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Although coparenting has been widely studied, little is known about the daily processes of coparenting between mothers and fathers in early parenthood. Based on family systems theory and the ecological model of coparenting, we investigated new parents' day-to-day within-family processes of cooperative and tensioned coparenting. Mothers and fathers from 144 Finnish first-time couples completed daily mobile diaries for 7 consecutive days when their firstborn was 4-6 months old. The random-intercept cross-lagged panel model showed three types of within-family processes in daily coparenting, which we named continuity, spread, and shift. Continuity in cooperative coparenting occurred when a parent's previous-day cooperative coparenting positively predicted his or her own cooperative coparenting experiences the next day. We also found that coparenting experiences spread from one spouse to another: A parent's cooperative coparenting on the previous day negatively predicted his or her spouse's experiences of tensioned coparenting the following day. Finally, daily coparenting experiences also shifted from day to day: One parent's experience of tensioned coparenting the previous day positively predicted that parent's cooperative coparenting experiences the next day. No gender differences were found. These findings emphasize that the two daily coparenting dimensions seem to operate partly differently in daily life, as cooperative coparenting was slightly more often a cause and consequence in the observed processes than tensioned coparenting. Therefore, it seems that interventions should focus on enhancing cooperative coparenting. Moreover, the new concepts of continuity, spread, and shift are proposed as better descriptions of the three daily processes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessing mild oropharyngeal dysphagia (OD) raises the question where to draw the line between normal and pathological swallowing. There is a lack of clinical test methods appropriate in the subacute phase of recovery from dysphagia following stroke and other brain injuries. The aim of this pilot study was to investigate the diagnostic accuracy of a new test battery, called the Swallow Battery (SwaB), in relation to Fiberoptic Endoscopic Evaluation of Swallowing (FEES). SwaB consists of the validated tests Repetitive Saliva Swallowing Test (RSST), Timed Water Swallowing Test (TWST) and parts of the Test of Masticating and Swallowing Solids (ToMaSS). Nineteen adult patients with acquired brain injury who were enrolled in a rehabilitation programme underwent the SwaB and a FEES, both resulting in a pass or fail outcome. The pass or fail results were based on RSST's and TWST's suggested cutoffs, normative values of ToMaSS and on established rating scales used for FEES. The SwaB's ability to predict FEES results was 74% according to a binary logistic regression analysis, with a 92% correct prediction of fail results and 33% correct prediction of pass results. The ToMaSS was sensitive to small changes in eating ability, failing 13 out of 19 patients using 95% CI normative values as cutoff, including patients with a passed FEES. Alternative cutoffs were therefore suggested, depending on purpose of dysphagia assessment. The results of this study indicate that the SwaB may be a useful tool when assessing mild dysphagia following brain injury. Further studies of SwaB's validity and clinical utility are suggested., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: In a pilot study we aimed to identify biomarkers in repeated muscle biopsies and paired blood samples, taken before and after conventional immunosuppressive therapy, in order to predict long-term therapeutic response in patients with idiopathic inflammatory myopathies (IIM)., Methods: Muscle biopsies were selected from 13 new onset patients, six responders and seven non-responders. Repeated muscle biopsies after a median of 11 months follow-up were available from 9 patients and paired peripheral blood mononuclear cells (PBMCs) from 5 patients. Treatment response after 3 years was defined by MMT-8 measuring muscle strength and the ACR/EULAR 2016 improvement criteria. Frozen biopsy sections were immunohistochemically stained for expression of CD3, CD66b, IL-15, CD68, CD163 and myosin heavy chain neonatal (MHCn). PBMCs were analysed by flow cytometry for monocyte phenotypes (CD14, CD16, CD68, CX3CR1, and CCR2)., Results: Before treatment there were no significant differences in any clinical or muscle biopsy variables or monocyte subsets between responders and non-responders. MMT-8 was significantly higher compared to baseline in the responders at 3-year follow-up. In responders the expression of CD68 in the repeated biopsies was significantly lower compared to non-responders (p<0.05)., Conclusions: Baseline biopsy, monocyte profile or clinical data did not predict long-term treatment response, but in the repeated biopsy within 1 year of immunosuppressive treatment, the lower number of macrophages (CD68+) seemed to predict a more favourable long-term clinical response with regard to improved muscle strength.

