Diffuse lesion in the splenium of the corpus callosum in patients with methyl bromide poisoning.
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Adult↗
Biomedical subjects
K Kang
Publications and source records attributed to K Kang.
Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1alpha gene in a Korean family with MODY3.
AIMS/HYPOTHESIS: After screening 16 Korean families with early onset Type 2 diabetes in search for hepatocyte nuclear factor (HNF) -1alpha gene mutation, we identified a novel missense mutation (R263L) associated with MODY phenotype. We studied the biological characteristics of the mutation and the potential functional consequences based on the crystallographic structure of HNF-1alpha in complex with DNA. METHODS: DNA from subjects with a familial form of early onset diabetes was isolated and HNF-1alpha was sequenced. The R263L substitution was generated by PCR-based sited-directed mutagenesis. Functional and biochemical studies were conducted by reporter assay using glucose-transporter type 2 (GLUT2) or insulin promoters and electrophoretic mobility shift assay, respectively. RESULTS: Transfection of wild-type HNF-1alpha increased the reporter activities of GLUT2 and insulin promoters in NIH3T3 and SK-Hep1 cells, while R263L mutant was defective in transactivation of those promoters. Both wild-type HNF-1alpha and R263L mutant could not transactivate GLUT2 and insulin promoters in MIN6N8 insulinoma cells. R263L mutant had a defective cooperation with its heterodimeric partner HNF-1beta or coactivator p300. R263L mutant protein displayed greatly reduced DNA binding ability, despite its comparable protein stability to the wild-type HNF-1alpha. CONCLUSION/INTERPRETATION: These results suggest that the mutation of HNF-1alpha at codon 263 from arginine to leucine leads to the development of MODY3 through decreased insulin production and defective glucose sensing. These findings are in good agreement with the crystal structure in which R263 makes hydrogen bonds with phosphorus atoms of DNA backbone to mediate the stable binding of HNF-1alpha homeodomain to the promoter.
Amino Acid Substitution↗
Intravenous clonidine prolongs bupivacaine spinal anesthesia.
BACKGROUND: Prolongation of spinal anesthesia by oral clonidine premedication has been known. We hypothesized that intravenous clonidine administered after the spinal block may prolong spinal anesthesia. METHODS: To assess the prolongation of spinal anesthesia by intravenous clonidine, we designed a double-blind, placebo-controlled, prospective study. Patients scheduled for orthopedic surgery received 12 mg of 0.5% hyperbaric bupivacaine and were randomly divided into three groups (n = 26 in each group). In the clonidine 10-min group, 3 microg x kg-1 of clonidine was administered for 10 min immediately after the spinal block. In the clonidine 60-min group, 3 microg x kg-1 of clonidine was administered for 10 min, 50 min after the spinal block. The control group received normal saline. Sensory block was evaluated by pinprick and the duration was defined as the time for sensory block to regress to L1 dermatome. Duration of motor block was defined as the time required for the patient to flex his or her knee. RESULTS: The duration of sensory block was longer in both the clonidine 10-min and clonidine 60-min groups compared with the control group (196 +/- 42 min, 179 +/- 41 min vs. 125 +/- 25 min, P < 0.05). The duration of motor block was longer in the clonidine 10-min group than in the control group (153 +/- 26 min vs. 131 +/- 29 min, P < 0.05). The lowest heart rate and mean blood pressure were not different among groups. CONCLUSIONS: Intravenous clonidine administration within 1 h after the spinal block prolonged bupivacaine spinal anesthesia for approximately 1 h without adverse effects.
Adult↗
Benchmarks for the forward observables at RHIC, the Tevatron-run II, and the LHC.
We present predictions on the total cross sections and on the rho parameter for present and future pp and (-)pp colliders, and on total cross sections for gammap-->hadrons at cosmic-ray energies and for gammagamma-->hadrons up to sqrt[s]=1 TeV. These predictions are based on an extensive study of possible analytic parametrizations invoking the largest hadronic dataset available at t=0. The uncertainties on total cross sections reach 1.9% at the Relativistic Heavy Ion Collider, 3.1% at the Tevatron, and 4.8% at the Large Hadron Collider, whereas those on the rho parameter are, respectively, 5.4%, 5.2%, and 5.4%.
Journal Article↗
Population coding in neuronal systems with correlated noise.
