Phosphorylation of plasma proteins with emphasis on complement component C3.

Phosphorylation of complement component C3 by different protein kinases in vitro has been demonstrated to alter the functional properties of the protein. Extracellular phosphorylation mediated by activated platelets is a newly described mechanism by which the function of plasma proteins can be regulated. Upon activation of platelets a casein kinase is released concomitant with large amounts of ATP and Ca2+. These components are sufficient to phosphorylate proteins e.g., C3 extracellularly. In vivo, in patients with SLE, the phosphate content in plasma proteins, including C3 has been demonstrated to increase during exacerbation. The changes were linked to platelet activation by a covariation with the levels of beta-thromboglobulin. The purpose of this review is to summarise the findings in this field.     

Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease

Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%–60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune–regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE–K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1β, and tumor necrosis factor (TNF)-α. BCHE-K noncarriers displayed 100%–150% higher glial fibrillary acidic protein and 64%–110% higher S100B than BCHE-K carriers, who, in contrast, had 40%–80% higher interleukin-1β and 21%–27% higher TNF-α compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low β-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-α and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status.     

Muscle strength, endurance, and aerobic capacity in rheumatoid arthritis: a comparative study with healthy subjects.

Isometric/isokinetic muscle strength and isokinetic endurance of the lower extremities as well as aerobic capacity were evaluated in 67 patients (43 female, 24 male; mean age 53 years, range 23-65) with classical/definite rheumatoid arthritis (RA) of functional class II. Results obtained were compared with those of a healthy reference group matched for age and sex. Disease characteristics of the group with RA were registered and lifestyle characteristics, such as work load, exercise, diet, smoking, and alcohol habits, were reported by both groups. Generally, results showed that the group with RA had decreased functional capacity. Isometric hip and knee muscle strength of the rheumatoid group was reduced to about 75% of normal function, isokinetic knee muscle strength at the velocities of 60 and 180 degrees/s to about 65% and 75% of normal function respectively, isokinetic endurance of the knee muscle groups to about 45%, and aerobic capacity to about 80% of the results obtained for the healthy reference group. Analyses of variance showed that the rheumatoid group, compared with the healthy group, had significantly reduced function on all isometric and isokinetic tests of the extensors and flexors of the knee. Results for isometric hip muscle strength were similar--all tests but one yielding highly significant differences. To avoid unnecessary functional deficits it seems important to include muscular training in rehabilitation programmes for patients with RA.     

Health-related quality of life in primary Sjögren's syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36

OBJECTIVE: To investigate the health-related quality of life in women with primary Sjogren's syndrome (prim SS) and compare with normative data and the health-related quality of life in women with rheumatoid arthritis (RA) and women with fibromyalgia. METHODS: A questionnaire including the MOS Short-Form 36 (SF-36) was completed by 42 prim SS women, 59 RA women, and 44 women with fibromyalgia. RESULTS: All three patient groups experienced a decreased quality of life level ranging from 5 to 65 % in all SF-36 scales compared to normative data. Differences between groups were seen in 7 of the 8 scales (p< or = 0.004). The prim SS patients experienced a higher quality of life level with regard to physical function than the women with RA and fibromyalgia, whereas in the psychological dimensions the quality of life level was comparable to that of the two other groups. CONCLUSION: The health-related quality of life was significantly decreased as compared to norms in prim SS women and comparable to the levels of women with RA and fibromyalgia.     

To tame a volcano: patients with borderline personality disorder and their perceptions of suffering

The aim of the study was to investigate life situations, suffering, and perceptions of encounter with psychiatric care among 10 patients with borderline personality disorder. The results are based on a hermeneutic interpretation of narrative interviews in addition to biographical material (diary excerpts and poems). The interpretation revealed three comprehensive theme areas: life on the edge , the struggle for health and dignity-a balance act on a slack wire over a volcano , and the good and the bad act of psychiatric care in the drama of suffering . These theme areas form a movement back and forth-from despair and unendurable suffering to struggle for health and dignity and a life worth living. Common beliefs regarding these patients among personnel and implications for psychiatric care are discussed in relation to the results.     

Modelling the spread of penicillin-resistant Streptococcus pneumoniae in day-care and evaluation of intervention

In 1995, a disease control and intervention project was initiated in Malm?hus county in southern Sweden to limit the spread of penicillin-resistant pneumococci. Since most of the carriers of pneumococci are preschool children, and since most of the spread is believed to take place in day-care, a mathematical model, in the form of a stochastic process, for the spread in a day-care group was constructed. Effects of seasonal variation and size of the day-care group were particularly considered. The model was then used for comparing results from computer simulations without and with intervention. Results indicate that intervention is highly effective in day-care groups with more than ten children during the second half of the year.     

Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system

Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcgamma RII antibodies, whereas Fcgamma R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.     

Timeliness of case reporting in the Swedish statutory surveillance of communicable diseases 1998--2002

To prepare for a new communicable disease act in Sweden, we performed an in-depth analysis of the performance of the present notification system (1998--2002). Four diseases were selected for analysis (meningococcal infection, salmonellosis, infection with penicillin-resistant pneumococci and tularaemia). Each step in the double notification flow (clinical and laboratory notifications) was studied and paper-based and electronic notifications compared. More than 15 possible single dates in the notification flows were analysed for 27,000 cases. The shortest notification flows (from date of sample collection to when the first notification was received at SMI--clinical or laboratory notification) were seen for meningococcal infections and salmonellosis (median 7 d) and the longest for tularaemia (11 d). Laboratory notifications were faster than clinical notifications, and electronic reporting 1.5-1.7 times faster than paper notifications. Further gains should be expected from the new electronic reporting system (SmiNet2), which will allow also clinical reporting electronically over the internet.