The L1 protein as a new indicator of inflammatory activity in patients with juvenile rheumatoid arthritis

L1 is a major granulocyte and monocyte protein with Mr 36.5 kDa. It is released during leukocyte activation and detected in plasma by use of an enzyme immunoassay. In our study, L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid and haptoglobin were analyzed in 127 patients with juvenile rheumatoid arthritis (79 pauci, 33 poly and 15 systemic). L1, ESR and the acute phase proteins were all found to have positive correlations with the clinical joint assessments, with L1 having the strongest correlations. High correlation coefficients were found between L1 and orosomucoid (r = 0.83), ESR (r = 0.72), haptoglobin (r = 0.71) and CRP (r = 0.65), with p less than 0.001 for all the correlations.     

The leukocyte protein L1 in plasma and synovial fluid from patients with rheumatoid arthritis and osteoarthritis.

L1 is a major granulocyte and monocyte protein, released during activation and turnover of such cells. Blood and synovial fluid (SF) from 41 patients with rheumatoid arthritis (RA) and 6 patients with osteoarthritis (OA), were analyzed for L1 and the acute phase proteins C-reactive protein, orosomucoid, haptoglobin, alpha 1-antitrypsin and albumin as well as for differential leukocyte count. L1 levels in plasma and SF showed highly significant differences (p less than 0.0001), between the RA and OA patients. All the OA patients had normal plasma concentrations of L1 and low concentrations of L1 in SF. All the RA patients had elevated plasma levels of L1 and high L1 concentrations in SF. In the RA patients, the ratios between the protein concentrations in SF and blood were 3.29 for L1 and less than or equal to 0.64 for the acute phase proteins. In the SF, the L1 levels did not correlate with the monocyte count, while a low, positive correlation was found between L1 and the granulocyte count. The high L1 concentrations observed in SF from RA patients probably reflected an increased turnover of leukocytes in the inflamed joints. In SF from RA patients, high L1 concentrations were found in joints with a high amount of swelling. The present study suggests that L1 may represent a marker of both local and systemic inflammation.     

Treatment of insomnia with two benzodiazepines: a double-blind crossover study

Summary Twenty-eight patients (12M, 16F) with insomnia were treated with nitrazepam 5 mg/d and oxazepam 25 mg/d, each for 11 days, in a double-blind crossover comparison with placebo. Half the patients received nitrazepam in the first drug period, and oxazepam in the second and the other half followed the contrary sequence.Both nitrazepam and oxazepam were found to be effective in inducing sleep and increasing sleep quality. No effects on dreaming or adverse effects were found. Nitrazepam did influence the frequency of awakening, but only in the second drug period. In the first period it reduced self-waking.It is concluded that both nitrazepam and oxazepam were effective in inducing sleep and in improving sleep quality.This study was in part supported by NATO (project no. RG. 0029/88)     

Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).     

A strategy for bacterial production of a soluble functional human neonatal Fc receptor

The major histocompatibility complex (MHC) class I related receptor, the neonatal Fc receptor (FcRn), rescues immunoglobulin G (IgG) and albumin from lysosomal degradation by recycling in endothelial cells. FcRn also contributes to passive immunity by mediating transport of IgG from mother to fetus (human) or newborn (rodents), and may translocate IgG over mucosal surfaces. FcRn interacts with the Fc-region of IgG and domain III of albumin with binding at pH 6.0 and release at pH 7.4. Knowledge of these interactions has facilitated design of recombinant proteins with altered serum half-lives and/or altered biodistribution. To generate further research in this field, there is a great need for large amounts of soluble human FcRn (shFcRn) for in vitro interaction studies. In this report, we describe a novel laboratory scale production of functional shFcRn in Escherichia coli (E. coli) at milligram level. Truncated wild type hFcRn heavy chains were expressed, extracted, purified from inclusion bodies under denaturing non-reducing conditions, and subsequently refolded in the presence of human beta(2)-microglobulin (hbeta(2)m). The secondary structural elements of refolded heterodimeric shFcRn were correctly formed as demonstrated by circular dichroism (CD). Furthermore, functional and stringent pH dependent binding to IgG and human serum albumin were demonstrated by ELISA and surface plasmon resonance (SPR). This method may be easily adapted for the expression of large amounts of other FcRn species and MHC class I related molecules.     

