A familial case of Blau syndrome caused by a novel NOD2 genetic mutation / 소아과

Blau syndrome (BS) is a rare autosomal dominant, inflammatory syndrome that is characterized by the clinical triad of granulomatous dermatitis, symmetric arthritis, and recurrent uveitis. Mutations in the nucleotide oligomerization domain 2 (NOD2) gene are responsible for causing BS. To date, up to 30 Blau-associated genetic mutations have been identified within this gene. We report a novel NOD2 genetic mutation that causes BS. A girl, aged 8 years, and her brother, aged 10 years, developed erythematous skin rashes and uveitis. The computed tomography angiogram of the younger sister showed features of midaortic dysplastic syndrome. The brother had more prominent joint involvement than the sister. Their father (38 years) was also affected by uveitis; however, only minimal skin involvement was observed in his case. The paternal aunt (39 years) and her daughter (13 years) were previously diagnosed with sarcoidosis. Mutational analysis revealed a novel c.1439 A>G mutation in the NOD2 gene in both siblings. The novel c.1439 A>G mutation in the NOD2 gene was found in a familial case of BS. Although BS is rare, it should always be considered in patients presenting with sarcoidosis-like features at a young age. Early diagnosis of BS and prompt multisystem workup including the eyes and joints can improve the patient's outcome.

The Pathophysiologic Roles of TRPM7 Channel

Transient receptor potential melastatin 7 (TRPM7) is a member of the melastatin-related subfamily and contains a channel and a kinase domain. TRPM7 is known to be associated with cell proliferation, survival, and development. It is ubiquitously expressed, highly permeable to Mg2+ and Ca2+, and its channel activity is negatively regulated by free Mg2+ and Mg-complexed nucleotides. Recent studies have investigated the relationships between TRPM7 and a number of diseases. TRPM7 regulates cell proliferation in several cancers, and is associated with ischemic cell death and vascular smooth muscle cell (VSMC) function. This review discusses the physiologic and pathophysiologic functions and significance of TRPM7 in several diseases.

Effects of Histamine on Cultured Interstitial Cells of Cajal in Murine Small Intestine

Interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal tract, and histamine is known to regulate neuronal activity, control vascular tone, alter endothelial permeability, and modulate gastric acid secretion. However, the action mechanisms of histamine in mouse small intestinal ICCs have not been previously investigated, and thus, in the present study, we investigated the effects of histamine on mouse small intestinal ICCs, and sought to identify the receptors involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials (in current clamp mode) from cultured ICCs. Histamine was found to depolarize resting membrane potentials concentration dependently, and whereas 2-PEA (a selective H1 receptor agonist) induced membrane depolarizations, Dimaprit (a selective H2-agonist), R-alpha-methylhistamine (R-alpha-MeHa; a selective H3-agonist), and 4-methylhistamine (4-MH; a selective H4-agonist) did not. Pretreatment with Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor in endoplasmic reticulum) abolished the generation of pacemaker potentials and suppressed histamine-induced membrane depolarization. Furthermore, treatments with U-73122 (a phospholipase C inhibitor) or 5-fluoro-2-indolyl des-chlorohalopemide (FIPI; a phospholipase D inhibitor) blocked histamine-induced membrane depolarizations in ICCs. On the other hand, KT5720 (a protein kinase A inhibitor) did not block histamine-induced membrane depolarization. These results suggest that histamine modulates pacemaker potentials through H1 receptor-mediated pathways via external Ca2+ influx and Ca2+ release from internal stores in a PLC and PLD dependent manner.

Canine behavioral problems and their effect on relinquishment of the Jindo dog

The purpose of this study was to evaluate behavior problems of the Jindo dog, the native dog of Korea, based on an owner's survey and their effect on pet relinquishment. To live a better life with their own pet and prevent relinquishment, it is important to understand the innate behavior characteristics of dog breed and the potential causes of relinquishment. Information concerning various factors and demonstration of the five most common behavior problems was collected via 189 completed questionnaires. No factors significantly affected the demonstration of behavior problem. A total 151 of 189 dogs had behavior problems (79.9%) and 38 dogs did not have behavior problems (20.1%). Among 151 dogs, 139 dogs showed single behavior problem (92.1%). They were 'excessive excitability' (46.8%), 'excessive vocalization' (30.2%), 'inappropriate elimination' (17.3%), 'destructive behavior' (4.3%), and 'aggressive behavior' (1.4%), respectively. In addition, 12 dogs showed two concurrent behavior problems (7.9%) According to the results, the relinquishment of Jindo dogs was not significantly associated with canine behavior problems, which is the single greatest risk factor of relinquishment in general. The possible reasons for potential behavior problems include improper raising, lack of socialization, and insufficient dog training classes, therefore canine behavior would be improved by owner education.

