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Biomedical subjects

J H Chung

Publications and source records attributed to J H Chung.

At least 73 records · Page 4Linked to original sources

Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases.

BACKGROUND: Medullary thyroid carcinoma (MTC) is characterized by a high concentration of serum calcitonin. Routine measurement of serum calcitonin concentration has been advocated for detection of MTC among patients with nodular thyroid diseases. However, a minimal to moderate increase of serum calcitonin concentration has been frequently observed in diseases other than MTC. Fine-needle aspiration cytology (FNAC) is not a reliable method for detection of MTC. Therefore, we evaluated the usefulness of routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases, and studied the validity of pentagastrin stimulation test and FNAC in these patients. SUBJECTS AND METHODS: We performed routine measurement of serum calcitonin concentrations in 1,448 patients (male, 285, female, 1,163) with nodular thyroid diseases. The average age was 46 years (range, 14-86 years). Initial examination included thyroid examination, thyroid scan or ultrasonography, measurements of serum free triiodothyronine) (T3), free thyroxine (T4), thyrotropin (TSH) levels, and antithyroid autoantibodies. FNAC was performed in all patients who had palpable or visible thyroid nodule by ultrasonography, and pentagastrin stimulation test was performed in 39 patients who consented. Serum calcitonin concentration was measured with a two-site immunoradiometric assay using commercial kits. We also measured the serum calcitonin concentration in 407 healthy subjects without thyroid or nonthyroid diseases. RESULTS: Serum calcitonin concentration was 10 pg/mL or less in 403 normal subjects (99.0 percentile), and 11-13 pg/mL in the remaining 4 subjects. We found that 56 (3.87%) of 1,448 patients with nodular thyroid diseases had serum calcitonin level above 10 pg/mL. Ten patients (0.69%) with histologically confirmed MTC were detected by the routine measurement of serum calcitonin. The prevalence of MTC was 5.2% in 194 patients with thyroid carcinoma. Five of 10 patients with MTC had basal serum calcitonin level above 100 pg/mL. The remaining 5 patients had minimal or moderate elevation of basal serum calcitonin (range, 12-86 pg/mL). Serum calcitonin concentration increased to more than 100 pg/mL by pentagastrin in all patients with MTC (2.4- to 37.7-fold increase). FNAC suggested MTC in only 2 patients (22.2%), and failed to diagnose MTC in 7 patients. FNAC was not performed in 1 patient with MTC, because he had no visible mass by ultrasonography. CONCLUSION: These results suggested that routine measurement of serum calcitonin is useful in the early detection of MTC among patients with nodular thyroid diseases. Pentagastrin stimulation test may also be a reliable way for evaluating thyroid nodular patients with mild or moderate elevation of serum calcitonin concentrations. However, FNAC was not sensitive in detecting MTC. We recommend routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases.

Adolescent↗

Association of quinone-induced platelet anti-aggregation with cytotoxicity.

Various anti-platelet drugs, including quinones, are being investigated as potential treatments for cardiovascular disease because of their ability to prevent excessive platelet aggregation. In the present investigation 3 naphthoquinones (2,3-dimethoxy-1,4-naphthoquinone [DMNQ], menadione, and 1,4-naphthoquinone [4-NQ]) were compared for their abilities to inhibit platelet aggregation, deplete glutathione (GSH) and protein thiols, and cause cytotoxicity. Platelet-rich plasma, isolated from Sprague-Dawley rats, was used for all experiments. The relative potency of the 3 quinones to inhibit platelet aggregation, deplete intracellular GSH and protein thiols, and cause cytotoxicity was 1,4-NQ > menadione >> DMNQ. Experiments using 2 thiol-modifying agents, dithiothreitol (DTT) and 1-chloro-2,4-dintrobenzene (CDNB), confirmed the key roles for GSH in quinone-induced platelet anti-aggregation and for protein thiols in quinone-induced cytotoxicity. Furthermore, the anti-aggregative effects of a group of 12 additional quinone derivatives were positively correlated with their ability to cause platelet cytotoxicity. Quinones that had a weak anti-aggregative effect did not induce cytotoxicity (measured as LDH leakage), whereas quinones that had a potent anti-aggregative effect resulted in significant LDH leakage (84-96%). In one instance, however, p-chloranil demonstrated a potent anti-aggregative effect, but did not induce significant LDH leakage. This can be explained by the inability of p-chloranil to deplete protein thiols, even though intracellular GSH levels decreased rapidly. These results suggest that quinones that deplete GSH in platelets demonstrate a marked anti-aggregative effect. If this anti-aggregative effect is subsequently followed by depletion of protein thiols, cytotoxicity results.

