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We describe the new version (v2.38j) of the code hfodd which solves the nuclear SkyrmeHartree-Fock or Skyrme-Hartree-Fock-Bogolyubov problem by using the Cartesian deformed harmonic-oscillator basis. In the new version, we have implemented: (i) projection on good angular momentum (for the Hartree-Fock states), (ii) calculation of the GCM kernels, (iii) calculation of matrix elements of the Yukawa interaction, (iv) the BCS solutions for statedependent pairing gaps, (v) the HFB solutions for broken simplex symmetry, (vi) calculation of Bohr deformation parameters, (vii) constraints on the Schiff moments and scalar multipole moments, (viii) the D T transformations and rotations of wave functions, (ix) quasiparticle blocking for the HFB solutions in odd and odd-odd nuclei, (x) the Broyden method to accelerate the convergence, (xi) the Lipkin-Nogami method to treat pairing correlations, (xii) the exact Coulomb exchange term, (xiii) several utility options, and we have corrected two insignificant errors.

We calculate the nuclear matrix elements involved in the elastic and inelastic scattering of the lightest supersymmetric particle (LSP) on the 129Xe and 131Xe dark-matter detector nuclei. This is the first time when both channels are addressed within the same unified microscopic nuclear framework, namely we perform large-scale shell-model calculations with a realistic two-body interaction to produce the participant nuclear wave functions. These wave functions successfully reproduce the spectroscopic data on the relevant magnetic moments and M1 decays. The tested wave functions are used to produce annual average detection rates for both the elastic and inelastic channels. It is found that the inelastic channel has great detection potential for 129Xe if the LSP is heavy and stems from a SUSY model that enhances the spin-dependent scattering.

To investigate the combined effects of size at birth and maternal education on prevalence of overweight and obesity among 18-year-old men. We studied the associations of weight for gestational age and maternal education with body mass index (BMI), overweight and obesity by multivariate linear and logistic regression, adjusted for mother's age, parity and diabetes in a register-based cohort of 6535 men born between 1973 and 1985. Further adjustments for mother's height, pre-pregnancy weight, weight gain and smoking during pregnancy were made in a subsample of 1103 men born between 1982 and 1985. Mean BMI and prevalence of overweight and obesity decreased with higher maternal education. Mother's BMI and smoking were the strongest predictors of sons' overweight and obesity and essentially accounted for the variation in son's overweight by maternal education. The association of size at birth with later overweight was present only in sons born to mothers who were nonsmokers (odds ratio per 1 standard deviation weight for gestational age z-score 1.46, 95% CI 1.18–1.81) and became substantially reduced on adjustment for mother's pre-pregnancy BMI. Length of gestation was not statistically significantly associated with BMI at age 18. Maternal overweight and maternal smoking were the strongest determinants of offspring overweight and its social patterning, and should be a priority for public health policies.

A description of a detector-based realization of the unit of luminous flux (lumen) at the Helsinki University of Technology (HUT) is presented. The realization is based on the absolute integrating-sphere method developed at the National Institute of Standards and Technology (NIST), with some modifications. The measurement set-up consists of a 1.65 m integrating sphere, two photometers, a precision aperture and an external luminous-flux source. The characterization and maintenance of the measurement system are described and the uncertainty budget of the realization is presented. The uncertainty analysis indicates a relative expanded uncertainty (k = 2) of 4.7 × 10−3 for the realization. According to the results of an earlier bilateral comparison between the HUT and the NIST, the ratio of the measured luminous flux value of HUT to that of NIST was 1.0006 with an expanded uncertainty (k = 2) of 10 × 10−3, including uncertainties due to realization of the units. Another indirect test measurement indicated a corresponding ratio of 0.9984 with the luminous flux measurements of BIPM with an expanded uncertainty (k = 2) of 11 × 10−3, including uncertainties due to realization of the units.

A series of observations have led to the hypothesis that normal intestinal microbiota in patients with rheumatoid arthritis may harbour, for genetic reasons, bacteria with cell walls capable of inducing arthritis. Differences occur between bacterial species, and even between strains of a single species, because some cell walls induce experimental chronic arthritis, whereas some others induce only a transient acute arthritis or no arthritis at all. In susceptible subjects, with continuous seeding of bacterial products from the gut, the synovial inflammation is followed by erosion, exposition of cartilage antigens, and self perpetuating chronic arthritis.

Results of filter radiometer characterization with a wavelength-tunable Ti : sapphire laser in the wavelength band around 900 nm are presented. The effect of interference between the reflections from filter surfaces in the case of coherent laser light was studied and reduced with a special filter design with antireflection coatings. Measuring the responsivity as a function of wavelength over a very narrow band was used to reveal the remaining interference effects. Uncertainty analysis and test results indicate that filter radiometers can be characterized with a relative standard uncertainty of 9×10−4 using the scanning method. The results agree well with more conventional monochromator-based measurements.

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler® and Turbuhaler® for the delivery of budesonide 200 μg/dose twice daily in steroid-naı̈ve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-naı̈ve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 μg/day either via Easyhaler® (n = 159) or via Turbuhaler® (n = 167), plus salbutamol inhalation powder (100 μg/dose) via Easyhaler® as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler® group and 149 in the Turbuhaler® group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7–8. At weeks 7–8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from −8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler® more acceptable than Turbuhaler®. The results show that budesonide via Easyhaler® is clinically as effective as Pulmicort® Turbuhaler® when equal daily doses of budesonide are delivered to steroid-naı̈ve asthmatic patients. Moreover, patients found Easyhaler® more acceptable than Turbuhaler®, and a majority would prefer Easyhaler® if given a choice.