Functional Analysis of TRPV6 Polymorphisms / 한국실험동물학회지

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel transient receptor potential vanilloid 6 (TRPV6). The putatively-selected TRPV6 haplotype contains three candidate sites for functional differences, namely derived non-synonymous substitutions C157R, M378V and M681T. Functional electrophysiological characteristics between wild-type and mutant (C157R, M378V and M681T) TRPV6 proteins were investigated by cloning the mutant TRPV6 forms, transfecting cell lines, and carrying out electrophysiology experiments via patch clamp analysis. No statistically significant differences in biophysical channel function were found although one property, namely Ca2+-dependent inactivation, may show functionally-relevant differences between the wild-type and mutant TRPV6 proteins. This study shows that Ca2+-dependent inactivation is one of the good differentiation characteristics in TRPV6, and will be useful in an advancing our knowledge about TRPV6.

Association study of polymorphism in leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes with phenotype of asthma and clinical parameters in Korean children / 소아과

PURPOSE: Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. METHODS: A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(+927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC+CC or TC+CC) genotypes in asthmatics, atopic asthmatics, and EIA (+) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. CONCLUSION: LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

Optimized Immunohistochemical Analysis of Cerebellar Purkinje Cells Using a Specific Biomarker, Calbindin D28k

Cerebellar Purkinje cells (PCs) play a crucial role in motor functions and their progressive degeneration is closely associated with spinocerebellar ataxias. Although immunohistochemical (IHC) analysis can provide a valuable tool for understanding the pathophysiology of PC disorders, the method validation of IHC analysis with cerebellar tissue specimens is unclear. Here we present an optimized and validated IHC method using antibodies to calbindin D28k, a specific PC marker in the cerebellum. To achieve the desired sensitivity, specificity, and reproducibility, we modified IHC analysis procedures for cerebellar tissues. We found that the sensitivity of staining varies depending on the commercial source of primary antibody. In addition, we showed that a biotin-free signal amplification method using a horseradish peroxidase polymer-conjugated secondary antibody increases both the sensitivity and specificity of ICH analysis. Furthermore, we demonstrated that dye filtration using a 0.22 micrometer filter eliminates or minimizes nonspecific staining while preserving the analytical sensitivity. These results suggest that our protocol can be adapted for future investigations aiming to understand the pathophysiology of cerebellar PC disorders and to evaluate the efficacy of therapeutic strategies for treating these diseases.

Inhibition of the Desensitization of Canonical Transient Receptor Potential Channel 5 by Dimethyl Sulfoxide

The classic type of transient receptor potential channel (TRPC) is a molecular candidate for Ca2+-permeable cation channel in mammalian cells. TRPC5 is rapidly desensitized after activation by G protein-coupled receptor. Herein we report the effect of dimethyl sulfoxide (DMSO) on the desensitization of TRPC5. TRPC5 was initially activated by muscarinic stimulation with 50microM carbachol (CCh) and then decayed rapidly even in the presence of CCh (desensitization). DMSO in the pipette solution slowed the rate of this desensitization. Under the control conditions, TRPC5 current spontaneously declined to 6+/-1% of the initial peak amplitude 60 sec after CCh application and to 1+/-0.5% after 120 sec. But, in the presence of 0.01%, 0.1% and 1% DMSO, TRPC5 current spontaneously declined to 55+/-2%, 68+/-1% and 100+/-0.2% of the initial peak amplitude 60 sec after CCh application and to 38+/-2%, 61+/-1% and 100+/-1% after 120 sec, respectively. The results suggest that DMSO can internally attenuate the desensitization of TRPC5 current through unknown mechanisms that remain to be elucidated.

pH-mediated Regulation of Pacemaker Activity in Cultured Interstitial Cells of Cajal