Objectives: To study the effects of abatacept on disease activity and on muscle biopsy features of adult patients with dermatomyositis (DM) or polymyositis (PM)., Methods: Twenty patients with DM (n=9) or PM (n=11) with refractory disease were enrolled in a randomised treatment delayed-start trial to receive either immediate active treatment with intravenous abatacept or a 3 month delayed-start. The primary endpoint was number of responders, defined by the International Myositis Assessment and Clinical Studies Group definition of improvement (DOI), after 6 months of treatment. Secondary endpoints included number of responders in the early treatment arm compared with the delayed treatment arm at 3 months. Repeated muscle biopsies were investigated for cellular markers and cytokines., Results: 8/19 patients included in the analyses achieved the DOI at 6 months. At 3 months of study, five (50%) patients were responders after active treatment but only one (11%) patient in the delayed treatment arm. Eight adverse events (AEs) were regarded as related to the drug, four mild and four moderate, and three serious AEs, none related to the drug. There was a significant increase in regulatory T cells (Tregs), whereas other markers were unchanged in repeated muscle biopsies., Conclusions: In this pilot study, treatment of patients with DM and PM with abatacept resulted in lower disease activity in nearly half of the patients. In patients with repeat muscle biopsies, an increased frequency of Foxp3 + Tregs suggests a positive effect of treatment in muscle tissue., Competing Interests: Competing interests: IEL: research grant and advisory board consultant for BMS, research grant from AstraZeneca, consultant for MedImmune, aTyr and IDERA. RA: research grant from BMS., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: It is known from clinical practice and observational studies that elderly patients with a diagnosis of inflammatory rheumatic diseases (IRD) bear a significantly increased risk for cardiovascular diseases such as coronary artery disease (CAD) and heart failure. The molecular mechanism, however, is still not known. Recently, high mobility group protein B1 (HMGB1), a ubiquitous, highly conserved single polypeptide expressed in all mammal eukaryotic cells, has been identified to mediate myocardial dysfunction in vitro once released from the nuclei of cardiomyocytes., Objective: To investigate whether HMGB1 and its receptors are expressed in cardiac muscles of elderly patients with CAD with or without IRD., Methods: HMGB1 and its 3 well-known receptors, receptor for advanced glycation end products, Toll-like receptor 2 (TLR2), and TLR4, were examined by immunohistochemistry on myocardial biopsy specimens from 18 elderly patients with CAD (10 with IRD, 8 without IRD). Furthermore, total HMGB1 protein levels were measured by Western blot from the cardiac biopsies in 5 patients with and 5 without IRD., Results: Pathologic cytosolic HMGB1 in cardiomyocytes was massively recorded in all patients with IRD, but only slightly expressed in 1 patient without IRD. Total HMGB1 levels were also consistently lower in myocardial muscle biopsies of patients with IRD compared to those without IRD. Furthermore, all 3 HMGB1 receptors were expressed in cardiomyocytes of all patients., Conclusion: The increased cytosolic expression of HMGB1 in cardiomyocytes and the lower total amount of HMGB1 in the cardiac specimens of IRD patients is consistent with a greater release of HMGB1 from the myocardial nuclei in IRD than non-IRD individuals. Thus, the HMGB1 signaling pathways may be more easily activated in elderly CAD patients with concomitant IRD and trigger a detrimental inflammatory process causing severe cardiovascular problems. Therefore, targeting HMGB1 in IRD patients might reduce the risk for cardiovascular events., (© 2017 S. Karger AG, Basel.)

Objective: Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM., Methods: Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry-based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise., Results: Compared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up-regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down-regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm(2) in follow-up biopsy samples (P < 0.05)., Conclusion: Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients' muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies., (© 2016, American College of Rheumatology.)

