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Biomedical subjects

C Jung

Publications and source records attributed to C Jung.

At least 19 recordsLinked to original sources
PubMed2002

Expression of bacterial poly(3-hydroxybutyrate) synthesis genes in hairy roots of sugar beet (Beta vulgaris L.).

Three genes from Ralstonia eutropha necessary for poly(3-hydroxybutyrate) (PHB) synthesis were introduced into the hairy roots of sugar beet. Transformation of a vector construct harbouring the PHB genes, each fused to the coding region of the pea ribulose-bisphosphate carboxylase plastid targeting sequence, resulted in 20 transgenic hairy-root clones, producing up to 55 mg high molecular PHB/g dry weight, as identified by gas chromatography, gel permeation chromatography and HPLC. Accumulation of PHB polymer in sugar beet root leucoplasts was confirmed by transmission electron microscopy. Thus, for the first time, plastidic PHB production was demonstrated for roots of a carbohydrate-storing crop plant.

Beta vulgaris↗
PubMed2002

Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome P450cam and chloroperoxidase.

It is generally assumed that the putative compound I (cpd I) in cytochrome P450 should contain the same electron and spin distribution as is observed for cpd I of peroxidases and catalases and many synthetic cpd I analogues. In these systems one oxidation equivalent resides on the Fe(IV)=O unit (d(4), S=1) and one is located on the porphyrin (S'=1/2), constituting a magnetically coupled ferryl iron-oxo porphyrin pi-cation radical system. However, this laboratory has recently reported detection of a ferryl iron (S=1) and a tyrosyl radical (S'=1/2), via Mössbauer and EPR studies of 8 ms-reaction intermediates of substrate-free P450cam from Pseudomonas putida, prepared by a freeze-quench method using peroxyacetic acid as the oxidizing agent [Schünemann et al., FEBS Lett. 479 (2000) 149]. In the present study we show that under the same reaction conditions, but in the presence of the substrate camphor, only trace amounts of the tyrosine radical are formed and no Fe(IV) is detectable. We conclude that camphor restricts the access of the heme pocket by peroxyacetic acid. This conclusion is supported by the additional finding that binding of camphor and metyrapone inhibit heme bleaching at room temperature and longer reaction times, forming only trace amounts of 5-hydroxy-camphor, the hydroxylation product of camphor, during peroxyacetic acid oxidation. As a control we performed freeze-quench experiments with chloroperoxidase from Caldariomyces fumago using peroxyacetic acid under the identical conditions used for the substrate-free P450cam oxidations. We were able to confirm earlier findings [Rutter et al., Biochemistry 23 (1984) 6809], that an antiferromagnetically coupled Fe(IV)=O porphyrin pi-cation radical system is formed. We conclude that CPO and P450 behave differently when reacting with peracids during an 8-ms reaction time. In P450cam the formation of Fe(IV) is accompanied by the formation of a tyrosine radical, whereas in CPO Fe(IV) formation is accompanied by the formation of a porphyrin radical.

Binding Sites↗
PubMed2002

Syphilis 2001--a palaeopathological reappraisal.

The origin and subsequent spread of the treponematoses, especially that of venereal syphilis, has been the subject of considerable scientific attention. Various theories were put forth and palaeopathological specimens were used for their validation in recent times. One influential contribution was the paper by Baker & Armelagos in 1988. Numerous new findings and results on both sides of the Atlantic call for a new evaluation of the available osseous material. A review of the recent literature leads to the suggestion of a worldwide distribution of non-venereal treponemal disease since the emergence of Homo and to a first epidemic outbreak of venereal syphilis in Europe of the late 15th and the early 16th century, which was a time of change and enormous sexual liberty. Old World specimens with pathological alterations attributed to venereal syphilis and dated to precolumbian times seem to invalidate the Columbian theory and call for a more differentiated analysis of the phenomenon of syphilis than a theory based on a single factor can provide. With the help of molecular methods which now allow a positive identification of Treponema pallidum pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease.

Anthropology, Physical↗
PubMed2001

Insulin-mimetic signaling by the sulfonylurea glimepiride and phosphoinositolglycans involves distinct mechanisms for redistribution of lipid raft components.

