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Biomedical subjects

J H Jung

Publications and source records attributed to J H Jung.

At least 19 recordsLinked to original sources

Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistant Staphylococcus aureus and the DNA gyrase-inhibitory activity.

Psammaplin A, a natural bromotyrosine derivative from an associated form of two sponges (Poecillastra sp. and Jaspis sp.) was found to possess the antimicrobial effect on the Gram-positive bacteria, especially on methicillin-resistant Staphylococcus aureus (MRSA). The minimal inhibitory concentration of psammaplin A against twenty one MRSAs ranged from 0.781 to 6.25 microg/ml, while that of ciprofloxacin was 0.391-3.125 microg/ml. Psammaplin A could not bind to penicillin binding protein, but inhibited the DNA synthesis and the DNA gyrase activity with the respective 50% (DNA synthesis) and 100% (DNA gyrase) inhibitory concentration 2.83 and 100 microg/ml. These results indicate that psammaplin A has a considerable antibacterial activity, although restricted to a somewhat narrow range of bacteria, probably by inhibiting DNA gyrase.

Animals

Cytotoxic polyacetylenes from the marine sponge Petrosia sp.

Three C46 (1-3) and three C30 (4-6) polyacetylenic alcohols with cytotoxic activity against a small panel of human solid-tumor cell lines have been isolated from the marine sponge Petrosia sp. Although compound 1 was identified as the stereoisomer of petrocortyne A, the structures of compounds 2-5 have not been previously reported and were established by spectral methods. Compound 6 was identified as the known compound petrosiacetylene D. The stereochemistry of compounds 1-5 was determined by the modified Mosher's method.

Acetylene

New cytotoxic polyacetylenes from the marine sponge Petrosia.

New polyacetylenic alcohols with a C(45) carbon skeleton (2) and with an enone moiety in the alkyl chain (C(46), 1) were isolated from the marine sponge Petrosia sp. The gross structures of 1 and 2 were established by spectral methods, and the absolute stereochemistry was determined by the modified Mosher's method. Compounds 1 and 2 displayed considerable cytotoxicity against a small panel of human solid tumor cell lines. Significant inhibitions on DNA replication by 1 and 2 were also observed which could be explanative of their cytotoxicity.

Acetylene

Lyso-PAF analogues and lysophosphatidylcholines from the marine sponge Spirastrella abata as inhibitors of cholesterol biosynthesis.

A series of phospholipids, including previously undescribed compounds 4-7, were isolated by a bioactivity-guided fractionation from the marine sponge Spirastrella abata as inhibitors of cholesterol biosynthesis in human liver cells. These compounds were identified as lyso-PAF analogues (1-5) and lysophosphatidylcholines (6, 7) based on NMR and MS analyses. Compounds 1-7 specifically blocked the conversion of lanosterol into cholesterol in the Chang liver cell.

Animals

Cytotoxic constituents of Saussurea lappa.

The crude extract of Saussurea lappa displayed significant lethality to brine shrimp larvae. Investigation of the causative components by bioactivity-directed fractionation resulted in the isolation of three C17-polyene alcohols. Based on various nmr spectral data, these compounds were identified as shikokiols which had been previously isolated from Cirsium nipponicum and/or Centaurea aegyptica. These C17-polyene alcohols exhibited moderate cytotoxicities against the human tumor cell lines, A549, SK-OV-3, SK-MEL-2, XF498, and HCT15.

Animals

Reynosin from Sassurea lappa as inhibitor on CINC-1 induction in LPS-stimulated NRK-52E cells.

An inhibitor on CINC-1 (cytokine-induced neutrophil chemoattractant-1) induction in LPS-stimulated rat kidney epithelioid NRK-52E cells was purified from the roots of Sassurea lappa Clarke, a herbal medicine used in Korean traditional prescriptions for gastric intestinal diseases by a variety of column chromatographic procedures. The inhibitor was identified as reynosin, a sesquiterpene lactone isolated and characterized previously from Ambrosia confertiflora DC., and Magnolia grandiflora L. Reynosin exhibited a dose-dependent inhibition on CINC-1 induction in LPS-stimulated NRK-52E cells, where 50% of inhibitory effect was shown at the concentration of about 1 microM.