An international comparison has been conducted to compare the illuminance responsivity scales (A/lx) and the units of luminous flux (lm) maintained at the National Institute of Standards and Technology (NIST, USA) and the Helsinki University of Technology (HUT, Finland). Both laboratories realize the illuminance unit by absolutely calibrated photometers and the luminous flux unit by the absolute integrating-sphere method. Standard photometers were used as transfer standards for the illuminance responsivity comparison, and standard lamps in the luminous flux comparison. The ratio of the measured illuminance responsivity values (HUT/NIST) was 0.9992 with an expanded uncertainty (k = 2) of 0.0013, and the ratio of the measured luminous flux values was 1.0006 with an expanded uncertainty (k = 2) of 0.0018. The relative expanded uncertainties of the agreement of the units, including the uncertainties of the realizations of the units as well as the uncertainty of the comparison, were 0.0047 and 0.0101, respectively.

The aim of this study was to compare the preference, efficacy and tolerability of Easyhaler®, a metered-dose, dry powder inhaler, with a pressurised metered-dose inhaler (pMDI) plus spacer in the treatment of asthma in children. Forty-three asthmatic children, aged 6–16 years, were enrolled in this open, crossover study. All the children were previously treated with inhaled corticosteroids. After a two-week run-in period, patients were randomised to either salbutamol via Easyhaler® 100 μg/day (Buventol Easyhaler®) and beclomethasone dipropionate via Easyhaler® (Beclomet Easyhaler®) 400 μg/day, or salbutamol pMDI plus spacer 100 μg/day and beclomethasone dipropionate pMDI plus spacer 400 μg/day After a four-week treatment period the medication was changed in a crossover manner. The preference of the inhalers was assessed after each treatment period using a 10-point rating scale. Patient perceptions of the two inhalers were further investigated using a questionnaire, which was completed at the end of the study. The primary efficacy variable was morning peak expiratory flow (PEF). Secondary efficacy variables were evening PEF, the number of sympathomimetic inhalations, daily symptom scores, and spirometry performed at the follow-up visits. The results of the questionnaire showed that in 11 of 14 questions more than 50% of the patients preferred Easyhaler® to pMDI plus spacer, and Easyhaler® was found to be significantly easier to handle than pMDI plus spacer: mean (SD) score for Easyhaler was 7.7 (2.1), compared with 6.6 (2.1) for pMDI. Lung function values remained stable with both treatments. Throughout the study salbutamol delivered via Easyhaler® produced equivalent bronchodilation to pMDI plus spacer. There were no significant differences in asthma symptom scores and the use of rescue medication between the two treatment regimens. Fewer patients reported adverse events during treatment with Easyhaler® (13) compared with pMDI plus spacer (16). Asthma therapy delivered via Easyhaler® was more acceptable to patients than the same therapy delivered via pMDI plus spacer. There were no significant differences in the efficacy of treatments, and they were equally well tolerated.

Realizations of the units of luminance and spectral radiance at the Helsinki University of Technology (HUT) are presented. These realizations are linked to HUT units of luminous intensity and spectral irradiance using a characterized photometer, a spectroradiometer and an integrating-sphere light source. A new method for determining the spatial uniformity of the output of the integrating-sphere source is described. The uncertainty analysis indicates a relative expanded uncertainty of 3.6 × 10−3 (coverage factor k = 2) for the realization of the unit of luminance. The expanded uncertainty for the realization of the unit of spectral radiance varies between 6 × 10−3 and 2.5 × 10−2 in the wavelength region 360 nm to 830 nm.

In the absolute integrating-sphere method, the total luminous flux of a lamp inside an integrating sphere is determined by comparing it with a known flux introduced into the sphere from an external light source. As the measurement geometry of the lamps to be compared is different, the spatial non-uniformity of the sphere surface may affect the results. In order to evaluate this effect, the spatial response must be measured. Miniature incandescent lamps have been used as scanning-beam sources in previous realizations, but these lamps are not widely available. In the present realization of the luminous-flux unit by the Helsinki University of Technology (HUT), light-emitting diodes (LEDs) were used as the light source in scanning the spatial response. Preliminary results confirm the applicability of the LED scanner and indicate moderate deviations of about 1 % from earlier luminous-flux calibrations.

Objective: The aim of this study was to compare the bronchodilating effect, tolerability and acceptability of a single 100μg dose of salbutamol inhaled via Easyhaler® multidose dry powder inhaler with a single 250μg dose of terbutaline inhaled via Turbuhaler®, also a multidose dry powder inhaler. Design, Setting and Patients: The study was conducted according to a single-dose, crossover, randomised, double-blind with double-dummy design in four centres in Finland. A total of 29 adult patients with stable asthma without previous experience with the tested devices completed the study, which comprised 2 study days with 4-hour follow-up periods including spirometric measurements. The acceptability of the devices to the patients in the study was also evaluated. Results: The mean (SD) maximum value of forced expiratory volume in 1 second (FEV1max) after salbutamol Easyhaler® was 3.14L (1.26L), and after terbutaline Turbuhaler® was 3.07L(1.11L). The mean (SD) percentage change from baseline of forced expiratory volume in 1 second (FEV1) to FEV1max was 12.7% (12.4%) after Easyhaler® and 13.1% (10.8%) after Turbuhaler®. The observed differences in the increase in FEV1 and in the area under the curve (AUC) of FEV1 between the treatments were not statistically significant. Four patients reported mild adverse events after inhaling salbutamol via Easyhaler®, compared with five patients who reported adverse events after inhaling terbutaline via Turbuhaler®. Based on the VAS assessment of the acceptability, Easyhaler® was found to be better accepted than Turbuhaler® in terms of ease of administration, ease of inhaling, and the strength of sensation on receiving a dose. Overall, 62% of the patients would have chosen Easyhaler®. Conclusions: Easyhaler® containing salbutamol (100μg/dose) is comparable in efficacy and as well tolerated as Turbuhaler® containing terbutaline (250μg/dose), and Easyhaler® was well accepted by patients.