Animals↗

Androgen receptor gene mutation associated with complete androgen insensitivity syndrome and Sertoli cell adenoma.

We report a case of Sertoli cell adenoma in complete androgen insensitivity syndrome (CAIS) in a 22-year-old woman. Polymerase chain reaction-single strand conformation polymorphism and DNA sequencing revealed a single nucleotide substitution on exon 7 of the human androgen receptor (hAR) gene, resulting in a change of CGA (arginine) to CAA (glutamine) in codon 831.

Adenoma↗

Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase.

We have previously reported that green tea catechins (GTC) display a potent antithrombotic activity, which might be due to antiplatelet rather than anticoagulation effects. In the current study, we investigated the antiplatelet mechanism of GTC. We tested the effects of GTC on the aggregation of human platelets and on the binding of fluorescein isothiocyanate-conjugated fibrinogen to human platelet glycoprotein (GP) IIb/IIIa. GTC inhibited the collagen-, thrombin-, adenosine diphosphate (ADP)-, and calcium ionophore A23187-induced aggregation of washed human platelets, with 50% inhibitory concentration values of 0.64, 0.52, 0.63, and 0.45 mg/ml, respectively. GTC significantly inhibited fibrinogen binding to human platelet surface GPIIb/IIIa complex but failed to inhibit binding to purified GPIIb/IIIa complex. These results indicate that the antiplatelet activity of GTC may be due to inhibition of an intracellular pathway preceding GPIIb/IIIa complex exposure. We also investigated the effects of GTC on intracellular calcium levels, which are critical in determining the activation status of platelets and on induction of platelet aggregation by thapsigargin, which is a selective inhibitor of the Ca(2+)-ATPase pump. Pretreatment of human platelets with GTC significantly inhibited the rise in intracellular Ca(2+) concentration induced by thrombin treatment, and GTC significantly inhibited the thapsigargin-induced platelet aggregation. We also examined the effect of GTC on the second messenger, inositol 1,4,5-triphosphate (IP(3)). GTC significantly inhibited the phosphoinositide breakdown induced by thrombin. Taken together, these observations suggest that the antiplatelet activity of GTC is be mediated by inhibition of cytoplasmic calcium increase, which leads to the inhibition of fibrinogen-GPIIb/IIIa binding via the activation of Ca(2+)-ATPase and inhibition of IP(3) formation.

Blood Platelets↗

The evolution of agriculture in beetles (Curculionidae: Scolytinae and Platypodinae).

Beetles in the weevil subfamilies Scolytinae and Platypodinae are unusual in that they burrow as adults inside trees for feeding and oviposition. Some of these beetles are known as ambrosia beetles for their obligate mutualisms with asexual fungi--known as ambrosia fungi--that are derived from plant pathogens in the ascomycete group known as the ophiostomatoid fungi. Other beetles in these subfamilies are known as bark beetles and are associated with free-living, pathogenic ophiostomatoid fungi that facilitate beetle attack of phloem of trees with resin defenses. Using DNA sequences from six genes, including both copies of the nuclear gene encoding enolase, we performed a molecular phylogenetic study of bark and ambrosia beetles across these two subfamilies to establish the rate and direction of changes in life histories and their consequences for diversification. The ambrosia beetle habits have evolved repeatedly and are unreversed. The subfamily Platypodinae is derived from within the Scolytinae, near the tribe Scolytini. Comparison of the molecular branch lengths of ambrosia beetles and ambrosia fungi reveals a strong correlation, which a fungal molecular clock suggests spans 60 to 21 million years. Bark beetles have shifted from ancestral association with conifers to angiosperms and back again several times. Each shift to angiosperms is associated with elevated diversity, whereas the reverse shifts to conifers are associated with lowered diversity. The unusual habit of adult burrowing likely facilitated the diversification of these beetle-fungus associations, enabling them to use the biomass-rich resource that trees represent and set the stage for at least one origin of eusociality.

Agriculture↗

Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica.

