Biomedical subjects

S Jung

Publications and source records attributed to S Jung.

At least 55 records · Page 3Linked to original sources

PubMed2001

The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.

In a reconstituted flow chamber system, preincubation with chemokines can trigger the arrest of rolling monocytes, suggesting that this interaction could help recruit these cells to early atherosclerotic lesions. To date, however, the contribution of endothelium-derived chemokines found in these lesion to monocyte arrests has not been investigated. The endothelium of lesion-prone carotid arteries from apolipoprotein E-deficient (ApoE(-/-)) mice, but not control mice, presents the chemokines KC (mouse GRO-alpha) and JE (mouse monocyte chemoattractant protein-1 [MCP-1]). Arrest of a monocytic cell line or mouse blood monocytes perfused through carotid arteries of ApoE(-/-) mice was reduced by treating with either pertussis toxin, an antagonist of CXCR2, or an antibody to KC, but this process was insensitive to agents that blocked CCR-2 or JE. Conversely, monocyte accumulation more than doubled upon pre-perfusion of the carotid artery with KC but not with mouse MCP-1. Blockade of alpha(4)beta(1) integrin (VLA-4) or vascular cell adhesion molecule-1, but not CD18 or intercellular adhesion molecule-1, almost completely inhibited the arrest of monocytes. We conclude that when presented by early atherosclerotic lesions, KC but not murine MCP-1 triggers VLA-4-dependent monocyte recruitment.

Animals↗

PubMed2001

Differential antioxidant responses to norflurazon-induced oxidative stress in maize.

This study examined the contribution of catalase (CAT) and superoxide dismutase (SOD) in the overall antioxidant response to norflurazon (NF)-induced oxidative stress in leaves, mesocotyls and scutella of maize (Zea mays). Maize catalase null mutants were used to provide insights into the role(s) of these isozymes. A substantial increase in Cat1 and Cat2 transcript levels occurred in NF-treated leaves in all maize lines examined. However, these two transcripts did not show a particular pattern of change in NF-treated scutella from 5-day postimbibition (dpi) and 18-day postpollination (dpp) maize. The NF-induced increase in Cat1 appeared to be dependent on excessive light energy caused by a lack of photoprotectant carotenoids. especially in leaves. In NF-treated leaves, the chloroplastic Cu/Zn-SOD-1 isozyme responded strongly compared to the cytosolic Cu/Zn-SOD and mitochondrial Mn-SOD-3 isozymes, suggesting the critical role of SOD-1 as a major component in chloroplastic antioxidant defenses. All SOD isozymes in the NF-treated scutella of various maize lines were consistent in their response to NF. The most significant increase was observed with Sod1 in NF-treated leaves; however, no significant Sod1 changes were observed in similarly treated scutella at 5 dpi and 18 dpp. These results suggest that the response of the Cat and Sod genes to NF is likely developmental and tissue-specific.

Antioxidants↗

PubMed2001

Effects of leucocyanidines on activities of metabolizing enzymes and antioxidant enzymes.

Procyanidolic oligomers (leucocyanidines, LCs) extracted from grape seeds (Vitis vinifera) are known to have antioxidant and antimutagenic activities, and a protective effect against cardiovascular disease. In the present study we examined the influence of LCs on the activities of phase 1 enzymes and conjugation enzymes and on antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Administration of LCs (25, 50, and 100 mg/kg. p.o. for 7 d) markedly decreased the activities of NADPH-cytochrome P450 reductase, P4501A1, P4501A2, and P4503A4, but significantly increased the activities of glutathione S-transferase and phenolsulfotransferase in rat liver. However, the activities of antioxidant enzymes were not affected by LC administration. The inhibition of P450s and increases in phase II enzyme activities indicate a role for LCs as a chemopreventive agent against toxic or carcinogenic metabolites of P450 isozymes.

Animals↗

PubMed2001

Tracking the invasiveness of human astrocytoma cells by using green fluorescent protein in an organotypical brain slice model.

