Search PubMed⌕ Search

Biomedical subjects

G Jung

Publications and source records attributed to G Jung.

At least 217 records · Page 12Linked to original sources
PubMed1996

[Postoperative follow-up in hepatic echinococcosis].

OBJECTIVE: To determine whether the monitoring of patients who have undergone surgical excision of hydatid cysts of the liver is useful. Furthermore, sonographic and computertomographic criteria of recurrent hydatid disease should be described. PATIENTS AND METHODS: Of 84 patients operated on for hepatic hydatid disease 42 (22 men, 20 women; mean age 44 [25-82] years) were examined between 6 months and 15 years post-operatively (median of 6 years) clinically, serologically (complement-fixation reaction, immunohaemagglutination) and by ultrasound. If the latter was positive, computed tomography was also performed. RESULTS: Recurrence of hydatid disease in the liver was diagnosed in three patients and in the peritoneal cavity in one patient. The demonstration of internal septa by solitary or multiple daughter cysts proved to be a reliable imaging criterion. CONCLUSION: Ultrasonography should be performed as a baseline test after surgical removal of hydatid cysts in the liver and specific antibody titres measured. This will make it easier to distinguish a recurrence from postoperative changes.

Adult↗
PubMed1996

The sequence of the dictyostelium myo J heavy chain gene predicts a novel, dimeric, unconventional myosin with a heavy chain molecular mass of 258 kDa.

The complete sequence of the Dictyostelium myo J heavy chain gene has been determined from overlapping genomic clones. The gene spans approximately 7400 base pairs, is split by two small introns, and encodes a 2241-residue, 258-kDa heavy chain polypeptide that that is composed of an N-terminal 944-residue myosin head domain, a central 863-residue domain that is predicted to form an alpha helical coiled-coil containing six hinges, and a C-terminal 434-residue globular domain. The head domain is notable in that it contains a approximately 30 residue insert near the nucleotide binding pocket, and five potential calmodulin/myosin light chain binding sites at the head/tail junction. The existence within the Myo J tail domain of both an extensive coiled-coil structure and a large globular domain suggests that this myosin is dimeric and incapable of self-assembly into filaments. While these properties, as well as the overall predicted structure of the Myo J protein, are reminiscent of class V myosins, the sequence of the 434-residue globular tail piece of Myo J shows no similarity to that of either yeast or vertebrate myosins V. Consistent with this, phylogenetic analyses based on myosin head sequence comparisons do not classify Myo J as a type V myosin. These and other sequence comparisons indicate that Myo J and two as-yet-unclassified unconventional myosins from Arabidopsis represent members of the newest class within the myosin superfamily (class XI). Northern blots analyses suggest that Myo J may function predominantly in vegetative Dictyostelium cells. Finally, Southern blot analyses suggest that Dictyostelium possesses another myosin that is very closely related to Myo J.

Amino Acid Sequence↗
PubMed1996

Amino acid preferences in the octapeptide subunit of the major histocompatibility complex class I heterotrimer H-2Ld.

Major histocompatibility complex class I (MHC-I) molecules are heterotrimers composed of polymorphic alpha-chains, monomorphic beta-chains, and peptides of eight or nine amino acids. The peptides are derived from various intracellularly occurring proteins and are very heterogeneous. They are essential for a stable conformation of the MHC-I protein at physiological temperature. This study presents results from stabilization experiments that were designed to determine the impact of the amino acids in every sequence position of octapeptides on the thermal stability of the mouse MHC-I molecule H2-Ld. OX7 octapeptide libraries with one defined and seven randomized positions were employed as they allow the effects of individual amino acids to be determined. The results confirm the importance of the motif amino acids proline and leucine for positions 2 and 8, respectively, of octapeptides. They are among the most efficient amino acids for these positions. However, with a few exceptions, all amino acids are permitted in all eight sequence positions. Hydrophobic amino acids are generally favored. Charged amino acids, especially aspartic acid and glutamic acid, are disfavored. Stabilization indices were defined as measures for the MHC stabilization power of the amino acids. These indices can serve to predict the efficiency of peptide binding to H-2Ld and can guide the design of T-cell epitopes.

Amino Acid Sequence↗
PubMed1996

T- and B-cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-hepatitis C virus--positive blood donors without viremia.

As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV-related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core- and E1-related 25-mer peptides were examined in 10 healthy anti-HCV-seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B). In addition, cellular recognition of recombinant HCV proteins (core, NS3, NS4A, NS5A, NS5B) were investigated. In group A, stronger T-cell responses were detected against both HCV proteins (core, P = .03; NS4, P = .005; NS5B, P = .03) and peptides. Proliferation was induced by the same peptides in each group, defining at least five distinctive epitopes within core (amino acids [aa] of 20-44, aa 39-63, aa 79-103, aa 118-152 and aa 148-172) and three regions within E1(aa 198-252, aa 308-372, and aa 368-392). Subjects with strong T-cell responses had low or no detectable levels of peptide-specific antibodies, and vice versa. In particular, T-cell responses were more common in group A; B-cell responses were more common in group B. From our data, we conclude that a benign course of HCV infection may be the consequence of the effective activation of T-helper lymphocytes.

