Biomedical subjects

Dongsoo Kim

Publications and source records attributed to Dongsoo Kim.

17 recordsLinked to original sources

PubMed2006

Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments.

Visual processing deficits are an integral component of schizophrenia and are sensitive predictors of schizophrenic decompensation in healthy adults. The primate visual system consists of discrete subcortical magnocellular and parvocellular pathways, which project preferentially to dorsal and ventral cortical streams. Subcortical systems show differential stimulus sensitivity, while cortical systems, in turn, can be differentiated using surface potential analysis. The present study examined contributions of subcortical dysfunction to cortical processing deficits using high-density event-related potentials. Event-related potentials were recorded to stimuli biased towards the magnocellular system using low-contrast isolated checks in Experiment 1 and towards the magnocellular or parvocellular system using low versus high spatial frequency (HSF) sinusoidal gratings, respectively, in Experiment 2. The sample consisted of 23 patients with schizophrenia or schizoaffective disorder and 19 non-psychiatric volunteers of similar age. In Experiment 1, a large decrease in the P1 component of the visual event-related potential in response to magnocellular-biased isolated check stimuli was seen in patients compared with controls (F = 13.2, P = 0.001). Patients also showed decreased slope of the contrast response function over the magnocellular-selective contrast range compared with controls (t = 9.2, P = 0.04) indicating decreased signal amplification. In Experiment 2, C1 (F = 8.5, P = 0.007), P1 (F = 33.1, P < 0.001) and N1 (F = 60.8, P < 0.001) were reduced in amplitude to magnocellular-biased low spatial frequency (LSF) stimuli in patients with schizophrenia, but were intact to parvocellular-biased HSF stimuli, regardless of generator location. Source waveforms derived from inverse dipole modelling showed reduced P1 in Experiment 1 and reduced C1, P1 and N1 to LSF stimuli in Experiment 2, consistent with surface waveforms. These results indicate pervasive magnocellular dysfunction at the subcortical level that leads to secondary impairment in activation of cortical visual structures within dorsal and ventral stream visual pathways. Our finding of early visual dysfunction is consistent with and explanatory of classic literature showing subjective complaints of visual distortions and is consistent with early visual processing deficits reported in schizophrenia. Although deficits in visual processing have frequently been construed as resulting from failures of top-down processing, the present findings argue strongly for bottom-up rather than top-down dysfunction at least within the early visual pathway. Deficits in magnocellular processing in this task may reflect more general impairments in neuronal systems functioning, such as deficits in non-linear amplification and may thus represent an organizing principle for predicting neurocognitive dysfunction in schizophrenia.

Adult↗

PubMed2006

A case of acute ventricular capture threshold rise associated with flecainide acetate.

Antiarrhythmic agents may increase capture threshold, but this is rarely of clinical significance. Flecainide acetate, a class IC agent, is reported to have a significant effect on the myocardial capture threshold. In this presentation, we report the case of a 72-year-old male, with a previously implanted VVI pacemaker due to sick sinus syndrome, who was treated with flecainide acetate for paroxysmal atrial arrhythmia control. During the fifteenth day of treatment, an abrupt rise in the ventricular capture threshold with ventricular pacing failure was noted. The capture threshold decreased two days after discontinuation of flecainide acetate.

Action Potentials↗

PubMed2006

Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia.

Functional outcome for individuals with schizophrenia has been associated with cognitive impairment. Deficits in attention, memory, speed of information processing and problem-solving skills affect independent functioning, vocational performance, and interpersonal functioning. This study investigated the relationship between neurocognitive functioning, clinical symptoms and daily problem-solving skills in seriously and persistently ill persons. Thirty-eight inpatients and outpatients were administered a neurocognitive battery for attention, working memory, processing speed, perceptual organization, and executive functioning; and semi-structured clinical interviews using the BPRS and SANS. Estimates of daily problem-solving skills were obtained using the relevant factor subscale from the Independent Living Scales (ILS-PB). Daily problem-solving skills were significantly correlated with negative symptoms, processing speed, verbal memory, and working memory scores. A regression model using an enter method suggests that working memory and negative symptoms are significant predictors of daily problem-solving skills and account for 73.2% of the variance. Further analyses demonstrate that daily problem-solving skills and negative symptoms were significantly different for inpatients and outpatients and significantly correlated with community status. The findings suggest the ILS-PB has utility as a proxy measure for assessing real-world functioning in schizophrenia.

