Search PubMed⌕ Search

Biomedical subjects

J Uhl

Publications and source records attributed to J Uhl.

31 records · Page 2Linked to original sources
PubMed1988

Interleukin-1 activates phospholipase A2 in human synovial cells.

Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1.

Arthritis, Rheumatoid↗
PubMed1988

The distribution and clearance of radiolabeled human interleukin-1 beta in mice.

Mice were injected with radiolabeled human interleukin-1 beta (IL-1) and monitored for tissue localization and route of clearance. IL-1 was labeled with no apparent loss of in vitro biological activity. Mice were injected by intravenous (i.v.), intraperitoneal (i.p.), and subcutaneous (s.c.) routes with either low dose (10 ng radiolabeled) or high dose (10 ng radiolabeled with 10 micrograms unlabeled) IL-1. Blood and urine were monitored and various tissues were counted for radioactivity after 2, 24 or 48 hours. Injection of either dose of IL-1 by i.v. route demonstrates a rapid initial loss of IL-1 from the circulation followed by a slower loss over the next hour. Injection by i.p. or s.c. routes gives an initial peak in circulating IL-1 after 10 minutes which is sustained over at least the next 7 hours with the high dose. Circulating IL-1 is associated with the plasma fraction and is not cell associated. Two hours after injection, most tissues examined were found to contain an equal amount of IL-1 on a weight basis with the exception of bone, which contains half the level found in other tissues, and kidney, which contains 4-8 fold more IL-1. The major route of clearance is the kidney with 10-20% of label found in the urine within hours of injection. IL-1 found in the urine contains intact 17 kD IL-1.

Animals↗
PubMed1986

Evidence that interleukin-1 induction of synovial cell plasminogen activator is mediated via prostaglandin E2 and cAMP.

Addition of the cyclooxygenase inhibitor indomethacin to human synovial cells in culture, at concentrations which completely block prostaglandin E2 (PGE2) synthesis, reversibly inhibited the interleukin-1 (IL-1) stimulation of cell-associated and extracellular plasminogen activator (PA) production. Results of mixing experiments suggested that the inhibition by indomethacin was not due to stimulation of production and/or activation of a PA inhibitor, but reflected inhibition of PA synthesis. Simultaneous addition of PGE2 or dibutyryl cAMP prevented the inhibition by indomethacin. Addition of the phosphodiesterase inhibitor, theophylline, the adenylate cyclase stimulator, forskolin, or dibutyryl cAMP caused an enhancement of the IL-1 induction of synovial cell PA. These results suggest that the IL-1 induction of synovial cell PA occurs via generation of endogenous PGE2 and cAMP.

Bucladesine↗
PubMed1986

Bradykinin does not mediate activation of glucose transport by muscle contraction.

The purpose of this study was to evaluate the report that bradykinin is the "muscle activity hypoglycemia factor" responsible for the activation of glucose transport that occurs in response to muscle contractile activity. Stimulation of rat epitrochlearis muscles to contract resulted in approximately a fourfold increase in the rate of intracellular accumulation of the nonmetabolizable glucose analog 3-O-methylglucose. Incubation of the muscles with high concentrations of aprotinin (Trasylol), a polypeptide inhibitor of kallikrein which blocks formation of kinins, did not inhibit the activation of sugar transport by contractile activity. Furthermore incubation of muscles with bradykinin did not have a stimulatory effect on the uptake of 3-methylglucose either at a physiological concentration or at high concentrations. These results provide no support for the claims that aprotinin prevents the activation of sugar transport in muscle by contractile activity or that bradykinin is the muscle activity hypoglycemia factor.

3-O-Methylglucose↗
PubMed1986

Interleukin 1 stimulation of synovial cell plasminogen activator production.

Addition of human monocyte interleukin 1 (IL-1) to cultured human synovial cells can cause an increase in both cell associated (30-fold) and extracellular (40-fold) plasminogen activator (PA) activity. This increase was inhibited by antibody directed against IL-1 and phenylglyoxal. PA activity could be detected 3 h after the addition of IL-1, continued to increase for 24 h and was dependent on RNA and protein synthesis. The molecular weight of the PA produced from the IL-1 stimulated synovial cells was 55,000 +/- 1,000. Mononuclear cell conditioned media (MCCM) also stimulated synovial cells to produce PA. This stimulation was partly inhibited by anti-IL-1 thus suggesting the presence of appreciable IL-1 activity in MCCM. These results could provide clues as to how immune events are linked to cartilage destruction associated with rheumatoid arthritis.