To investigate the role of the CD40-CD154 interaction in rheumatoid arthritis (RA), we analysed the expression of CD154 on CD3+ and CD4+ T cells in synovial fluid (SF) from patients with RA and in peripheral blood (PB) from patients and normal controls. As interleukin (IL)-15 is a potent activator of synovial T cells we wanted to study whether IL-15 also regulated the expression of CD154 on these T cells. Freshly isolated synovial T cells did not express significant levels of CD154, as evaluated using flow cytometry, whereas the expression of CD86 and human leucocyte antigen (HLA)-DR was significantly elevated on SF T cells when compared with PB T cells from patients or controls. Synovial T cells could up-regulate their CD154 expression following activation with phorbol 12-myristate 13-acetate (PMA) + ionomycin or anti-CD3 + anti-CD28 monoclonal antibodies (mAbs), but the maximal level of expression remained lower than in control T cells. IL-15 significantly increased the expression of CD154 on SF and PB T cells from patients, whereas IL-2 had minimal effects. Furthermore, IL-15 induced extensive proliferation in SF T cells. Our results show that SF T cells up-regulate the expression of CD154 in the presence of IL-15, a cytokine present in the synovium of patients with RA. These results further emphasize the role of IL-15 in the pathogenesis of RA.

A description is presented of an upgraded trap-detector-based realization of the units of luminous intensity (candela) and illuminance (lux) at the Helsinki University of Technology (HUT). The realization is accomplished using a reference photometer, a light source and a distance-measurement system. A thorough characterization is presented of the reference photometer, consisting of a reflection trap detector, a temperature-controlled V(λ) filter and a high-precision aperture. The maintenance of the units is described. An updated uncertainty budget of the realization is given. Two of the three main uncertainty components of our earlier realizations have been significantly decreased. The uncertainty analysis indicates a relative expanded uncertainty of 2.2 × 10-3 for the realization of the candela and 1.8 × 10-3 for that of the lux. The HUT has participated in three international measurement comparisons, whose results are reviewed. According to the results, the HUT candela deviates by +4.0 × 10-3 from the candela of the Swedish National Testing and Research Institute with an expanded uncertainty of 10-2, -2.7 × 10-3 from that of the National Physical Laboratory (UK) with an expanded uncertainty of 5.6 × 10-3 and -3.3 × 10-3 from the world mean with an expanded uncertainty of 5.9 × 10-3.

We compared the bronchodilating effect and tolerability of salbutamol administered by means of 2 Easyhaler models in a double-masked, randomized, crossover study in 20 adult patients with chronic asthma. Spirometry was done immediately before and 15, 30, 45, 60, 120, 180, and 240 minutes after salbutamol administration using Easyhalers. An analysis of variance and Hodges-Lehman estimation were used in the statistical analysis. Bronchodilating efficacy and tolerability were similar in both the old and new versions of Easyhaler concerning administration of salbutamol into the lungs. Maximal relative changes in forced expiratory volume in 1 second (FEV 1 ) were 12.9% and 13.2% after use of the new and old versions of Easyhaler, respectively. Absolute FEW 1 values and areas under the FEV 1 curve were also similar after use of both Easyhaler models. Easyhaler is a rational substitute for metered-dose inhalers in administering salbutamol into the lungs because chlorofluorocarbon propellants will be banned as soon as alternative ways exist to treat asthma.

A method developed at the Helsinki University of Technology (HUT) for calibrating standard lamps of spectral irradiance in UV-A and UV-B regions is presented. The method is based on a compact filter radiometer that is characterized absolutely to measure spectral irradiance. The filter radiometer can be brought to laboratories where accurate calibrations are needed. The method overcomes some of the instability problems encountered when using lamps as transfer standards, which makes it also useful in intercomparison campaigns. Test measurements are presented where two standard lamps issued by the National Institute of Standards and Technology (NIST), USA, are compared with the HUT scale held by the radiometer. The results suggest that the agreement between the two scales (HUT and NIST) is approximately 1%-2% in the wavelength region from 300 nm to 400 nm.

The balance between T helper type 1 (Th1) and Th2 cytokines is thought to be important in the initiation and outcome of autoimmune diseases. The goal of the present study was to compare the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by synovial fluid (SF) and peripheral blood (PB) CD4+ and CD8+ cells from patients with rheumatoid arthritis (RA) using three-colour immunofluorescence staining and flow cytometry, and to investigate the capacity of IL-4, IL-10 and IL-12 to modify the cytokine production profile of SF T cells. The frequency of IFN-gamma-producing CD4+ and CD8+ cells was significantly increased in SF when compared with PB. In contrast to IFN-gamma, the expression of IL-4 in SF and PB T cells was comparable. The majority of IL-4-producing cells in SF belonged to Th0/T cytotoxic (Tc) type 0 phenotype, whereas there were significantly more Th2/Tc2 cells in PB than in SF. Interestingly, IL-4 was unable to induce differentiation of non-adherent SF mononuclear cells (SFMC) into Th2 cells, whereas PB mononuclear cells (PBMC) under similar culture conditions differentiated into cells producing high levels of IL-4, IL-10 and IL-13. In contrast, there were no major differences in the effects of IL-10 and IL-12 on the cytokine production profile of SFMC when compared with PBMC. Taken together, the present results suggest that SF T cells from patients with RA are terminally differentiated into Th1/Tc1-like phenotype, and Th2/Tc2 differentiation-inducing agents, such as IL-4, may not be able to reverse the inflammatory process occurring in the joints.

The results are presented of an international comparison of the SI photometric base unit, the candela, as realized and maintained at the National Physical Laboratory (NPL, UK) and the Metrology Research Institute at Helsinki University of Technology (HUT, Finland). Both laboratories base their luminous intensity units on absolutely calibrated photometers and these, as well as the more traditional transfer standard lamps, were used for the comparison. The results show that the units established and maintained at the two laboratories agree to well within the expanded uncertainty.