OBJECT: Although it is known that malignant astrocytomas infiltrate diffusely into regions of normal brain, it is frequently difficult to identify unequivocally the solitary, invading astrocytoma cell in histopathological preparations or experimental astrocytoma models. The authors describe an experimental system that facilitates the tracking of astrocytoma cells by using nonneoplastic cerebral tissue as the substrate for invasion. METHODS: Cerebral tissue was cut into 1-mm-thick slices and cultured in the upper chamber of a Transwell culture dish on top of a polyester membrane (0.4-mm pore size) that was bathed in medium supplied by the lower chamber. Two astrocytoma cell lines, U-87 MG (U87) and U343 MG-A (U343), were selected because of their differing basal cell motilities in monolayer cultures. The astrocytoma cells were stably transfected with vectors that expressed green fluorescent protein (GFP), either alone or as a fusion protein with the receptor for hyaluronic acid-mediated motility (RHAMM) in either sense or antisense orientations. Stably transfected clones that had high levels of GFP expression were selected using the direct visualization provided by fluorescence microscopy and fluorescence-activated cell-sorter analysis. The GFP-expressing astrocytoma cell clones were implanted into the center of the brain slice and the degree of astrocytoma invasion into brain tissue was measured at different time points by using the optical sectioning provided by the confocal laser microscope. The authors observed that GFP-expressing astrocytoma cells could be readily tracked and followed in this model system. Individual astrocytoma cells that exhibited green fluorescence could be readily identified following their migration through the brain slices. The GFP-labeled U87 astrocytoma cells migrated farther into the brain slice than the U343 astrocytoma cells. The RHAMM-transfected GFP-labeled astrocytoma cells also infiltrated farther than the GFP-labeled astrocytoma cells themselves. The expression of antisense RHAMM virtually abrogated the invasion of the brain slices by both astrocytoma cell lines. CONCLUSIONS: The authors believe that this organotypical culture system may be of considerable utility in studying the process of astrocytoma invasion, not only because it provides a better representation of the extracellular matrix molecules normally encountered by invading astrocytoma cells, but also because the GFP tag enables tracking of highly migratory and invasive astrocytoma cells under direct vision.

Astrocytoma↗

PubMed2001

p53 mutation and epidermal growth factor receptor overexpression in glioblastoma.

Recent molecular studies indicate two different genetic pathways leading to the development of glioblastoma; final progression of astrocytoma and de novo formation. To define the mutual relationships of cytogenetic changes in the pathogenesis of glioblastoma, molecular histopathologic alterations of p53 and epidermal growth factor receptor (EGFR) were evaluated by single stranded conformational polymorphion, reverse transcriptase-polymerase chain reaction and immunohistochemical stains in 15 primary and 21 secondary glioblastomas. Mutations in p53 gene and positive immunoreactivity to p53 protein (DO1) were more prevalent in secondary glioblastomas than in primary glioblastomas. A correlation between p53 mutations and p53 immunopositivities in glioblastomas was observed in 83.3% of the cases. All cases with positive p53 immunoreactivities showed p53 mutations; however, 13.9% of glioblastomas with p53 immuno-positivities lacked the relevant mutations. EGFR amplifications were detected in 73.3% of primary glioblastomas and 9.5% of secondary glioblastomas (p<0.001). The concurrence of p53 mutation and EGFR amplification was revealed in only 2 out of 15 primary glioblastomas and none among the secondary glioblastomas. Immunoreactivities for EGFR were noted in 66.7% of primary glioblastomas and in 9.5% of secondary glioblastomas (p<0.001). A correlation between EGFR amplification and EGFR immunopositivity in glioblastomas was observed in 91.7% of the cases. These data indicate that EGFR amplification and p53 mutations are two independent genetic events in the development of glioblastomas.

Adolescent↗

PubMed2001

Secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis : report of two cases.

Amenorrhea is rarely presented as a manifestation of endocrinological disturbances in patients of chronic hydrocephalus. We describe two cases of secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis. Two female patients of age 30 and 20 yr presented with amenorrhea and increasing headache. Magnetic resonance images revealed marked, noncommunicating hydrocephalus without any tumorous lesion. In one patient, emergent extraventricular drainage was necessary because of progressive neurological deterioration. Each patient underwent surgical intervention for the hydrocephalus-ventriculoperitoneal shunt and endoscopic third ventriculostomy. Both resumed normal menstruation continuing so far with further normal menstrual bleeding. These two cases and others reported in the literature indicated that the surgical intervention for hydrocephalus resolves amenorrhea in all the cases of amenorrhea due to hydrocephalus. The suspected role of the surgery is the correction of increased intracranial pressure, which is an important pathogenetic factor in the development of amenorrhea.

Adult↗

PubMed2000

Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk.

The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220(+)CD43(+) stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)M(lo)IgD(hi) B cells. Although Tec/Btk(null) mice were able to form germinal centers, the response to T cell-dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2000

Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE.

