Fibronectin production by synovial intimal cells

Summary The distribution of fibronectin in the inflamed synovium has been described previously using immunohistochemical methods. Under favourable conditions, it is possible to demonstrate apparent cytoplasmic staining of the intimal cell layer. We have further investigated the localisation of fibronectin in the synovial intimal cells using higher resolution techniques with peroxidase-antiperoxidase staining and high power light microscopy of semithin Araldite sections and immunoelectron microscopy using a protein A-gold technique. Synovia from 11 mechanical/traumatic, or osteoarthritic joints; 12 seropositive rheumatoid arthritis and nine cases from other joint diseases made a total of 32 cases examined in semithin sections, while six rheumatoid and two osteoarthritis synovia were studied by immunoelectron microscopy. Fibronectin was demonstrated in individual cells of the synovial intimal layer in 22 out of 32 samples examined by the light microscope method, and electron microscopy of adjacent sections showed that the positvely staining cells were type B synoviocytes. Immunoelectron microscopy confirmed the presence of fibronectin within the rough endoplasmic reticulum of type B synoviocytes in all but one of the eight samples examined. The results provide evidence that the type B synoviocyte is responsible for fibronectin production.     

Immunodeficiency-related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer Study Group Registry

Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant-related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug-induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)-related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European-American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high-grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non-Hodgkin's lymphoma (NHL), 10 were localized and 32 non-localized. Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive. Thirty-five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.     

Fibronectin in the synovium of chronic inflammatory joint disease

Summary The localisation of fibronectin in the synovial membrane of rheumatoid arthritis (RA) and other chronic inflammatory joint diseases has been studied using a peroxidase-antiperoxidase immunohistochemical method. Synovia were studied from seven cases of seropositive RA three cases of seronegative RA, six cases of ankylosing spondylitis, four cases of Reiter's syndrome and five of psoriatic arthritis. Six were small biopsies and the remaining tissues were obtained at open surgery for orthopaedic procedures or biopsies.Fibronectin was demonstrated in all of the synovia examined and was present in intimal cells, synovial giant cells, the walls of small blood vessels, basement membrane of larger vessels and deposits of fibrin. No difference in this distribution of fibronectin was found in seropositive and seronegative RA, ankylosing spondylitis, Reiter's syndrome or psoriatic arthritis, neither was there any difference in the amount of fibronectin at various sites.     

Proliferative activity of cells in the synovium as demonstrated by a monoclonal antibody,Ki67

Summary The presence of proliferating cells has been sought in the synovium of rheumatoid arthritic (RA) and osteoarthritic (OA) joints using the monoclonal antibody Ki67, which marks a nuclear antigen present in all stages of the cell cycle apart from Go. Synovia were studied from 21 RA and 14 OA cases using the indirect immunoperoxidase technique. Double-staining was performed on 18 RA and 17 OA synovia with the simultaneous labelling of lysozyme (muramidase) by the immuno-alkaline phosphatase method and with Ki67 by the indirect immunoperoxidase method.Most of the RA and OA synovia showed an absence of Ki67-positive cells in the intimal cell layer. Three RA and four OA synovia showed no more than ten proliferating cells in the whole of the intimal layer examined. Similar results were obtained when double-labelling was performed. Eight RA and six OA synovia showed the presence of occasional Ki67-positive cells in the intimal layer. The total number of intimal cells was measured for each histological section, and the proliferation index calculated as the percentage of total cells in the intimal layer showing Ki67-positive staining. This varied between 0.03% and 0.0033% (between 1 : 2800 and 1 : 30 000 cells). In contrast, there were plentiful Ki67-positive cells present in the lymphocytic infiltrate and around blood vessels in the RA synovia and in the synovial infiltrate, where present, in the OA cases. The results provide further support for the suggestion that the intimal cell layer of the synovium is predominantly composed of macrophages, with some fibroblasts, and that the macrophages have not arisen locally by cell division (hyperplasia) but have migrated from the underlying synovial blood vessels.     

Salbutamol plus beclomethasone dipropionate, but not salbutamol alone, completely prevent early and late asthmatic responses to allergen.