The facilities of the Metrology Research Institute at the Helsinki University of Technology, and methods for characterisation of optical detectors for spectral radiant intensity and irradiance responsivity, are described. The instrumentation for such characterisations includes a reference spectrometer with a number of auxiliary set-ups, and equipment for the spectral irradiance measurements with a filter radiometer based on a trap detector. The methods of realising the spectral responsivity scales based on an absolute cryogenic radiometer in house are addressed. The procedures and results of characterisation of a multipoint measuring system of photosynthetically active radiation, by employing the available facilities, are briefly described. The absolute irradiance responsivity of the device is determined by using a photometric lamp, whose spectral irradiance has been measured with the filter radiometer. The combined standard uncertainty of this set of calibrations is 3.6% at the 1σ level. The uncertainty is caused almost completely by the multipoint measuring system.

Objective To investigate whether microbial components are present in the cells of synovial fluid or peripheral blood from patients with Salmonella-triggered reactive arthritis (ReA). Methods Synovial fluid cells and/or peripheral blood cells from 23 patients with Salmonella-triggered ReA and from 19 control patients with newly diagnosed rheumatoid arthritis were studied using 3 different polymerase chain reaction (PCR) techniques and immunocytochemical staining. Muramic acid from the synovial fluid was studied by gas chromatography–mass spectrometry. Results Salmonella chromosomal DNA was not detectable in the synovial fluid cells and peripheral blood leukocytes of patients with Salmonella ReA. Initially, positive reactions were observed in the synovial fluid cells and peripheral blood leukocytes of 3 of 17 and 3 of 18 patients with ReA, respectively, but in the subsequent PCR studies, these findings were not reproducible. Salmonella-specific antigen was detectable by immunofluorescence in the synovial fluid cells and peripheral blood leukocytes of 4 of 11 and 2 of 7 patients with ReA, respectively. Muramic acid was present in 2 of 15 synovial fluid samples from patients with ReA, but the bacterial cultures from synovial fluid were negative. Conclusion These findings indicate the presence of bacterial degradation products, but not bacterial DNA, in the inflamed joints of patients with Salmonella-triggered ReA.

This study examined the attachment kinetics of Yersinia enterocolitica serotype O:3 to determine the optimum conditions for its isolation from meat enrichment systems using a novel surface adhesion technique. Minced beef was inoculated with Y. enterocolitica at an initial level of 10 cfu g-1 and incubated at 25 degrees C in an enrichment broth. Yersinia was recovered from enriched samples on polycarbonate membranes by surface adhesion and enumerated using immunofluorescence microscopy. The surface adhesion immunofluorescence technique (SAIF) had a minimum detection limit of approximately 4.0-4.5 log10 cfu ml-1 and provided good correlation between the estimation of the numbers of Yersinia in the enrichment broth derived from plate counts on Yersinia Selective agar (CIN) and those determined by SAIF (r2 = 0.94; rsd = +/- 0.21). A derived regression equation of the SAIF count vs plate counts was used to predict Y. enterocolitica numbers in spiked meat samples stored at 0 degree C for up to 20 d. The numbers as predicted by the SAIF method showed good correlation with counts derived by plating techniques (r2 = 0.78; rsd = +/- 0.42). The application of the SAIF technique for the rapid detection of Y. enterocolitica serotype O:3 from meat is discussed.

We have developed a direct optical method for aperture area measurement, based on constant, known irradiance over the aperture. The method is described and results of test measurements are given, including wavelength dependence of the effective aperture area. Systematic uncertainty components are studied experimentally to reach a relative uncertainty of 10 -4 for aperture sizes down to 3 mm in diameter. The most important advantages of the direct optical method are that it does not require any reference aperture, it can be applied to apertures of any shape, and the calibration setup is similar to the actual use of the apertures in filter radiometers.

Objective: The clinical efficacy, tolerability and acceptability of a new multidose powder inhaler (MDPI) [Easyhaler®, Orion Pharma, Finland] containing a high dose (500 μg/dose) of beclomethasone dipropionate (BDP) were compared with those of BDP metered dose inhaler administered with a large volume spacer (MDI-spacer). Patients and Study Design: Recruited patients were adult asthmatics currently receiving 800 to 1000 μg/day of inhaled corticosteroid. The dose of BDP during the study was 1000 μg/day The study was an open, randomised, parallel-group multicentre study and included a 2-week run-in period followed by a 12-week treatment period. Results: 74 patients were randomised to both groups. During the run-in period the mean morning peak expiratory flow (PEF) was 489 and 478 L/min in the MDPI and MDI-spacer groups, respectively. During the last 2 weeks of the study the morning PEF was 485 L/min in the MDPI group and 477 L/min in the MDI-spacer group. Asthma symptom scores and use of rescue medication were low in both groups. The median dose of histamine required to decrease forced expiratory volume in 1 second (FEV1) by 15% was 1.05mg in the MDPI group and 0.64mg in the MDI-spacer group. The most frequent adverse events were hoarseness and sore throat. Mean serum cortisol levels were not affected in either treatment group. Patients’ personal opinion regarding acceptability of the devices clearly favoured the MDPI. Conclusion: In conclusion, the novel powder inhaler was well tolerated and at least equally effective compared with the conventional MDI-spacer combination in the treatment of asthma with BDP. However, in everyday use the patients clearly favoured the powder inhaler.

One hundred fifteen adult patients with asthma participated in this open-label, randomized, parallel-group study that compared the acceptability, clinical efficacy, and tolerability of salbutamol inhalation aerosol and powder in the treatment of asthma. There were no significant differences between groups in terms of demographic variables. Before the study the patients had used inhaled steroids at least for 6 months and had shown an improvements in forced expiratory volume in 1 second (FEV 1 ) or in peak expiratory flow rate (PEFR) of more than 15% after the inhalation of 200 μg of salbutamol. The treatment period was 12 weeks and was preceded by a 2-week run-in period. The medications were delivered from a metered dose inhaler (MDI) and from a new multidose powder inhaler (MDPI). During the study, home PEFR was measured daily in the mornings and in the evenings. In the mornings PEFR was measured both before and 15 minutes after the inhalation of 200 μg of salbutamol. FEV 1 and forced vital capacity (FVC) were measured after the run-in period and after 4 and 12 weeks of treatment. FEV 1 and FVC were measured immediately before and 15 and 30 minutes after the inhalation of 200 μg of salbutamol. Asthma symptom scores, adverse events, and the use of rescue medication were recorded daily. Patients' preference of the inhalers (acceptability) was evaluated during the study after 4 weeks of treatment. No significant differences were found between the treatments in any of the efficacy variables measured. Of the 77 patients allocated to use the new MDPI, 72 gave their opinion about the inhalers: 34 patients (47%) rated MDPI easier to use than the MDI; 28 (39%) did not find any differences in handling between the two devices; and 10 (14%) felt the MDPI was more difficult to use than the MDI. We conclude that the new MDPI is clinically equivalent to the MDI in the long-term treatment of asthma, and the patients found it easy to use.