Activities of Daily Living↗

PubMed2006

Effect on blood pressure control of switching from valsartan monotherapy to losartan/hydrochlorothiazide in Asian patients with hypertension: results of a multicentre open-label trial.

STUDY DESIGN: An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50 mg plus hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80 mg. METHODS: A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95-115 mmHg and a mean trough sitting systolic blood pressure (SiSBP) < 190 mmHg entered the baseline period of treatment with valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90 mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily for a further 4 weeks. RESULTS: Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (p < or = 0.001 for both outcomes). The goal of SiDBP < or = 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80 mg/day. Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5 mg combination was > 99%. CONCLUSION: These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBP < or = 90 mmHg with valsartan monotherapy at 80 mg once-daily, switching to a single-tablet combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.

Adult↗

PubMed2005

Magnocellular contributions to impaired motion processing in schizophrenia.

Patients with schizophrenia show impairments in motion processing, along with deficits in lower level processing primarily involving the magnocellular visual pathway. The present study investigates potential magnocellular contributions to impaired motion processing in schizophrenia using a combined neurophysiological and behavioral approach. As compared to prior motion studies in schizophrenia, thresholds were determined for both incoherent and coherent visual motion. In this study, velocity discrimination thresholds were measured for schizophrenia patients (n=14) and age-matched normal control subjects (n=16) using a staircase procedure. Early visual processing was evaluated using steady-state visual evoked potentials (ssVEP), with stimuli biased toward activation of either the magnocellular or parvocellular visual pathways through luminance contrast manipulation. Patients with schizophrenia showed poor velocity discrimination for both incoherent and coherent motion, with no significant group x task interaction. Further, when coherent motion performance was measured at individually determined incoherent motion thresholds, accuracy levels for patients were similar to controls, also indicating similarity of deficit for incoherent vs. coherent motion discrimination. Impairments in velocity discrimination correlated significantly with reduced amplitude of ssVEP elicited by magnocellular -- but not parvocellular -- selective stimuli. This study demonstrates that deficits in motion processing in schizophrenia are significantly related to reduced activation of the magnocellular visual system. Further, this study supports and extends prior reports of impaired motion processing in schizophrenia, and indicates significant bottom-up contributions to higher-order cognitive impairments.

Adult↗

PubMed2005

Serum levels of advanced glycation end products are associated with in-stent restenosis in diabetic patients.

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (<or=170 U/ml) (19.6%) (p<0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients.

Aged↗

PubMed2005

Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque.

From experimental and clinical studies it is known that matrix conservation and degradation by matrix metalloproteinases (MMPs) plays a major role in plaque progression and destabilization with related onset of acute vascular events such as acute coronary syndromes or cerebrovascular accidents. Recently, extracellular MMPs inducer (EMMPRIN) has been reported to induce and activate the expression of MMPs in myocardium and plays an important role in the ventricular remodeling in human heart failure. Similarly to heart failure myocardium, EMMPRIN may be expressed in human atheroma and play a role in the extracellular matrix (ECM) remodeling and atherogenic cell differentiation. This study was designed to investigate the possible biological role of EMMPRIN in human atheroma. Immunohistochemical analysis for MMPs and EMMPRIN was performed on human carotid endarterectomy specimens and control aortas. EMMPRIN showed significant immunoreactivity in human atherosclerotic carotid lesions, and was colocalized with macrophage/monocyte infiltrates in atherosclerotic intima, plaque itself and vascular smooth muscle cells (VSMCs). Zymography and Western blot analysis revealed EMMPRIN expression in the carotid atheromas, but not in the control aortas. Human bone marrow monocytes, which were cultured with atherogenic proinflammatory cytokine stimulation revealed increased EMMPRIN and MMPs expressions. ECM remodeling is under the control of induction and inhibition of matrix degrading protease and the novel MMP inducer, EMMPRIN may play a role in influx and differentiation of monocytes and destabilizing atheroma.