OBJECTIVES: Patients with paralysis periodica paramyotonica exhibit a clinical syndrome with characteristics of both hyperkalaemic periodic paralysis and paramyotonia congenita. In several types of periodic paralysis associated with hyperkalaemia, mutations in the skeletal muscle sodium channel (SCN4A) gene have been previously reported. Phenotypic variations of mutations in SCN4A, however, have not been described yet. The present study aimed to evaluate genetic variations in a family with clinical and electrophysiological characteristics of paralysis periodica paramyotonia. METHODS: Seven members of a family affected with symptoms of paralysis periodica paramyotonia were studied by electrophysiological and genetic analyses. There were increased serum potassium concentrations in four members during paralytic attacks induced by hyperkalaemic periodic paralysis provocation tests. Short exercise tests before and after cold immersion were carried out in four patients to distinguish electrophysiological characteristics of hyperkalaemic periodic paralysis and paramyotonia. Sequencing analyses of SCN4A were performed on one patient and a normal control to identify polymorphisms. Restriction fragment length polymorphism (RFLP) analysis was then performed at the identified polymorphic sites. RESULTS: Electrophysiological studies showed both exercise sensitivity and temperature sensitivity. Compound motor action potential (CMAP) amplitudes were decreased (7.3%-28.6%) after short exercise tests. The CMAP amplitudes were even more severely decreased (21.7%-56.5%) in short exercise tests after cold exposure. Three polymorphic sites, Gln371Glu, Thr704Met, and Aspl376Asn were identified in SCN4A. RFLP analyses showed that all affected patients carried the Thr704Met mutation, whereas unaffected family members and a normal control did not. CONCLUSION: Phenotypic variation of the Thr704Met mutation, which was previously reported in patients with hyperkalaemic periodic paralysis, is described in a family affected with paralysis periodica paramyotonia.

Adult↗

Protective effects of puerariaeflos against ethanol-induced apoptosis on human neuroblastoma cell line SK-N-MC.

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.

Alcohol Deterrents↗

Auricular acupuncture increases cell proliferation in the dentate gyrus of Sprague-Dawley rats.

In a previous study, we have reported that acupuncture increases cell proliferation in the dentate gyrus after transient global ischemia in gerbils. In the present study, the effect of auricular acupuncture (AA) on dentate cell proliferation was examined in appropriately fed and food-deprived adult Sprague-Dawley (S-D) rats. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry revealed a significant increase in cell birth in the dentate gyrus of both groups after AA treatment. In addition, the effect of AA on cell proliferation in the dentate gyrus was more profound in the food-supplied group. These findings demonstrate that AA enhances cell proliferation in the dentate gyrus of adult rats.

Acupuncture Points↗

Cutaneous photodamage in Koreans: influence of sex, sun exposure, smoking, and skin color.

BACKGROUND: Severe wrinkles and pigmentary changes of the exposed skin indicate substantial damage due to UV radiation. Many investigators believe that the principal manifestation of photodamage in Asians is pigmentary change rather than wrinkles. However, to our knowledge, no well-designed study has investigated the characteristics of cutaneous photodamage in Asian skin. OBJECTIVE: To access the severity of wrinkles and dyspigmentation in Koreans exposed to sun and who smoked. METHODS: We developed new photographic scales for grading wrinkles and dyspigmentation in 407 Koreans to assess the severity of the wrinkles and dyspigmentation. We interviewed subjects to determine cumulative sun exposure and smoking history, and measured the skin color of individual subjects. RESULTS: Our photographic scales provided a reliable evaluation of photodamage severity in Koreans. The pattern of wrinkling in both sexes is similar, but women tended to have more severe wrinkles (prevalence odds ratio, 3.7). However, the pattern of dyspigmentation differed between the sexes. Seborrheic keratosis is the major pigmentary lesion in men, whereas hyperpigmented macules are the prominent features in women. Cigarette smoking is an independent risk factor for wrinkles, but not for dyspigmentation, in Koreans, and causes additive detrimental effects to wrinkles induced by aging and sun exposure. The constitutive skin color did not show any correlation with wrinkles or dyspigmentation. However, facultative pigmentation (sun exposure index) may reflect lifetime sun exposure, and it shows a good correlation with wrinkles in Koreans. CONCLUSION: Wrinkling is a major feature of photoaging in Koreans, as are pigmentary changes; smoking, sun exposure, and female sex are independent risk factors for wrinkles.

