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Biomedical subjects

H Kang

Publications and source records attributed to H Kang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Even-odd alternation in mass spectrum of thymine and uracil clusters: evidence of intracluster photodimerization.

Multiphoton ionization of thymine and uracil clusters generated by a supersonic molecular beam gave rise to a remarkable alternation of mass spectral intensities between even- and odd-numbered clusters. Such alternation was observed in clusters of up to 30 molecules. Excitation to the two lowest electronically excited states seemed to be a strong prerequisite. In view of the well known photodimerization reaction of thymine and uracil in the bulk phase, it is proposed that such alternation in the mass spectral intensity resulted from formation of photodimer units within the cluster on intense UV irradiation. Several analogues of thymine with no known propensity for photodimerization in the bulk phase did not exhibit any sign of such alternation in the cluster mass spectrum. The intrinsic UV window for photodimerization, and hence photoinduced mammalian mutagenesis, was estimated to be approximately 210-280 nm, significantly narrower than the previously reported bulk values of 150-300 nm.

DNA↗
PubMed2001

Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit.

Calmodulin-dependent protein kinase IV (CaMKIV) is a key mediator of Ca(2+)-induced gene expression. In this study, CaMKIV was found to directly associate with and phosphorylate the nuclear factor-kappaB (NFkappaB) component p65 both in vitro and in vivo. The phosphorylation of p65 by CaMKIV resulted in recruitment of transcription coactivator cAMP-response element-binding protein-binding protein and concomitant release of corepressor silencing mediator for retinoid and thyroid hormone receptors, as demonstrated by the glutathione S-transferase pull down and mammalian two hybrid assays. In addition, cotransfection of CaMKIV resulted in cytosolic translocation of the silencing mediator for retinoid and thyroid hormone receptors. Consistent with these results, cotransfected CaMKIV dramatically stimulated the NFkappaB transactivation in mammalian cells. From these results, NFkappaB is suggested to be a novel downstream effector molecule of CaMKIV.

Animals↗
PubMed2001

Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability.

Microsatellite instability (MSI) and frameshift mutations in genes containing nucleotide repeats have been reported in a subset of colorectal and gastric carcinomas. This study describes the analysis of MSI-positive colorectal (39 cases) and gastric carcinomas (36 cases) for the presence of frameshift mutations of the six genes known to be involved in DNA repair and containing mononucleotide repeats in their coding region. Our mutational study of the 75 MSI-positive tumors revealed frequent mutations in hRAD50 (23 cases, 31%), BLM (16 cases, 21%), and hMSH6 (16 cases, 21%); rare mutations in BRCA1 (1 case, 1%) and ATM (3 cases, 4%); and no mutation in NBS1. In contrast, no frameshift mutation was found in 60 MSI-negative colorectal and gastric carcinomas. The mutation of hRAD50, a gene that is involved in the response to cellular DNA damage and forms a complex with hMRE11 and NBS1, has not been reported previously. Our results suggest that frameshift mutations of hRAD50, BLM, and hMSH6 are selected and play a role in the tumorigenesis of colorectal and gastric carcinomas with MSI. The MSI targeting of the hRAD50 and BLM genes represents an additional link between MSI and DNA repair because alteration of these genes could accelerate defective DNA repair.

Acid Anhydride Hydrolases↗
PubMed2001

Pregnancy outcomes among U.S. Gulf War veterans: a population-based survey of 30,000 veterans.

PURPOSE: We evaluated an association between veterans' Gulf War service and reported adverse pregnancy outcomes. METHODS: We conducted a health survey in which selected reproductive outcomes of a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared to those of 15,000 non-Gulf veteran controls. RESULTS: Male Gulf veterans, compared with their non-Gulf veteran controls, reported a significantly higher rate of miscarriage (odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.32-1.99). Female Gulf veterans also reported more miscarriages than their respective controls, although their excess was not statistically significant (OR= 1.35; CI = 0.97-1.89). Both men and women deployed to the Gulf theater reported significant excesses of birth defects among their liveborn infants. These excess rates also extended to the subset of "moderate to severe" birth defects [males: OR= 1.78 (CI = 1.19-2.66); females: OR = 2.80 (CI = 1.26-6.25)]. No statistically significant differences by deployment status were found among men or women for stillbirths, pre-term deliveries or infant mortality. CONCLUSION: The risk of veterans reporting birth defects among their children was significantly associated with veteran's military service in the Gulf War. This observation needs to be confirmed by a review of medical records to rule out possible reporting bias.

Abortion, Spontaneous↗
PubMed2001

Requirement of non-T cells that produce gamma interferon for prevention of reactivation of Toxoplasma gondii infection in the brain.