Adolescent↗
PubMed1996

Structures of lantibiotics studied by NMR.

During the last decade, Nuclear Magnetic Resonance has played an important role in the unravelling of the primary and tertiary structures of lantibiotics. A short overview of these studies, together with typical spatial structures obtained, is presented.

Amino Acid Sequence↗
PubMed1996

Protein engineering of lantibiotics.

Whereas protein engineering of enzymes and structural proteins nowadays is an established research tool for studying structure-function relationships of polypeptides and for improving their properties, the engineering of posttranslationally modified peptides, such as the lantibiotics, is just coming of age. The engineering of lantibiotics is less straightforward than that of unmodified proteins, since expression systems should be developed not only for the structural genes but also for the genes encoding the biosynthetic enzymes, immunity protein and regulatory proteins. Moreover, correct posttranslational modification of specific residues could in many cases be a prerequisite for production and secretion of the active lantibiotic, which limits the number of successful mutations one can apply. This paper describes the development of expression systems for the structural lantibiotic genes for nisin A, nisin Z, gallidermin, epidermin and Pep5, and gives examples of recently produced site-directed mutants of these lantibiotics. Characterization of the mutants yielded valuable information on biosynthetic requirements for production. Moreover, regions in the lantibiotics were identified that are of crucial importance for antimicrobial activity. Eventually, this knowledge will lead to the rational design of lantibiotics optimally suited for fighting specific undesirable microorganisms. The mutants are of additional value for studies directed towards the elucidation of the mode of action of lantibiotics.

Amino Acid Sequence↗
PubMed1996

Bone marrow-derived macrophage lines and immortalized cloned macrophage and dendritic cells support priming of Borrelia burgdorferi--specific T cell responses in vitro and/or in vivo.

In vitro propagated bone marrow-derived macrophage populations (BMMO) as well as cloned immortalized macrophage (MT2/1) and dendritic (D2SC/1) cell lines were analyzed for their capacity to promote activation and/or proliferation of naïve T cells to Borrelia burgdorferi antigens in vitro and in vivo. All three cell types constitutively express high levels of MHC class I structures as well as the co-stimulatory molecules B7/BB1 and heat-stable antigen (HSA); MHC class II molecules (I-A) are upregulated following incubation with either intact spirochetes or the purified lipoprotein OspA (Lip-OspA) but not with its delipidated from (MDP-OspA). Only BMMO were able to induce proliferation of naïve T cells or T cells derived from infected mice to intact spirochetes in vitro. However, all three accessory populations could support primary and secondary T cell responses to Lip-OspA but not, or only marginally, to MDP-OspA under similar conditions. The number of accessory cells required for optimal stimulation of naïve or pre-sensitized T cells was approximately 3 x lower for D2SC 1 than for BMMO or MT2/1. In addition, BMMO pre-pulsed with Lip-OspA were able to prime T cells in vivo, indicating a crucial role for the lipid moiety in antigen presentation. From two truncated lipopeptides of Lip-OspA containing either 20 or 6 aminoterminal residues, only Lip-OspApep20 but not Lip-OspApep6 induced significant proliferation in naïve for pre-sensitized T cells in vitro, suggesting that T cells mainly respond to the protein rather than the lipid moiety of OspA. Thus, the data demonstrate that BMMO, MT2/1 and D2SC/1 have differential capacities to prime spirochete-reactive T cells and to support their growth in vitro, suggesting that optimal activation and propagation of T cells also depends on the quality of the antigen.

Amino Acid Sequence↗
PubMed1996

A 'mixed' self-assembled monolayer for an impedimetric immunosensor.

A synthetic peptide with the amino acid sequence 135-154 of the capsid protein VP1 of the foot-and-mouth-disease virus was modified with omega-hydroxyundecanethiol and applied together with non-derivatised omega-hydroxyundecanethiol for consecutive adsorption onto gold electrodes according to self-assembling procedures. The binding of a specific antibody to prepared recognition layers could be monitored by measurement of impedance or capacitance. In order to avoid non-specific effects, all measurements were performed in the presence of BSA. The complex between the antigenic peptide and the antibody was split by applying 6 M urea solution. The gold electrodes were mounted into an optimised flow-through system in order to perform capacitance-time measurements. The immobilised peptide can be recognised repeatedly by specific antibodies.

Amino Acid Sequence↗
PubMed1996

Synthetic peptides coupled to the lipotripeptide P3CSS induce in vivo B and Thelper cell responses to HIV-1 reverse transcriptase.