In the present study the expression and function of signaling lymphocytic activation molecule (SLAM) in lymphocytes from patients with rheumatoid arthritis (RA) were investigated. The expression levels of SLAM were significantly up-regulated on synovial fluid and synovial tissue T cells from patients with RA compared with peripheral blood T cells from the same patients or from healthy volunteers. In addition, the expression of SLAM on peripheral blood B cells from patients with RA was elevated compared with that in healthy volunteers. SLAM+ T cells in synovial fluid coexpressed CD45RO and demonstrated decreased expression of CD27, indicative of a primed phenotype. In addition, the activation state of SLAM+ T cells was enhanced, as judged by increased expression of CD25, CD28, CD69, and CD95 on these cells. Interestingly, SLAM expression on activated CD4+ and CD8+ T cells from both patients and healthy individuals could be down-regulated by IL-10, which has been previously shown to function as an anti-inflammatory molecule in rheumatoid synovium. Furthermore, anti-SLAM mAbs increased the production of IL-10, IFN-gamma, and TNF-alpha by in vitro activated synovial fluid mononuclear cells, supporting the idea that signaling through SLAM may play a role in the regulation of synovial inflammation in patients with RA. Given the fact that SLAM was recently shown to be a high affinity self ligand, our data suggest that synovial T cells may stimulate their own cytokine production through homophilic SLAM-SLAM interactions.

The complex interactions between the triggering microbe and the defense mechanisms of the host in reactive arthritis have been studied in several laboratories around the world, and interesting observations have been made. Research has also focused on the mediators in the inflammatory process in joints, and these results are helping to slowly build a comprehensive picture about the pathogenetic process in reactive arthritis. For the practicing clinician, some important new findings have emerged. It is known that asymptomatic urogenital infections are quite common as a trigger of reactive arthritis. More aggressive treatment, including disease-modifying drugs as used in the therapy of rheumatoid arthritis, is becoming accepted. The value of antibiotic treatment is being studied, but final conclusions will not be made for perhaps a few years.

OBJECTIVE: To find out the effect of carmustine (bischloroethyl-nitrosourea) combined with a biodegradable polymer in the treatment of malignant (Grades III and IV) gliomas, applied locally, at the time of the primary operation. METHODS: Prospective, randomized double-blind study of an active treatment group versus a placebo group. Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki, Tampere, and Turku in Finland and Trondheim in Norway. The study consisted of 32 patients (16 in each treatment group) enrolled between March 23, 1992, and March 19, 1993. The study was planned to include 100 patients but had to be terminated prematurely, because the drug that was being used had become unobtainable. The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo. RESULTS: The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group (P = 0.012). For 27 patients with Grade IV tumors, the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group (P = 0.008). At the end of the study, six patients were still alive, five of whom belonged to the active treatment group. CONCLUSION: Carmustine applied locally in a biodegradable polymer at the time of primary operation, seems to have a favorable effect on the life span of patients with high-grade gliomas.

Lewis rats were injected i.v. with live Yersinia enterocolitica, resulting in 1- 2 weeks in an arthritis greatly resembling human reactive arthritis. Starting on day 3, 5, 10 or 13 after the bacterial inoculation, the rats were treated for 3 weeks with 20 mg/kg/day of ciprofloxacin. The development of arthritis was completely prevented if the antibiotic treatment was started on day 3. In a group of rats treated with ciprofloxacin from day 5 onwards. 2/14 rats already showed mild arthritis at the time when the treatment was started. Antibiotic treatment cured the arthritis of these rats as well as that of one additional individual in this group which developed arthritis. No later exacerbations occurred. If the antibiotic treatment was started on day 10 or 13, i.e. at the time of well-developed arthritis, no effect on arthritis was observed; rather, increased faecal excretion of Yersinia occurred following the antibiotic treatment. We conclude that experimental Yersinia reactive arthritis can be cured by antibiotics introduced at an early phase of arthritic development. Regarding acute human enterogenic arthritis, the decision on antibiotic treatment is not a straightforward matter. Our experimental results indicate that the earlier the treatment is started, the better the result, whereas late treatments seem to favour bacterial persistence.

Acute anterior uveitis AAU) and ankylosing spondylitis AS) are, like reactive arthritis ReA), strongly associated with HLA-B27. Mucosal infections play a role in the pathogenesis of ReA. To investigate whether these micro- organisms are also involved in the pathogenesis of AAU and AS, we examined blood samples from patients with AAU, AS or both, and healthy controls for presence of antibodies against Klebsiella pneumoniae (K 30), Salmonella enteritidis and S. typhimurium, Chlamydia trachomatis, Proteus mirabilis and Borrelia burgdorferi. The IgA, IgG and IgM classes of these antibodies were measured using an enzyme- linked immunosorbent assay. p]No significant differences were found in the frequency in which these antibodies occurred in HLA- B27 positive patients with AAU or AS and healthy controls. However, IgA antibodies against K. pneumoniae p < 0.01) and IgA and IgG antibodies against P mirabilis (p < 0.01 and p < 0.05) were detected more frequently in HLA- B27 negative patients with AAU than in healthy controls. p]The results of this study are in contrast with various earlier reports in which antibodies against Klebsiella strains were more frequently found in patients with HLA- B27 associated ankylosing spondylitis than in healthy controls.