Objective: We examined the relationships between dentition, nutritional status and dietary intakes of energy, protein and micronutrients among older people in assisted living facilities in Helsinki., Background: Poor dentition is associated with malnutrition. Less is known about how dentition is associated with detailed nutrient intakes in institutionalised older people., Materials and Methods: This cross-sectional study assessed 343 participants (mean age 83 years). Dentition was assessed by trained ward nurses and divided into edentulous participants without dentures (group 1), edentulous participants with removable dentures (group 2) and those with any natural teeth (group 3). Nutritional status was assessed by Mini Nutritional Assessment (MNA). The energy, protein and nutrient intakes were calculated from detailed 1-day food diaries and compared with the recommendations of the Finnish National Nutrition Council as a measure of dietary adequacy. Assessment included also participants' cognitive and functional status., Results: Of the participants, 8.2, 39.1 and 52.8% were in groups 1, 2 and 3, respectively. Altogether 22% were malnourished according to MNA. Group 1 had the poorest nutritional status. A large proportion of participants consumed less than the recommended amounts of energy, protein or micronutrients. Half of the participants consumed <60 g/day of protein. The intake of protein was significantly lower in group 1 than in other two groups., Conclusion: Malnutrition and inadequate protein intake were very common and associated with dentition among older people with multiple disabilities in assisted living facilities. Assessment of dental status should be part of good nutritional care in long-term care., (© 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.)

Introduction: Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers., Methods: Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1)., Results: BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08)., Conclusions: The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.

Objective: The aim of this study is to explore the prevalence of swallowing difficulties (SWD) and their associations with nutritional status, eating habits, nutritional care, and mortality among older people in assisted living., Design: A cross-sectional study with interviews and nutritional assessments at baseline and 3-year follow-up for mortality., Setting: Assisted living facilities in the Helsinki metropolitan area, Finland., Participants: All residents (N=1466) in assisted living facilities., Measurements: Personal interviews yielded information on demographics, medical history, functional status, SWDs and eating habits. Residents' nutritional status was assessed with the Mini Nutritional Assessment (MNA). Three-year mortality data were retrieved from central registers., Results: SWDs were common; 11.8% of subjects suffered from them. Those with SWDs were older, more often female, and more frequently had Parkinson's disease, chronic obstructive pulmonary disease (COPD), and chronic/ recurrent infections than those without SWDs. No differences were present between the groups in prevalence of stroke or dementia, but more severe cognitive decline occurred among those with SWDs. According to the MNA, 30.6% of those with SWDs were malnourished (<17 points), whereas the respective figure for those without SWDs was 11.0% (p < .001). Those with SWDs ate more often fluid or puréed food (27.8% vs. 3.8%, p < .001), ate more often little or quite little of their food portion (32.6% vs. 23.5%, p < .010), and consumed less fluids (< 5 cups/day 51.7% vs. 35.6%, p< .001) than those without SWDs. Of those with SWDs, 55.0% died by the end of follow-up, whereas the respective figure for those without SWDs was 41.5%. In logistic regression analysis using age, sex, comorbidities, and MNA as covariates, SWDs continued to predict mortality (OR=1.49, 95% CI=1.04 -2.12)., Conclusions: SWDs are common and associated with poor nutrition and risk of death of patients in assisted living facilities. Nurses should be trained to assess SWDs and nutritional problems in order to take optimal care of these residents.

Nitric oxide donors and inhaled nitric oxide (iNO) may decrease ischemia/reperfusion injury as reported in animal and human models. We investigated whether the attenuation of reperfusion injury, seen by others, in patients undergoing knee arthroplasty could be reproduced when patients had spinal anesthesia. 45 consecutive patients were randomized into three groups (n = 15). Groups 1 and 3 were receiving iNO 80 ppm or placebo (nitrogen, N2) throughout the entire operation, and group 2 only received iNO in the beginning and at the end of the operation. Blood samples were collected before surgery, at the end of the surgery, and 2 hours postoperatively. Muscle biopsies were taken from quadriceps femoris muscle before and after ischemia. There were no increases in plasma levels of soluble adhesion molecules: ICAM, VCAM, P-selectin, E-selectin, or of HMGB1, in any of the groups. There were low numbers of CD68+ macrophages and of endothelial cells expression of ICAM, VCAM, and P-selectin in the muscle analyzed by immunohistochemistry, prior to and after ischemia. No signs of endothelial cell activation or inflammatory response neither systemically nor locally could be detected. The absence of inflammatory response questions this model of ischemia/reperfusion, but may also be related to the choice of anesthetic method EudraCTnr.