Adolescent↗

PubMed2004

Dysfunction of early-stage visual processing in schizophrenia: harmonic analysis.

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.

Adult↗

PubMed2004

Angiotensin II increases phosphodiesterase 5A expression in vascular smooth muscle cells: a mechanism by which angiotensin II antagonizes cGMP signaling.

Angiotensin II (Ang II) and nitric oxide (NO)/natriuretic peptide (NP) signaling pathways mutually regulate each other. Imbalance of Ang II and NO/NP has been implicated in the pathophysiology of many vascular diseases. cGMP functions as a key mediator in the interaction between Ang II and NO/NP. Cyclic nucleotide phosphodiesterase 5A (PDE5A) is important in modulating cGMP signaling by hydrolyzing cGMP in vascular smooth muscle cells (VSMC). Therefore, we examined whether Ang II negatively modulates intracellular cGMP signaling in VSMC by regulating PDE5A. Ang II rapidly and transiently increased PDE5A mRNA levels in rat aortic VSMC. Upregulation of PDE5A mRNA was associated with a time-dependent increase of both PDE5 protein expression and activity. Increased PDE5A mRNA level was transcription-dependent and mediated by the Ang II type 1 receptor. Ang II-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) was essential for Ang II-induced PDE5A upregulation. Pretreatment of VSMC with Ang II inhibited C-type NP (CNP) stimulated cGMP signaling, such as cGMP dependent protein kinase (PKG)-mediated phosphorylation of vasodilator-stimulated-phosphoprotein (VASP). Ang II-mediated inhibition of PKG was blocked when PDE5 activity was decreased by selective PDE5 inhibitors, suggesting that upregulation of PDE5A expression is an important mechanism for Ang II to attenuate cGMP signaling. PDE5A may also play a critical role in the growth promoting effects of Ang II because inhibition of PDE5A activity significantly decreased Ang II-stimulated VSMC growth. These observations establish a new mechanism by which Ang II antagonizes cGMP signaling and stimulates VSMC growth.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

A case of pulmonary artery intimal sarcoma diagnosed with multislice CT scan with 3D reconstruction.

Pulmonary artery intimal sarcoma is a rare highly lethal disease, with additional retrograde extension to pulmonic valve and right ventricle being an extremely rare condition. It is frequently mistaken for pulmonary thromboembolism. We report a case of 64-year-old woman with progressive dyspnea initially suspected and treated for pulmonary thromboembolism. Her helical chest CT scan with 3 dimensional (3D) reconstruction combined with echocardiography revealed a compacting main pulmonary artery mass extending to the right ventricular outflow tract and the right pulmonary artery. After excision of the mass, the patient's condition improved dramatically, and the pathologic findings revealed pulmonary intimal sarcoma. This report emphasizes that helical chest CT with 3D reconstruction can be an important tool to differentiate the characteristics of pulmonary artery lesions, such as intimal sarcoma and thromboembolism.

Diagnosis, Differential↗

PubMed2004

Assessment of extent of myocardial ischemia in patients with non-ST elevation acute coronary syndrome using serum B-type natriuretic peptide level.

