Biomedical subjects
Publications and source records attributed to Y Kim.
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The genomic organization of the human protocadherin alpha, beta, and gamma gene clusters (designated Pcdh alpha [gene symbol PCDHA], Pcdh beta [PCDHB], and Pcdh gamma [PCDHG]) is remarkably similar to that of immunoglobulin and T-cell receptor genes. The extracellular and transmembrane domains of each protocadherin protein are encoded by an unusually large "variable" region exon, while the intracellular domains are encoded by three small "constant" region exons located downstream from a tandem array of variable region exons. Here we report the results of a comparative DNA sequence analysis of the orthologous human (750 kb) and mouse (900 kb) protocadherin gene clusters. The organization of Pcdh alpha and Pcdh gamma gene clusters in the two species is virtually identical, whereas the mouse Pcdh beta gene cluster is larger and contains more genes than the human Pcdh beta gene cluster. We identified conserved DNA sequences upstream of the variable region exons, and found that these sequences are more conserved between orthologs than between paralogs. Within this region, there is a highly conserved DNA sequence motif located at about the same position upstream of the translation start codon of each variable region exon. In addition, the variable region of each gene cluster contains a rich array of CpG islands, whose location corresponds to the position of each variable region exon. These observations are consistent with the proposal that the expression of each variable region exon is regulated by a distinct promoter, which is highly conserved between orthologous variable region exons in mouse and human.
The crystal structure of the title compound, catena-poly[bis[aqua(18-crown-6)potassium] diaqua(18-crown-6)potassium [[tetra-mu-benzoato-2:3 kappa(8)O:O'-mu-cyano-1:2 kappa(2)C:N-tetracyano-1 kappa C-irondirhodium(Rh-Rh)]-mu-cyano-1 kappa C:3' kappa N] octahydrate], [K(18-crown-6)(H(2)O)](2)[K(18-crown-6)(H(2)O)(2)][FeRh(2)(C(7)H(5)O(2))(4)(CN)(6)] x 8H(2)O, where (18-crown-6) is 1,4,7,10,13,16-hexaoxacyclooctadecane (C(12)H(24)O(6)), has been determined. Ferric cyanides connect the dirhodium units to form a one-dimensional chain compound. [K(18-crown-6-ether)(H(2)O)(2)] cations (with inversion symmetry) and [K(18-crown-6-ether)(H(2)O)] cations (in general positions) are located between the chains.
An antimicrobial protein from seeds of Pharbitis nil (Pn-AMP) which shows an antifungal activity towards several agriculturally important plant pathogens has been crystallized in the presence of equimolar N-acetylglucosamine with sodium citrate as precipitant. The crystal belongs to the hexagonal space group P6(1)22 (or P6(5)22), with unit-cell parameters a = b = 29.33 (5), c = 133.44 (12) A. Native data were collected using a crystal at 100 K to a resolution of 1.78 A.
Finite-element (FE) modeling has been widely used in studies of bioelectric phenomena of tissues, including ventricular defibrillation. Most FE models, whether built from anatomical atlases or subject-specific tomographic images, treat the myocardium as an isotropic tissue. However, myocardium has been experimentally shown to have significant anisotropy in its resistivities, although myocardial fiber directions are difficult to measure on a subject-specific basis. In this paper, we: 1). propose a method to incorporate a widely known myocardial fiber direction model to a specific individual and 2). assess the effects of myocardial anisotropy on myocardial voltage gradients computed for a study of implantable defibrillators. The thoracic FE model was built from CT images of a young pig, and the myocardial fiber structures were incorporated via elastic mapping. Our results demonstrate a good mapping of geometry between the source and target hearts with an average root-mean-square error of less than 2.3 mm and a mapped fiber pattern similar to those known to exist in vivo. With the mapped fiber information, we showed that the estimated minimal myocardial voltage gradient over 80% of the myocardium differs by less than 10% between using an isotropic and anisotropic myocardial models. Thus, myocardial anisotropy is expected to have only a small effect on estimates of defibrillation threshold obtained from computed voltage gradients. On the other hand, anisotropy may be essential if defibrillation efficacy is analyzed by transmembrane voltage of the myocardial cells.