The effect of a week treatment with inhaled salbutamol plus placebo (S+P) vs. salbutamol combined with beclomethasone dipropionate (S+BDP) on early and late asthmatic responses to inhaled allergen was studied in ten atopic patients in a randomized, double-blind, cross-over study. All patients had previously shown a dual type response to the specific bronchial provocative test (sBPT). Each patient performed two periods of treatment for a week, with a 15 day interval between them: (a) salbutamol 0.3 mg, tid + placebo; (b) salbutamol 0.3 mg+BDP 0.2 mg, tid; at the end of each treatment period, sBPT was performed and the last treatments were given 1.5-2 h before and 3-4 h after allergen challenge. S + BDP completely prevented both early and late responses to allergen, while S + P reduced but did not completely inhibit early and late responses. The difference between the two treatments was significant for early and late asthmatic responses. Non-specific bronchial hyperresponsiveness to methacholine was performed before each treatment period, after 6 days of treatment before sBPT and the day after sBPT at the end of the treatment period; there was only a mild increase in PD15FEV1 methacholine after 6 days of treatment with S + BDP in comparison with S + P treatment. These results suggest that salbutamol plus beclomethasone may be used effectively in the prophylaxis of early and late asthmatic reactions induced by allergen in sensitized subjects.     

The distribution of neurokinin-1 and neurokinin-2 receptors in human central airways

The precise locations of neurokinin (NK)-1 and NK-2 receptors in human airways, and their role in airway inflammatory diseases, have not been carefully examined. To determine the distribution of NK-1 and NK-2 receptors in human central airways, and to determine whether their distribution was different in smokers, we examined surgical specimens from patients undergoing lung resection for limited lung lesions. We mapped NK-1 and NK-2 receptors in four groups of subjects: four asymptomatic nonsmokers, seven asymptomatic smokers, seven symptomatic smokers with normal lung function, and eight symptomatic smokers with chronic airflow limitation. Tissues were immunostained with anti-NK-1- and anti-NK-2-receptor antibodies. Expression of NK-1 and NK-2 receptors was quantified through light microscopy and image analysis. Both NK-1 and NK-2 receptors were found in bronchial glands, bronchial vessels, and bronchial smooth muscle. Although no receptors were observed in the epithelium, receptors were occasionally found in nerves (NK-1) and in inflammatory cells (NK-2) such as T lymphocytes, macrophages, and mast cells. The distribution of both NK-1 and NK-2 receptors was similar in all the tissues examined in the four groups of subjects. These data show that NK-1 and NK-2 receptors are present in human central airways and that their expression is not modified by cigarette smoking.     

Mycosis fungoides and Sézary syndrome: Australian clinical practice statement

Primary cutaneous lymphomas represent a heterogeneous group of T‐ and B‐cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T‐cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following ( http://www.australasianlymphomaalliance.org.au ).     

PPD and hsp65 induced monoarthritis initiates spontaneous recurrent flares in Lewis rats.

OBJECTIVES--To investigate the time course of a monoarthritis induced with the purified protein derivative of tuberculin (PPD) or a recombinant 65 kDa heat shock protein (rhsp65) in two different strains of sensitised rats. METHODS--Wistar and Lewis rats, sensitised with heat killed Mycobacterium tuberculosis in oil, were challenged intraarticularly with PPD or rhsp65 and monitored for six weeks. Inflammation was assessed by joint swelling, histology, and radiographic studies. RESULTS--Sensitised Lewis rats injected with PPD or rhsp65 showed a chronic response with recurrent spontaneous flares, while Wistar rats showed one inflammatory episode. CONCLUSIONS--The Wistar strain response to PPD resembles a transient reactive arthritis, while the response of the Lewis strain mimics the relapsing nature of rheumatoid synovitis, providing an interesting model to determine dominant immunopathogenic mechanisms.     

Esophageal Manifestations of Multisystem Diseases

The esophagus may be involved directly or indirectly by numerous disease conditions. On occasion, the esophageal process may be the key to the diagnosis. In some situations, the esophageal manifestation of a disease may be more immediately life-threatening than the primary process.