Animals

Inhibitory effect of sesquiterpene lactones from Saussurea lappa on tumor necrosis factor-alpha production in murine macrophage-like cells.

Total methanol extract of Saussurea lappa radix (Compositae) showed potent inhibitory effect on the production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, in murine macrophage-like cell (RAW264.7 cells) in our previous screening studies on 120 Korean medicinal plants. The activity-guided purification of the plant resulted in the isolation of three components. The chemical structures of the components isolated were established by spectroscopic analyses as sesquiterpene lactones [cynaropicrin (1), reynosin (2), and santamarine (3)]. These three compounds inhibited TNF-alpha production in a dose-dependent manner. The molar concentrations of cynaropicrin, reynosin, and santamarine producing 50% inhibition (IC50) of TNF-alpha production were 2.86 micrograms/ml (8.24 microM), 21.7 micrograms/ml (87.4 microM), and 26.2 micrograms/ml (105 microM), respectively. However, treatment with sulphydryl (SH) compounds such as L-cysteine, dithiothreitol, and 2-mercaptoethanol abrogated the inhibitory effect of cynaropicrin on TNF-alpha production. Therefore, we conclude that the principal inhibitory component of Saussurea lappa is cynaropicrin and its inhibitory effect is mediated through conjugation with SH-groups of target proteins.

Animals

OA1 mutations and deletions in X-linked ocular albinism.

X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (approximately 90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.

Albinism, Ocular

HLA class II allele associations in Korean patients with pemphigus.

BACKGROUND: Studies at the population level have demonstrated associations between pemphigus (pemphigus vulgaris, PV, and pemphigus foliaceus, PF) and particular HLA haplotypes, which suggests that there may be a genetic predisposition for the disease. OBJECTIVE/METHODS: The aim of the present study was to examine the distribution/frequency pattern of HLA class II alleles (DRB1, DQA1 and DQB1) from a group of 30 Korean patients with pemphigus (15 PV and 15 PF) by PCR amplification with sequence-specific primers. RESULTS: In PV, the frequency of DRB1*01 allele was found to be significantly high (pc = 0.0014); in PF, DRB1*01, DQA1*0302 and DQB1*0603 alleles showed positive associations with statistical significances (pc = 0.0002, 0.0007 and 0.0067, respectively), when compared with those found in Korean controls. CONCLUSIONS: In this small-sample study, findings of allelic frequencies among Korean patients with pemphigus are somewhat different from those found in other populations.

Alleles

Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene.

Neurofibromatosis type 1 (NF1) is among the most common human genetic disorders, having a constellation of cutaneous and skeletal manifestations, intellectual impairment, and an increased risk for a variety of malignancies. The NF1 gene has a high spontaneous mutation rate and is also associated with a variety of sporadic cancers in the general population. While a number of laboratories are involved in a coordinated effort to identify NF1 mutations, an important gap in our knowledge is an understanding of the mechanisms responsible for NF1 mutagenesis. In this present paper we describe our analysis of the sequence environment in the NF1 gene at those sites where small deletions, insertions and nucleotide substitution mutations have been reported. Our objective was to determine whether specific nucleotide sequences commonly occur at these mutation sites within the NF1 gene. We assessed how frequently independent NF1 mutations occur at the site of short direct repeats, single nucleotide repeats (homonucleotides) and at CpG and CpNpG motifs. We have established that homonucleotide and short direct repeats are commonly involved in the majority of small deletions and insertions analysed. Substitution mutations are frequently associated with homonucleotide repeats and methylatable CpG dinucleotides and CpNpG trinucleotides. We suggest that NF1 mutations are acquired and retained by cells through an intricate balancing of repair and replication mechanisms. Such mutations may provide a proliferative advantage for that cell and its progeny.

Base Sequence

Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308.