Traditional impedance cardiography (ICG) technique uses band electrodes both for delivering current to and measuring impedance change in the thorax. The use of spot electrodes increases the ease of electrode placement and comfort level for patients. Research has shown that changes in thoracic impedance can have multiple causes. In this study, we used finite element modeling to investigate the sources of impedance change for both band-electrode and spot-electrode ICG, and focused on how differences in electrode location affect the contribution of different sources to changes in impedance. The ultimate purpose is to identify the optimal electrode type and placement for the sensing of stroke volume (SV). Our models were built on sets of end-diastolic and end-systolic magnetic resonance images of a healthy human subject. The results showed that the effect of ventricular contraction is opposite to that of the other changes in systole: the expansion of major vessels, decrease in blood resistivity due to increased blood flow velocity, and decrease in lung resistivity due to increased blood perfusion. Ventricular contraction, the only factor that tends to increase systolic impedance, has a larger effect than any of the other factors. When spot electrodes are placed on the anterior chest wall near the heart, ventricular contraction is so dominant that the measured impedance increases from end-diastole to end-systole, and the change represents 82% of the contribution from ventricular contraction. When using the common band-electrode configuration, the change in measured impedance is a more balanced combination of the four effects, and ventricular contraction is overcome by the other three factors so that the impedance decreases. These results suggest that the belief that ICG can be used to directly measure SV based on the change in the whole thoracic impedance may be invalid, and that spot electrodes may be more useful for understanding local physiological events such as ventricular volume change. These findings are supported by previously reported experimental observations.
The results from this research supported our primary hypothesis that the adoption of avoidance (relative to approach) personal goals varies as a function of individualism-collectivism (across representations of this distinction). Interdependent self-construals were positively related and independent self-construals were negatively related to adoption of avoidance goals (Study 1), Asian Americans adopted more avoidance goals than non-Asian Americans (Study 2), andpersonsfrom South Korea and Russia adopted more avoidance goals than those in the United States (Studies 3 and 4, respectively). Studies 3 and 4 investigated andfound supportfor our secondary hypothesis that avoidance personal goals are a negative predictor of subjective well-being in individualistic (the United States), but not collectivistic (South Korea and Russia), countries. The findings are discussed in terms of other approach-avoidance constructs and motivational processes.
Two combined rotavirus vaccination regimens were evaluated in a gnotobiotic pig model of rotavirus infection and disease and were compared to previously tested rotavirus vaccination regimens. The first (AttHRV/VLP2x) involved oral inoculation with one dose of attenuated (Att) Wa human rotavirus (HRV), followed by two intranasal (i.n.) doses of a rotavirus-like particle (2/6-VLPs) vaccine derived from Wa (VP6) and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were coadministered with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT) adjuvant. For the second regimen (VLP2x/AttHRV), two i.n. doses of 2/6-VLPs+mLT were given, followed by one oral dose of attenuated Wa HRV. To compare the protective efficacy and immune responses induced by the combined vaccine regimens with individual rotavirus vaccine regimens, we included in the experiments the following vaccine groups: one oral dose of attenuated Wa HRV (AttHRV1x and Mock2x/AttHRV, respectively), three oral doses of attenuated Wa HRV (AttHRV3x), three i.n. doses of 2/6-VLPs plus mLT (VLP3x), three i.n. doses of purified double-layered inactivated Wa HRV plus mLT (InactHRV3x), mLT alone, and mock-inoculated pigs. The isotype, magnitude, and tissue distribution of antibody-secreting cells (ASCs) in the intestinal and systemic lymphoid tissues were evaluated using an enzyme-linked immunospot assay. The AttHRV/VLP2x regimen stimulated the highest mean numbers of intestinal immunoglobulin A (IgA) ASCs prechallenge among all vaccine groups. This regimen induced partial protection against virus shedding (58%) and diarrhea (44%) upon challenge of pigs with virulent Wa HRV. The reverse VLP2x/AttHRV regimen was less efficacious than the AttHRV/VLP2x regimen in inducing IgA ASC responses and protection against diarrhea (25% protection rate) but was more efficacious than VLP3x or InactHRV3x (no protection). In conclusion, the AttHRV/VLP2x vaccination regimen stimulated the strongest B-cell responses in the intestinal mucosal immune system at challenge and conferred a moderately high protection rate against rotavirus disease, indicating that priming of the mucosal inductive site at the portal of natural infection with a replicating vaccine, followed by boosting with a nonreplicating vaccine at a second mucosal inductive site, may be a highly effective approach to stimulate the mucosal immune system and induce protective immunity against various mucosal pathogens.