Objective: The aim of this study was to investigate signs of inflammation in muscle of patients with prior polio, since the main symptoms in these patients are muscle pain, weakness and fatigue. In the context of pain and inflammation, the prostaglandin E2 pathway is of interest. Prostaglandin E2 has many biological actions and is a mediator of inflammation and pain., Patients and Methods: Skeletal muscle biopsies from 8 patients with prior polio and post-polio symptoms, presenting with pain and muscular weakness, and from 6 healthy controls were studied. Immunohistochemistry, conventional microscopy, and computerized image analysis were performed., Results: There was statistically significant higher expression of enzymes of the prostaglandin E2 synthetic pathway, in muscle from patients, compared with controls. Expression of prostaglandin enzymes was mainly in scattered cells and blood vessels, and may indicate an inflammatory process of the muscle, which could be secondary to systemic inflammation., Conclusion: This data may indicate an inflammatory process in muscle of prior polio patients. Up-regulation of the prostaglandin E2 pathway reveals a potential background to the pain experienced by these patients, and may provide opportunities for directed pharmacological and physical therapies, which could lead to better outcomes of rehabilitation interventions.

Objectives: To investigate the expression of interleukin (IL)-15 and IL-15 receptor α (IL-15Rα) in muscle tissue from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive (IS) treatment., Methods: Muscle biopsies from 17 patients before and after conventional IS treatment and seven healthy individuals were investigated by immunohistochemistry using antibodies against IL-15 and IL-15Rα. Quantification was performed by computerised image analysis. Cellular localisation of IL-15 was determined by double immunofluorescence. Clinical outcome was measured by the functional index and serum creatine kinase. Human myotubes were cultured and IL-15 staining was performed by immunocytochemistry., Results: IL-15 was observed in mononuclear inflammatory cells of muscle tissue while IL-15Rα was localised to mononuclear inflammatory cells, capillaries and large vessels. Double staining showed localisation of IL-15 to CD163+ macrophages. A significantly larger number of IL-15 and IL-15Rα-positive cells were seen in muscle tissue of patients compared with healthy individuals. Baseline IL-15 expression correlated negatively with improvement in muscle function. After conventional IS treatment, a significantly lower number of IL-15 and IL-15Rα-positive cells was found. However, compared with controls, eight of 17 patients still had more IL-15-positive cells and less muscle function improvement was shown in this group of patients, both in short-term and long-term observations. Human differentiated myotubes were negative for IL-15 staining., Conclusions: IL-15 and its receptor are expressed in the muscle tissue of patients with myositis and IL-15 expression is correlated with improvement in muscle function. IL-15 may play a role in the pathogenesis of myositis and could be a biological treatment target, at least in a subgroup of patients with polymyositis or dermatomyositis.