Adult↗

A novel epigenetic control operating on Vme1+ locus leads to variegated monoallelic expression.

Vme1, located near an imprinted region containing Peg1/Mest, Copg2, and Mit1/Lb9 on mouse chromosome 6, was identified and characterized to be under novel epigenetic regulations mediating nonimprinted monoallelic expression. The gene was transcribed independently from at least four promoters and alternatively spliced. Variable expression of the gene was found among individuals and was not affected by genetic backgrounds, in contrast to a relatively consistent expression of unlinked Peg3 under different genetic backgrounds. Monoallelic expression of the gene was confirmed in several tissues of hybrid F1s between a domesticus and a molossinus subspecies. The nature of monoallelic expression was different from those of its neighboring genes with respect to the allelic preference for the expression. The observed variable expression and monoallelic expression propose a mechanism that operates to variegate the Vme1 transcription acting asynchronously on parental alleles. In addition, we observed that some biallelically expressed tissues exhibited allele-specific splicing such that expression from one parental allele yields elongated splice variants, whereas the other allele is spliced into a short version. This unusual finding suggests that an epigenotype of the promoter can determine the splicing fate of the transcript.

Alleles↗

An intronless gene encoding a poly(A) polymerase is specifically expressed in testis.

Previous work demonstrated that a single pre-mRNA could generate multiple forms of mammalian poly(A) polymerase mRNAs by alternative splicing or alternative polyadenylation. A cDNA encoding a testis-specific poly(A) polymerase was isolated in this study. The transcription level of Papt in testis of a 2 weeks old mouse was much lower than that of the general poly(A) polymerase gene, Pap. However, the transcription ratio of Papt to Pap was reversed in testis of a 4 weeks old mouse. Transient expression analysis showed that GFP-Papt fusion protein is present both in the nucleus and cytoplasm of HeLa cells. These results suggest that Papt is involved in polyadenylation of transcripts expressed during spermatogenesis.

Alternative Splicing↗

Duplication of genes encoding non-clathrin coat protein gamma-COP in vertebrate, insect and plant evolution.

Coatomer is a major component of COPI vesicles and consists of seven subunits. The gamma-COP subunit of the coatomer is believed to mediate the binding to the cytoplasmic dilysine motifs of membrane proteins. We characterized cDNAs for Copg genes encoding gamma-COP from mouse, zebrafish, Drosophila melanogaster and Bombyx mori. Two copies of Copg genes are present in vertebrates and in B. mori. Phylogenetic analysis revealed that two paralogous genes had been derived from a single ancestral gene by duplication independently in vertebrates and in B. mori. Mouse Copg1 showed ubiquitous expression with the highest level in testis. Zebrafish copg2 was biallelically expressed in hybrid larvae in contrast to its mammalian ortholog expressed in a parent-of-origin-specific manner. A phylogenetic analysis with partial plant cDNA sequences suggested that copg gene was also duplicated in the grass family (Poaceae).

Amino Acid Sequence↗

Differential expression of nicotinamide adenine dinucleotide phosphate-diaphorase in hypothalamic areas of obese Zucker rats.

Several studies have suggested that the activity of nitric oxide synthase (NOS) may be involved in the regulation of food intake in the genetically obese Zucker rats. In the present study, we investigated the expression of NOS in various hypothalamic regions of obese and lean Zucker rats using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Obese Zucker rats showed significantly lower staining intensities of NADPH-diaphorase-positive neurons in the paraventricular nucleus (PVN), lateral hypothalamic area (LHA) and ventromedial hypothalamic nucleus (VMH) than lean Zucker rats did. The differences in staining intensities between obese and lean Zucker rats were large in both the PVN and LHA, but such differences were relatively small in the VMH.

Animals↗

Affinity maturation of natural antibody using a chain shuffling technique and the expression of recombinant antibodies in Escherichia coli.

