It has been known that granule neurons of the dentate gyrus (DG) are born in adulthood as well as during development. Apoptotic cell death also occurs normally throughout the life of the rat brain. The present study was designed to determine the effect of transient global ischemia on the apoptosis and/or neurogenesis of granule cells in the dentate gyrus. TUNEL study revealed that the ischemia produced an significant increase in apoptosis mainly in the granular zone (GZ) of the DG. The percentage of TUNEL-positive cells in the DG was maximal (37.3+/-2.5%) 8 hr after ischemia and declined thereafter. However, immunocytochemical studies showed that there was an increase in neurogenesis mainly in the subgranular zone (SGZ) although the induction of neurogenesis took longer than the apoptosis. As a neurogenesis marker, proliferating cell nuclear antigen (PCNA)-positive cells, possibly progenitor cells, were significantly increased by 34.1+/-2.2%(n=3, p<0.05) mainly in the dentate SGZ 4 days after ischemia. In addition, the gradual increase in Bcl-2 expression was only paralleled with the neurogenesis in the SGZ, but not with the apoptosis in the GZ of the DG. The expression level of Bcl-2 in the SGZ was increased significantly (optical density 43.7+/-3.4; n = 3, p<0.05) 4 days after the ischemic insult. Furthermore, the ischemia-induced neurogenesis in the SGZ was also indirectly supported by the observation that the expression of synapsin-alpha was significantly increased (176%; n=3 p<0.05) in the CA3 region 4 days after the ischemia. Taken together, these results strongly suggest that the transient global ischemia induces the apoptosis in the GZ, whereas the cell proliferation in the SCZ of the DG. In situ hybridization using the antisense probes to the NR2A and NR2B subunits of NMDA receptors revealed that the ischemia produced a more profound effect on the mRNA expression of NR2A (61.9% reduction) than NR2B (20.5% reduction). Thus, we also suggest a possibility that ischemia could induce the neurogenesis in the SGZ of the DG through downregulation of the number of functional NMDA receptors.
Animals ; Antisense Elements (Genetics) ; Apoptosis* ; Brain ; Cell Death ; Cell Proliferation ; Dentate Gyrus* ; Down-Regulation ; In Situ Hybridization ; In Situ Nick-End Labeling ; Ischemia* ; Neurogenesis* ; Neurons ; Proliferating Cell Nuclear Antigen ; Rats* ; Receptors, N-Methyl-D-Aspartate ; RNA, Messenger ; Stem Cells

The expression of aquaporin-4 (AQP4) protein, bi-directional water channel, in the blood-brain barrier of the hippocampal formation (HF) was studied in the rat to determine the role of AQP4 in the pathophysiology of systemic hyponatremia. Systemic hyponatremia was induced by coadministration of 30 ml (~12% body weight) dextrose solution (140 mM) intraperitoneally and a 3-microg subcutaneous dose of 1-deamino-8-D-arginine vasopressin (dDAVP). Two and six hours after the drug administration, there were significant reductions in the serum osmolarity (252+/-5.1 and 252+/-6.4 mOsm/L) and in Na+/- concentration (117+/-1.7 and 97.2 mM) from the control values (296+/-5.2 mOsm/L, 140+/-4.7 mM). Brain injury in the HF and the expression of AQP4 were determined by using TUNEL, immunohistochemistry and quantitative immunoblotting. TUNEL revealed apoptotic cell death in the dentate gyrus (DG), presumably resulting from brain edema and a subsequent elevation of intracranial pressure after 2 h of systemic hyponatremia. However, AQP4 expression was decreased by 82%+/-6% after 2 h of systemic hyponatremia and then normalized after 6 h (108%+/-9%) compared with that of the control. Therefore, apoptotic cell death in the DG from brain swelling in this systemic hyponatremic model is likely associated with decrease of excessive brain water elimination because reincreased AQP4 expression/function accelerates the elimination of apoptotic cells from the DG.
Animals ; Apoptosis ; Aquaporin 4* ; Blood-Brain Barrier ; Brain ; Brain Edema ; Brain Injuries ; Cell Death ; Deamino Arginine Vasopressin ; Dentate Gyrus ; Glucose ; Hippocampus* ; Hyponatremia* ; Immunoblotting ; Immunohistochemistry ; In Situ Nick-End Labeling ; Intracranial Pressure ; Osmolar Concentration ; Rats

