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To compare the cytokine profile with the degree and composition of cellular infiltration in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium, synovial membranes from patients with RA (n = 14) and OA (n = 5) were examined, employing immunohistochemistry and competitive reverse-transcriptase polymerase chain reaction (RT-PCR), for interleukin (IL)-I beta, IL-2, IL-4, IL-5, IL-6, and IL-10, and tumour necrosis factor-alpha (TNF-alpha) gene expression. It was found that the strength of cytokine gene expression within the synovial membranes of patients with RA was not significantly correlated with the degree of synovial infiltration of T-cells, B-cells, or macrophages. No IL-2, IL-4, or IL-5 RNA was detected in the synovium of either RA or OA. Quantitative cytokine determination showed a similar pattern in RA and OA, although the two diseases differed in total synovial infiltration and the composition of infiltrating cellular elements. Thus the number of cell types known to produce certain cytokines does not appear to determine the strength of synovial cytokine expression measured by quantitative RT-PCR. Furthermore, the pattern of T-cell specific cytokines found in RA synovium does not accord with the concept of the TH0, TH1, and TH2.

Recent clinical observations support the hypothesis that persistent parvovirus B19 is a triggering factor of rheumatoid arthritis (RA) in certain genetically predisposed individuals. If this hypothesis is correct, a number of RA patients may exhibit parvovirus B19 DNA in their synovial membranes. We tested the synovial tissue and peripheral blood leukocytes of 20 patients with RA, 24 patients with other arthritides or osteoarthritis (non-RA), and 34 healthy blood donors for the presence of parvovirus B19 DNA using specific DNA amplification by polymerase chain reaction (PCR). Using this technique, parvovirus B19 DNA was demonstrated in the synovial biopsies of 75% of patients with RA but in those of only 16.7% of patients with non-RA. In autologous peripheral blood mononuclear cells the percentage of PCR-positive patients was about 15% in both RA and non-RA groups and did not differ from that in healthy controls. When the PCR data were correlated with the presence of anti-parvovirus B19 IgG antibodies in serum and synovia all patients with parvovirus B19 DNA in peripheral blood alone or in both peripheral blood and synovial membrane were seropositive. In contrast, about 40% of patients with parvovirus B19 DNA restricted to the synovial membrane were seronegative. These data indicate a highly disease-related persistence of parvovirus B19 in the rheumatoid synovium.

Neo-synovial membranes, which formed after "primary" synovectomy in 21 patients with rheumatoid arthritis (RA), were studied at resynovectomy. The clinical, histomorphological, and immunohistological data were compared with data derived from "primary" synovial membranes from RA and osteoarthritis (OA) patients. The clinical data suggest a less active rheumatoid inflammatory response after synovectomy. Histomorphologicaly, the synovitis in resynovectomized neosynovial membranes of RA revealed no qualitative differences when compared with synovitis in the "primary" synovium. However, the degree of the inflammatory rection evaluated by the different parameters was found to be distinctly lower. The immunohistological data correlated with these findings.

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.

To evaluate the extent of psychosomatical complaints in patients with primary keratoconjunctivitis sicca (pKCS).20 patients (m:f = 1.19; mean age 49 +/- 7 years) with pKCS were rated according to the von Zerssen Symptom List (psychosomatical discomfort), the Maudsley Personality Inventory (MPI)-N (emotional status) and -E (extroverted-introverted) and to Beck Depression Inventory (BDI). 54 subjects (m:f = 35:17; mean age 46 +/- 17 years) without any ocular or general chronic disease were used as control group.In comparison to the control group the patients with pKCS showed significantly (p0.0001) more complaints (von Zerssen Symptom List), were more (p0.0001) emotionally unstable (MPI-N) and more (p0.0001) depressive (BDI). No group differences were found regarding extroversion-introversion (MPI-E).Our results demonstrate that many patients with pKCS showed psychological problems and disturbances. We therefore recommend an additional psychological treatment (e.g. autogenic training) for these patients to stabilize their emotional condition, which may even have a positive effect on their dry eye problems.

In spite of differences in etiology, RA and OA lead to astonishingly similar synovitic alterations. Fibroblastic transformation of the synovial membrane and an increase in monocytes constitute a rare but highly characteristic feature of RA. Monocytes synthesize factor (F) XIII, implying that FXIII (a and s) in synovial tissue might help to differentiate between RA and OA. Biopsies were obtained at open surgery from 98 unselected patients with the clinical diagnosis of RA (n = 54) or OA (n = 44). In a three-stage (ABC) immunoperoxidase technique, polyclonal antisera against factor XIIIa and factor XIIIs were investigated. Compared to OA sections. RA synovium showed more FXIIIa-positive cells-monocytes, fibrocytes, fibroblasts and synovial lining cells. In the subsynovial layer, band-like structure of FXIIIa-stained cells was observed in 27.8% of the RA patients, but in only one OA specimen. Higher proportions of FXIIIa-positive monocytes, macrophages, histiocytes and fibroblasts, as well as positive Langhans giant cells and vascular wall regions (except endothelial cells), were observed in RA. OA specimens revealed more intense FXIIIa labeling of these cells with a lower percentage of stained cells. Overall, labeling with FXIIIs antibody resulted in less intense staining. In conclusion, distinction between synovitis caused by RA and synovitis due to OA is possible, as the former show higher numbers of FXIIIa-positive cells, including monocytes, fibroblasts, fibrocytes and synovial lining cells. Further more, RA tissue is stained less intensely than OA tissue. There is evidence for continuous excretion of FXIII in the synovial membrane by the above-mentioned cell systems.