The insulin signal transduction cascade provides a number of sites downstream of the insulin receptor (IR) for cross-talk from other signaling pathways. Tyrosine phosphorylation of the IR substrates IRS-1/2 and metabolic insulin-mimetic activity in insulin-responsive cells can be provoked by soluble phosphoinositolglycans (PIG), which trigger redistribution from detergent-insoluble glycolipid-enriched raft domains (DIGs) to other areas of the plasma membrane and thereby activation of nonreceptor tyrosine kinases (NRTK) [Müller, G., Jung, C., Wied, S., Welte, S., Jordan, H., and Frick, W. (2001) Mol. Cell. Biol. 21, 4553-4567]. Here we describe that stimulation of glucose transport in isolated rat adipocytes by a different stimulus, the sulfonylurea glimepiride, is also based on IRS-1/2 tyrosine phosphorylation and downstream insulin-mimetic signaling involving activation of the NRTK, pp59(Lyn), and pp125(Fak), as well as tyrosine phosphoryation of the DIGs component caveolin. As is the case for PIG 41, glimepiride causes the concentration-dependent dissociation of pp59(Lyn) from caveolin and release of this NRTK and the glycosyl-phosphatidylinositol-anchored (GPI) proteins, Gce1 and 5'-nucleotidase, from total and anti-caveolin-immunoisolated DIGs. This results in their movement to detergent-insoluble raft domains of higher buoyant density (non-DIGs areas). IRS-1/2 tyrosine phosphorylation and glucose transport activation by both glimepiride and PIG are blocked by introduction into adipocytes of the caveolin scaffolding domain peptide which mimicks the negative effect of caveolin on pp59(Lyn) activity. Tyrosine phosphorylation of the NRTK, IRS-1/2, and caveolin as well as release of the NRTK and GPI proteins from DIGs and their redistribution into non-DIGs areas in response to PIG is also inhibited by treatment of intact adipocytes with either trypsin plus salt or N-ethylmaleimide (NEM). In contrast, the putative trypsin/salt/NEM-sensitive cell surface component (CIR) is not required for glimepiride-induced glucose transport, IRS-1/2 tyrosine phosphorylation, and redistribution of GPI proteins and NRTK. The data suggest that CIR is involved in concentrating signaling molecules at DIGs vs detergent-insoluble non-DIGs areas. These inhibitory interactions are relieved in response to putative physiological (PIG) or pharmacological (sulfonylurea) stimuli via different molecular mechanisms (dependent on or independent of CIR, respectively) thereby inducing IR-independent positive cross-talk to metabolic insulin signaling.

Adipocytes↗
PubMed2001

A comparison of laparoscopic Toupet versus Nissen fundoplication in gastroesophageal reflux disease.

BACKGROUND AND AIMS: Laparoscopic Nissen fundoplication is used very frequently but may lead to postoperative bloating, inability to belch, and dysphagia. Partial wrapping has been reported to be equally effective but associated with fewer unfavorable postoperative symptoms. The aim of this retrospective analysis was to compare the results of a 270-degree wrap (Toupet, T) and a 360-degree wrap (Nissen, N) in patients with gastroesophageal reflux disease (GERD). PATIENTS/METHODS: A total of 162 patients with severe GERD and/or hiatal hernia underwent laparoscopic antireflux surgery between January 1997 and December 2000. All patients were assigned to the T group before January 2000; after January 2000, they were assigned to either the T or the N group depending on preexisting motility disorders. The pre- and postoperative gastrointestinal quality of life index (GIQLI) was assessed. RESULTS: A total of 122 patients were treated using the T procedure, and 40 patients underwent N fundoplication; 124 patients (77%) had a lower esophageal sphincter (LES) pressure of less than 15 mmHg, and 34 (21%) had a low esophageal body peristaltic pressure of less than 35 mm Hg. All of the latter 34 had undergone partial fundoplication. The average operation time was 140 +/- 5 min in the T group and 118 +/- 6 min in the N group ( P=0.03). Postoperative hospitalization averaged 3.8 days in the T group and 3.4 days in the N group. Operative complications only occurred in the T group (2%), and none of the patients died. No statistical difference was seen preoperatively or at follow-up (mean 19 months; range 4-36 months) between the quality of life score after partial versus complete wrapping (88 and 123 in the T group, 87 and 118 in the N group preoperatively and at follow-up, respectively). CONCLUSIONS: Both partial and complete wrapping offer an effective form of therapy for reflux disease with over 85% patient satisfaction.

Adult↗
PubMed2001

Osteocalcin is incompletely spliced in non-osseous tissues.

Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communication, we provided evidence to demonstrate that tissue-specific expression of OC was also regulated at the RNA splicing level. We identified incompletely spliced variants of human OC mRNA, which retain one or more introns during RNA splicing, existing dominantly in non-osseous organs. Northern blot analysis identified two OC RNA transcripts expressed in normal human tissues, but the expression level of the transcripts varied between the tissues. Most non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marrow. Sequence analysis showed that four of five RNA variants contained intron 1 in common and the dominant one contained all three introns. MG63, an osteoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor cells. Combined study of in situ hybridization and immunohistochemistry revealed that OC RNA was highly expressed in prostate tumor epithelial cells while only very low levels of protein were detected, which confirms that there are OC RNA variants in non-osseous tissues. In conclusion, we demonstrated that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be further investigated.

Alternative Splicing↗
PubMed2001

Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes motoneuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause of this disease. It is widely suspected that increased reactive oxidative species (ROS) is involved in motoneuron degeneration but whether such an involvement plays a role in ALS progression in vivo is uncertain. We treated mice expressing human mutant SOD1 G93A with EUK-8 and EUK-134, two synthetic SOD/catalase mimetics that have shown efficacy in several animal models of human diseases. These treatments reduced levels of oxidative stress and prolonged survival. The results suggest that oxidative stress plays an active role in ALS and illustrate the potential for treatment strategies aimed specifically against ROS.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Studying hadronic structure of the photon in lattice QCD.

We show that the matrix element of a local quark-gluon operator in the photon state, , can be calculated in lattice QCD. The result is generalized to other quantities involving spacelike photons, including the transition form factor gammagamma*-->pi(0) and the virtual-photon-nucleon Compton amplitude which can be used to define the generalized Drell-Hearn-Gerasimov and Bjorken sum rules.

Journal Article↗
PubMed2001

Age- and sex-specific differences in the 1H-spectrum of vertebral bone marrow.

Correct interpretation of 1H magnetic resonance (MR) studies of the red vertebral bone marrow in patients with disorders of the hematopoietic system requires knowledge of the dependence of the proton spectrum on age and sex. Infiltration of malignant cells causes a decreased red bone marrow fat signal, which is reversed upon successful treatment. The aim of this study was to establish a database of normal water/fat relations from a large group of volunteers. In all, 154 healthy volunteers from 11 to 95 years of age were examined using a 1.5-T MR system (ACS-NT, Philips). A volume of 2-8 ml in the center of a normal vertebral body was selected for spectroscopy using the PRESS sequence without water suppression (TR/TE 2 sec/40 msec). Signal intensities and T2 times of lipid and water resonances were determined. The relative fat signal intensity was calculated corrected for T2 relaxation. The relative proportion of protons in the fat signal increases with age from 24% in the age group 11-20 years to 54% in the group > or = 61 years. The proportion of fat in the vertebral bone marrow in female subjects is less than that in male subjects in the same age group (statistically significant at P < or = 0.01). In the central age group between 31 and 50 years, the difference is largest, at 12%; in the youngest and oldest age group this difference is small. T2 times are neither age nor sex dependent.

Adipose Tissue↗
PubMed2001

High-resolution mapping of YACs and the single-copy gene Hs1(pro-1) on Beta vulgaris chromosomes by multi-colour fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) is a powerful approach for physical mapping of DNA sequences along plant chromosomes. Nematode-resistant sugar beets (Beta vulgaris) carrying a Beta procumbens translocation were investigated by FISH with two differentially labelled YACs originating from the translocation. At mitotic metaphases, the translocation was identified with both YACs in the terminal region on a pair of chromosomes. Meiotic chromosomes, representing a far more extended hybridization target, were used to determine the orientation of YACs with respect to chromosomal domains in combination with chromosomal landmark probes for telomeres and centromeres. The in situ detection of plant single-copy sequences is technically difficult, and the wild beet translocation was used to explore the potential resolution of the FISH approach and to introduce the chromosomal mapping of single-copy genes into genome analysis of Beta species. An internal fragment of the nematode resistance gene Hs1(pro-1), 684 bp long, was detected on both chromatids of different Beta chromosomes and represents one of the shortest unique DNA sequences localized on mitotic plant chromosomes so far. Comparative chromosomal mapping of the 684 bp Hs1(pro-1) probe in the translocation line, a monosomic addition line and in B. procumbens revealed the origin of the wild beet translocation leading to nematode-resistant sugar beets.

Chenopodiaceae↗
PubMed2001

Phytoseiid dispersal at plant to regional levels: a review with emphasis on management of Neoseiulus fallacis in diverse agroecosystems.