Interstitial cells of Cajal (ICCs) are pacemakers in gastrointestinal tracts, regulating rhythmicity by activating nonselective cation channels (NSCCs). In the present study, we investigated the general characteristics and pH-mediated regulation of pacemaker activity in cultured interstitial cells of Cajal. Under voltage clamp mode and at the holding potential of -60 mV, the I-V relationships and difference current showed that there was no reversal potential and voltage-independent inward current. Also, when the holding potentials were changed from +20 mV to -80 mV with intervals of 20 mV, there was little difference in inward current. In pacemaker activity, the resting membrane potential (RMP) was depolarized (In pH 5.5, 23+/-1.5 mV depolarized) and the amplitude was decreased by a decrease of the extracellular pH. However, in case of increase of extracellular pH, the RMP was slightly hyperpolarized and the amplitude was decreased a little. The melastatin type transient receptor potential (TRPM) channel 7 has been suggested to be required for intestinal pacemaking activity. TRPM7 produced large outward currents and small inward currents by voltage ramps, ranging from +100 to -100 mV from a holding potential of -60 mV. The inward current of TRPM7 was dramatically increased by a decrease in the extracellular pH. At pH 4.0, the average inward current amplitude measured at -100 mV was increased by about 7 fold, compared with the current amplitude at pH 7.4. Changes in the outward current (measured at +100 mV) were much smaller than those of the inward current. These results indicate that the resting membrane potential of pacemaking activity might be depolarized by external acidic pH through TRPM7 that is required for intestinal pacemaking activity.

The Effect of External Divalent Cations on Intestinal Pacemaking Activity

Electrical rhythmicity in the gastrointestinal (GI) muscles is generated by pacemaker cells, known as interstitial cells of Cajal (ICC). In the present study, we investigated the effect of external divalent cations on pacemaking activity in cultured ICC from murine small intestine by using whole-cell patch clamp techniques. ICC generated pacemaker currents under a voltage clamp or electrical pacemaker potentials under a current clamp, and showed a mean amplitude of -500+/-50 pA or 30+/-1 mV and the frequency of 18+/-2 cycles/min. Treatments of the cells with external 0 mM Ca2+ stopped pacemaking activity of ICC. In the presence of 2 mM Ca2+, 0 mM external Mg2+ depolarized the resting membrane potential, and there was no change in the frequency of pacemaking activity. However, 10 mM external Mg2+ decreased the frequency of pacemaking activity (6.75+/-1 cycles/min, n=5). We replaced external 2 mM Ca2+ with equimolar Ba2+, Mn2+ and Sr2+, and they all developed inward current in the sequence of Ba2+> Mn2+> Sr2+. Also the frequency of the pacemaking activity was stopped or irregulated. We investigated the effect of 10 mM Ba2+, Mn2+ and Sr2+ on pacemaking activity of ICC in the presence of external 0 mM Mg2+, and found that 10 mM Ba2+ and Mn2+ induced large inward current and stopped the pacemaking activity of ICC (n=5). Interestingly, 10 mM Sr2+ induced small inward current and potentiated the amplitude of pacemaking activity of ICC (n=5). These results indicate that extracellular Ca2+ and Mg2+ are requisite for the pacemaking activity of ICC.

The Role of Mitochondrial ATP-sensitive Potassium Channel on Intestinal Pacemaking Activity

Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. In the present study, we investigated the effect of mitochondrial ATP-sensitive potassium (mitoKATP) channel on pacemaking activity in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. Under current clamp mode, at 10microM glibenclamide, there was no change in pacemaking activity of ICCs. At 30microM glibenclamide, an inhibitor of the ATP sensitive K+ channels, we could find two examples. If pacemaking activity of ICCs was irregulating, pacemaking activity of ICCs was changed into regulating and if in normal conditions, membrane potential amplitude was increased. At 50microM glibenclamide, the resting membrane potential was depolarized. At 3mM 5-HDA, an inhibitor of the mitoKATP channels, inhibited the pacemaking activity of ICCs. Both the amplitude and the frequency were decreased. At 5 mM 5-HDA, both the amplitude and the frequency were completely abolished. Diazoxide, an opener of the mitoKATP channels, was applied to examine its effect on pacemaking activity of ICCs. At 50microM concentration, the pacemaking activity of ICCs was inhibited. Both the amplitude and the frequency were decreased. At 1 mM concentration, both the amplitude and the frequency were completely abolished and the resting membrane potential was shaked. These results indicate that mitoKATP channel has an important role in pacemaking activity of ICCs.

