Synovial fluid CD146 (MUC18), a marker for synovial membrane angiogenesis in rheumatoid arthritis.

OBJECTIVE: CD146 (MUC18/MCAM/S-Endo) is a marker of tumor progression and metastasis formation in human melanoma. This molecule has also been identified in smooth muscle, endothelial cells, and activated T lymphocytes. We measured the synovial fluid levels of soluble CD146 in various human joint diseases, including rheumatoid arthritis (RA). In addition, we studied the distribution of CD146 in normal and RA synovial tissues. METHODS: CD146 was isolated from MEL-OH melanoma cells and characterized by Coomassie blue staining and Western blotting. Soluble CD146 was measured by competitive enzyme-linked immunosorbent assay in synovial fluids of 3 healthy individuals and 7 cadavers (controls), as wells as in patients with traumatic joint injury (n = 10), osteoarthritis (OA; n = 10), psoriatic arthritis (PsA; n = 10), other non-RA polyarthritis (NRAP; n = 10), and RA (n = 31). Immunohistochemistry was performed on 3 normal and 3 RA synovial tissues. Flow cytometric, reverse transcription-polymerase chain reaction, and Western blot analyses were performed on enzymatically separated RA synovial tissue cells. RESULTS: Compared with controls (mean +/- SD 10 +/- 2 ng/ml), significantly elevated synovial fluid levels of soluble CD146 were detected in patients with OA, PsA, and RA (17 +/- 7, 21 +/- 11, and 39 +/- 16 ng/ml, respectively; P < 0.02-0.001), but not in patients with traumatic joint injury or NRAP. Patients with early RA (<1 year after diagnosis) revealed the highest levels (51 +/- 15 ng/ml, n = 10; P < 0.001 versus controls). In RA, soluble CD146 correlated significantly with morning stiffness (P < 0.001), the number of tender joints (P < 0.02), and the number of swollen joints (P < 0.005), but not with the erythrocyte sedimentation rate (P = 0.07) or the C-reactive protein level (P = 0.57). CONCLUSION: Since CD146 is expressed almost exclusively by vascular endothelium, high levels of soluble CD146 found in RA synovial fluid, particularly in patients with early disease, could reflect increased activity of endothelial cells and angiogenesis.

Organ-specific differences in the ratio of alternatively spliced chorismate synthase (LeCS2) transcripts in tomato.

The primary transcript of one of the two chorismate synthase genes (LeCS2) of tomato is differentially processed due to an alternative splicing of the third intron. A novel observation was made when the abundances of the two LeCS2-specific transcripts in different organs were analysed. The ratio of these two transcripts differs in RNA populations from different organs. Possible explanations for this finding and its potential physiological impact for plant metabolism are discussed.

[Early diagnosis of bronchial carcinoma using thoracic roentgen imaging and sputum cytology]. / Früherfassung des Bronchialkarzinoms mit Thorax-Röntgenbild und Sputum-Zytologie.

Chest roentgenography and sputum cytology have been used for the early detection of lung cancer since the beginning of the 1950s. Surprisingly, the yield of screening is sufficiently high. In view of the estimated prevalence of lung cancer of 0.5-2% in high risk persons, the detection rate was 0.32-0.95% in three large randomized clinical trials (Cooperative Pilot Study of the American Cancer Society and Veterans Administration 1969, Canadian study of Grzybowski and Coy 1970, National Cancer Institute Cooperative Early Lung Cancer Detection Program 1984). Screening by chest roentgenogram was superior to sputum cytology. More than 70% of all lung cancers were detected by roentgenography alone. Adding sputum cytology, 10-20% more cancers were found. Lung cancers which were additionally detected by cytology were slowly-growing, central squamous cell carcinomas with good prognosis. The sensitivity of chest X-rays varied between 49 and 77% and the sensitivity of sputum cytology between 33-52%. Specificity was higher, the range being 95-99% for chest X-rays and 96-99% for sputum cytology. The costs per lung cancer detected and treated are very high. To these are added the costs which arise from the evaluation of false positive results. The prognosis of lung cancer detected by screening is good: more patients survive, and they live longer than unscreened patients. The overall 5-year survival of patients screened by chest X-rays and sputum cytology of the NCI-study was 35-55% compared with only 15% of patients not screened. However, whether long survival means reduced mortality is uncertain, since long survival only reflects early detection.