Dispersal behaviors of phytoseiid and tetranychid mites are key factors in understanding predator-prey dynamics and biological control of pest mites at different spatial levels in agricultural and natural ecosystems. In this review, ambulatory and aerial dispersal of both mite groups are discussed at spatial levels of leaf, plant, crop and region. Emphasis is on dispersal of phytoseiids, and specifically, the specialist-predator, Neoseiulusfallacis (Garman), and two-spotted spider mite prey, Tetranychus urticae (Koch). Dispersal aspects that are discussed are ambulation on a leaf; plant or in a prey patch; aerial dispersal between plants; behavior and aerodynamics of aerial take-off; modeling vs. monitoring of dispersal distance; fates of dispersing mites that land on soil substrates; plants as take-off platforms and landing targets for dispersers; and regional dispersal patterns and integrated mite management.

Agriculture↗
PubMed2001

Inhibition of endothelin-converting enzyme activity in the rabbit basilar artery.

OBJECTIVE: Endothelin (ET)-1 may be involved in the regulation of cerebrovascular resistance under pathological conditions, most notably during the development of vasospasm after subarachnoid hemorrhage. Blocking ET-converting enzyme activity may be a promising approach to the prevention of cerebral vasospasm after subarachnoid hemorrhage. METHODS: In this study, the effects of several putative ET-converting enzyme inhibitors were investigated after intracisternal application in rabbits, to inhibit basilar artery contractions induced by big ET-1 (2 x 10(-6) mol/L). RESULTS: In the group pretreated with [D-Val22]big ET-1[16-38] (2 x 10(-5) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.63 +/- 0.12 mm to 0.66 +/- 0.12 mm. In the control group (n = 8), the diameter of the basilar artery decreased from 0.71 +/- 0.13 mm to 0.57 +/- 0.15 mm. These results corresponded to an increase in vessel diameter of 5 +/- 10% in the treatment group and a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014). In the group pretreated with captopril (2 x 10(-4) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.64 +/- 0.11 mm to 0.71 +/- 0.10 mm. These results corresponded to an increase in vessel diameter of 14 +/- 19% in the treatment group, compared with a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014). CONCLUSION: These results demonstrate that [D-Val22]big ET-1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors, affecting big ET-1-induced contraction of the rabbit basilar artery.

Animals↗
PubMed2001

Redistribution of glycolipid raft domain components induces insulin-mimetic signaling in rat adipocytes.

Caveolae and caveolin-containing detergent-insoluble glycolipid-enriched rafts (DIG) have been implicated to function as plasma membrane microcompartments or domains for the preassembly of signaling complexes, keeping them in the basal inactive state. So far, only limited in vivo evidence is available for the regulation of the interaction between caveolae-DIG and signaling components in response to extracellular stimuli. Here, we demonstrate that in isolated rat adipocytes, synthetic intracellular caveolin binding domain (CBD) peptide derived from caveolin-associated pp59(Lyn) (10 to 100 microM) or exogenous phosphoinositolglycan derived from glycosyl-phosphatidylinositol (GPI) membrane protein anchor (PIG; 1 to 10 microM) triggers the concentration-dependent release of caveolar components and the GPI-anchored protein Gce1, as well as the nonreceptor tyrosine kinases pp59(Lyn) and pp125(Fak), from interaction with caveolin (up to 45 to 85%). This dissociation, which parallels redistribution of the components from DIG to non-DIG areas of the adipocyte plasma membrane (up to 30 to 75%), is accompanied by tyrosine phosphorylation and activation of pp59(Lyn) and pp125(Fak) (up to 8- and 11-fold) but not of the insulin receptor. This correlates well to increased tyrosine phosphorylation of caveolin and the insulin receptor substrate protein 1 (up to 6- and 15-fold), as well as elevated phosphatidylinositol-3' kinase activity and glucose transport (to up to 7- and 13-fold). Insulin-mimetic signaling by both CBD peptide and PIG as well as redistribution induced by CBD peptide, but not by PIG, was blocked by synthetic intracellular caveolin scaffolding domain (CSD) peptide. These data suggest that in adipocytes a subset of signaling components is concentrated at caveolae-DIG via the interaction between their CBD and the CSD of caveolin. These inhibitory interactions are relieved by PIG. Thus, caveolae-DIG may operate as signalosomes for insulin-independent positive cross talk to metabolic insulin signaling downstream of the insulin receptor based on redistribution and accompanying activation of nonreceptor tyrosine kinases.

