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Biomedical subjects

S Jung

Publications and source records attributed to S Jung.

At least 199 records · Page 11Linked to original sources
PubMed1991

T cell vaccination does not induce resistance to experimental autoimmune neuritis.

The effectiveness of T cell vaccination was analyzed in experimental autoimmune neuritis (EAN) that can be induced by immunization with bovine P2 protein or a peptide representing the amino acids 53-78 of P2 (P2 53-78). Lewis rats were vaccinated with glutaraldehyde-fixed lymph node cells which had been primed in vivo with P2 protein or P2 53-78 and had been activated in vitro with concanavalin A. Vaccinated animals were not protected from EAN induced by immunization with P2 protein in complete Freund's adjuvant (CFA). In a second set of experiments Lewis rats were vaccinated with irradiated or fixed P2-specific T cell lines of different specificity and neuritogenicity and were subsequently challenged with P2 53-78 in CFA. Likewise, severity of P2 53-78-induced EAN was not different between naive and T line-vaccinated groups. In spleens of vaccinated animals a substantial suppressive activity was demonstrated which was positively correlated with a weak anti-ergotypic response of these spleen cells. The fact that development of actively induced EAN was not prevented or even mitigated by T cell vaccination, in spite of an apparent vaccination-induced response to and on T lymphocytes, suggests that protection from disease is not readily induced in every autoimmune disease model.

Animals↗
PubMed1991

Monoamine turnover in the brain of mice during development of tolerance to the anticonvulsant effect of clonazepam.

Mice were treated for 14 days with clonazepam, 0.5 mg/kg i.p. twice daily, during which time partial tolerance to the anticonvulsant effect against pentetrazole developed. The development of tolerance was paralleled by a reduced turnover of noradrenaline in the whole brain, and of dopamine in the midbrain. The turnover of 5-HT was increased during the first week of treatment, but decreased thereafter. These changes in monoamine turnover, which are thought to be GABA-mediated, are consistent with an increased seizure susceptibility, and may contribute to the development of tolerance to the anticonvulsant effect of benzodiazepines.

Animals↗
PubMed1991

Nicotinamide ethers: novel inhibitors of calcium-independent phosphodiesterase and [3H]rolipram binding.

The synthesis and biological properties of a series of nicotinamide ethers are described. These compounds, structurally novel calcium-independent phosphodiesterase inhibitors, also inhibit the binding of [3H]rolipram to rat brain membranes and reverse reserpine-induced hypothermia in the mouse. Several compounds exhibited potent in vivo activity comparable to the standard agent, rolipram.

Animals↗
PubMed1991

Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

Animals↗
PubMed1990

Prophage lambda libraries for isolating cDNA clones by functional screening.

Isolation of cDNA clones from lambda gt11 phage libraries by functional screening is limited by the low amount of lacZ-cDNA-encoded fusion protein synthesized in an isolated phage plaque. The amount of specific cDNA-encoded protein can be significantly enhanced by expression in bacterial colonies rather than phage plaques. Escherichia coli was lysogenized with a lambda gt11 cDNA expression library from Dictyostelium discoideum. Bacteria were selected for the presence of the lambda gt11 prophage by elimination of nonlysogenic parental cells with a lambda cI phage. The usefulness of the lysogen library was demonstrated by immuno-screening and functional screening with two different radiolabeled ligands. cDNA clones encoding a well-characterized D. discoideum protein, the regulatory subunit of the cAMP-dependent protein kinase, were isolated by screening the lysogen library with antibodies. Clones encoding this protein could also be identified by functional screening with [3H]cAMP, demonstrating that the limit of detection of positive clones by ligand screening is at least an order of magnitude lower for the lysogen library than for the corresponding phage library. We have subsequently used the lysogen library to isolate cDNA clones encoding calmodulin-binding protein(s) from D. discoideum by functional screening with [125I]calmodulin. For these clones, screening of the corresponding phage library had previously been found unsuccessful.

Bacteriophage lambda↗
PubMed1990

Slow tight-binding inhibition of prolyl endopeptidase by benzyloxycarbonyl-prolyl-prolinal.