We investigated 86 synovial membranes from patients suffering either from rheumatoid arthritis (RA) or osteoarthritis (OA). Iron deposits in the synovial membrane were stained by the Prussian blue reaction, and the amount of stained iron was quantitatively assessed by microscope photometry. We found a statistically significant increase in iron deposits in the synovial membrane of RA patients when compared to OA patients. The amount of iron deposits correlated with the histological subtype of synovitis, those presenting with more exudative and proliferative features showing greater amounts of iron deposits. We also observed an inverse correlation between the haemoglobin concentration and erythrocytes in the serum and the amount of iron in the synovial membrane. From our data we concluded that iron deposits in the synovial membrane can contribute by several mechanisms, including activation of oxygen radicals, to the chronic inflammatory reaction in RA synovitis.

We report the occurrence of bilateral sacroiliitis in 2 cases of biopsy-proven sarcoidosis. Tuberculosis was excluded by tuberculin testing and bronchoalveolar lavage in both cases. In the literature, 5 cases of sacroiliitis and sarcoidosis have thus far been described, but in all tuberculosis was not excluded (tuberculin testing was not performed or revealed a positive test result). In 1 of these cases tuberculosis was even simultaneously suspected to be present. In all previous cases, antituberculous or other antimicrobial agents were given. Previously reported cases of sacroiliitis in sarcoidosis are briefly reviewed, and possible relations between seronegative spondylarthropathies, slow bacterial infections, sarcoidosis and other granulomatous diseases are discussed.

From the about 400 virus species known to cause illness in man, only a small but growing list of representatives are able to induce arthritis. Although virus-associated arthritides are mostly of acute and short-living type, some patients develop long-lasting or even chronic joint inflammation. The viral or host factors which contribute to chronicity or severity of viral joint disease are not known. However, the study of patients with long-lasting viral arthritis and of patients with idiopathic chronic arthritides may allow unique insights into the potential role of viruses in the pathogenesis of inflammatory joint disease.

The case of a 30-year-old man with primary systemic amyloidosis is reported. Three months prior to admission the patient developed fever, night sweats, dyspnea, and bilateral ankle swelling. Recurrent left-sided pleural effusion led to further investigation when massive proteinuria with free monoclonal lambda chains in the urine became evident. Abdominal subcutaneous fat aspiration and renal biopsy confirmed the diagnosis of amyloidosis. Bone marrow biopsy and bone scan did not reveal multiple myeloma. Echocardiography showed a sparkling texture of the interventricular septum. Pulsed-wave Doppler recording of the left ventricular inflow profile showed the pattern of advanced cardiac amyloidosis consistent with markedly impaired diastolic heart function. Electrocardiogram-gated magnetic resonance imaging was carried out for noninvasive evaluation of cardiac function. The patient was started on repeated courses of melphalan, prednisone, and colchicine therapy. Despite increasing deterioration of renal function the therapy was tolerated quite well, and the patient is still alive 10 months after initial diagnosis. Although very rare in this age, primary systemic amyloidosis should be considered as a cause of pleural effusion, proteinuria, and congestive heart failure and should lead to further investigation.

In a study aimed at correlating cytokine levels in synovial fluid with the pathology of rheumatoid arthritis (RA), tumour necrosis factor alpha, interleukin 1 beta and interferon gamma were immunoassayed in 27 patients with RA, 16 patients with other arthritides, 23 with osteoarthritis, 13 patients with trauma, and 18 patients at necropsy without inflammatory disease and not known to have had joint disease (median 27 hours after death). The results for interleukin 1 beta clearly show higher cytokine levels in patients with RA and other arthritides than in patients with osteoarthritis, trauma, or the patients at necropsy. Interferon gamma levels in patients with osteoarthritis and the patients at necropsy, however, were significantly greater than in patients with RA, and tumour necrosis factor alpha levels were also greater in the patients at necropsy compared with patients with RA. This study also correlated histomorphological patterns of synovitis and indicators of local inflammatory activity with synovial fluid cytokine levels, showing, for example, a positive association of interleukin 1 beta titre and a negative association of interferon gamma titre with ulcerogranulomatous synovitis (itself associated with RA). Taken together, these results extend and strengthen data suggesting a possible part played by increased synovial fluid levels of interleukin 1 beta in joint destruction in RA, but provide no evidence for increases in levels of tumour necrosis factor alpha or interferon gamma affecting the disease pathology.