Cells, Cultured↗
PubMed1985

Pseudomonas aeruginosa cytotoxin stimulates prostacyclin production in cultured pulmonary artery endothelial cells: membrane attack and calcium influx.

The effects of highly purified Pseudomonas aeruginosa cytotoxin were investigated on cultured pulmonary artery endothelial cells. This toxin dose-dependently (7.5-60 micrograms/ml) and time-dependently (20-75 minutes) stimulated the release of radiolabeled arachidonic acid and metabolites and the synthesis of prostacyclin in the absence of overt cell damage (no enhanced lactate dehydrogenase [LDH] release). Preincubation of the toxin with neutralizing antibodies abolished the effect. The toxin response on endothelial cells required extracellular calcium but not magnesium and was accompanied by a calcium influx. Interference with intracellular calcium function by TMB 8 or with (calcium)-calmodulin function by trifluoperazine and W7 dose-dependently reduced the cytotoxin mediated synthesis of prostacyclin. Calcium channel blockers (nimodipine, diltiazem, verapamil, D 888), however, were ineffective in this system. Following addition of cytotoxin to endothelial cells, an increased passive permeability for small marker molecules (potassium, 45calcium, 3H-sucrose), but for large ones (3H-inulin, 3H-dextran, LDH) was noted, suggesting that cytotoxin creates discrete hydrophilic transmembrane lesions of about 0.5-1.5 nm in diameter. These data are compatible with the notion that Pseudomonas aeruginosa cytotoxin triggers the arachidonic acid pathway in cultured pulmonary artery endothelial cells by calcium influx and suggest that this calcium influx may proceed through toxin created transmembrane lesions.

Animals↗
PubMed1984

Elevations in synovial fluid plasminogen activator in patients with rheumatoid arthritis.

Plasminogen activator (PA) activity in synovial fluid (SF) obtained from patients with rheumatoid arthritis (RA) is elevated when compared to SF obtained from patients with osteoarthritis (OA). Immunological studies and lack of evidence for a decrease in PA inhibitors, or an increase in PA stimulators, suggest that elevations in RA SF PA activity reflect increases in PA level. Although the origin(s) of SF PA was not identified, the enzyme resembles urokinase and RA synovium may be a contributing source. These observations are consistent with a possible active role of PA in the pathogenesis of RA.

Adult↗
PubMed1983

[Diagnosis and radio-chemotherapy of the neuroblastoma in adults].

The neuroblastoma in the adult is a rare disease which has a bad prognosis. Until now, there are no generally accepted therapy conceptions. The clinical symptoms of the patient whose case is presented here were above all pains in the pelvic region. The histologic diagnosis was difficult and could be proved only by additional examinations of other metastases. Although the primary tumor was searched for intensively, is was only found 20 months later. Especially radiotherapy, but also chemotherapy (CYVADIC regimen) have proved to be effective. Above all, the quality of life could be largely maintained over a period of 26 months.

Adult↗
PubMedDate not supplied

Role of bradykinin in inflammatory arthritis: identification and functional analysis of bradykinin receptors on human synovial fibroblasts.

Receptor type and function of bradykinin (BK) receptors on human synovial fibroblasts (HSF) was determined. Scatchard analysis of [3H]BK saturation binding to intact synovial cells revealed a single binding site, with a Kd of 3.8 +/- 0.6 nM. HSF express approximately 50,000 BK sites/cell. Specificity of [3H]BK binding was confirmed by the ability of several BK peptide agonists and antagonists to inhibit binding in a dose dependent manner. The rank order of potency for agonist inhibition of [3H]BK and the inability of selective antagonists of the B1-type to displace binding suggest that the BK receptor on HSF is a B2 subtype receptor. The addition of BK to HSF caused a time and concentration dependent increase in PGE2 production. This BK induced PGE2 production was blocked by specific B2 type BK antagonists and not by B1 antagonists. The results of this study identify B2 type BK receptors on synovial fibroblasts and suggest that BK may be a primary mediator in inflammatory arthritis.

Arthritis, Rheumatoid↗