To evaluate the ability of the lipotripeptide P3CSS to increase peptide-specific immune responses in vivo, we immunized mice from different inbred strains (BALB/c, C3H/HeJ, C57BL/6) with the 22-mer lipopeptide conjugates P3CSS-[RT-(522-543)] and P3CSS-[RT-(528-549)] of HIV-1 reverse transcriptase (RT) which included an immunodominant Th epitope [i.e. RT-(528-543)] characterized previously. Analysis of T and B cell responses to these lipopeptide conjugates indicated that specific Th responses could be readily induced in vivo. The peptide segments could also efficiently prime mice for secondary recognition of native RT. The use of shorter peptides permitted a delineation of the minimal T cell recognition site of this RT C-terminal region [i.e. RT-(528-540)]. Close to this T cell epitope we identified a B cell determinant containing the motif EQVD [RT-(546-549)] which was recognized in three different strains of mice (H-2b, H-2d and H-2k). A comparison with X-ray analysis of the C-terminal region of HIV-1 reverse transcriptase indicated exposed positions of these Th and B cell epitopes. Both the presence of T and B cell sites and its limited polymorphism make the region RT-(528-549) a promising candidate for vaccine design. The use of the P3CSS adjuvant/carrier principle as a nontoxic adjuvant may be of major importance in the development of vaccines applicable to humans.

Adjuvants, Immunologic↗
PubMed1996

Protection against bacterial infection by urea extracts from Salmonella.

Immunization assays were performed in NMRI mice using urea extracts from both the S-form and an R-mutant of S. typhimurium. Our results show that, apart from providing protection against infection, both vaccines induced a DTH (delayed type hypersensitivity) reaction against the antigen extract. The strength of the DTH reaction depended on the type of test antigen used, the urea extracts proving to be superior to extracts obtained by ultrasonication. With the urea extract, all animals responded in the foot pad test. Both parameters of the immune response, protection against infection and the strength of DTH, could be further enhanced by a lipopeptide adjuvant, which was effective both in mixture and conjugate form; the humoral immune response was not enhanced. Thus, urea extract vaccines from S. typhimurium induce a cell-mediated response which can be further enhanced by lipopeptide adjuvants.

Animals↗
PubMed1996

Isolation of a new epidermin variant from two strains of Staphylococcus epidermidis--frequency of lantibiotic production in coagulase-negative staphylococci.

A novel lantibiotic identified during the screening of 187 coagulase-negative staphylococci, has been structurally characterised. (Val1, Leu6)-epidermin was purified from culture supernatants of two Staphylococcus epidermidis strains, BN-V1 and BN-V301 following successive separation by adsorption, cation exchange and C18 reversed-phase chromatography. Separation of the purified peptides by SDS-polyacrylamide gel electrophoresis suggested a molecular mass of ca. 2000 Da and electrospray mass spectrometry subsequently demonstrated that both peptides had a mass of 2151 Da; a mass which is different from that of all previously described antimicrobial peptides. Amino acid analysis showed that both peptides contained lanthionine and were very similar to epidermin, while automated N-terminal sequencing by Edman degradation confirmed the identity of the two peptides as a natural variant of the antimicrobial lantibiotic epidermin, and demonstrated the conservative amino acid exchanges in positions one and six.

Alanine↗
PubMed1996

Hierarchic T-cell help to non-linked B-cell epitopes.

The induction of antibodies against peptides requires the presence of a T helper cell epitope. In the absence of an added T-cell epitope only 10% of the mice, or less depending on the strain, gave an antibody response to a series of peptides of the measles virus (MV) fusion (F) protein. After coimmunization with a non-covalently coupled T-cell epitope more than 60% of the peptides became immunogenic. Considerable differences became apparent when BALB/c mice were immunized with peptides in the presence of different T-cell epitopes. An immunodominant T-cell epitope of the MV-F protein was more efficient than a subdominant or a cryptic T-cell epitope in providing help to a non-linked B-cell epitope. There is both a ranking order of the amount of help which B-cell epitopes require and a ranking order for the help T-cell epitopes are able to provide. The capability of a T-cell epitope to provide help to a B-cell epitope correlated with its own immunogenicity, i.e. the intensity of the antibody response to the peptide representing the T-cell epitope. The data suggest that for each MHC class II allele there is an optimal T-cell epitope which can provide help to a maximal number of B-cell epitopes and that such a peptide can be identified by its ability to induce antibodies against itself. By using this strategy, the authors were able to induce antibodies which cross-reacted with the MV.

Animals↗
PubMed1996

[Comparison of fast turbo-spin-echo and gradient- and spin-echo sequences as well as echo planar imaging with conventional spin-echo sequences in MRI of focal liver lesions at 1.0 tesla].

