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S Lindblad

Publications and source records attributed to S Lindblad.

At least 37 records · Page 2Linked to original sources

Quantitative microscopic analysis of inflammation in rheumatoid arthritis synovial membrane samples selected at arthroscopy compared with samples obtained blindly by needle biopsy.

OBJECTIVE: To evaluate microscopic measures of inflammation in rheumatoid arthritis synovial tissue samples selected at arthroscopy compared with those obtained blindly by needle biopsy from the suprapatellar pouch (SPP) of the same joint. METHODS: Samples were selected at knee arthroscopy from the SPP and the lateral and medial gutters. Immediately following arthroscopy, a biopsy needle was inserted through the same portal into the SPP by a second investigator, and 3 further samples were obtained blindly. Using standard immunohistologic methods, all samples were analyzed by a single investigator without knowledge of the original tissue location and biopsy technique. Following staining with anti-CD3 and anti-CD68 monoclonal antibodies, T lymphocyte and macrophage infiltration were measured by quantitative analysis. RESULTS: Synovial tissues from 14 patients were analyzed. In comparing microscopic measures of inflammation using the 2 procedures, mean scores of lining cell depth and the percentage of CD68+ cells in the lining layer correlated positively (tau = 0.59, P = 0.003 and tau = 0.73, P = 0.0003, respectively). In the sublining layer, CD3+ cell counts also correlated significantly (tau = 0.71, P = 0.0004). Sublining CD68+ cell counts did not correlate. This was explained by the observation that CD68+ cell infiltration in areas adjacent to articular cartilage was significantly greater than in the SPP (P = 0.01), suggesting preferential trafficking to this site by macrophages, but not by T lymphocytes. Macroscopic appearance at arthroscopy did not predict microscopic features. CONCLUSION: Most microscopic measures of inflammation in synovial tissue samples obtained blindly from the SPP were similar to those determined in samples selected at arthroscopy. However, measurements in samples from the SPP may underestimate the intensity of macrophage infiltration in areas more adjacent to cartilage. These observations have important implications for future study of macrophage function in synovial tissue.

Arthritis, Rheumatoid↗

Decreased expression of signal-transducing CD3 zeta chains in T cells from the joints and peripheral blood of rheumatoid arthritis patients.

Although T cells from patients with rheumatoid arthritis (RA) have previously been determined to have poor proliferative responses to a variety of stimuli, the underlying mechanism is not known. We have investigated the expression of the signal-transducing zeta molecule in subsets of T cells and natural killer (NK) cells derived from the peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of RA patients using quantitative flow cytometry, Western blot analysis and immunohistochemistry. A decrease of zeta expression was apparent in all investigated lymphocyte subsets from the PBMC and SFMC of RA patients, as compared to the corresponding subsets from healthy age- and sex-matched controls. A less pronounced reduction of cell surface-located CD3 epsilon, CD4 and CD8 was also located in T cells from SFMC as compared to PBMC from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image analysis also confirmed the low expression of zeta chains in synovial tissue of RA patients. The possibility that the decreased expression of zeta and of immune functions of T cells from RA patients may be related to the presence of free oxygen radicals, as we have previously reported in cancer patients, should be considered.

Arthritis, Rheumatoid↗

Temporomandibular joint involvement in generalized osteoarthritis and rheumatoid arthritis: a clinical, arthroscopic, histologic, and immunohistochemical study.

Twenty patients having generalized osteoarthritis (GOA) and symptomatic temporomandibular joints (TMJs) were compared with 22 patients having rheumatoid arthritis (RA) and TMJ symptoms, and also with an age-matched reference tissue material obtained at autopsy from 17 TMJs. Muscle tenderness was commoner in GOA. Arthroscopically, high frequencies of synovitis, degenerative changes, and fibrosis were observed in both groups, with more pronounced inflammatory and degenerative changes in RA patients, despite a shorter duration of TMJ symptoms. A correlation was noted between lateral joint tenderness and pronounced synovitis in RA patients. Histologic and immunohistochemical examinations added useful information to arthroscopy and showed similarly high frequencies of synovial inflammation in GOA and RA patients, differing clearly from those in the reference material. Connective-tissue degeneration was commoner in GOA patients. GOA and RA probably have different causes, but, interestingly, the tissue reaction was similar in the TMJs, although pronounced inflammatory and degenerative changes seemed to develop faster in RA.

Adolescent↗

Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.

The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.

Adolescent↗

Olsalazine-induced lupus syndrome.

A 73 year-old woman with ulcerative colitis developed skin rashes after long-standing sulphasalazine treatment. After a switch to olsalazine, she developed a severe SLE with multiorgan involvement. When the treatment was terminated, the disease manifestations and serological findings resolved.

Aged↗

Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis.