A central challenge in ischemia-induced neuronal death research is understanding the mechanisms by which apoptotic or necrotic cascades are initiated and affected. We tested potential roles for AMPA and NMDA receptor protein levels and activation of calpain, caspase-3 in the hippocampus at times after transient global ischemia when detectable necrotic or apoptotic cell damage was observed by neurofilament 200 (NF200) degradation, TUNEL, and H & E. We determined that the decrease in the AMPA receptor subunit, GluR2, in response to the transient global ischemia plays a major role in triggering the neuronal cell death in hippocampus. We also examined potential roles for calpain and caspase-3 in ischemic cell death and found that (1) calpain is activated at a time following caspase-3 activation and paralleled degradation of NR2A, NR2B, and GluR2 and irreversible necrotic neuronal changes, (2) caspase-3 is has their maximal expression at the time of highest apoptosis, (3) the NF200 degradation, one of the neuronal deathinducing factors was correlated well with the calpain activation and necrotic changes in the hippocampal CA1 neurons. These results suggest that the significant degradation of GluR2 subunits of AMPA receptor and calpain activation are possibly involved in NF 200 degradation-mediated necrotic hippocampal cell death after transient global ischemia.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* ; Animals ; Apoptosis ; Calpain* ; Caspase 3* ; Cell Death* ; Hippocampus* ; In Situ Nick-End Labeling ; Ischemia* ; N-Methylaspartate ; Neurons* ; Rats* ; Receptors, AMPA

The organization of the striatal projection fibers from the hippocampal formation (HF) was studied in the monkey with particular emphasis on specific projections of the ventral striatum. Retrograde tracers were injected into the five different regions of the ventral striatum such as the ventromedial caudate nucleus, ventral shell, central shell, and dorsal core of the nucleus accumbens (NA), and ventrolateral putamen. The ventromedial caudate nucleus and the shell of the NA received dense projections from the HF. Although the ventromedial caudate nucleus and the shell of the NA are both innervated by the HF, the shell receives the larger of these projections. This suggests that the HF is more strongly connected with the shell of the NA than with the ventromedial caudate nucleus. There are no differences between the ventral shell and central shell of the NA. Labeled neurons were mainly observed in the rostral parts of the dorsomedial CA1 and adjacent subicular complex (prosubiculum, subiculum, presubiculum, and parasubiculum) of the HF. These results suggest that the shell of the NA is the main converging site receiving hippocampal projections primarily related to integrating visuospatial and limbic information.
Basal Ganglia* ; Caudate Nucleus ; Haplorhini ; Hippocampus ; Neurons ; Nucleus Accumbens ; Primates* ; Putamen

Cornelia de Lange syndrome (CdLS) is a rare, clinically and genetically heterogeneous, multi-system developmental disorder caused by mutations in genes that encode components of the cohesin complex. X-linked CdLS caused by an SMC1A mutation is an extremely rare disease characterized by phenotypes milder than those of classic CdLS. In the Republic of Korea, based on a literature review, one family with SMC1A-related CdLS with mild phenotypes has been genetically confirmed to date. In this study, we describe the clinical features of a Korean boy with a hemizygous novel missense mutation and his mother with a heterozygous mutation, i.e., c.2447G>A (p.Arg816His) in SMC1A, identified by multi-gene panel sequencing. The proband had a mild phenotype with typical facial features and his mother exhibited a mild, subclinical phenotype. This study expands the clinical spectrum of patients with X-linked CdLS caused by SMC1A variants. Moreover, these findings reinforce the notion that a dominant negative effect in a carrier female with a heterozygous mutation in SMC1A results in a phenotype milder than that in a male patient with the same mutation.
De Lange Syndrome* ; Female ; Genes, X-Linked ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mothers ; Mutation, Missense* ; Phenotype ; Rare Diseases ; Republic of Korea