No demonstrable effect of sobrerol as an expectorant in patients with stable chronic bronchial diseases.

A randomized double-blind cross-over study compared the clinical effectiveness of a 14-day treatment with 400 mg X day-1 of sobrerol and placebo in 23 patients with stable chronic bronchial disease. During the seven week trial, subjective symptoms and findings (cough frequency and severity, difficulty in raising sputum, dyspnoea) were recorded, pulmonary function tests performed and sputum physical characteristics (24-h sputum volume, purulence, cell concentration, protein, sputum dry weight and "apparent" viscosity) determined on a regular basis. Side-effects were closely monitored. Both subjective assessment of overall clinical efficacy as well as statistical analysis of the above mentioned factors failed to show any significant advantage of sobrerol to placebo--except for a transient decrease of the 24-h sputum volume. Sobrerol appears to be another example of an expectorant lacking evidence of clinical effectiveness in the management of chronic bronchial secretions.

Adult vertebral osteomyelitis caused by Haemophilus influenzae.

Two cases of adult vertebral osteomyelitis with typical symptoms are reported. Haemophilus influenzae serotypes b and c, respectively, were isolated from needle biopsies of the vertebrae. Both patients recovered with antimicrobial treatment, immobilization, and subsequent physiotherapy. No source or predisposing factor for the infection could be found. Only one similar case has been reported in the literature.

Susceptibility and tolerance of beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus towards seven broad-spectrum penicillins.

The activity of penicillin G, ampicillin, carbenicillin, ticarcillin, azlocillin, mezlocillin and piperacillin against 102 beta-lactamase-producing, methicillin-sensitive strains of Staphylococcus aureus was determined by agar dilution (method A) and broth microdilution (method B) techniques. By NCCLS breakpoint criteria, 4% of the strains were "sensitive" to penicillin and ampicillin, and almost 100% were "sensitive" to the other drugs when method A was used. Results with method B were only significantly lower as far as the cumulative percentage of strains "sensitive" to azlocillin, mezlocillin and piperacillin was concerned (63-71%). Bactericidal effects at "sensitive" levels were observed in 0-2% (penicillin, ampicillin), 31-35% (carbenicillin, ticarcillin) and 10-14% (azlocillin, mezlocillin, piperacillin). While differences in MIC and MBC levels ranged from 0 to 8 dilution steps, tolerance (a greater than 32-fold difference) was seen in at least 9-22% of all strains (depending on the drug tested); experimental limitations, however, excluded a determination of tolerance in all our strains. In a semi-quantitative nitrocefin assay, "strong" beta-lactamase production was correlated to high MIC and/or MBC levels.

Side-effects due to the intravenous infusion of erythromycin lactobionate.

A double-blind study was designed to test the hypothesis that local side-effects during i. v. administration of erythromycin lactobionate depend on the drug concentration and that they can therefore be minimized by dissolving erythromycin in a larger infusion volume. Forty healthy students were assigned in a randomized sequence to four 30 min infusions: 120 and 250 ml of erythromycin lactobionate (1 g in 0.9% NaCl) and 120 and 250 ml of placebo (0.9% NaCl). An unexpectedly high incidence (95% and 80% for the infusion volumes of 120 and 250 ml, respectively) of severe systemic side-effects was observed during the first 79 infusions. Because all of these systemic side-effects were associated with the infusion of erythromycin, the study was terminated at this point. Side-effects included abdominal cramps, nausea, vomiting, dizziness and profuse sweating. The postulated positive effect of lower erythromycin concentrations in the infusion on local side-effects (pain at the infusion site, erythema) was marginal (63% vs. 45%). Compared to the systemic side-effects, the problem of local tolerance is less important. In young adults, 30 min infusions of 1 g erythromycin lactobionate are associated with a high incidence of systemic side-effects which may be due to an age-dependent effect of the drug on smooth muscle.