Following the intravenous injection of live Yersinia enterocolitica O:8, 50-69% of SHR rats developed arthritis; these rats were antibody free against all rat pathogens tested. In contrast, only 20-25% of SHR rats which had serum antibodies against Bacillus piliformis, Kilham rat virus, and Toolan H-1 virus developed arthritis. The results indicate that the microbial load of the host has a profound effect on the susceptibility to experimental arthritis.

We discuss the dark-matter detection rates for the elastic and inelastic scattering of the lightest supersymmetric particle (LSP) off nuclei. For this we use an easily accessible formalism where the underlying nuclear physics is condensed in structure coefficients multiplying the key parameters of supersymmetric theories. In this work we compute these coefficients for the stable iodine, xenon, and cesium nuclei by application of the nuclear shell model in a model space involving the 2s, 1d, 0g 7/2 , and 0h 11/2 single-particle orbitals. As an interaction we use the renormalized Bonn-CD G matrix. By using fitted nuclear gyromagnetic factors we have successfully reproduced the relevant spectroscopic data on magnetic moments and M 1 decays in the discussed nuclei.

Elastic and inelastic scattering of the lightest supersymmetric particle (LSP) off nuclei is discussed. The LSP dark‐matter detection rates for the stable iodine, xenon and cesium detectors are derived. The parameters of the supersymmetric theory are decoupled from the nuclear structure by tabulating a set of nuclear‐structure coefficients. These coefficients are calculated by using the nuclear shell model in the valence space containing the 2s, 1d, 0g7/2, and 0h11/2 single‐particle orbitals. A realistic effective two‐nucleon interaction based on the Bonn‐CD G‐matrix is used. By using fitted nuclear gyromagnetic factors we successfully reproduce the relevant spectroscopic data on magnetic moments and M1 decays in the discussed nuclei.Elastic and inelastic scattering of the lightest supersymmetric particle (LSP) off nuclei is discussed. The LSP dark‐matter detection rates for the stable iodine, xenon and cesium detectors are derived. The parameters of the supersymmetric theory are decoupled from the nuclear structure by tabulating a set of nuclear‐structure coefficients. These coefficients are calculated by using the nuclear shell model in the valence space containing the 2s, 1d, 0g7/2, and 0h11/2 single‐particle orbitals. A realistic effective two‐nucleon interaction based on the Bonn‐CD G‐matrix is used. By using fitted nuclear gyromagnetic factors we successfully reproduce the relevant spectroscopic data on magnetic moments and M1 decays in the discussed nuclei.

SUMMARY Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologous sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the H LA B27 molecule: between amino acids 70 to 78 in the variable region of α1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.

The occurrence of D-D recombination during the embryonic differentiation of chicken B cells was studied. Ig heavy (H) chains were amplified by polymerase chain reaction from day-12 bursal cDNA, and 30 random V-D-J regions were analysed by DNA sequencing. No gene conversion events were observed in any of the V regions, indicating that diversification of the H chains by gene conversion is not yet activated at this stage of embryonic B-cell development. In contrast, the V-D-J joint regions were extremely heterogeneous. Most of the sequenced V-D-J joints were formed by direct joining of the single-germline V mu 1 gene, one of the multiple-germline D elements, and the single J gene. However, three V-D-J regions were clearly longer in size, and their D-region structure indicated recombination between two or three different germline D elements. Thus, the present data suggest that D-D recombination may have a role in diversification of the Ig H-chain repertoire.

Analysis of bacteria-derived cellular fatty acids was applied to study differences in faecal floras of inbred mice. The bacterial composition of the faecal flora clearly changes with age, whereas the sex does not affect it. Most interestingly, different mouse strains were found to have different faecal floras. This was particularly observed at the age of 17-19 weeks for stool samples of four different mouse strains; the mice were handled identically in identical environments, and the two congenic strains used were different from each other only by the major histocompatibility complex (MHC). These results suggest that composition of the faecal flora is genetically regulated.

To assess the presence of circulating IgA and IgG antibodies to Chlamydia trachomatis in sera of patients with reactive arthritis (ReA) and other arthritides.A peptide based enzyme immunoassay (EIA) was used to study 132 patients divided into 5 groups: C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and rheumatoid arthritis (RA). Followup sera were available from 19 patients.An increased prevalence of C. trachomatis antibodies was observed in patients with ReA triggered by C. trachomatis; 18/23 (78%) had IgA and 19/23 (83%) had IgG antibodies. In patient groups with uroarthritis (n = 12), enteroarthritis (n = 56), oligoarthritis (n = 16), and RA (n = 25), C. trachomatis IgA/IgG antibodies were detected in 58%/75%, 27%/21%, 25%/31%, and 20%/32% of patients, respectively. Both the IgA and IgG antibodies were positive in 74%, 50%, 16%, 25%, and 12% of the patients with C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and RA, respectively. Based on positivity of both isotypes the sensitivity of the assay was 74% and specificity 84%. In the followup sera, an association between circulating C. trachomatis-specific antibody concentrations and clinical disease outcome of the arthritis was seen in patients with culture-positive C. trachomatis triggered ReA.C. trachomatis species-specific peptide EIA correlates well with conventional diagnosis of primary C. trachomatis infection in patients with ReA. This assay may be a valuable contribution to the diagnosis of C. trachomatis triggered ReA.