Neuronal representations of external events are often distributed across large populations of cells. We study the effect of correlated noise on the accuracy of these neuronal population codes. Our main question is whether the inherent error in the population code can be suppressed by increasing the size of the population N in the presence of correlated noise. We address this issue using a model of a population of neurons that are broadly tuned to an angular variable in two dimensions. The fluctuations in the neuronal activities are modeled as Gaussian noises with pairwise correlations that decay exponentially with the difference between the preferred angles of the correlated cells. We assume that the system is broadly tuned, which means that both the correlation length and the width of the tuning curves of the mean responses span a substantial fraction of the entire system length. The performance of the system is measured by the Fisher information (FI), which bounds its estimation error. By calculating the FI in the limit of a large N, we show that positive correlations decrease the estimation capability of the network, relative to the uncorrelated population. The information capacity saturates to a finite value as the number of cells in the population grows. In contrast, negative correlations substantially increase the information capacity of the neuronal population. These results are supplemented by the effect of correlations on the mutual information of the system. Our analysis provides an estimate of the effective number of statistically independent degrees of freedom, denoted N(eff), that a large correlated system can have. According to our theory N(eff) remains finite in the limit of a large N. Estimating the parameters of the correlations and tuning curves from experimental data in some cortical areas that code for angles, we predict that the number of effective degrees of freedom embedded in localized populations in these areas is less than or of the order of approximately 10(2).
Animals↗
trans-10,cis-12-Conjugated linoleic acid reduces leptin secretion from 3T3-L1 adipocytes.
The trans10,cis12 (t10c12) isomer of conjugated linoleic acid (CLA) has been shown to inhibit heparin-releasable lipoprotein lipase activity, reduce lipid stores in cultured 3T3-L1 adipocytes, and, when fed to mice, reduce body fat gain. We now report that t10c12 CLA significantly reduced leptin secretion from cultured 3T3-L1 adipocytes, and reduced leptin mRNA levels within the cells. Similar effects were produced by conjugated nonadecadienoic acid (a 19-carbon CLA cognate that is more effective than CLA in reducing body fat gain in mice), the lipoxygenase inhibitor nordihydroguaiaretic acid (which is synergistic with CLA in reducing body fat gain in mice), and ciglitazone (TZD, a PPARgamma agonist). Feeding mice diet supplemented with 0.5% t10c12 CLA for 4 weeks significantly reduced body fat gain, serum leptin levels and adipocyte leptin mRNA expression, without affecting feed intake or body weight. These data provide new insights into apparent mechanistic similarities among t10c12 CLA, CNA, NDGA, and TZD.
3T3 Cells↗
Mutual information of population codes and distance measures in probability space.
We studied the mutual information between a stimulus and a system consisting of stochastic, statistically independent elements that respond to a stimulus. Using statistical mechanical methods the properties of the mutual information (MI) in the limit of a large system size N are calculated. For continuous valued stimuli, the MI increases logarithmically with N and is related to the log of the Fisher information of the system. For discrete stimuli the MI saturates exponentially with N. We find that the exponent of saturation of the MI is the Chernoff distance between response probabilities that are induced by different stimuli.
Brain↗
Differential changes in neuropeptide Y and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in rat hippocampus after kainic acid-induced seizure.
Changes in neuropeptide Y (NPY) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in the hippocampus were investigated 5, 10 and 20 days after kainic acid (KA) administration using a double labeling method. The numbers of NADPH-d-positive-only and NPY/NADPH-d-positive neurons decreased in the CA1/2-CA3 regions of the hippocampus, 5, 10 and 20 days after KA administration, however, the number of NPY-positive-only neurons increased in the same regions 5 and 10 days after KA administration. In the dentate gyrus (DG) region of the hippocampus, the numbers of NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons increased 5 days after KA administration, and 20 days after KA administration, the number of NADPH-d-positive-only neurons decreased to levels similar to or lower than the level of the controls. However, the numbers of NPY/NADPH-d-positive and NPY-positive-only neurons in the DG region 20 days after KA administration remained at control levels. These results indicate that, NADPH-d-positive-only neurons are vulnerable to, and NPY-positive-only neurons are resistant to KA-induced seizures in the whole hippocampus, but that NPY/NADPH-d-positive neurons have different sensitivities in subregions of the hippocampus to KA-induced seizures. In addition, the present findings provide the first statistical and morphological evidence, which demonstrates that NPY-positive-only, NADPH-d-positive-only and NPY/NADPH-d-positive neurons in the hippocampus have different sensitivities to KA-induced seizures.
Animals↗
Recombinant baculoviruses for insect control.