Proper lymph node (LN) development requires tumor necrosis factor-related activation-induced cytokine (TRANCE) expression. Here we demonstrate that the defective LN development in TRANCE(-/)- mice correlates with a significant reduction in lymphotoxin (LT)alphabeta(+)alpha(4)beta(7)(+)CD45(+)CD4(+)CD3(-) cells and their failure to form clusters in rudimentary mesenteric LNs. Transgenic TRANCE overexpression in TRANCE(-/)- mice results in selective restoration of this cell population into clusters, and results in full LN development. Transgenic TRANCE-mediated restoration of LN development requires LTalphabeta expression on CD45(+) CD4(+)CD3(-) cells, as LNs could not be induced in LTalpha(-/)- mice. LTalpha(-/)- mice also showed defects in the fate of CD45(+)CD4(+)CD3(-) cells similar to TRANCE(-/)- mice. Thus, we propose that both TRANCE and LTalphabeta regulate the colonization and cluster formation by CD45(+) CD4(+)CD3(-) cells in developing LNs, the degree of which appears to correlate with the state of LN organogenesis.

Animals↗

PubMed2000

Effect of initial carbon sources on the performance of microbial fuel cells containing Proteus vulgaris.

Mediator-coupled microbial fuel cells containing Proteus vulgaris were constructed and the cell performance was tested. Fuel cell efficiency depended on the carbon source in the initial medium of the microorganism. Maltose and trehalose were not utilized substantially by P. vulgaris; however, their presence in the initial medium resulted in enhanced cell performance. In particular, galactose showed 63% coulombic efficiency in a biofuel cell after P. vulgaris was cultured in a trehalose-containing medium. This work demonstrates that optimum utilization of carbon sources by microorganisms, which leads to the maximization of fuel cell performance, is possible simply by adjusting initial carbon sources.

Bioelectric Energy Sources↗

PubMed2000

Sequential expression of chemokines in experimental autoimmune neuritis.

Recruitment of inflammatory cells is of critical importance in the pathogenesis of immune-mediated demyelinating diseases in the peripheral nervous system (PNS). Evidence is increasing that chemokines might play a key role in this process, since they promote leukocyte entry into the nervous system during immune-mediated inflammation. In the present study we report the expression pattern of the chemokines interferon-gamma-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated upon activation normal T cell expressed and secreted (RANTES) in sciatic nerves from animals with myelin-induced experimental autoimmune neuritis, using a semiquantitative reverse transcriptase-PCR dot-blot hybridization assay. The mRNAs for MIP-1alpha and MIP-1beta were found to be upregulated with peak values at day 13 post-immunization (p.i.), preceding maximum disease severity. In contrast, mRNAs for MCP-1, RANTES, and IP-10 exhibited peak levels coincident with peak of the disease at day 15 p.i. Increased mRNA expression was associated with enhanced protein levels, as demonstrated by immunoblotting for each chemokine investigated. Immunohistochemistry for IP-10 protein revealed immunoreactivity associated with perineurial endothelial cells. RANTES protein was localized immunohistologically to invading T lymphocytes. Our findings suggest that chemokines, which act towards T cells and mononuclear phagocytes, are sequentially upregulated during the clinical course of EAN and thus may contribute to the pathogenesis of inflammatory demyelinating diseases of the PNS.

Animals↗

PubMed2000

Monte Carlo simulations of the chiral recognition of fenoprofen enantiomers by cyclomaltoheptaose (beta-cyclodextrin).

Differential complexation of fenoprofen enantiomers by cyclomaltoheptaose (beta-cyclodextrin) was investigated by Monte Carlo docking simulations. The chiral discrimination of (R)- and (S)-fenoprofen by beta-cyclodextrin was discussed in terms of the difference in the interaction energies and the patterns of molecular interactions. The interaction energies between each enantiomer of fenoprofen and beta-cyclodextrin were consistent with the reported experimental results that showed that the S isomer interacted preferentially with beta-cyclodextrin and was retained longer in a separation process than the R isomer. The thermodynamic preference of inclusion complex formation of (S)-fenoprofen could be explained by the orientation of the phenyl group attached to the chiral carbon, which provided closer contact and thus more favorable intermolecular interactions between the host and guest molecule. The results presented here would be very useful for the prediction of chiral recognition ability of beta-cyclodextrin.

Carbohydrate Conformation↗

PubMed2000

Histamine-induced calcium entry in rat cerebellar astrocytes: evidence for capacitative and non-capacitative mechanisms.