OBJECTIVES: Dealing with mental diseases is an overriding concern which could bring about improvement in mental health, social equity, and quality of life. This paper analyzes the current state of research infrastructure of national mental health research in Korea and other developed countries and suggests activation plans for psychiatric research. METHODS: After performance of comparative analysis, shortcomings of Korean infrastructure are examined and activation plans are suggested. RESULTS: Korea is comparatively and absolutely lagging behind in terms of mental health Research and Development (R&D), owing to the small investment in R&D, inadequate government-led long-term developmental strategy and supporting system, absence of industrialization of developed techniques and government-led R&D project, and insufficient human resources, which impedes facilitation of mental health research. Thus, in order to facilitate mental health research, 1) Reinforce international cooperation and research capability through cultivation of professionals equipped with international competitiveness. 2) Construct a government-led R&D system by establishment of a comprehensive R&D system and mental health research institutes. 3) Build cooperative systems between industry and academic circles and promote translational research and its practical use in order to lay the cornerstone for industrialization. CONCLUSION: Developed countries have achieved significant growth and superb investment performance in the mental health industry due to constant and active investment by government. In addition, basic-clinical-mental health research regarding early diagnosis, early intervention, and tailored treatment, is actively being put into practice. In Korea, government-led long-term investment plans in psychiatric research and researcher cultivation programs should be implemented. In addition, infrastructure for application of developed techniques should also be established. If so, it will provide momentum for growth and facilitation of psychiatric research.
Academies and Institutes ; Developed Countries ; Early Diagnosis ; Early Intervention (Education) ; Humans ; International Cooperation ; Investments ; Korea ; Mental Health ; Quality of Life ; Translational Medical Research

BACKGROUND: As bladder cancer is a superficial tumor with frequent recurrences, early detection and confirmation of recurrence are important. We evaluated the usefulness of NMP22 BladderChek (NMP22BC) for the diagnosis and monitoring of bladder cancer. METHODS: From July to December 2004, we enrolled in the study 670 patients who visited the urology clinic in Ewha Womans University, Dongdaemun Hospital with hematuria or dysuria and were tested with NMP22BC. We also performed the NMP22BC and BTA stat tests simultaneously in 21 patients and interference test in 10 patients. RESULTS: NMP22BC tests were negative in 97% of the patients who had been cured of bladder cancer and were positive in 95% of the patients with recurred bladder cancer. The diagnostic sensitivity, specificity, positive and negative predictive value, and efficiency were 95.0%, 91.5%, 25.7%, 99.8%, and 91.6%, respectively, with 8.5% false positive and 5% false negative rates. Fifty-five patients showed false positive in the NMP22BC test, the main cause of which was the presence of WBCs in urine. There was a good agreement between the NMP22BC and BTA stat tests (kappa agreement value, 0.5; P=0.008). According to the interference test, two patients with more than 3+ in leukocyte esterase results showed false positive in the NMP22BC test. CONCLUSIONS: NMP22BC test was simple to perform, rapid to produce the results, and useful in diagnosing a bladder cancer recurrence; the test shows a high efficiency with a high sensitivity, specificity, negative predictive value, and low false negative rate.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Nuclear Matrix-Associated Proteins/*urine ; Nuclear Proteins/*urine ; Reagent Kits, Diagnostic ; Urinary Bladder Neoplasms/*diagnosis