Modulation of Chelidonii herba on gamma-aminobutyric acid (GABA) activated chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was studied by nystatin-perforated patch-clamp technique. High concentrations of Chelidonii herba elicited ion current, that was blocked by bicuculline. Low concentrations reduced the GABA activated current in PAG. Two types of inhibitory action of Chelidonii herba on GABA activated current have been implicated in PAG. One is the inhibitory action of Chelidonii herba on GABA was abolished by naltrexone and the other is that of Chelidonii herba was potentiated by naltrexone. In addition, all of two types of action of Chelidonii herba are linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest that the inhibitory modulation of Chelidonii herba on GABA activated current via G-proteins in PAG neuron is an important analgesic mechanism.
BACKGROUND: It is a difficult problem to manage refluxing distal ureteral stumps after an upper tract approach in the ectopic ureter and ureterocele. We evaluated the natural history of the remaining refluxing distal ureteral stumps through a close follow-up. PATIENTS AND METHODS: From 1991 to 1998, nine patients with the ectopic ureter or ureterocele, whose age ranged from one to 20 (median 5.0) months, had undergone an upper tract surgery for ectopic ureter (2) or ectopic ureterocele (7). The upper tract surgery for ureterocele or ectopic ureter included a total nephrectomy (2), a partial nephrectomy (6) or a proximal ureteroureterostomy (1), leaving distal ureteral stump. We evaluated the clinical results of the remaining ureteral stumps every 6 or 12 months. The postoperative follow-up period was 51 (median; range 21-96) months. RESULTS: Among the 9 patients, 5 showed disappearance of the reflux and a markedly reduced stump size in the follow-up study. Improvement was noted in 4 patients within 6 months and in 1 by 20 months postoperatively. Two patients subsequently underwent a bladder level surgery due to problems not associated with the ureteral stump itself. Two patients have been followed up for 30 and 39 months, but without any improvement. An intermittent asymptomatic bacteriuria was noted in all patients during the follow-up, but no patient suffered from symptomatic urinary tract infection requiring an additional surgery. CONCLUSIONS: Since refluxing distal ureteral stumps were spontaneously resolved in more than half of the cases and did not cause significant problems during the follow-up, it is not necessary to remove the refluxing ureter simultaneously at the time of the upper tract surgery.
OBJECTIVE: High rates of medical morbidity have been reported in subjects with posttraumatic stress disorder (PTSD). The authors examined immune function in subjects in remission from past PTSD. METHOD: The initial study group was composed of 1,550 Japanese male workers. Japanese versions of the Events Check List, the Impact of Event Scale-Revised, and the Diagnostic Interview Schedule for DSM-IV were used to identify subjects who had a past history of PTSD. Twelve of the workers were identified as having such a history. These men were matched in age and smoking habits, which affect immunity, to 48 comparison subjects who had similar stressful life experiences but no current or past history of PTSD. Natural killer (NK) cell activity, lymphocyte subset counts, and production of interferon gamma (IFN-gamma) and interleukin-4 (IL-4) were measured in the 60 men by means of phytohemagglutinin stimulation. RESULTS: The number of lymphocytes, number of T cells, NK cell activity, and total amounts of IFN-gamma and IL-4 were significantly lower in the 12 men with a past history of PTSD. CONCLUSIONS: PTSD leaves a long-lasting immunosuppression and has long-term implications for health.
The authors studied 52 patients who had undergone surgery because of intractable temporal lobe epilepsy. Investigation of postoperative psychiatric illnesses focused on psychotic disorder (293.81 and 293.82) and mood disorder (293.83) due to a general medical condition diagnosed according to DSM-IV criteria. Presurgically, two episodic psychotic syndromes, acute interictal and postictal psychosis, were defined operationally. A correlation was confirmed between presurgical acute interictal psychosis and postsurgical psychotic disorder, as well as between presurgical postictal psychosis and postsurgical mood disorder. An excellent final outcome for postoperative mood disorder in contrast to a less favorable one for psychotic disorder was also suggested.
The inhibitory effects of ethaverine on dopamine content in PC12 cells were investigated. Ethaverine decreased dopamine content in a concentration-dependent manner in PC12 cells and showed 33.6% inhibition of dopamine content at a concentration of 1.0 microM for 24-48 h. The IC50 value of ethaverine was 1.4 microM. Dopamine content was lowered at 6h and reached a minimal level at 12h after exposure to ethaverine at 2.0 microM. The decreased dopamine level was maintained up to 48 h and then recovered to the control level at about 72 h. Tyrosine hydroxylase (TH) was inhibited at 6 h following treatment with ethaverine in PC12 cells and the activity was maintained at a reduced level up to 36 h (12-22% inhibition at 2.0 microM). These results indicate that ethaverine leads to a decrease in dopamine content by inhibition of TH activity.