Objective: Polymyositis and dermatomyositis are idiopathic, inflammatory myopathies characterized by proximal muscle fatigue. Conventional immunosuppressive treatment gives a variable response. Biopsies from chronic patients display a low proportion type I and a high proportion of type II muscle fibres. This raised a suspicion that the low proportion of type I fibres might play a role in the muscle fatigue., Aim: To investigate whether the muscle fibre attributes evident in chronic myositis are characteristic for the polymyositis and dermatomyosistis diseases themselves., Methods: Muscle biopsies were obtained from thigh muscle from untreated patients (n = 18), treated responders (n = 14) and non-responders (n = 6) and from healthy controls (n = 11), respectively. For clinical evaluations, creatine kinase, functional index of myositis and cumulative dose of cortisone were established., Results:   Chronic patients had a lower proportion of type I fibres and a higher proportion of type II fibres compared to untreated myositis patients and healthy controls. Fibre cross-sectional area (CSA) did not differ between patients and healthy individuals but all women had a 20% smaller type II fibre CSA compared to men., Conclusions: Untreated polymyositis and dermatomyositis patients and healthy controls have a different fibre type composition than chronic polymyositis and dermatomyositis patients. Fibre CSA did not differ between healthy controls or any of the patient groups. A low proportion of oxidative muscle fibres can therefore be excluded as a contributing factor causing muscle fatigue at disease onset and the gender difference should be taken into consideration when evaluating fibre CSA in myositis., (© 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Objective: Sporadic inclusion body myositis (IBM) is characterized by T cell infiltrates in muscle tissue, but their functional role is unclear. Systemic signs of inflammation are lacking, and the absence of beneficial effects following immunosuppression has challenged the notion of a role for the immune system. This study was undertaken to investigate the phenotype and functionality of T cells, specifically a subset of proinflammatory, cytotoxic, and apoptosis-resistant T cells defined as CD28(null) T cells, in the pathogenesis of sporadic IBM., Methods: A cohort of 27 patients with sporadic IBM was analyzed for the frequency of circulating and muscle-infiltrating CD28(null) T cells. The T cell receptor (TCR) V(β) usage was determined using flow cytometry and immunohistochemistry. Anti-CD3-stimulated peripheral blood mononuclear cells were analyzed for intracellular interferon-γ and cytotoxic potential by flow cytometry., Results: We found striking accumulations of both CD8+CD28(null) and CD4+CD28(null) T cells, which represented the TCR V(β) -expanded T cells in sporadic IBM. Such CD28(null) T cells were abundant both in the inflamed muscle tissue and in the circulation. Although the specific TCR V(β) expansions varied between patients, both CD8+CD28(null) and CD4+CD28(null) T cells consistently displayed a highly proinflammatory and cytotoxic potential., Conclusion: Our results suggest that CD28null T cell expansions represent the previously described expanded T cell subsets in sporadic IBM, and their proinflammatory capacity and presence in both muscle tissue and the circulation may imply a role of immune activation in sporadic IBM. In addition, CD4+CD28(null) T cells may exert cytotoxic effects directly on muscle fibers due to a cytotoxic potential similar to that in CD8+ T cells., (Copyright © 2010 by the American College of Rheumatology.)

Dermatomyositis and polymyositis are disabling rheumatic diseases characterized by an appreciable number of T cells infiltrating muscle tissue. The precise phenotype, function and specificity of these cells remain elusive. In this study, we aimed to characterize T cells in muscle tissue and circulation and to investigate their association to clinical phenotype. Twenty-four patients with dermatomyositis and 42 with polymyositis were screened for frequency of CD4+CD28(null) and CD8+CD28(null) T cells in peripheral blood by flow cytometry. Presence of these cells in inflamed muscle tissue from 13 of these patients was analyzed by three-color immunofluorescence microscopy. Effector functions, proliferation and Ag specificity were analyzed by flow cytometry after in vitro stimulation. The clinical relevance of CD28(null) T cells was analyzed by multiple regression analyses including six separate and combined disease variables. We demonstrate that muscle-infiltrating T cells are predominantly CD4+CD28(null) and CD8+CD28(null) T cells in patients with dermatomyositis and polymyositis. Muscle-infiltrating CD28(null) T cells were found already at time of diagnosis. Disease activity correlated with the frequency of CD8+ T cells in the inflamed muscles of polymyositis patients. Circulating CD4+CD28(null) and CD8+CD28(null) T cells were significantly more frequent in human CMV (HCMV) seropositive individuals, responded to HCMV Ag stimulation, and correlated with disease duration. These cells also display a proinflammatory cytokine profile, contain perforin and lack the costimulatory molecule CD28. Our observations imply that CD28(null) T cells represent clinically important effector cells in dermatomyositis and polymyositis, and that HCMV might play a role in propagating disease in a subset of patients.