The objective of this study was to compare the systemic effects of a moderate dose (800 microg/day) with the highest recommended dose (1600 microg/day) of beclomethasone dipropionate (BDP) inhaled via either Easyhaler or Diskhaler in 15 healthy adult male volunteers.This was an open, placebo-controlled, randomised study conducted according to a crossover design and consisting of a 1-week baseline period and five 1-week treatment periods, each separated by a 1-week washout period. Subjects received in randomised order 800 microg/day BDP via Easyhaler, 1600 microg/day BDP via Easyhaler, placebo via Easyhaler, 800 microg/day BDP via Diskhaler and 1600 microg/day BDP via Diskhaler. Subjects inhaled BDP twice daily at 0800 hours and 2000 hours. The last dose of each period was inhaled at the study site. Venous blood samples were drawn prior to and at 2-hour intervals for 20 h after the last dose. Serum cortisol area under the curve (AUC0-20) and morning serum cortisol values were determined using radioimmunoassay. Urine for analysis of urine cortisol/creatinine ratios (UCC) was collected over a 12-h period after the last dose of each treatment period.According to serum cortisol values, no systemic effects were detected with BDP 800 microg/day inhaled via Easyhaler. The mean (+/-SD) change in serum cortisol AUC0-20 was +118.3+/-1391 nmol h/l compared with placebo. Mean (SD) changes from placebo in serum cortisol AUC0-20 values after BDP 1600 microg/day were--546.3+/-1004 nmol h/l with Easyhaler and -769.3+/-596 nmol h/l with Diskhaler. However, there were no statistically significant differences in systemic bioactivity between the active treatments. Morning serum cortisol levels and UCC ratios were consistent with the serum cortisol AUC0-20 data.In conclusion, BDP 800 microg/day inhaled via Easyhaler did not reduce serum cortisol AUC0-20 compared with placebo. Although the decrease in hypothalamic pituitary-adrenal (HPA) axis function after BDP 1600 microg/day was statistically significant compared with placebo, the reduction was small and similar with both devices.

The basis of the different susceptibility to bacterial cell wall-induced arthritis between Lewis and Fischer rats is unclear. Likewise, it is not known why cell walls of some species of Lactobacillus are arthritogenic and those of others are not. With these two questions in mind, we investigated the role of anti-inflammatory (interleukin (IL)-10, IL-4) and proinflammatory (tumour necrosis factor (TNF)-alpha, IL-1 beta) cytokines in Lewis and Fischer rats injected intraperitoneally with cell walls from arthritogenic or nonarthritogenic species of Lactobacillus. Cytokine levels in the serum and in vitro production by peritoneal macrophages and splenocytes were studied. The results obtained indicate that the differences in the production of IL-10, IL-4, TNF-alpha or IL-1 beta do not explain the difference in the arthritis susceptibility between Lewis and Fischer rats. Likewise, the arthritogenicity of different Lactobacillus cell walls appears not to be dependent on their capacity to stimulate cytokine production.

To investigate the role of the CD40-CD154 interaction in rheumatoid arthritis (RA), we analysed the expression of CD154 on CD3+ and CD4+ T cells in synovial fluid (SF) from patients with RA and in peripheral blood (PB) from patients and normal controls. As interleukin (IL)-15 is a potent activator of synovial T cells we wanted to study whether IL-15 also regulated the expression of CD154 on these T cells. Freshly isolated synovial T cells did not express significant levels of CD154, as evaluated using flow cytometry, whereas the expression of CD86 and human leucocyte antigen (HLA)-DR was significantly elevated on SF T cells when compared with PB T cells from patients or controls. Synovial T cells could up-regulate their CD154 expression following activation with phorbol 12-myristate 13-acetate (PMA) + ionomycin or anti-CD3 + anti-CD28 monoclonal antibodies (mAbs), but the maximal level of expression remained lower than in control T cells. IL-15 significantly increased the expression of CD154 on SF and PB T cells from patients, whereas IL-2 had minimal effects. Furthermore, IL-15 induced extensive proliferation in SF T cells. Our results show that SF T cells up-regulate the expression of CD154 in the presence of IL-15, a cytokine present in the synovium of patients with RA. These results further emphasize the role of IL-15 in the pathogenesis of RA.

Background: Problems in using conventional inhalation aerosols, in addition to environmental reasons, have driven development of the dry powder inhalers. Objective: To compare therapeutic equivalence and acceptability of two dry powder inhalers, Easyhaler (EH) and Diskhaler (DH), in the delivery of beclomethasone dipropionate (BDP) in the treatment of asthma. Methods: Adult asthmatics (n = 185), previously treated with inhaled steroids, were recruited in this open parallel-group study. After a run-in period of 2 weeks during which the patients inhaled 800 μg/day of BDP via DH, the patients were randomly allocated into three groups: EH 200 group (62 patients) using EH 200 μg/dose inhaler (1 inhalation q.i.d.), EH 400 group (62 patients) using EH 400 μg/dose inhaler (1 inhalation b.i.d.), and DH group (61 patients) using DH 200 μg/dose inhaler (1 inhalation q.i.d.) for 12 weeks. The primary outcome variables were PEF and FEV1. Results: The 95% CI for treatment difference in morning PEF between the EH 200 and DH groups was –16 to 23 litres/min and between the EH 400 and DH groups –18 to 21 litres/min. There was an increase in the morning PEF of 13 litres/min (p < 0.05) in the EH 200 group, and 9 and 11 litres/min in the DH and EH 400 groups. No differences between the groups were seen in the lung function parameters, in the symptom scores, in the use of rescue medication or in the incidence of adverse events. The treatments had no effects on morning cortisol levels. The patients in the EH groups compared the inhalers by using an 11-item questionnaire. In 8 questions the majority of the patients rated EH superior to DH. Conclusion: The tested inhalers were therapeutically equal. However, based on the acceptability data, the EH was better accepted by the patients than DH.

We investigated a patient with Salmonella infantis triggered reactive arthritis (ReA) for a possible occurrence of S. infantis-specific antigens and DNA in the synovial fluid (SF) cells. S. infantis-specific antigens were abundantly observed by immunofluorescence in SF cells of the patient during acute joint inflammation. Salmonella-specific DNA was detected by Southern blotting of the amplified polymerase chain reaction product once, but the result could not be repeated. It seems that if bacterial DNA exists in inflamed joints in Salmonella triggered ReA, its amount is extremely low. This is the first report of intraarticular S. infantis antigens and potentially of Salmonella DNA in Salmonella triggered ReA.