OBJECTIVES: To develop and evaluate a new immunohistochemical method to study the localisation and phenotype of individual cytokine producing cells in synovial biopsy specimens in rheumatoid arthritis. METHODS: Cryopreserved sections of synovial tissue from nine patients with rheumatoid arthritis were incubated with carefully selected cytokine specific antibodies detecting 19 different cytokines, after fixation of the specimens with paraformaldehyde and using saponin to permeabilise the cell membranes. RESULTS: The immunohistochemical method yielded reproducible and distinct staining patterns, in which the cytokines accumulated mainly in the Golgi apparatus of producer cells, indicating that the method preferentially detected local synthesis rather than cytokine uptake. The cytokine production patterns varied considerably between biopsy specimens from different patients. CONCLUSION: The present modified immunohistochemical method may provide a simple and rapid way to determine the local production of a wide array of cytokines in the synovium. The data obtained with this method also indicated that more T cell derived cytokines than previously recognised were present in active synovitis, as located and sampled by arthroscopy.

Adult↗

[Structured assessment of the treatment of rheumatoid arthritis].

As prognosis in rheumatoid arthritis has been shown to be much poorer than formerly believed, new treatment strategies have been proposed. However, trials of these strategies require improved evaluation of their effect on the disease course and its consequences for the patient. International guidelines and a Swedish model for such evaluation are presented in the article.

Arthritis, Rheumatoid↗

Correlation between increased hyaluronan localized in arthritic synovium and the presence of proliferating cells. A role for macrophage-derived factors.

OBJECTIVE: To determine whether the increased levels of circulating hyaluronan seen in patients with arthritis also occur locally. METHODS: Biopsy specimens of normal synovium and synovium from patients with various arthropathies were studied using histochemical and immunohistochemical staining procedures, to determine the tissue distribution of hyaluronan and infiltrating cells. RESULTS: Hyaluronan was found in increased concentrations in inflamed tissues, and was co-localized in sites containing Ki-67+ cells. In vitro analyses showed that macrophage-released factors increased hyaluronan production by fibroblasts. Hydrocortisone inhibited this in vitro production of hyaluronan. CONCLUSION: Edema and swelling seen in inflamed joints may be due to the presence of large amounts of hyaluronan. One possible mechanism of action of corticosteroids in the alleviation of acute joint inflammation may occur via the inhibition of hyaluronan production.

Arthritis↗

Characterization of T-cell receptor alpha beta repertoire in synovial tissue from different temporal phases of rheumatoid arthritis.

With the aim of investigating the distribution of T cells expressing different T-cell receptors (TCR) in the inflamed synovial tissue of rheumatoid arthritis patients, we have used the polymerase chain reaction to amplify TCR V alpha and V beta transcripts from synovial biopsies obtained by arthroscopy from patients with arthritis of variable duration. From each of nine patients a single biopsy was taken. Southern hybridization analysis of amplified products revealed extensive heterogeneity of TCR V beta in most patients. On the other hand, restriction in V alpha gene expression was seen in several patients. A highly restricted V alpha repertoire was observed in all cases with arthritis of short duration. In addition, two of three samples of short duration yielded a more limited number of V beta transcripts than the others. No conformity was, however, seen in usage of individual V alpha and V beta transcripts among the investigated patients. The present data thus demonstrate variability in synovial TCR expression between rheumatoid arthritis patients, but they also indicate a development towards greater diversity with increasing disease duration, implicating the necessity for careful choice of cases, preferentially selecting for early stages of disease, when further analysing rheumatoid synovial T cells for TCR usage as well as for antigen specificity.

Adult↗

Liver denervation does not alter the circadian rhythm of bile acid synthesis in rats.

In both rats and humans there is a distinct circadian rhythm of bile acid synthesis that is independent of feedback regulation. To determine whether the circadian rhythm is directly mediated via hepatic nerves, bile acid synthesis was studied in selectively liver-denervated male Sprague-Dawley rats in a bile fistula model. Complete denervation was confirmed by histofluorescent staining for neural elements in frozen sections of livers. There was no significant difference in mean bile acid synthesis, amplitude of the circadian rhythm, or time of peak synthesis between the denervated rats and nondenervated controls. In one denervated rat studied four times at weekly intervals, there was no shift in acrophase, indicating that the rhythm had not become free running. We conclude that signals arriving via hepatic nerves neither directly cause nor entrain the circadian rhythm of bile acid synthesis in rats.

Animals↗

Ultrastructural study of hepatic regeneration following one-lobe, two-lobe, and subtotal hepatectomy in the rat.

The sequential and comparative ultrastructural features of regenerating rat liver following one-lobe, two-lobe, and subtotal hepatectomy were studied. All three groups demonstrated glycogen depletion at the 12 h post-hepatectomy interval with reaccumulation occurring at 24 h in the first two groups but not until 72 h in the subtotal hepatectomy group. Other hepatocellular alterations attributed to regenerative activity were similar in the three groups, however the onset and magnitude of those changes occurring in the two-lobe and subtotally hepatectomized rats differed significantly from those alterations occurring in the one-lobe hepatectomy group. These changes were characterized by a greater and more prolonged mitotic activity, increased proliferation of RER and smooth endoplasmic reticulum (SER), and by increased Golgi bodies. These two groups also manifested greater hepatocellular accumulation of phagolysosomes, myelin figures, and lipid bodies when compared with the one-lobe hepatectomy group.