We have investigated the effects of histamine on the intracellular calcium concentration ([Ca2+]i) of cultured rat cerebellar astrocytes using fura-2-based Ca2+ imaging microscopy. Most of the cells responded to the application of histamine with an increase in [Ca2+]i which was antagonized by the H1 receptor blocker mepyramine. When histamine was applied for several minutes, the majority of the cells displayed a biphasic Ca2+ response consisting of an initial transient peak and a sustained component. In contrast to the initial transient [Ca2+]i response, the sustained, receptor-activated increase in [Ca2+]i was rapidly abolished by chelation of extracellular Ca2+ or addition of Ni2+, Mn2+, Co2+ and Zn2+, but was unaffected by nifedipine, an antagonist of L-type voltage-activated Ca2+ channels. These data indicate that the sustained increase in [Ca2+]i was dependent on Ca2+ influx. When intracellular Ca2+ stores were emptied by prolonged application of histamine in Ca2+-free conditions, Ca2+ re-addition after removal of the agonist did not lead to an 'overshoot' of [Ca2+]i indicative of store-operated Ca2+ influx. However, Ca2+ stores were refilled despite the absence of any substantial change in the fura-2 signal. Depletion of intracellular Ca2+ stores using cyclopiazonic acid in Ca2+-free saline and subsequent re-addition of Ca2+ to the saline resulted in an increase in [Ca2+]i that was significantly enhanced in the presence of histamine. The results suggest that besides capacitative mechanisms, a non-capacitative, voltage-independent pathway is involved in histamine-induced Ca2+ entry into cultured rat cerebellar astrocytes.

Animals↗

PubMed2000

Is it possible to differentiate mtDNA by means of HVIII in samples that cannot be distinguished by sequencing the HVI and HVII regions?

The mitochondrial control region includes three so-called hypervariable (HV) regions, in which the polymorphic positions show a particularly high frequency. According to a population study of 200 unrelated individuals from Germany, HVI (positions 16,024-16,365, according to Anderson) showed 88 variable positions in a total length of 342 bp (26%) and HVII (positions 73-340) displayed 65 mutable sites in 268 bp (24%). HVIII (positions 438-574) exhibited a slightly lower variability, with 25 polymorphic sites within 137 bp (18%), but contrasted clearly with the background, which showed variability rates of only 7% (positions 16,366-16,569, 1-72) and 3% (positions 341-437), respectively. At present, the displacement (D)-loop database in Magdeburg comprises 904 sequences of the mitochondrial HVI region and HVII region from Germans, Austrians and Swiss. By means of this material, the extent to which the mtDNA sequences that do not differ in the HVI and HVII regions can be differentiated by additionally sequencing HVIII was investigated.

Austria↗

PubMed2000

Mitochondrial DNA in the Central European population. Human identification with the help of the forensic mt-DNA D-loop-base database.

Sequencing of mtDNA is an advanced method for the individualisation of traces. Disadvantages of this method are expensive and time-consuming analysis and evaluation procedures as well as the necessary stock of population-genetic data which is still insufficient. Central European institutes of forensic medicine from Germany, Austria, and Switzerland have been working together since the beginning of 1998 to establish a mtDNA database. The aim is to build up a large stock of forensically established data and provide population-genetic data for frequency investigations, which will serve as a basis for expert opinions and scientific research. Good data quality is ensured by using original sequences only. Ring tests, which have been conducted to enhance analytical reliability, revealed a high correspondence rate of the analytical results obtained by the individual member institutes. Today 1410 sequences are available for comparison, of which 1285 sequences in the HV1 and HV2 regions cover the full ranges from 16051 to 16365 and from 73 to 340 (according to Anderson). The major part is formed by Central European sequences comprising 1256 data sets from Germany, Austria, and Switzerland. Today the database contains sequences from a total of 12 European, six African and three Asian countries including 100 sequences from Japan. This paper is aimed at discussing the individualisation potentials of mtDNA as well as the possibilities and limits of ethnic differentiation by means of pairwise sequence differences on the basis of the data stock available.

Austria↗

PubMed2000

IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2 cytokine production.