Baculoviruses are double-stranded DNA viruses which are highly selective for several insect groups. They are valuable natural control agents, but their utility in many agricultural applications has been limited by their slow speed of kill and narrow host specificity. Baculoviruses have been genetically modified to express foreign genes under powerful promoters in order to accelerate their speed of kill. In our and other laboratories, the expression of genes coding for insect juvenile hormone esterases and various peptide neurotoxins has resulted in recombinant baculoviruses with promise as biological insecticides. These viruses are efficacious in the laboratory, greenhouse and field and dramatically reduce damage caused by insect feeding. The recombinant viruses synergize and are synergized by classical pesticides such as pyrethroids. Since they are highly selective for pest insects, they can be used without disrupting biological control. Because the recombinant virus produces fewer progeny in infected larvae than the wild-type virus, they are rapidly out-competed in the ecosystem. The viruses can be used effectively with crops expressing endotoxins of Bacillus thuringiensis. They can be produced industrially but also by village industries, indicating that they have the potential to deliver sustainable pest control in developing countries. It remains to be seen, however, whether the current generation of recombinant baculoviruses will be competitive with the new generation of synthetic chemical pesticides. Current research clearly indicates, though, that the use of biological vectors of genes for insect control will find a place in agriculture. Baculoviruses will also prove valuable in testing the potential utility of proteins and peptides for insect control.
Animals↗
Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the carboxyl acid group.
Synaptically released Zn2+ ions enter into neurons primarily through voltage-gated Ca2+ channels (VGCC) or N-methyl-d-aspartate (NMDA) receptors, which can mediate pathological neuronal death. We studied the possibility (and underlying mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 microM Zn2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca2+]i through VGCC and selective binding of omega-conotoxin, sensitive to N-type Ca2+ channel. The omega-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+ neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.
Acetylcysteine↗
Hyphae and yeasts of Candida albicans differentially regulate interleukin-12 production by human blood monocytes: inhibitory role of C. albicans germination.
The role of Candida albicans yeast-to-hyphae transition in interleukin-12 (IL-12) production by monocytes was investigated. Germinating C. albicans not only failed to induce IL-12 p70 but also suppressed IL-12 production induced by heat-killed C. albicans. Comparison of the abilities of germinating C. albicans and agerminating mutants to inhibit IL-12 production showed that germination of C. albicans plays a critical role in the inhibition of IL-12 production.
Candida albicans↗
Mesoscopic Kondo effect in an Aharonov-Bohm ring.
An interacting quantum dot inserted in a mesoscopic ring is investigated. A variational ansatz is employed to describe the ground state of the system in the presence of the Aharonov-Bohm flux. It is shown that, for an even number of electrons with the energy level spacing smaller than the Kondo temperature, the persistent current has a value similar to that of a perfect ring with the same radius. On the other hand, for a ring with an odd number of electrons, the persistent current is found to be strongly suppressed compared to that of an ideal ring, which implies the suppression of the Kondo-resonant transmission. Various aspects of the Kondo-assisted persistent current are discussed.
Journal Article↗
Enzymatic and molecular biochemical characterizations of human neutrophil elastases and a cathepsin G-like enzyme.
Human neutrophil elastase (HNE, IEC 3. 4. 21. 37) is a causative factor of inflammatory diseases, including emphysema and rheumatoid arthritis. Enzymatic characterization is important for the development of new drugs involved in the regulation of this enzyme. In this study, we investigated the enzymatic and biochemical properties of five different elastolytic enzymes, with a molecular mass between 24 kDa and 72 kDa. Three elastases, molecular masses of 27, 29, 31 kDa, might be elastase isozymes that have the same NH2-terminal amino acid sequences of Ile-Val-Gly-Gly-Arg-Arg-Ala. The 24-kDa enzyme, which showed the identical NH2-terminal amino acid sequences to elastase, was a degraded fragment of native elastase. The elastolytic activity was conserved at the 6/7 domain of the NH2-terminal region. The inhibitory characteristics of PMSF, DipF were the same as those of native elastases. The 72-kDa molecule, which showed elastolytic activity, might be a trimer formed between native elastases (31 kDa and 29 kDa) and a cathepsin G-like enzyme, which did not show elastolytic activity but enhanced the elastolytic activity of neutrophil elastase. Although this cathepsin G-like enzyme showed weak cathepsin G activity, it has distinguishable NH2-terminal sequences of Ile-Val-Gly-Gly-Ser-Arg-Ala- from those of elastase or cathepsin G. The potentiation of elastolytic activity could be a result of the trimerization of native elastase with a cathepsin G-like enzyme, and was then weakly inhibited by serine protease inhibitors, such as PMSF, DipF. Therefore, we suggest the cathepsin G-like enzyme to be a novel enzyme, which has an important role in the development of inflammation.