Since B-type natriuretic peptide (BNP) concentration has been shown by recent studies to be elevated in patients presenting acute coronary syndrome (ACS) even in the absence of overt heart failure, other mechanisms for elevating plasma BNP (p-BNP) concentrations may be suggested to exist. We have studied the correlation between p-BNP level and the extent of myocardial ischemia (EMI) in non-ST elevation (NSTE) ACS and evaluated the BNP level as an objective marker of EMI. In 204 patients with NSTE ACS, we estimated the EMI by the echocardiographic wall motion score index (WMSI) and the coronary angiographic Gensini score. As the positive control group, 44 patients with stable angina were enrolled into the study. We compared their initial p-BNP levels with WMSI and the Gensini score. Additionally, peak troponin-T level was compared with p-BNP level in NSTE myocardial infarction (MI) patients. Using the multiple regression analysis, adjustments for age, left ventricle (LV) wall stress, LV mass amount and ejection fraction (EF) were made. Patients with LVEF < 45% or age > 75 years or underlying diseases that could elevate BNP levels were excluded from the study. P-BNP level was increased in NSTE ACS patients compared with stable angina patients (133.9 +/- 87.4 vs. 12.2 +/- 9.2 pg/ml, p < 0.05). P-BNP levels were found to correlate with WMSI and the Gensini score in unstable angina (r=0.519, p < 0.01; r=0.680, p < 0.01) and NSTEMI (r=0.716, p < 0.01; r=0.684, p < 0.01) patients, respectively. Additionally, p-BNP levels correlated with the peak troponin-T level in patients with NSTEMI (r=0.700, p < 0.01). P-BNP level might be a useful marker in the assessment of EMI.

Acute Disease↗

PubMed2004

Splenic norepinephrine and serum corticosterone level fluctuations associated with bacteria-induced stress.

Corticosterone (CORT) and norepinephrine (NE), two effector molecules of the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-lymphoid (SL) axes, respectively, differentially influence murine host resistance to Listeria monocytogenes (LM). Serum CORT and splenic NE levels early (< or =24 h) after infection correlated positively with host resistance, as long as the LM burden did not exceed approximately 10(6) cfu LM per spleen. As previously reported, mice with right-circling preference (R-mice) have significantly greater host resistance to LM than those with left-circling preference (L-mice) and early after infection, R-mice had significantly higher serum CORT levels than L-mice. However, rapid pathogenesis with a high bacterial burden induced high activation of the HPA and SL axes, which prevented observable differences in the defense against LM, especially later in infection. With the high bacterial inoculum (10(5) LM), the splenic NE levels significantly increased, but no differences among R- and L-mice were discernible. We suggest that endogenous asymmetry of neuroimmune circuits contributes to differential host resistance, but the level of stress (bacterial inoculum) is critical. With regard to the neuroendocrine factors assessed, CORT, but not NE, levels significantly correlated with the enhanced defenses of R-mice in comparison to L-mice. The differential host resistance based on brain laterality seems to be more a function of the HPA axis and possibly other CNS effects on peripheral immunity than neurotransmitter release by the sympathetic innervation of the spleen.

Animals↗

PubMed2003

Functional interplay between angiotensin II and nitric oxide: cyclic GMP as a key mediator.

Angiotensin II (Ang II) and nitric oxide (NO) signaling pathways mutually regulate each other by multiple mechanisms. Ang II regulates the expression of NO synthase and NO production, whereas NO downregulates the Ang II type I (AT1) receptor. In addition, downstream effectors of Ang II and NO signaling pathways also interact with each other. A feedback mechanism between Ang II and NO is critical for normal vascular structure and function. Imbalance of Ang II and NO has been implicated in the pathophysiology of many vascular diseases. In this review, we focus on the diverse ways in which Ang II and NO interact and the importance of the balance between the signaling pathways activated by these mediators.

Angiotensin II↗

PubMed2002

Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: the potential role of Chlamydia pneumoniae infection in the progression of atherosclerosis.

Chlamydia pneumoniae infection implicated as an important etiologic factor of atherosclerosis, especially in coronary artery disease (CAD), was found in vitro to be associated with the induction of matrix metalloproteinases (MMPs). An extracellular matrix metalloproteinase inducer (EMMPRIN)/ membrane-type 1 matrix metalloproteinase (MT1-MMP) system which induces and activates MMPs, is suggested to be functional and were upregulated in the failing myocardium. However, the upstream regulation of MMPs by C. pneumoniae within atheroma itself remains unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in CAD patients (n= 391) and controls (n=97) and performed histopathological and in vitro analysis in atherosclerotic vascular tissues obtained from patients with seropositive to C. pneumoniae (n=20), by using immunochemistry for C. pneumoniae, EMMPRIN/MT1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C. pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group (P=0.033). Seropositive rate was increased in subgroups of CAD patients without conventional coronary risk factors compared to those with conventional risk factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased in the atheromatous plaque itself, predominantly in immunoreactive macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot analysis showed that EMMPRIN and MMP-2 were detected more prominently in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more increased in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. The present study demonstrated upstream regulation of MMPs can be induced by C. pneumoniae within atheromatous plaque itself. These findings help to understand the potential role of C. pneumoniae in the progression of atherosclerosis.