The Effects of DTBNP on Intracellular Ca2+ Signaling in Cultured Bovine Aortic Endothelial Cells

The mechanism underlying oxidant-induced intracellular Ca2+ ([Ca2+]i) increase was studied in cultured bovine aortic endothelial cells (BAECs) using fura-2 AM. In the presence of 2 mM extracellular Ca2+, the application of DTBNP (20microM), a membrane-permeable oxidant, caused an increase in [Ca2+]i, and DTT (2 mM) as a reductant completely reversed the effect of DTBNP. The [Ca2+]i increase induced by DTBNP was also observed in an extracellular Ca2+-free/2 mM EGTA solution, indicating the release of Ca2+ from intracellular store (s). After endoplasmic reticulum was depleted by an IP3-generating agonist, ATP (30microM) or an ER Ca2+ pump inhibitor, thapsigargin (1microM), DTBNP-stressed BAECs showed an increase of [Ca2+]i in Ca2+-free/2 mM EGTA solution. Ratio-differences before and after the application of DTBNP after pretreatment with ATP or thapsigargin were 0.42+/-0.15 and 0.49+/-0.07, respectively (n=7), which are significantly reduced, compared to the control value of 0.72+/-0.07 in a Ca2+-free/2 mM EGTA solution. After the protonophore CCCP (10microM) challenge to release mitochondrial Ca2+, the similar result was obtained. Ratio-difference before and after the application of DTBNP after pretreatment with CCCP was 0.46+/-0.09 (n=7). Simultaneous application of thapsigargin and CCCP completely abolished the DTBNP-induced [Ca2+]i increase. The above results together indicate that the increase of [Ca2+]i by DTBNP resulted from the release of Ca2+ from both endoplasmic reticulum and mitochondria.

Cognitive Changes after Open Heart Surgery with Cardiopulmonary Bypass / 대한마취과학회지

BACKGROUND: Cognitive dysfunction after open heart surgery under the cardiopulmonary bypass is one of major problems in modern cardiac surgery. We designed this study to evaluate the incidence of postoperative neuropsychological changes after routine cardiac surgery with the cardiopulmonary bypass. METHODS: We assessed the patients with four cognitive function tests on the day before, 4-5 days after and 9-10 days after cardiac surgery. The test batteries which used in this study were Trail-Making Test part A, Digit Substitution test, Digit Span Test, Grooved Pegboard test. RESULTS: The incidence of cognitive dysfunction was 12.8-25% at postoperative 4-5 days, 2.3-11.5% at postoperative 9-10 days. About 80% of patients who showed cognitive dysfunction at postoperative 4-5 days had gained normal cognitive function score at postoperative 9-10 days. CONCLUSIONS: The incidence of cognitive dysfunction after heart surgery is not low, and we must try to find how to reduce these complications.

The Effect of Ghrelin on Ca2+ Concentration in Thyroid FRTL-5 Cells

Ghrelin is a newly discovered peptide, which is released from the stomach and neurons in the hypothalamic arcuate nucleus (ARC), and potently stimulates growth hormone release and food intake. In the present study, we investigated the effect of ghrelin on [Ca2+]i in thyroid FRTL-5 cells. Ghrelin (5 nM) increased [Ca2+]i and TSH (1 unit/l) had an additive effect on [Ca2+]i when extracellular normal solution was 1.1mM Ca2+ containing Coon's modified Ham's F12 medium. When Ca2+-free medium containing 2 mM EGTA replaced the above normal solution, ghrelin also induced a similar rise in [Ca2+]i. In the middle of [Ca2+]i increment by ghrelin, nifedipine (1 micrometer), nickel (100micrometer) and La3+ (100micrometer) had no effect on [Ca2+]i. After endoplasmic reticulum was depleted by cyclopiazonic acid (CPA; 10micrometer), ghrelin caused no visible change on [Ca2+]i in Ca2+-free/2 mM EGTA solution. These results suggest that ghrelin can increase [Ca2+]i through endoplasmic reticulum in thyroid FRTL-5 cells.