Adipocytes↗
PubMed2001

Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts.

CPT-11, a DNA topoisomerase I inhibitor, has demonstrated clinical activity in colorectal cancer. Flavopiridol, a cyclin-dependent kinase inhibitor, is rapidly emerging as a chemotherapy modulator. To enhance the therapeutic index of CPT-11 in colon cancer, we studied the combination of these two drugs in relatively resistant human colon cancer cells, Hct116. Exposure of parental Hct116 cells to clinically achievable concentrations of SN-38 (the active metabolite of CPT-11) induces p21 and a G(2) arrest. However, these conditions fail to induce apoptosis. In contrast, Hct116 cells that are p21 deficient (p21-/- Hct116) readily undergo apoptosis after treatment with SN-38. In this study we show that the parental Hct116 cells can be sensitized to undergo apoptosis by the addition of flavopiridol after SN-38 treatment. The induction of apoptosis was greatest with sequential therapy consisting of SN-38 followed by flavopiridol. Clonogenic assays also showed greatest inhibition with this sequence. Sequential treatment with SN-38 followed by flavopiridol was associated with higher activation of caspase-3 and greater cleavage of both p21 and XIAP, an inhibitor of apoptosis, compared with other treatment schedules. CPT-11 induced some tumor regressions but no complete responses in the p21-intact Hct116 xenografts. CPT-11 with flavopiridol more than doubled tumor regression, compared with CPT-11 alone, and produced a 30% complete response rate. Our studies indicate that CPT-11 induces cell cycle arrest rather than cell death and that flavopiridol, by activating the caspase cascade, cleaves the inhibitors of apoptosis and sensitizes the cells to undergo cell death. Thus, flavopiridol combined with CPT-11 may provide a completely new therapeutic approach in the treatment of colon cancer.

Animals↗
PubMed2000

Measuring the quantity and activity of mitochondrial electron transport chain complexes in tissues of central nervous system using blue native polyacrylamide gel electrophoresis.

Mitochondrial dysfunction and degeneration are associated with many neurodegenerative disorders. A dysfunctional mitochondrial electron transport chain (ETC) impairs ATP production and accelerates the generation of free radicals. To evaluate mitochondrial function, reliable methods are needed. Conventional spectrophotometric assays may not eliminate interference from nonspecific enzyme activities and do not measure quantities of specific ETC complexes. Blue native polyacrylamide gel electrophoresis (BN-PAGE) has been used to resolve mitochondrial ETC complexes. Combined with histochemical staining, it has also been applied to measure ETC enzyme activities in muscles. The current study is to determine (1) whether BN-PAGE can be used to detect ETC complexes from different regions of the central nervous system (CNS) and (2) the quantitative range of BN-PAGE in measuring the amounts and activities of different ETC complexes. By systematically varying the protein amount and the time of histochemical reactions, we have found linear ranges comparable to spectrophotometric assays for measuring enzyme activities of several ETC complexes. In addition, we found linear ranges for measuring protein quantities in several ETC complexes. These results demonstrate that BN-PAGE can be used to measure the amount and activity of the ETC enzymes from the nerve tissues and, thus, can be applied to evaluate the functional changes of mitochondria in neurodegenerative disorders.

Animals↗
PubMed2000

Autocatalytic nitration of P450CAM by peroxynitrite.

Peroxynitrite (PN) gains high selectivity as a physiological oxidizing and nitrating agent through catalysis by metal ions. This was established for the heme-thiolate (P450) enzyme prostacyclin synthase which was tyrosine nitrated and inhibited at low PN levels [FEBS Lett. 382 (1996) 101]. Other P450 proteins reacted in a similar manner and a ferryl species (Compound II) has been identified as an intermediate during reactions with PN [Nitric Oxide 3 (1999) 142]. Here we investigated cytochrome P450CAM and found that it catalyzes the decomposition of PN as well as an increased nitration of phenol. The latter at the expense of phenol hydroxylation is characteristic for the proton-assisted PN action. PN also caused self-nitration of P450CAM at several tyrosine residues. Two of them, Y96 and Y305 were largely protected in the presence of the ligand metyrapone. Unlike other heme-thiolate proteins P450CAM did not form distinct spectral intermediates characteristic for Compound II. We conclude that P450CAM serves as a model for the nitration of prostacyclin synthase with respect to its autocatalytic tyrosine nitration and its prevention by blocking the active site.

Binding Sites↗