Prolyl endopeptidase is a serine proteinase that specifically cleaves peptides on the carboxy side of proline residues. Wilk & Orlowski [(1983) J. Neurochem. 41, 69-75] have shown that benzyloxycarbonyl-prolyl-prolinal (Z-prolyl-prolinal) is a potent inhibitor of prolyl endopeptidase. We show that Z-prolyl-prolinal is a slow-binding inhibitor of mouse brain prolyl endopeptidase with Ki 0.35 +/- 0.05 nM. Kinetic analysis indicates that the mechanism is a simple, but slow, reversible equilibrium between free and bound enzyme (E + I in equilibrium EI) with rate constants for association (kon) and dissociation (koff) of 1.6 X 10(5) M-1.s-1 and approx. 4 X 10(-5) s-1 respectively. Slow-binding inhibition is dependent on the presence of the aldehyde group since the alcohol (Z-prolyl-prolinol) is a rapid and 50,000-fold poorer inhibitor (Ki 19 microM). Prolyl endopeptidase from human brain is also inhibited by Z-prolyl-prolinal with kinetics similar to those of the mouse brain enzyme.

Animals↗
PubMed1990

Substrate specificity for myelin basic protein-specific protein methylase I.

The substrate specificity of bovine brain myelin basic protein (MBP)-specific protein methylase I (S-adenosyl-L-methionine:protein-L-arginine N-methyltransferase, EC 2.1.1.23), which methylates arginine residues of protein, has been studied using various MBPs, several synthetic peptides and heterogeneous nuclear ribonucleoprotein complex protein (hnRNP). (1) Among MBPs from different species of brain, the carp MBP was found to be the best substrate for MBP-specific protein methylase I. This high degree of methyl acceptability is most likely due to the fact that carp MBP is not in vivo methylated at the arginine residue (Deibler, G.E. and Martenson, R.E. (1973) J. Biol. Chem. 248, 2387-2391) and that the methylatable amino acid sequence is present in this protein. (2) In order to study the minimum chain length of MBP polypeptide which functions as the methyl acceptor, several synthetic polypeptides whose sequences are identical to the region surrounding the residue 107 of bovine MBP (the in vivo methylation site) were synthesized. It was found that the hexapeptide, Gly-Lys-Gly-Arg-Gly-Leu (corresponding to residues 104-109 of bovine MBP), was the shortest methyl accepting peptide, while the tetrapeptide, Gly-Arg-Gly-Leu (corresponding to residues 106-109) was inactive as a substrate. (3) hnRNP protein is known to contain methylarginine at residue 193 (Williams, K.R., Stone, K.L., LoPresti, M.B., Merrill, B.M. and Plank, S.R. (1985) Proc. Natl. Acad. Sci. USA 82, 5666-5670) which is post-translationally modified. Thus, the RNP protein overproduced in Escherichia coli and therefore did not contain methylarginine was examined for its methyl acceptability. It was found that neither MBP-specific nor histone-specific protein methylase I could methylate this methylarginine-less RNP protein. This suggests a possible existence of a distinct protein methylase I specific for this nuclear protein.

Amino Acid Sequence↗
PubMed1990

Carrageenan inflammation increases bradykinin sensitivity of rat cutaneous nociceptors.

The present study examined the hypothesis that the sensitivity of polymodal nociceptors to bradykinin (BK) might be increased in inflamed tissue. Inflammation was induced in the rat dorsal hindpaw skin by subcutaneous injection of blue stained carrageenan. Three hours later skin and saphenous nerve were excised and the chemical sensitivity of mechano-heat-sensitive C- and A delta fibres was examined in vitro using repeated superfusion of the receptive fields with 10(-5) M BK. Only units within and at the border of the inflamed area showed signs of sensitization, in the form of ongoing activity and lower thresholds to heat stimuli. No sensitization to mechanical (von Frey) stimulation occurred. The incidence of BK responsiveness was significantly higher and the tachyphylaxis to repeated BK application was smaller inside the inflamed skin than outside or in unconditioned skin. Thus, more nociceptive afferents would be driven more effectively than in normal skin, supporting the particular role of BK in inflammatory pain.

Action Potentials↗
PubMed1990

Susceptibility and resistance of human autoimmune T cell activation to the immunoregulatory effects of transforming growth factor (TGF) beta 1, beta 2, and beta 1.2.