IL-11 is a pleiotropic cytokine that induces tissue remodeling with subepithelial fibrosis when expressed in the airway. Its effects on the Th2-dominated airway inflammation that is characteristic of asthma, however, are poorly understood. To characterize the effects of IL-11 on Th2 tissue inflammation, we compared the inflammatory responses elicited by OVA in sensitized mice in which IL-11 is overexpressed in a lung-specific fashion (CC10-IL-11) with that in transgene- wild-type littermate controls. Transgene- and CC10-IL-11 transgene+ mice had comparable levels of circulating Ag-specific IgE after sensitization. OVA challenge of sensitized transgene- mice caused airway and parenchymal eosinophilic inflammation, Th2 cell accumulation, and mucus hypersecretion with mucus metaplasia. Exaggerated levels of immunoreactive endothelial cell VCAM-1, mucin (Muc) 5ac gene expression and bronchoalveolar lavage and lung IL-4, IL-5, and IL-13 protein and mRNA were also noted. In contrast, OVA challenge in CC10-IL-11 animals elicited impressively lower levels of tissue and bronchoalveolar lavage inflammation, eosinophilia, and Th2 cell accumulation, and significantly lower levels of VCAM-1 and IL-4, IL-5, and IL-13 mRNA and protein. IL-11 did not cause a comparable decrease in mucus hypersecretion, Muc 5ac gene expression, or the level of expression of RANTES, monocyte chemoattractant protein-2, or monocyte chemoattractant protein-3. In addition, IL-11 did not augment IFN-gamma production demonstrating that the inhibitory effects of IL-11 were not due to a shift toward Th1 inflammation. These studies demonstrate that IL-11 selectively inhibits Ag-induced eosinophilia, Th2 inflammation, and VCAM-1 gene expression in pulmonary tissues.

Administration, Inhalation↗

PubMed2000

Molecular dynamics simulations of cyclohenicosakis-[(1-->2)-beta-D-gluco-henicosapyranosyl], a cyclic (1-->2)-beta-D-glucan (a 'cyclosophoraose') of DP 21.

We report molecular dynamics simulations of cyclohenicosakis-[(1-->2)-beta-D-gluco-henicosapyranosyl], termed 'cyclosophohenicosamer', a member of a class of cyclic (1-->2)-beta-D-glucans ('cyclosophoraoses'). Our goals were to provide insights into the conformational preferences of these cyclosophoraoses. Simulated annealing and constant-temperature molecular dynamics calculations were performed on the DP 21 cyclosophohenicosamer. The radius of gyration (R(G)) of the molecule and the conformation of glycosidic dihedral angles were used to analyze the result of computational studies. Most glycosidic linkages were concentrated in the lowest-energy region of the phi-psi energy map, and the values of radius of gyration from our simulations were consistent with the reported experimental value. The simulations produced various types of compact and asymmetric conformations within reasonable ranges of the glycosidic linkage conformation and radius of gyration. The results indicate the presence of a high degree of molecular flexibility of cyclosophohenicosamer and suggest the uniqueness of inclusion complexation with other molecules through this molecular flexibility.

Carbohydrate Conformation↗

PubMed2000

Forbidden light detection from single molecules

We present a new concept for ultrasensitive detection of surface-generated fluorescence which is made possible by a new optical module. The detection method leads to an enhancement in fluorescence collection efficiency to more than 65% of the total of emitted light, whereas high-aperture microscope objectives are able to collect 44% at best. Moreover, by employing this new optical module, the detection volume can be restricted to approximately 10(-17) L. This allows for an exceptional discrimination of bulk-generated against surface-generated fluorescence, which may be of great value when surface-binding processes are monitored. We demonstrate the performance of the new detection system by detecting single fluorescent molecules and by determining antigen concentrations down to 5 fmol.

Journal Article↗

PubMed2000

Antioxidant responses of cucumber (Cucumis sativus) to photoinhibition and oxidative stress induced by norflurazon under high and low PPFDs.

Photooxidative damage is exacerbated by norflurazon (NF), which blocks carotenoid biosynthesis. This study examined the influence of photosynthetic photon flux density (PPFD) on the overall responses of both non-enzymatic and enzymatic antioxidants to NF-caused oxidative damage in leaves of cucumber (Cucumis sativus). Seven-day-old cucumber plants were exposed to NF under either low PPFD (30 µmol m(-2) s(-1)) or high PPFD (300 µmol m(-2) s(-1)) for 3 days. The NF plants exposed at high PPFD had lower levels of F(v)/F(m) ratio, quantum yield of electron transport, and 33-kDa protein of photosystem II as compared with the NF plants at low PPFD. In the NF plants, there was a reduction in total chlorophylls and carotenoids except newly formed zeaxanthin in either PPFD. The NF plants at high PPFD resulted in less level of photochemical quenching, q(P), and Stern-Volmer quenching, NPQ, than those of the plants at low PPFD, whereas both plants had similar level of non-photochemical quenching coefficient, q(N). However, the level of PPFD did not significantly affect the NF-caused induction of antioxidant enzymes including peroxidase, superoxide dismutase, glutathione reductase, and ascorbate peroxidase.

Journal Article↗