To study the tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls (CWs), using arthritogenic Eubacterium aerofaciens and non-arthritogenic Eubacterium limosum.Eubacterium aerofaciens or Eubacterium limosum CW was injected into Lewis rats intraperitoneally. Inflammatory changes in the synovium and periarticular tissues were graded histologically. On days 14, 28 and 56 after the injection, the presence of CW in the liver, spleen, mesenteric lymph nodes and synovium was studied by indirect immunofluorescence. In parallel, CW-derived muramic acid in the liver and spleen was measured by gas chromatography-mass spectrometry. In addition, serum TNF-alpha, IL-1 beta and IL-10 concentrations were determined by ELISA.Systemic injection of Eubacterium aerofaciens CW, but not of Eubacterium limosum CW, resulted in chronic arthritis. Both E. aerofaciens and E. limosum CWs were observed in the liver and spleen at all of the time points studied. In addition, Eubacterium limosum CW was present in non-arthritic synovium on day 14. It was not, however, detected in the synovium or lymph nodes on days 28 and 56, in clear contrast to the rats injected with E. aerofaciens CW. According to the analysis by gas chromatography-mass spectrometry, non-arthritogenic E. limosum CW had accumulated in the liver cells on days 14 and 28 after the injection to a greater extent than arthritogenic E. aerofaciens CW, leading to a lesser distribution in the other organs. A weak trend was observed suggesting that the production of TNF-alpha and IL-1 beta, but not of IL-10, is stimulated better by arthritogenic CW than by non-arthritogenic CW.Our results indicate that non-arthritogenic CWs are handled by the rat's defence mechanisms in a different way than arthritogenic CWs. The tissue distribution and persistence of CWs play a role in arthritogenicity, but additional factors must exist to determine why the CWs of certain bacteria are arthritogenic and those of others are not.

We have investigated the effects of interleukin (IL)-10, IL-4 + granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor alpha (TNF-alpha) on the phenotype and antigen-presenting capacity of synovial fluid (SF) macrophages from patients with rheumatoid arthritis.The effects of IL-4, IL-10, GM-CSF and TNF-alpha on the expression of surface antigens on SF macrophages were studied using flow cytometry. The effects of these cytokines on the capacity of SF macrophages to activate T cells was investigated using the allogeneic mixed lymphocyte reaction (MLR).IL-10 reduced the expression of CD40, CD86 and HLA-DR, and increased the expression of CD14, on SF macrophages. IL-10 had no effect on the expression of CD80. Importantly, these effects of IL-10 on the phenotype of SF macrophages appear to have functional consequences, because cells incubated with IL-10 had a significantly reduced capacity to activate T cells in MLR. The effects of IL-4, GM-CSF and TNF-alpha were generally opposite to those observed in response to IL-10. IL-4 + GM-CSF, a combination of cytokines known to induce differentiation of dendritic cells, increased the expression of CD40, CD80 and CD86, and decreased the expression of CD14 on SF macrophages. Accordingly, IL-4 + GM-CSF increased the capacity of SF macrophages to activate T cells in MLR. IL-10 inhibited the effects of IL-4 + GM-CSF on SF macrophages.IL-10 inhibits the antigen-presenting capacity of SF macrophages, which further emphasizes the anti-inflammatory potential of IL-10 in RA. Importantly, IL-10 is able to downregulate the APC function of SF macrophages even when they are efficiently activated.

To assess the persistence of bacterial antigens in peripheral blood cells from patients with Yersinia enterocolitica O:3-triggered reactive arthritis (ReA).Peripheral blood samples were obtained from 20 patients with Y. enterocolitica O:3 infection (11 with ReA and 9 without). These samples were studied by immunochemical techniques for the presence of Yersinia antigens at the beginning of infection and up to 4 years thereafter. Synovial fluid samples from 6 of the 11 ReA patients were also studied.The Yersinia antigens lipopolysaccharide and heat-shock protein (HSP) were detected in peripheral blood mononuclear cells and polymorphonuclear phagocytes from all patients studied at the early phase of the disease. They were also found in the synovial fluid cells of patients with Yersinia-triggered ReA. At 4 years after the onset of infection, these bacterial antigens were still detected in the peripheral blood cells of most of the ReA patients studied.This study has, for the first time, directly demonstrated that bacterial antigens persist for a long time in patients who develop ReA after Y. enterocolitica O:3 infection. The finding of bacterial HSP in synovial fluid cells could provide a link to the pathogenesis of ReA, since T cell responses of synovial cells have been shown to be directed against that structure. A close similarity between the bacterial and host HSP might contribute to the development of the relatively common, chronic form of this complication.

To study the role of microbial infection in rheumatic diseases.Sera from 39 Chinese patients with rheumatoid arthritis (RA), 52 patients with ankylosing spondylitis (AS) and 51 healthy subjects (HS) were examined for IgG, IgA, and IgM class antibodies against Proteus mirabilis, Escherichia coli, Campylobacter jejuni, Salmonella typhimurium and enteritidis, Yersinia enterocolitica, and Klebsiella pneumoniae (capsular serotypes 31 and 43), using an enzyme-linked immunosorbent assay.In patients with RA, IgA class antibodies against all bacterial strains used as the antigen were increased when compared to healthy controls. In patients with AS, significantly elevated IgA levels were observed against Campylobacter and Klebsiella K43. IgM class antibodies were less frequently elevated in RA and in AS than IgA class antibodies. In RA patients, IgG antibodies against Klebsiella K43 and Proteus were significantly increased. No differences were observed in IgG class antibodies between AS patients and healthy controls.Increases in serum bacterial antibodies in RA and AS suggest that in both diseases stimulation of the intestinal immune system by enterobacteria may have a role. However, the question whether this phenomenon is due to increased intestinal permeability and/or represents cross reactions between different enterobacteria remains open.