Aged↗

PubMed2002

Helix-loop-helix proteins regulate pre-TCR and TCR signaling through modulation of Rel/NF-kappaB activities.

E2A and HEB are basic helix-loop-helix transcription factors essential for T cell development. Complete inhibition of their activities through transgenic overexpression of their inhibitors Id1 and Tal1 leads to a dramatic loss of thymocytes. Here, we suggest that bHLH proteins play important roles in establishing thresholds for pre-TCR and TCR signaling. Inhibition of their function allows double-negative cells to differentiate without a functional pre-TCR, while anti-CD3 stimulation downregulates bHLH activities. We also find that the transcription factor NF-kappaB becomes activated in transgenic thymocytes. Further activation of NF-kappaB exacerbates the loss of thymocytes, whereas inhibition of NF-kappaB leads to the rescue of double-positive thymocytes. Therefore, we propose that E2A and HEB negatively regulate pre-TCR and TCR signaling and their removal causes hyperactivation and apoptosis of thymocytes.

Animals↗

PubMed2002

Diminished arteriolar responses in nitrate tolerance involve ROS and angiotensin II.

Our purpose was to evaluate hyporesponsivity to nitric oxide (NO)-induced dilation in small arterioles during nitrate tolerance. An Alza osmotic pump was implanted in the left flank of adult rats (n = 56) for continuous administration of nitroglycerin (140 microg/h) or vehicle (propylene glycol). On postoperative day 3, arcade (approximately 50-microm diameter) and terminal (approximately 20 microm) arterioles were observed in the cremaster preparation with in vivo video microscopy. Local vascular responses were obtained with micropipette-applied NO donors, with and without superoxide dismutase (SOD), Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP), or losartan. On day 3, NO-mediated dilation was significantly attenuated in nitroglycerin-treated rats. Attenuation was greater in the terminal arterioles compared with the arcades. Control responses were restored by SOD, MnTBAP, or losartan, suggesting a role for elevated angiotensin II and reactive oxygen species (ROS) as mediators of the attenuated NO dilation (nitrate tolerance). Addition of losartan to the drinking water likewise prevented nitrate tolerance. In summary, terminal arterioles are affected by nitrates to a greater extent than the arcade arterioles that feed them, in a process dependent on angiotensin II and ROS.

Angiotensin II↗

PubMedDate not supplied

Differential expression of genes from nitrate-tolerant rat aorta.

Organic nitrates act as vasodilators and have long been used for treatment of cardiovascular diseases. However, the therapeutic effect of nitrates is limited by induction of nitrate tolerance which is associated with endothelial dysfunction and enhanced vasoconstriction. Multiple mechanisms cause nitrate tolerance including alterations in gene expression. To identify genes whose expression is altered due to chronic treatment with nitroglycerin (NTG), nitrate-tolerant rats were made by infusion of NTG for 3 days (10 microg/kg/min) using an osmotic minipump. We constructed a PCR-selected cDNA subtracted library from NTG-treated and vehicle-treated rat aortas. Screening of approximately 500 clones in the subtracted library showed that four genes were regulated by NTG treatment. Specifically, mRNA levels of beta-globin, tropoelastin, gelsolin and a small G protein were confirmed to be upregulated consistently by NTG treatment. These identified genes may play important roles in the development of nitrate tolerance and represent promising candidates to understand the mechanisms of nitrate tolerance and endothelial dysfunction in the vasculature.

Animals↗