The affinity of natural antibody (Ka = 8 x 10(6) M(-1)) recognizing preS1 of hepatitis B virus (HBV) was improved by replacing the heavy (H) chain gene with repertoires of VH genes, obtained from two nonimmunized donors. Two separate clones, 1C2 and 1E4, showed affinities of 2.3 x 10(7) and 5.2 x 10(7) M(-1), which were increased by factors of 2.8 and 6.5, respectively, compared to the parental clone. Recombinant scFvs (rscFvs) were expressed as fusion protein with minor coat protein, pIII, and secreted into medium after 3 h of induction with 1 mM IPTG. The expression level of functional rscFv capable of binding to preS1 reached a peak after 6-10 h (1C2) and 8-10 h (1E4) of IPTG induction, and afterwards decreased gradually. In order to achieve the overexpression of rscFv in E. coli, gene encoding scFv of 1C2 or 1E4 was inserted into pRSET vector. RscFvs were overexpressed as cytoplasmic inclusion bodies in E. coli BL 21 strain, which were denatured and carefully refolded using a continuous dialysis system. The purified recombinant fragments were pure when analyzed by SDS-PAGE and had the predicted size of 34 kDa. Clone 1E4 used the heavy chain gene belonging to family VII and subgroup III. Chain shuffling offers an alternative to random point mutation for affinity maturation of human antibody in vitro.

Amino Acid Sequence↗

De novo methylation at intronic CpG islands of Igf2r is associated with decreased expression of antisense RNA in aged mice.

Changes in cytosine methylation status of several genes have been implicated in the aging process. We have examined methylation status of differentially methylated regions of insulin-like growth factor II receptor gene during mouse senescence. Bisulfite-aided genomic sequencing revealed that methylated CpG residues were extended beyond the 3' boundary of de novo methylation sequence of DMR2 in aged mice. Furthermore, the de novo methylation of DMR2 in aged mice was associated with decreased expression of antisense transcript which recruits DMR2 as a promoter. On the contrary, methylation status of DMR1 was well-maintained during senescence. Accordingly, no significant changes in expression levels of sense transcripts were observed during the course of mouse aging.

Aging↗

Mit1/Lb9 and Copg2, new members of mouse imprinted genes closely linked to Peg1/Mest(1).

Two mouse genes, Mit1/Lb9 and Copg2, linked to Peg1/Mest on mouse chromosome 6, were identified to be imprinted maternally and paternally, respectively. Mit1/Lb9 encoding untranslated transcripts resides within the intron 20 of Copg2. The gene is maternally imprinted in adult mouse brain, partially imprinted in other tissues. Copg240 kb genomic region, being expressed ubiquitously in mouse tissues with a partial imprinting pattern in embryos, neonates, and adult brain in contrast to maternally imprinted human COPG2. In addition, we identified an antisense transcript of Copg2, Copg2AS, which overlaps 3'-UTRs of Copg2 and Peg1/Mest. The Copg2AS transcript is maternally imprinted in embryos, neonates, and adult tissues.

Amino Acid Sequence↗

Characterization of JDP genes, an evolutionarily conserved J domain-only protein family, from human and moths.

We characterized evolutionarily conserved J domain containing protein (JDP) genes from human, Bombyx mori, and Manduca sexta. Each of the JDP proteins contains a J domain at its N-terminus and a highly conserved C-terminal domain. Southern blot analysis revealed that the human JDP1 gene is present as a single copy in the human genome. Expression was higher in brain, heart, and testis than in kidney or stomach. Human JDP1 was mapped in silico to chromosome 10q21.1, which exhibits a conserved synteny with the central region of mouse chromosome 10. Drosophila jdp is located at 99F4-99F11 on the right arm of the third chromosome.

Amino Acid Sequence↗

Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) binds to, and inhibits transactivation of, CREB-binding protein.

Kaposi's sarcoma-associated herpesvirus (KSHV) contains many cellular homologue genes. The K9 open reading frame (ORF) of KSHV encodes a virus-encoded interferon regulatory factor (vIRF) which functions as a repressor for cellular interferon-mediated signal transduction, and as an oncogene to induce cell growth transformation. In addition, KSHV vIRF plays an important role in the regulation of gene expression. From genetic and biochemical analysis, we demonstrate that KSHV vIRF1 binds to a transcriptional coactivator CREB-binding protein (CBP) in vivo and in vitro. KSHV vIRF1 binds to the KIX domain and CH/3 region of CBP. The CH/3 region of CBP coincides with the binding region of adenovirus E1A. We also show that vIRF1 inhibits the transactivational activity of CBP in HeLa cells. These results demonstrate that vIRF1 can modulate gene expression by inhibiting the transactivation function of coactivator CBP.

CREB-Binding Protein↗