Interleukin-6 (IL-6) is known as a proinflammatory cytokine involved in immune response, inflammation, and hematopoiesis. Inhibitory effects of anti-inflammatory drugs on IL-6 bioactivity using IL-6-dependent hybridoma have been evaluated. Three out of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) showed IC50 values of less than 100 microM, which were in the order of oxyphenylbutazone hydrate (IC50=7.5 microM)>meclofenamic acid sodium salt (31.9 microM)>sulindac (74.9 microM). Steroidal anti-inflammatory drugs (SAIDs) exhibited significant inhibitory effects at 100 microM on the IL-6 bioactivity, and their inhibitory potencies were in the order of budesonide (IC50=2.2 microM)>hydrocortisone 21-hemisuccinate (6.7 microM), prednisolone (7.5 microM), betamethasone (10.9 microM)>dexamethasone (18.9 microM) and triamcinolone acetonide (24.1 microM). The results would provide an additional mechanism by which anti-inflammatory drugs display their anti-inflammatory and immunosuppressive effects at higher concentrations.
The effects of benzylisoquinoline compounds such as ethaverine, laudanosine, and tetrahydropapaverine on monoamine oxidase (MAO, EC 1.4.3.4) activity in mouse brain were investigated. Ethaverine showed an inhibition of MAO activity in a concentration-dependent manner (57.6% inhibition at 40 microm). Papaverine also inhibited MAO activity (38.1% inhibition at 40 microM). However, laudanosine and tetrahydropapaverine did not inhibit MAO activity. The IC50 value of ethaverine for MAO was 25.5 microm. Ethaverine non-competitively inhibited MAO activity with a substrate kynuramine. The Ki value for ethaverine was 11.9 microM. In addition, ethaverine proved to preferentially inhibit type B MAO activity in a concentration-dependent manner, with an IC50 value of 32.8 microm. These results suggest that ethaverine partially contributes to the regulation of catecholamine content.
Effects of clonidine, an imidazoline derivative as well as alpha2-adrenoceptor agonist, on carbachol (CCh)-evoked contraction in guinea pig ileal smooth muscle were studied using isometric tension recording. To investigate the cellular mechanisms of the inhibitory effect of clonidine, its effects on CCh-evoked nonselective cationic current (I(CCh)), voltage-dependent Ca2+ current (I(Ca)) and voltage-dependent K+ current (I(K)) was also studied using patch-clamp recording techniques in single ileal cells. Clonidine inhibited the contraction evoked by CCh (1 microM) in a concentration-dependent manner with an IC50 valve of 61.7 +/- 2.5 microM. High K+ (40 mM)-evoked contraction was only slightly inhibited even when clonidine was used at 300 microM. Externally applied clonidine inhibited I(CCh) dose-dependently with an IC50 of 42.0 +/- 2.6 microM. When applied internally via patch pipettes, clonidine was without effect. An I(CCh)-like current induced by GTPgammaS was also inhibited by bath application of clonidine. None of KU14R and BU224, both imidazoline receptor blockers, and yohimbine, an alpha2-adrenergic blocker, significantly affects the inhibitory effect of clonidine on I(CCh). Clonidine (300 microM) only slightly decreased membrane currents flowing through voltage-gated Ca2+ channels or K+ channels. These data indicate that clonidine relaxes smooth muscle contraction produced by muscarinic receptor activation and suggest that the effect of clonidine seems due mainly to inhibition of I(CCh) via acting directly on the involved cationic channel.
Puerariaeflos (PF) is an oriental medical herb for alcohol abuse. To investigate whether PF possesses protective effects against ethanol (EtOH)-induced cytotoxicity in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometric analysis, DNA fragmentation assay, and reverse transcription-polymerase chain reaction were performed on SK-N-MC human neuroblastoma cells. Cells treated with EtOH exhibited several apoptotic features, while those pre-treated with PF prior to EtOH exposure showed a decreased occurrence of apoptotic features. In addition, PF pre-treatment inhibited the EtOH-induced increase in caspase-3 mRNA expression. These results suggest that PF may exert protective effects against EtOH-induced apoptosis in human neuroblastoma cells.
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