C57BL/10 and BALB/c mice differ in their abilities to clear infections with the intracellular bacterium Brucella abortus strain 2308. We have previously reported that in vivo of IL-10 in the susceptible BALB/c mice results in significantly fewer bacteria in their spleens 1 week after infection with 5 x 10(3) colony forming units (CFU) of 2308. Here we extend those studies and report a similar effect when IL-4 is neutralized. In contrast, in the more resistant C57BL/10 mice infected with 5 x 10(3) CFU, neither neutralization of IL-4 significantly decreased the level of infection nor did it in either BALB/c or C57BL/10 mice infected with a 1000-fold higher dose of strain 2308. While splenocytes from the later mentioned groups of mice produced IL-10 in response to stimulation with brucella antigen, they also produced higher levels of interferon (IFN)-gamma than those from BALB/c mice with the low challenge dose of 5 x 10(3) CFU. Results of in vivo neutralization of IFN-gamma by monoclonal antibodies (MAb) reported here and elsewhere indicated that IFN-gamma is important for control; thus, we postulate that the higher levels of IFN-gamma override the detrimental effects of Th2 cytokines. In vitro studies also showed that macrophages from the more resistant C57BL/10 mice were less susceptible to the ability of IL-10 to decrease anti-brucella activities than were BALB/c macrophages. CD4+ T cells were principally responsible for the production of IL-10 in BALB/c but not C57BL/10 splenocyte populations. C57BL/10 splenocytes produced more IFN-gamma than those from BALB/c mice in response to stimulation with brucella antigens. These differences between BALB/c and C57BL/10 mice may contribute to the superior capacity of C57BL/10 mice to control infections with B. abortus strain 2308.

Animals

Diacylglycerylgalactosides from Arisaema amurense.

Previously undescribed 1,2-O-diacyl-3-O-beta-D-galactopyranosyl glycerols and 1,2-O-diacyl-3-O-[alpha-D-galactopyranosyl-(1"-->6')-O-beta-D- galactopyranosyl] glycerols were isolated as single components from Arisaema amurense. The cytotoxicities of these compounds against P388 and DLD-1 are described.

Animals

Strategies and applications of DNA level diagnosis in genetic diseases: past experiences and future directions.

The development of technologies towards the detection of mutations represents one of the most important areas of molecular biology. It has played a pivotal role in the tremendous success of the elucidation of complex biological problems, including genetic diseases. Today, these proven and emerging technologies have become the basis of successful biological investigations. More importantly, they are expected to play a central role in medicine, particularly the diagnosis and prognosis of genetic diseases including genetic predispositions, the assessment of treatments including transplants and decisions on reproductive choices. In addition, these technologies hold the key to future breakthroughs. This review provides an up-to-date examination of the principles of genetic diseases, the theories behind current methods of genetic diagnosis and detection of mutations including strategies for modification and the development of future technologies as they impact on the practice of medicine and on society as a whole.

Animals

New bioactive cerebrosides from Arisaema amurense.

From Arisaema amurense, four new cerebrosides were isolated along with a known cerebroside. The new cerebrosides were characterized as 1-O-beta-D-glucopyranosyl- (2S,3R,4E,8Z)-2-[(2(R)- hydroxyicosanoyl)amido]-4,8-octadecadiene-1,3-diol (1), 1-O-beta-D- glucopyranosyl-(2S,3R,4E,8Z)- 2-[(2-hydroxyoctadecanoyl)amido]-4,8-octadecadiene-1,3-diol (2), 1-O-beta-D- glucopyranosyl- (2S,3R,4E,8E)-2-[(2-hydroxyicosanoyl)amido]-4,8-oct adecadiene-1,3-diol (4), and 1-O-beta-D- glucopyranosyl-(2S,3R,4E,8E)-2-[(2-hydroxyoctadecanoyl )amido]-4,8- octadecadiene-1,3-diol (5), respectively. These cerebrosides displayed significant antihepatotoxic activity.

Animals

Isolated sulfite oxidase deficiency.

Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

Base Sequence