Cognition and Memory Impairment after Operation in Ruptured Cerebral Aneurysm Patients

OBJECTIVE: The mortality rate of subarachnoid hemorrhage(SAH) has been reduced recently due to refinement of microsurgical technique and improved perioperative management. Also, many survivors of SAH show excellent neurological recoveries. However, we found that a high proportion of the survivors do not fully regain their premorbid status in cognitive and memory function. Object of this study is to evaluate which factors might influence on cognitive and memory impairment in ruptured aneurysmal SAH patients. METHODS: In this prospective study, a series of 66 patients with aneurysmal subarachnoid hemorrhage(SAH) from 1996 to 1998, most of whom had a "good" or "fair" neurological outcome, were assessed with various tests of cognition and memory function. All patients underwent clipping operation by pterional approach. Right side approach was performed in 16 case and left 21 cases. K-WAIS(Korean-Wechsler Adult Intelligence Scale) was used as method of cognition and memory function test. The time interval between SAH and assessment varied between 4 months and 8 months, averaging 6.2 months. Statistical analyses were carried out for each test score to see whether aneurysm site(A-com : non A-com), route of approach, age and sex, vasospasm, Hunt-Hess grade and Fisher CT group at admission, Glasgow Outcome Scale(GOS) at discharge affect cognitive and memory function. RESULTS: Aneurysm site was not shown to be associated with performance on any test, and the initial grade (Hunt-Hess grade, Fisher CT group) of SAH and vasospasm had only minimal predictive values. The grade at discharge(GOS) was proved to be the best predictor of impairment of cognition and memory function within 1 year after operation. CONCLUSION: The authors conclude that the diffuse effects of SAH are more important than focal neuropathology in relation to cognitive impairment in this group of patients.

A Case of Intracardiac Migration of Distal Ventriculo-Peritonal(V-P) Shunt Catheter

No abstract available.

Tracheal Rupture during the Use of Robertshaw Double-lumen Endobronchial Tube for One-lung Ventilation: A case report / 대한마취과학회지

Rupture of the trachea as a result of external trauma is well documented. But, rupture of the membranous trachea following tracheal intubation has been infrequently noted. Risk factors associated with tracheobronchial rupture include inexperienced endoscopists, intubating stylets, multiple vigorous attempts at intubation, tracheal abnormalities, overdistension of tracheal or bronchial cuff with high pressure, low volume cuffs, and old age. We report a case of tracheal rupture occurred during one lung ventilation using Robertshaw double-lumen endotracheal tube for right upper lobe lobectomy. The etiology and treatment are discussed and the recent literature is reviewed.

EXPERIMENTAL STUDY OF OSSEOINTEGRATION USING IMPLANT PLACEMENT WITH A SPLIT-CREST TECHNIQUE

The purpose of this study was to verify the split-crest technique experimentally for successful implantation at alveolar bone having unfavorable condition. Using inferior border of the mandible of the canine, we made comparable study about the state of osseointegration between conventional technique and split-crest technique. We set experimental group which was implanted at inferior border of the mandible of the canine by split-crest technique using the fixture of 3.75 mm width and 8mm length, and set control group which was implanted by conventional technique at the counter area of the mandible. The experimental animal was sacrificed at 1, 4, 8 and 16 week. We observed the changing process of bone formation following implantation with stereoscopy, light microscopy, electron microscopy and fluorescent microscopy, and studied histomorphometrically. Histologic results were as follow : 1. In control group, a bit of new bone formation was initiated on a portion of bone defect area at 1 week. The initiation of osseointegration between fixture and new bone was seen at 4 week. New bone tissue with normal shape and structure formed and filled defect area at 8 week. But complete bone remodeling was attained at 16 week. 2. In experimental group, bone formation around fixture was going on actively. But the shape and structure of new bone area was more irregular than that of control group, and bone density was also lower than that of control group. Active new bone formation was still observed at 16 week. 3. The osseointegrated new bone was remodeled to cancellous bone having trabeculae and marrow space composed of compact lamellar bone. 4. In fluorescent microscopic analysis, active bone formation was seen between 4 weeks and 8 weeks at control group. Otherwise, along the all experimental period new bone formation was observed evenly at experimental group. 5. Both control and experimental group, normal osseointegration was accomplished without bone resorption which is essential factor in split-crest technique. As previous results, when implantation using split-crest technique at alveolar bone attenthaving unfavorable condition, early bone formation was delayed slightly, but we could get attentive results along the long term period.

Immunohistochemical study of dendritic cells in vascular lesion of renal allografts with chronic rejection / 대한이식학회지

No abstract available.

Mediastinal lipoma: one case report / 대한흉부외과학회지

No abstract available.