A 51-yr-old man underwent mitral valve replacement and tricuspid valve repair due to mitral and tricuspid regurgitation under cardiopulmonary bypass. The pulmonary artery (PA) catheter was inserted easily via right internal jugular vein and functioned well until the end of surgery. The surgery was uneventful and patient's hemodynamics were stable both in the operating room and intensive care unit. All PA catheter functions were normal, but the balloon rupture was suspected because it was unable to obtain pulmonary capillary wedge pressure. On attempted removal of the PA catheter at the next day, considerable resistance was encountered and pulmonary artery tracing was dampened. A followed-up chest X-ray revealed the catheter to be in the right pulmonary artery without evidence of knotting. Suture related entrapment was suspected, and on reoperation, PA catheter was found to be sutured at the left atriotomy site. The PA catheter was removed under cardiopulmonary bypass and revealed a hole between proximal port and thermal filament.
Cardiopulmonary Bypass ; Catheters* ; Hemodynamics ; Intensive Care Units ; Jugular Veins ; Mitral Valve* ; Operating Rooms ; Pulmonary Artery* ; Pulmonary Wedge Pressure ; Reoperation ; Rupture ; Sutures ; Thorax ; Tricuspid Valve ; Tricuspid Valve Insufficiency

Catecholamine-induced cardiomyopathy associated with pheochromocytoma is a relatively well-recognized but rare entity. We report a case of 15-year old man with a pheochromocytoma and severe heart failure caused by a catecholamine-induced cardiomyopathy. He had symptoms such as fatigue, cold sweating, and dyspnea for 7 months. The chest x-ray showed an enlarged cardiac shadow and pulmonary edema. Echocardiography showed severe decreased left ventricular contractility with multiple thrombi and right ventricular hypokinesia with mild pulmonary hypertension. This report describes our experience of the anesthetic management for the removal of pheochromocytoma with catecholamine-induced cardiomyopathy, which barely responded to high vasopressin and epinephrine.
Cardiomyopathies ; Cold Temperature ; Dyspnea ; Echocardiography ; Epinephrine ; Estrogens, Conjugated (USP) ; Fatigue ; Heart Failure ; Hypertension, Pulmonary ; Hypokinesia ; Pheochromocytoma ; Pulmonary Edema ; Sweat ; Sweating ; Thorax ; Vasopressins

BACKGROUND: It is important to evaluate the right ventricular (RV) function intraoperatively for optimal management of patients undergoing cardiac surgery. The clinical relevance of thermodilution method to tranesophageal echocardiography (TEE) for the measurements of RV function during off-pump coronary artery bypass surgery (OPCAB) was evaluated in this study. METHODS: Fifty patients undergoing OPCAB were included. RV function was assessed with both thermodilution method and TEE after anesthesia induction (T1), 10 min after leg elevation (T2), 10 min after returning to the supine position (T3), 10 min after Y-graft formation started (T4), 10 min after sternum closure (T5) and 10 min after applying 5 cmH2O of positive end expiratory pressure (T6). Fractional area change (FAC) and tricuspid annular plane systolic excursion ratio (TAPSE) were measured by TEE and compared to RV ejection fraction (RVEF) measured by thermodilution technique. RV end diastolic area (EDA) derived from TEE was compared to RV end diastolic volume index (EDVI) derived from thermodilution technique. RESULTS: There was no significant correlation between echocardiographic data and thermodilution data by linear regression analysis. However, only in patients with right coronary artery stenosis less than 90%, TAPSE and FAC were significantly correlated with RVEF (P = 0.008 and 0.01, respectively) and EDA was significantly correlated with EDVI (P = 0.013) only at T4. CONCLUSIONS: RV performance measured by thermodilution technique did not correlate well with TEE finding in severe coronary artery disease patients. The correlation was significant during hemodynamically stable period (during Y-graft formation) in patients without severe right coronary artery disease.
Anesthesia ; Coronary Artery Bypass, Off-Pump ; Coronary Artery Disease ; Coronary Stenosis ; Echocardiography* ; Echocardiography, Transesophageal ; Humans ; Leg ; Linear Models ; Positive-Pressure Respiration ; Sternum ; Supine Position ; Thermodilution* ; Thoracic Surgery ; Ventricular Function, Right*