We examined the mechanism of resistance against reactivation of infection with Toxoplasma gondii in the brain. BALB/c-background gamma interferon (IFN-gamma)-knockout (IFN-gamma(-/-)) and control mice were infected and treated with sulfadiazine beginning 4 days after infection for 3 weeks. After discontinuation of treatment, IFN-gamma(-/-) mice succumbed to toxoplasmic encephalitis (TE) and died, whereas control animals did not develop TE and survived. Adoptive transfer of immune spleen cells from infected control mice did not prevent development of TE or mortality in the IFN-gamma(-/-) mice. To examine whether the failure of the cell transfer to protect against TE is unique to IFN-gamma(-/-) mice, athymic nude and SCID mice that lack T cells were infected and injected with the immune spleen or T cells in the same manner as IFN-gamma(-/-) mice. Whereas control nude and SCID mice that had not received the immune cells developed severe TE and died after discontinuation of sulfadiazine, those that had received the cells did not develop TE and survived. Before cell transfer, IFN-gamma mRNA was detected in brains of infected nude and SCID but not in brains of IFN-gamma(-/-) mice. IFN-gamma mRNA was also detected in brains of infected SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibody, and such animals did not develop TE after receiving immune T cells. Thus, IFN-gamma production by non-T cells, in addition to T cells, is required for prevention of reactivation of T. gondii infection in the brain. The IFN-gamma-producing non-T cells do not appear to be NK cells.

Adoptive Transfer↗
PubMed2001

Detection of antifungal activity in Belamcanda chinensis by a single-cell bioassay method and isolation of its active compound, tectorigenin.

The antifungal activity of Belamcanda chinensis was evaluated by a single-cell bioassay method. An active fraction was separated by silica gel column chromatography and reverse-phase HPLC. The isolated compound was found to be identical to tectorigenin (5,7-dihydroxy-3-(4-hydroxy phenyl)-6-methoxy-4H-1-benzopyran-4-one) which has formerly appeared in the literature without any remarks on its antimicrobial activity. Antimicrobial activity was investigated against 17 strains of fungi and 6 strains of bacteria. This compound showed marked antifungal activity against dermatophytes of the genera Trichophyton, the minimum inhibitory concentration (MIC) being in the range of 3.12-6.25 mg/ml.

Antifungal Agents↗
PubMed2001

Local strategic control of information in visual word recognition.

In the present studies, we examined strategic flexibility in the use of lexical and sublexical information in Korean word recognition. Korean readers show a large frequency effect for words printed in the alphabetic Hangul script only if these words are embedded in a list consisting largely of logographic (Hanza) words. In the first experiment, high- and low- frequency Hangul words were preceded by Hangul or Hanza words. Frequency effects were eliminated when a Hangul target word was preceded by two Hangul words, even when the overall proportion of Hanza words in the list was large. In the second experiment, one group saw each stimulus preceded by a cue indicating which script would be seen on that trial. Frequency effects for Hangul targets were absent under this condition, but were present when subjects were not so cued. These results indicate that Korean readers are able to control their use of lexical and sublexical information over a small number of stimuli or even trial by trial.

Adult↗
PubMed2001

Genome scan of idiopathic generalized epilepsy: evidence for major susceptibility gene and modifying genes influencing the seizure type.

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent-onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two-point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non-JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families.

Adolescent↗
PubMed2000

Cytoprotective effect of arginine deiminase on taxol-induced apoptosis in DU145 human prostate cancer cells.

We purified and partially sequenced a cytostatic protein from the ASC-17D Sertoli cell-conditioned media (rSCCM) showing a molecular weight of 90 kDa with homodimeric composition. N-terminal amino acid analysis revealed that the protein was homologous to the arginine deiminase (ADI) of Mycoplasma arginini. We found ADI enzyme activity in rSCCM and the abolishment of the growth inhibitory effect by the supplement of L-arginine. Thus, we confirmed that the cytostatic activity in rSCCM was due to the depletion of extracellular L-arginine by ADI. Apparent increase of cell death or DNA fragmentation was not observed in DU145 cells cultured in the presence of ADI. Incubation of DU145 cancer cells with taxol resulted in a marked DNA fragmentation, whereas pretreatment with ADI or cycloheximide protected the cells from taxol-induced apoptosis. Preincubation of the cells with ADI inhibited S35-methionine incorporation into protein synthesis in a dose dependent manner. These data suggest that ADI-induced arginine depletion may inhibit protein synthesis, and result in the protection of apoptotic cell death that requires new protein synthesis.