Amino Acid Sequence↗
Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal antiinflammatory drugs.
Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.
Anti-Inflammatory Agents, Non-Steroidal↗
Inhibition of homodimerization of poly(ADP-ribose) polymerase by its C-terminal cleavage products produced during apoptosis.
The biochemical role of the C-terminal fragment of poly(ADP-ribose) polymerase (PARP) was investigated in HeLa cells undergoing UV-mediated apoptosis. During the course of apoptosis, the C-terminal cleavage product of PARP interacted with intact PARP and down-regulated PARP activity by blocking the homodimerization of PARP. The basic leucine zipper motif in the auto-modification domain of the C-terminal fragment of PARP represented the site of association, and Leu(405) was critical to the ability of the basic leucine zipper motif to associate with intact PARP. The expression of the C-terminal fragment of PARP stimulated UV-mediated apoptosis. These results suggest that the C-terminal cleavage product of PARP produced during apoptosis blocks the homodimerization of PARP and inhibits the cellular PARP activity. The inhibition of the cellular PARP activity might prevent cellular NAD(+) depletion and stimulate apoptosis by maintaining the basal cellular energy level required for the completion of apoptosis.
Adenosine Diphosphate Ribose↗
Endometrial stripe thickness in tubal and intrauterine pregnancies.
OBJECTIVE: To evaluate endometrial stripe thickness (EST) among patients with tubal pregnancy (TP) and intrauterine pregnancy (IUP). DESIGN: Historical cohort. SETTING: City hospital. PATIENT(S): Ninety-four women suspected to have TP. INTERVENTION(S): Serum betaHCG and sonographic EST measurements. MAIN OUTCOME MEASURE(S): Comparison of age, gestational age (GA), EST, and log beta HCG. RESULT(S): The two groups of women, 65 with TP and 29 with IUP, had similar mean ages (+/-SD) of 28.6 +/- 5.7 and 28.6 +/- 6.1, respectively. The median values of GA in the 2 groups were similar, 46.6 and 44.6 d, respectively. The mean values for EST (+/-SD), adjusted for GA, were significantly different: 9.9 +/- 5.9 mm in the TP group and 12.6 +/- 5.3 mm in the IUP group. The mean values (+/-SD) of log beta HCG in the 2 groups also differed significantly: 6.90 +/- 1.29 and 7.52 +/- 0.97, respectively. No correlation was found between EST and GA or log beta HCG within either group. CONCLUSION(S): The mean EST in women with TP was significantly smaller than in women with IUP. The wide range of EST values and their overlap precludes the utilization of EST as a single feature in the diagnosis of a tubal pregnancy.
Adult↗
Macrophages and cutaneous inflammation.
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Animals↗
Candida albicans and Candida krusei differentially induce human blood mononuclear cell interleukin-12 and gamma interferon production.
Protection against Candida infection involves both innate and acquired immune responses, and cytokines produced by monocytes during the innate response may modify the acquired immune response by T cells. We hypothesized that Candida species which differ in pathogenicity can differentially induce production of immunoregulatory cytokines by human monocytes, which in turn modify T cells for immune responses to Candida. To test this hypothesis, we examined the effects of Candida albicans and Candida krusei on immunoregulatory cytokine production by human monocytes and gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells (PBMC). Purified monocytes were incubated with live or heat-killed strains of C. albicans and C. krusei at the optimal Candida/monocyte ratio of 0.5. Cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. Our data demonstrated that live C. albicans and C. krusei significantly induced interleukin-10 (IL-10), monocyte chemotactic factor 1, IL-1beta, and tumor necrosis factor alpha production by monocytes relative to unstimulated monocytes. In contrast, unlike C. krusei, pathogenic live strains of C. albicans induced no or only a minimal level of IL-12. The expression of IL-12 p40 mRNA levels by reverse transcription-PCR corroborated the IL-12 protein (p70) findings. In human PBMC, human blood monocytes were the major source of both IL-10 and IL-12 production in response to C. albicans and C. krusei. Upon activation of T cells in the presence of Candida-modified monocytes and antigen-presenting cells, IL-12 production by PBMC treated with Candida organisms correlated strongly with the level of IFN-gamma production by T cells. These results indicate that the virulence of C. albicans may be related to its ability to induce the monocytic type II cytokine IL-10, with a selective inhibition of IL-12 production, which may be responsible for the observed lack of T-cell IFN-gamma and may restrain an effective type I immune response to Candida.
Candida↗