The transforming growth factors type beta (TGF-beta) regulate immune responses by suppressing a variety of leukocyte functions. Using a panel of human autoimmune T cell lines specific for the acetylcholine receptor (AchR) we investigated the immunoregulatory effects of TGF-beta 1, TGF-beta 2, and TGF-beta 1.2. The cytokines have identical effects inhibiting activation of most T line cells and the activation-dependent changes in interleukin-2 (IL-2) receptor and T cell receptor expression. IL-2-dependent growth was not modulated by TGF-beta. However, autoimmune T cell lines specific for AchR differ in their susceptibility to TGF-beta and some are completely refractory. Resistance of autoimmune T cell activation to immunosuppressive cytokines might be an element in the development of chronic autoimmune disease.

Antigens, Surface↗
PubMed1986

Does neurogenic inflammation alter the sensitivity of unmyelinated nociceptors in the rat?

This study on neurogenic inflammation aimed at comparing the effects of antidromic nerve stimulation and of cutaneous application of mustard oil on the mechanical and thermal sensitivity of cutaneous C-fibres in the rat saphenous nerve. They were tested with von Frey hairs and series of radiant heat stimuli in 5-min intervals before and after one of the above treatments. Antidromic electrical stimulation was effective in evoking a plasma extravasation in the saphenous region as revealed by prior intravenous injection of Evans blue. However, it did not evoke spontaneous activity in the polymodal C-fibres tested nor did it markedly affect their mechanical and thermal excitability in periods of up to 1 h after stimulation. Mustard oil, topically applied to the receptive fields, also evoked localized Evans blue extravasation and strongly affected the C-units. They responded to the application of the irritant with sustained firing; most units showed an increased thermal sensitivity after the treatment. This involved a lowering of the threshold and an increase of the suprathreshold discharge. Even low threshold mechanosensitive C-fibres transiently developed heat sensitivity. In some polymodal units a transient sensitization was followed by a persistent desensitization which abolished their thermal and mechanical sensitivity. Mustard oil application and antidromic nerve stimulation seem to be similar in evoking cutaneous vasodilation and plasma extravasation but different in inducing nociceptor sensitization.

Action Potentials↗
PubMed1986

[Blood fibronectin changes in various neoplasms].

In 85 patients presenting with various cancers, changes in the frequencies of plasma fibronectin and of the carcino-embryonic antigen (CEA) were compared and the results were correlated with the degree of extension. Forty-six percent of patients with mammary adenocarcinoma had plasma fibronectin values higher than the age-related limit range, but only 18% had an increase in CEA. In patients with secondary metastases, the highest values were significantly different from those found in controls. In these cases, fibronectin was present in abnormal concentrations in more than 80% of the patients, and CEA in 50%. Positive fibronectin values were less frequent in other cancers, except those of the genital tract. Neither fibronectin nor CEA are organ-specific, yet these two tumoral markers differ in the frequency with which they appear, notably in patients with mammary carcinoma.

Adult↗
PubMed1981

[Motility of the small intestine in dogs before and after total colectomy, proctomucosectomy and endorectal ileal pull-through].

In healthy dogs the parameters (amplitude and frequency) of small intestinal motility of segmental and propulsive contractions demonstrate a pressure-gradient directed from oral to aboral. The frequency of segmental contractions in the colo-rectal region shows a vector in the opposite direction. One rarely finds propulsive activity in this area. Following on colectomy, proctomucosectomy and ileum pull-through a distinct increase in segmental small intestinal activity is noticed, while the frequency of propulsive movements simultaneously decrease. Thus it comes to a slowing of the passage of intestinal contents, and to increased water resorption. From these findings we conclude that the small intestine plays an essential part in the regaining of fecal continence in these animals.

Animals↗
PubMedDate not supplied

Multidrug transport in human autoimmune T line cells and peripheral blood lymphocytes.

We studied multidrug transport in human autoimmune T line cells and peripheral blood leukocytes, because multidrug transport is pleiotropically limiting the intracellular accumulation of immunosuppressive and chemotherapeutic agents. We observed that a subpopulation of peripheral blood leukocytes containing CD4+, CD8+ and Ig+ lymphocytes expressed a multidrug transport system. Lymphocytic multidrug transport was seen with all peripheral blood samples analyzed, but showed considerable variations between individuals. In further studies with human lymphocytic cell lines multidrug transport was seen with 18/23 human CD4+ T cell lines. Interestingly, expression of multidrug transport was independent of T cell activation. No significant transport was observed with EBV-transformed human B lymphocytes, rat T line cells or rat, mouse, or guinea pig leukocytes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