are critical findings in HCL. Hepatic involvement of HCL is a common feature and liver biopsy show diffuse mono-nuclear cell infiltration throughout the hepatic sinusoids and in the portal areas. We report a case of hairy cell leukemia in a 52-year-old man who presented with pneumonia and hepatic infiltration with review of the literatures.
Acid Phosphatase ; Biopsy ; Bone Marrow ; Humans ; Leukemia, Hairy Cell* ; Liver ; Middle Aged ; Pancytopenia ; Pneumonia ; Splenomegaly

BACKGROUND/AIMS: Gastric epithelial dysplasia is considered a precancerous lesion with a variable clinical course. There is disagreement, however, regarding histology-based diagnoses, which has led to confusion in choosing a therapeutic plan. New objective markers are needed to determine which lesions progress to true malignancy. We measured LINE-1 methylation levels, which have been reported to strongly correlate with the global methylation level in gastric epithelial dysplasia and intramucosal cancer. METHODS: A total of 145 tissue samples were analyzed by two histopathologists. All tissues were excised by therapeutic endoscopic mucosal resection and paired with adjacent normal tissue samples. A modified long interspersed nucleotide elements-combined bisulfite restriction analysis (COBRA-LINE-1) method was used. RESULTS: Gastric epithelial dysplasia and intramucosal cancer tissues had significantly lower levels of LINE-1 methylation than adjacent normal gastric tissues. High-grade dysplasia and intramucosal cancer were distinguishable from low-grade dysplasia based on LINE-1 methylation levels. Furthermore, the distinction could be determined with high sensitivity and specificity, as shown by the receiver operating characteristic (ROC) curve (AUC, 0.82; 95% confidence interval, 0.74 to 0.88). CONCLUSIONS: LINE-1 methylation levels may provide a diagnostic tool for identifying high-grade dysplasia and intramucosal cancer.
Methylation ; ROC Curve ; Sensitivity and Specificity ; Sulfites

A gastric carcinoid is a rare disease that accounts for only 0.3% of all primary gastric tumors. It can be multiple or occur with other types of tumor. However, there has been a recent increase in incidence. While carcinoids of the appendix and rectum are accompanied by adenoma or adenocarcinoma, a gastric carcinoid rarely occurs with an adenocarcinoma, particularly with a gastric adenoma. We encountered a case of a gastric adenoma and carcinoid mixed as a composite tumor, which became a lesion. The lesion resembled a type IIc early gastric cancer at the endoscopic examination and was removed by an endoscopic mucosal resection. We report a composite tumor of the gastric antrum composed of areas of adenoma and carcinoid, with an analysis of the histological components by immunohistochemical staining. Microscopically, the lesion was composed of a gastric adenoma and carcinoid as a composite tumor.
Adenocarcinoma ; Adenoma* ; Appendix ; Carcinoid Tumor* ; Incidence ; Pyloric Antrum ; Rare Diseases ; Rectum ; Stomach Neoplasms

PURPOSE: Genetic factor is an important predisposing element influencing the susceptibility to osteoporosis and related complications. The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. MATERIALS AND METHODS: In the present study, 144 Korean women with osteoporosis were included. Among 13 genetic polymorphisms found within the FDPS and GGPS1 gene, 4 genetic polymorphisms with frequencies > 5% were selected for further study. Bone mineral density (BMD) response after 1 year treatment of bisphosphonate therapy was analyzed according to the genotypes. RESULTS: Women with 2 deletion allele of GGPS1 -8188A ins/del (rs3840452) had significantly higher femoral neck BMD at baseline compared with those with one or no deletion allele (0.768 +/- 0.127 vs. 0.695 +/- 0.090 respectively; p = 0.041). The response rate of women with 2 deletion allele of GGPS1 -8188A ins/del (28.6%) was significantly lower than the rate of women with one (81.4%) or no deletion allele (75.0%) (p = 0.011). Women with 2 deletion allele of GGPS1 -8188A ins/del had 7-fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188 after adjusting for baseline BMD (OR = 7.48; 95% CI = 1.32-42.30; p = 0.023). Other polymorphisms in FDPS or GGPS1 were not associated with lumbar spine BMD or femoral neck BMD. CONCLUSION: Our study suggested that GGPS1 - 8188A ins/del polymorphism may confer susceptibility to femoral neck BMD response to bisphosphonate therapy in Korean women. However, further study should be done to confirm the results in a larger population.
Aged ; Asian Continental Ancestry Group ; Bone Density/*drug effects/*genetics ; Bone Density Conservation Agents/*pharmacology ; Dimethylallyltranstransferase/*genetics ; Diphosphonates/*pharmacology ; Farnesyltranstransferase/*genetics ; Female ; Geranyltranstransferase/*genetics ; Humans ; Middle Aged ; Polymorphism, Genetic/*genetics