Amino Acid Sequence↗
PubMed2000

Molecular cloning, expression, and functional analysis of a cis-prenyltransferase from Arabidopsis thaliana. Implications in rubber biosynthesis.

cis-Prenyltransferase catalyzes the sequential condensation of isopentenyl diphosphate with allylic diphosphate to synthesize polyprenyl diphosphates that play vital roles in cellular activity. Despite potential significance of cis-prenyltransferase in plant growth and development, no gene of the enzyme has been cloned from higher plants. Using sequence information of the conserved region of cis-prenyltransferase cloned recently from Escherichia coli, Micrococcus luteus, and yeast, we have isolated and characterized the first plant cis-prenyltransferase from Arabidopsis thaliana. Sequence analysis revealed that the protein is highly homologous in several conserved regions to cis-prenyltransferases from M. luteus, E. coli, and yeast. In vitro analyses using the recombinant protein overexpressed in E. coli revealed that the enzyme catalyzed the formation of polyprenyl diphosphates ranging in carbon number from 100 to 130 with a predominance of C(120). The enzyme exhibited a higher affinity for farnesyl diphosphate than for geranylgeranyl diphosphate, with the K(m) values being 0.13 and 3.62 micrometer, respectively, but a lower affinity for isopentenyl diphosphate, with a K(m) value of 23 micrometer. In vitro rubber biosynthesis analysis indicated that the Arabidopsis cis-prenyltransferase itself could not catalyze the formation of higher molecular weight polyprenyl diphosphates similar to natural rubber. A reverse transcriptase-polymerase chain reaction analysis showed that the gene was expressed at low levels in Arabidopsis plant, in which expression of the cis-prenyltransferase in leaf and root was higher than that in stem, flower, and silique. These results indicate the tissue-specific expression of cis-prenyltransferase and suggest a potential role and significance of the enzyme in the polyisoprenoid biosynthesis in plants.

Amino Acid Sequence↗
PubMed2000

SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55.

Src-homology 3 (SH3) domains recognize PXXP core motif preceded or followed by positively charged residue(s). Whether SH3 domains recognize motifs other than proline-based sequences is unclear. In this study, we report SH3 domain binding to a novel proline-independent motif in immune cell adaptor SKAP55, which is comprised of two N-terminal lysine and arginine residues followed by two tyrosines (i.e. RKxxYxxY). Domains capable of binding to class I proline motifs bound to the motif, while the class II domains failed to bind. Peptide precipitation, alanine scanning and in vivo co-expression studies demonstrated a requirement for the arginine, lysine and tandem tyrosines of the motif. Two-dimensional NMR analysis of the peptide bound FYN-SH3 domain showed overlap with the binding site of a proline-rich peptide on the charged surface of the SH3 domain, while resonance signals for other residues (W119, W120, Y137) were not perturbed by the RKGDYASY based peptide. Expression of the RKGDYASY peptide potently inhibited TcRzeta/CD3-mediated NF-AT transcription in T cells. Our findings extend the repertoire of SH3 domain binding motifs to include a tyrosine-based motif and demonstrate a regulatory role for this motif in receptor signaling.

Amino Acids, Diamino↗
PubMed2000

IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii.

The role for IL-10 in the immunopathogenesis of acute toxoplasmosis following peroral infection was examined in both genetically susceptible C57BL/6 and resistant BALB/c mice. C57BL/6-background IL-10-targeted mutant (IL-10-/-) mice all died in 2 wk after infection with 20 cysts of the ME49 strain, whereas only 20% of control mice succumbed. Histological studies revealed necrosis in the small and large intestines and livers of infected IL-10-/- mice. The necrosis in the small intestine was the most severe pathologic response and was not observed in control mice. Treatment of infected IL-10-/- mice with either anti-CD4 or anti-IFN-gamma mAb prevented intestinal pathology and significantly prolonged time to death. Treatment of these animals with anti-IL-12 mAb also prevented the pathology. Significantly greater amounts of IFN-gamma mRNA were detected in the lamina propria lymphocytes obtained from the small intestine of infected IL-10-/- mice than those from infected control mice. In common with C57BL/6-background IL-10-/- mice, BALB/c-background IL-10-/- mice all died developing intestinal pathology after infection. Control BALB/c mice all survived even after infection with 100 cysts and did not develop the intestinal lesions. Treatment with anti-IFN-gamma mAb prevented the pathology and prolonged time to death of the infected IL-10-/- mice. These results strongly suggest that IL-10 plays a critical role in down-regulating IFN-gamma production in the small intestine following sublethal peroral infection with Toxoplasma gondii and that this down-regulatory effect of IL-10 is required for prevention of development of IFN-gamma-mediated intestinal pathology and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice.

Administration, Oral↗
PubMed2000

Intracellular Ca(2+) signaling is required for neurotrophin-induced potentiation in the adult rat hippocampus.