The production of cytokines from T cells and macrophages is of potential importance for the histological changes apparent in coeliac disease (CoD). Small intestinal biopsy specimens from children with CoD and disease control subjects were investigated for their content of cytokines and tissue transglutaminase (tTG). The transforming growth factor-beta1 (TGF-beta1) expression was increased in the lamina propria of children with villous atrophy. In contrast, TGF-beta3 was expressed at a higher level in the epithelium and the lamina propria of the disease control subjects. The tTG expression was increased in the small intestine of CoD patients as compared with that in subjects. Interleukin-4 (IL-4) was detected in the lamina propria of both CoD patients and controls, and some of the investigated biopsy specimens also showed IL-4 expression in the epithelium. We conclude that children with active CoD could have an altered expression of TGF-beta and tTG in the small intestine and that a disturbed regulation of TGF-beta may be of importance in the immune pathogenesis of CoD.

The aim of our study was to address the question of whether muscle fibers express major histocompatibility complex (MHC) class II in inflammatory myopathies. For this purpose we performed a systematic study of MHC class II antigen expression on muscle fiber membranes in muscle tissue from polymyositis and dermatomyositis patients in various stages of disease activity. Thirty-two patients with classical clinical signs of myositis were divided into subgroups depending on duration of clinical signs of myositis and presence or absence of inflammatory infiltrates in muscle tissue. Immunohistochemistry as well as double-immunofluorescence stainings were used to identify the presence of MHC class II in muscle tissue. MHC class I was included for comparison. Quantification of positive staining was performed using an image analysis system in addition to evaluation by manual microscopic scoring and laser confocal microscopy. It was demonstrated that a significant proportion of skeletal muscle fibers in inflammatory myopathies express MHC class II as well as MHC class I and that MHC antigen expression is independent of the inflammatory cell infiltration. Furthermore, there were no differences in staining pattern between polymyositis and dermatomyositis patients. Our results indicate that MHC class II and MHC class I molecules may be involved in initiating and maintaining the pathological condition in myositis rather than only being a consequence of a preceding local inflammation.

We have investigated the inflammatory cell infiltrates and adhesion molecule expression in the synovial fluid (SF) and synovial membranes (SM) of rats with homologous collagen-induced arthritis. Immunohistochemical staining revealed that the majority of the cells in the SF were granulocytes, expressing CD11b and CD11c. In SM, the majority of the cells were monocytes/macrophages. CD49d and CD49f were expressed mainly in the erosion zone in SM, and ICAM-1 was expressed in the lining layer, in the capillaries, and in the erosion zone. In SF 7% of the cells were ICAM-1 positive. CD2 was more abundant in SM than in SF. These findings might explain the difference in granulocyte counts between SF and SM. CD49d and CD49f expression might retain lymphocytes and monocytes in SM, while granulocytes not expressing CD49d and CD49f are not retained.

The kinetics of cytokine production in arthritic limbs of mice with CIA was determined by using modified immunohistochemical techniques. Tissue cryostat sections of undecalcified whole paws were analysed for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-2, IL-4, IL-5 interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta2) and TGF-beta3. Locally produced TNF-alpha, IL-6 and TGF-beta2 were observed within the lining layer, sublining and pannus at all stages of disease. The staining of TNF-alpha was particularly intense at the cartilage-pannus junction. In contrast to the monokines, IFN-gamma and TGF-beta3 were only expressed in scattered cells within the deeper layers of the synovia. Interestingly, IFN-gamma was not present in the late phase of CIA, despite the continued presence of TNF-alpha and IL-6 in the pannus. Production of IL-2, IL-4 or IL-5 was not detected in any joint. The observed pattern of a relative paucity of T cell-derived cytokines and an abundance of monokines during the late phase of T cell-dependent CIA indicates that the synovial cytokine pattern previously described in rheumatoid arthritis (RA) is fully compatible with a pathogenic role of T cells. The temporal as well as spatial dissociation between expression of T cell-derived cytokines and monokines indicates that T cell-independent mechanisms may also be of importance in the triggering of monokine production during arthritis.