PURPOSE: To evaluate the value of rapid T2-weighted turbo-spin sequences (TSE), turbo-spin-echo sequences with shortened echo spacing (UTSE), gradient-and-spin-echo sequences (GraSE) and T1-weighted echo-planar imaging (EPI) in comparison with conventional spin-echo sequences (SE) in the diagnosis of focal liver lesions. METHODS: 20 patients with malignant focal liver lesions underwent magnetic resonance imaging at 1.0 tesla. RESULTS: The use of fast T2-sequences (TSE, UTSE, GraSE) reduced the examination time to about 35-50%. Artifacts were reduced compared with the conventional T2-SE sequence. Quantitative analysis demonstrated that UTSE imaging had the highest tumor/liver contrast-to-noise ratio (CNR) followed by TSE, T2-SE and GraSE sequences. CNR with EPI was lower than with the T1-SE sequence (p < 0.05). CONCLUSION: Turbo-spin-echo sequences with shortened echo spacing yield a shorter imaging time and improved image quality without loss of signal intensity in tumor/liver-CNR, compared with conventional T2-pulse sequences in liver imaging at 1.OT.

Adult↗
PubMed1996

Dictyostelium mutants lacking multiple classic myosin I isoforms reveal combinations of shared and distinct functions.

Dictyostelium cells that lack the myoB isoform were previously shown to exhibit reduced efficiencies of phagocytosis and chemotactic aggregation ("streaming") and to crawl at about half the speed of wild-type cells. Of the four other Dictyostelium myosin I isoforms identified to date, myoC and myoD are the most similar to myoB in terms of tail domain sequence. Furthermore, we show here that myoC, like myoB and myoD, is concentrated in actin-rich cortical regions like the leading edge of migrating cells. To look for evidence of functional overlap between these isoforms, we analyzed myoB, myoC, and myoD single mutants, myoB/myoD double mutants, and myoB/myoC/myoD triple mutants, which were created using a combination of gene targeting techniques and constitutive expression of antisense RNA. With regard to the speed of locomoting, aggregation-stage cells, of the three single mutants, only the myoB mutant was significantly slower. Moreover, double and triple mutants were only slightly slower than the myoB single mutant. Consistent with this, the protein level of myoB alone rises dramatically during early development, suggesting that a special demand is placed on this one isoform when cells become highly motile. We also found, however, that the absolute amount of myoB protein in aggregation-stage cells is much higher than that for myoC and myoD, suggesting that what appears to be a case of nonoverlapping function could be the result of large differences in the amounts of functionally overlapping isoforms. Streaming assays also suggest that myoC plays a significant role in some aspect of motility other than cell speed. With regard to phagocytosis, both myoB and myoC single mutants exhibited significant reductions in initial rate, suggesting that these two isoforms perform nonredundant roles in supporting the phagocytic process. In triple mutants these defects were not additive, however. Finally, because double and triple mutants exhibited significant and progressive decreases in doubling times, we also measured the kinetics of fluid phase endocytic flux (uptake, transit time, efflux). Not only do all three isoforms contribute to this process, but their contributions are synergistic. While these results, when taken together, refute the simple notion that these three "classic" myosin I isoforms perform exclusively identical functions, they do reveal that all three share in supporting at least one cellular process (endocytosis), and they identify several other processes (motility, streaming, and phagocytosis) that are supported to a significant extent by either individual isoforms or various combinations of them.

Animals↗
PubMed1996

Activation of T cells by the ragged tail of MHC class II-presented peptides of the measles virus fusion protein.

The efficient and sustained immune response of an antigen requires T cell epitopes, capable of inducing a long lasting T cell memory. To detect T cell epitopes of the measles virus fusion protein (MV-F), the proliferation of lymphocytes from late convalescent donors in response to overlapping pentadecapeptides covering the whole protein sequence was studied. Three major immunodominant regions (F51-70, F121-135 and F211-225) containing promiscuous peptides induce proliferation in peripheral blood lymphocytes in approximately 50% of the donors. Potential DR1-restricted epitopes were mapped using an MHC competition binding assay. Both the proliferation and the binding data identified a DR1-restricted T cell epitope (F51-65). Contact sites of the peptide HQSLVIKLMPNITLL with MHC were characterized using substitution analogs. Alanine substitutions at most positions did not interfere with F51-65 binding. These analogs were therefore useful for studying the residues which were recognized by the TCR of MV- and F51-induced T cells lines. In addition to amino acid residues of the core of peptide F51-65 both the C-terminal and the N-terminal amino acids were essential for T cell interaction. Since peptides presented by class II molecules vary in length, these findings suggest that residues of the ragged tail are important for T cell activation. It is speculated that in late convalescent donors the length of the flanking sequence of MHC II-restricted peptides may play a role in controlling the heterogeneity of MV-specific T cell clones recruited as T helper/memory cells.

Adult↗