Animals↗

Traumatic synovitis analysed by arthroscopy and immunohistopathology.

The synovitis induced in previously healthy subjects by knee joint trauma was investigated at arthroscopic surgery performed after 3-70 days. Synovitis was confined to the areas of the synovial membrane bordering the cartilage lesion and displayed a varied intensity of inflammation. Biopsies were sampled under direct vision from the area of the peak inflammatory intensity within each joint and analysed by immunohistopathology. Only sparse lymphocytic infiltration and a slight increase of lining cell layers were found in the biopsies after as long as 70 days. The restricted extent and limited intensity of the inflammatory changes contrast with previous findings in rheumatoid arthritis. However, the arthroscopic and immunohistopathological signs of synovitis were no different.

Adult↗

Macrophage phenotype within simple ganglia.

Immunohistological staining of the connective tissue stroma of simple ganglia using monoclonal antibodies demonstrated infiltrating mononuclear phagocytes. These cells were characterised by positive staining for the leukocyte common antigen, the monocyte associated CD14 phenotype and HLA-class II antigens. There was only occasional expression of an epitope associated with macrophage maturity, and of the iC3b receptor. No expression of the C3b receptor, the high affinity Fc receptor, the p150.95 adhesion molecule or the p8.14 molecule was observed. Polymorphonuclear leukocytes and lymphocytes were absent. The restricted epitope expression by the mononuclear phagocyte population of simple ganglia may be a reflection of the absence of other inflammatory cells and indicates that the micro-environment within inflammatory lesions such as subcutaneous rheumatoid nodules is very different to that present in ganglia.

Adult↗

Inhibitory neuromodulators do not alter the course of experimental hepatic encephalopathy.

The neuromodulators, adenosine, serotonin, and glycine, did not alter the course of hepatic encephalopathy (HE) that followed a portacaval shunt and hepatic artery ligation in rats. The substances were instilled into the brain ventricle through an intraventricular cannula in doses that affect other aspects of behavior in the normal rat (adenosine, suppression of food intake; serotonin, loss of muscle strength and ataxia; glycine, leaning and circling). A subconvulsive dose of the glycine antagonist, strychnine, also had no effect on the course of HE. A large dose of the adenosine antagonist, caffeine, had a depressive rather than excitatory effect and shortened the time taken to induction of coma. These studies and a similar previous one with gamma-aminobutyric acid (GABA) suggest that the inhibitory neuromodulators do not have a prominent role in the pathogenesis of hepatic coma.

Adenosine↗

Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis.

We studied 10 patients who had arthritis of the knee joint, but no other signs of rheumatic disease. The clinical diagnosis of osteoarthritis was corroborated by arthroscopic evidence of characteristic cartilage degeneration. Signs of inflammation were confined to areas of the synovial membrane that lay near the cartilage; thus, the major part of the joint cavity was not affected. The intensity of the synovial inflammation varied within the areas involved, but was always most pronounced in regions rimming the cartilage. Biopsy samples selected from regions of intensely inflamed synovium contained foci of T lymphocytes, which were bordered by immunoglobulin-carrying B lymphocytes and plasma cells, as well as strongly HLA-DR positive dendritic-like cells adjoined to alpha Leu-3a+ T helper lymphocytes. In tissue samples taken from macroscopically noninflamed areas, only a few infiltrating lymphocytes were seen. Thus, the inflammatory synovial changes found in osteoarthritis appear to be anatomically restricted and of varied intensity but, when present, are microscopically indistinguishable from the changes that have been previously described as indicative of rheumatoid arthritis.

Arthroscopy↗

The synovial membrane of healthy individuals--immunohistochemical overlap with synovitis.

The synovial membrane of healthy volunteers was analysed by immunohistochemical staining of biopsies sampled under direct vision at arthroscopy or obtained blindly by needle. Infiltrating Leu-4+ T lymphocytes were found scattered in all biopsies but frequently also perivascularly accumulated. A majority of the synovial lining cells expressed either the OKM1 monocyte/macrophage marker or HLA-DR antigens. Some OKM1- HLA-DR+ lining cells also expressed the Leu-3a T 'helper' cell marker. In the sublining tissue non-lymphoid cells with varying morphology including macrophage- and fibrocyte-like cells were found expressing either HLA-DR, or Leu-3a, or both antigens simultaneously, whereas OKM1+ macrophage-like sublining cells were rare. The perivascular T lymphocyte accumulation as well as the phenotypic heterogeneity of infiltrating and residing cells, previously thought indicative of synovitis, were thus also found in the synovial membrane of healthy individuals.

Adult↗