Effects of multiple cognitive coping strategies on laboratory pain

This experiment was designed to test cognitive strategies in regard to pain tolerance and subjective pain perception. Sixty subjects were tested with cold-pressor pain under two different experimental conditions. (1) Cognitive coping strategies were taught at three different levels: (a) training in multiple cognitive strategies, (b) training in a single cognitive strategy (pleasant imagery practice), or (c) no training (only information about the psychological dimensions of pain). (2) Exposure to pain was introduced at two different levels: (a) exposure six times to cold-pressor test before posttest, or (b) no exposure before posttest. Both single and multiple cognitive coping strategies significantly increased average pain tolerance. Multiple cognitive strategies were not found significantly more effective than a single coping technique. Exposure training had a negative effect on subjects' pain coping ability.A preliminary version of the present study was presented at the 15th European Congress of Behavior Therapy in Munich, September 1985. K. Gunnar Götestam is acknowledged for support in different phases of the project, and Ann Griffiths for language editing. Their critique and suggestions are gratefully acknowledged, as are those of the anonymous reviewers and the editor Dennis Turk. This research was supported by the Norwegian Research Council for Science and the Humanities (Project No. 13.35.65-004).     

Genital anatomy in non-abused preschool girls

AIM: To describe the normal variations in genital anatomy in preschool girls selected for non-abuse. METHODS: A total of 2731 girls aged 5 or 6 y were invited to take part in the study; 195 girls were recruited. Inclusion was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their children gave informed consent to participate. Several steps were taken to exclude abused girls and girls with previous accidental genital injuries. The genital examination, using a colposcope and a camera, was performed in supine position using a separation and traction technique, and in the prone knee-chest position. RESULTS: A number of genital anatomical features and hymenal measurements were described and found consistent with previous studies. An important finding was outward folding of the posterior hymenal rim in many girls, a feature that could be difficult to distinguish from attenuation of the posterior hymen. A gaping hymenal orifice, previously suggested to be a supportive sign of sexual abuse, was fairly frequently found and significantly associated with a large horizontal hymenal diameter. CONCLUSION: To distinguish between girls with outward folding of the posterior hymen and those with attenuated hymens, we recommend the use of the saline irrigation method. Even though normative hymenal measurement data now exist from a reasonable number of girls, these measurements should be used with caution in sexual abuse evaluations.     

The Tumor Necrosis Factor-Inducing Potency of Lipopolysaccharide and Uronic Acid Polymers Is Increased when They Are Covalently Linked to Particles

Lipopolysaccharide (LPS) and polymers of the uronic acid family stimulate monocytes to produce tumor necrosis factor (TNF). The TNF-inducing potency of these polysaccharides may depend on their supramolecular configuration. In this study detoxified LPS and uronic acid polymers have been covalently linked to particles which have been added to monocytes under serum-free conditions. Reducing the size of mannuronan from 350,000 to 5,500 Da (M-blocks) led to a 10- to 100-fold reduction in TNF-inducing potency. However, covalently linking the M-blocks to monodisperse suspensions of magnetic particles increased the TNF-inducing potency by up to 60,000-fold. Also, the TNF-inducing potency of glucuronic acid polymers was increased when they were linked to particles, but no potentiation was observed with guluronic acid blocks covalently attached to particles. Furthermore, O chains of LPS (detoxified LPS) became potent TNF inducers when they were presented to monocytes on a particle surface. No activation of the LPS-responsive SW480 adenocarcinoma cells was found with detoxified LPS or M-block particles, suggesting a preference for cells expressing CD14 and/or other membrane molecules. The potentiating effects were not restricted to polymers attached to aminated magnetic particles. Of particular interest, we found that short blocks of mannuronan induced TNF production also when covalently linked to biodegradable, bovine serum albumin particles.