Recent studies have demonstrated the importance of neurotrophin function in adult synaptic plasticity. In an effort to characterize the intracellular signaling pathways that couple Trk receptor activation to the final physiological effects of neurotrophins, we have examined the role of intracellular calcium rises in neurotrophin-induced synaptic enhancement in hippocampal slices. Using pharmacological blockers to two different calcium ion (Ca(2+)) sources, voltage-gated Ca(2+) channels and intracellular Ca(2+) stores, we show that the potentiating effects of neurotrophins in hippocampal slices are mediated by intracellular Ca(2+) signaling. Although basal synaptic transmission between hippocampal CA3 and CA1 neurons was not affected by nifedipine or thapsigargin, both drugs significantly attenuated brain-derived neurotrophic factor or neurotrophin-3-induced synaptic enhancement. The pharmacological blockade of Ca(2+) signaling is effective only during the initial period of neurotrophin-induced potentiation. These data suggest that the minimal requirements for inducing potentiation by neurotrophins involve a transient increase in intracellular Ca(2+) concentration, via voltage-gated Ca(2+) channels and/or intracellular Ca(2+) stores.

Animals↗
PubMed2000

Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase.

The role of B cells in resistance against Toxoplasma gondii was studied using B cell-deficient (muMT) mice. Following peroral infection with 10 cysts of the ME49 strain, all muMT mice survived the acute stage of the infection but died between 3 and 4 wk after infection. In contrast, all control mice were alive at 8 wk after infection. At the stage during which muMT animals succumbed to the infection, parasite replication and pathology were most evident in their brains; small numbers of tachyzoites were also detectable in their lungs. Significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of muMT than in control mice. Large areas of necrosis associated with numerous tachyzoites were observed only in brains of muMT mice. Anti-T. gondii IgG Abs were detected only in sera of control mice, whereas similar levels of IFN-gamma were detected in sera of both strains of mice. Amounts of mRNA for IFN-gamma, IL-10, and inducible NO synthase in the brain did not differ between infected muMT and control mice. Expression of mRNA for TNF-alpha was increased in brains of muMT mice. Administration of polyclonal rabbit anti-T. gondii IgG Ab prevented early mortality and pathology associated with tachyzoites in the brain in the infected muMT mice. These results indicate that B cells play an important role, most likely through their production of specific Abs, in resistance to persistent active (tachyzoite) infection with T. gondii in mice, especially in the brain and lung.

Animals↗
PubMed2000

No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q.

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a complex mode of inheritance. Several studies found evidence for a locus involved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al. [1997] reported evidence of linkage in JME to chromosome 15q14 assuming a recessive mode of inheritance with 50% penetrance and 65% linked families. The area on chromosome 15q14 encompasses the location of the gene for the alpha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hypothesis that there are two interacting loci, one on chromosome 6 and on chromosome 15 or that there is genetic heterogeneity in JME. In an independent dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage. Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplotype on chromosome 6. The lodscore for these same families on chromosome 15q14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alpha =.25. Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14. Our results indicate that this possible gene on chromosome 15 plays at most a minor role in our JME families. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:49-52, 2000.

Chromosome Mapping↗
PubMed2000

Synthesis of cefminox by cell-free extracts of Streptomyces clavuligerus.

In vitro synthesis of cefminox by cell-free extracts of Streptomyces clavuligerus was investigated using alpha-ketoglutarate, L-ascorbic acid, FeSO(4), S-adenosyl-L-methionine, and 7alpha-demethoxycefminox as the substrates. The formation of cefminox was detected both by a biological assay with Proteus vulgaris GN 76/C-1 and by high performance liquid chromatography. Although the conversion rate of 7alpha-demethoxycefminox to cefminox was observed to be quite low, it still demonstrated the potential for an enzymatic process to replace the chemical steps which are currently in use for the production of cefminox.

Cell Fractionation↗
PubMed2000

A fifty year mortality follow-up study of veterans exposed to low level chemical warfare agent, mustard gGas.

PURPOSE: To determine if there is an increased risk of any cause specific mortality associated with low level mustard gas exposure among World War II Navy veterans. METHODS: A retrospective mortality follow-up study was conducted comparing the mortality of World War II Navy veterans who received low-level non-lethal exposures of mustard gas to that of World War II Navy veterans who were not exposed. This study identified 1545 Navy recruits stationed at Bainbridge, Maryland, between 1944-1945, who voluntarily participated in mustard gas chamber tests. These veterans were exposed to mustard gas while wearing protective clothing and masks. Control veterans consisted of 2663 Navy veterans who served at the same location and time as the exposed, but did not participate in chamber tests. Cause specific mortality risks associated with mustard gas exposure and level of mustard gas exposure were examined using adjusted and unadjusted relative risk estimates. RESULTS: There was no excess of any cause specific mortality associated with varying levels of mustard gas exposures among Navy veterans subject to the chamber tests. CONCLUSIONS: The levels of mustard gas exposures experienced by World War II veterans, which were sufficient to cause skin reactions (erythema, vesicles, and ulceration), were not associated with any increased risk of cause specific mortality.

Adult↗