A sensitive and specific method to monitor suppression of cytomegalovirus (CMV) replication is essential in patients treated with ganciclovir after allogeneic bone-marrow transplantation. In this study, antiviral therapy of eighteen episodes of symptomatic CMV infection in 15 such patients were followed up clinically and by virus culture and polymerase chain reaction (PCR). Clinical improvement, culture, and PCR were assessed for their ability to predict the efficacy of ganciclovir therapy in each patient. In eleven successfully treated episodes of CMV disease (disappearance of symptoms and improvement in biochemical variables) clinical improvement was associated with an effective suppression of virus replication as shown by negative culture and PCR assays of blood and urine specimens obtained after antiviral therapy. 1 patient who did not improve clinically when receiving antiviral therapy remained both culture positive and PCR positive for CMV. 6 patients with early relapse of CMV disease or who died after an initial clinical improvement were PCR positive but culture negative after termination of therapy. Demonstration of CMV in blood and urine by PCR after stopping antiviral therapy (even when culture is negative) points to incomplete suppression of virus replication. The findings show that PCR is a better predictor of the efficacy of antiviral therapy than are culture or clinical assessment.

Corneal and conjunctival biopsies of 13 patients with rheumatoid arthritis and corneal ulceration (RA-keratomalacia) have been characterized by immunohistological and histochemical analysis. Biopsies from 13 patients with bacterial conjunctivitis, 7 patients with allergic conjunctivitis, 15 patients with senile cataract and 15 patients with keratokonus served as controls. The phenotypic composition of the conjunctival inflammatory infiltration of rheumatoid corneal ulceration was not significantly different from the other inflammatory eye diseases studied. However, conjunctival epithelial cells of all RA-patients showed strong de novo expression of HLA-DR- and DP-antigens. HLA-DQ-antigens were only weakly expressed in a minority of patients. In bacterial conjunctivitis a less intense HLA-class-II-expression was found to be restricted to HLA-DR-antigens. Furthermore, in RA patients stromal fibroblasts of the cornea expressed lysosomal elastase. Both observations could be explained by paracrine action of interleukins produced by infiltrating T-lymphocytes and macrophages. Thus, it might be tempting to speculate that immunologically induced, elastase mediated autodegradation of corneal stroma may be an important factor in the pathogenesis of rheumatoid corneal ulceration.

Recurring paroxysmal abdominal pain developed in a 19-year old woman suffering from acute lymphatic T-cell leukaemia, during induction chemotherapy with cyclophosphamide, cytarabine and mercaptopurine. Both the plain radiograph and CT of the abdomen showed pathognomonic intramural gas accumulations and free air below the right diaphragm, pointing to pneumatosis coli. There was marked pancytopenia (leucocytes 800/microliters,haemoglobin 7.6 g/dl, thrombocytes 10,000/microliters). Whereas the abdominal pain subsided rapidly under oxygen therapy and liquid nourishment, the radiological changes receded gradually. However, fever and diarrhoeas occurred subsequently. Fever persisted for 3 weeks despite treatment with antibiotics (three times 60 mg/d gentamicin, three times 2 g/d mefoxitin and three times 500 mg/d metronidazole, and later 30 mg/d amphotericin B) and subsided only after completion of the induction chemotherapy and an increase of leucocyte count.

Twenty-eight patients undergoing bone marrow transplantation (BMT) were followed-up at weekly intervals from day -10 to discharge from hospital after BMT for human cytomegalovirus (HCMV) infection using polymerase chain reaction (PCR), slot-blot hybridization, and conventional virus culture. High specificity of the PCR assay applied could be shown by failure to amplify DNA extracted from a wide range of other viruses frequently infecting marrow transplant recipients. The PCR technique allowed us to diagnose viremia and viruria in 20 (83%) of 24 seropositive patients after BMT, whereas culture assays showed 16 (67%) of 24 of these patients to be viruric and 9 (37%) of 24 cases to be viremic. Slot-blot hybridization showed a frequency of viruria and viremia in 12 (50%) of 24 seropositive patients. By application of PCR techniques, HCMV detection could be achieved even in the very early posttransplant period. HCMV was detected in five patients even before the onset of clinical symptoms of acute graft-versus-host disease. Analysis by PCR techniques of 33 organ biopsy specimens from patients after BMT showed the presence of HCMV in 13 of 14 liver samples obtained from patients with HCMV viremia; three liver specimens from patients without viremia were negative by all the techniques applied. HCMV could also be demonstrated in postmortem lung biopsy specimens from all patients (n = 10) with interstitial pneumonia.

A largely symptom-free swelling of the right submandibular lymph nodes developed in a 23-year-old woman with hyper-IgE syndrome who had suffered from recurrent staphylococcal abscesses since childhood. Histological examination of the lymph nodes revealed highly malignant non-Hodgkin lymphoma of centroblastic type. Extensive staging tests did not reveal any further tumour manifestations. Because granulocyte chemotaxis is abnormal in hyper-IgE syndrome and the patient also had an infection of an old lung cyst, treatment was restricted to local radiotherapy of the cervical lymph nodes. Since 12 months there has been no recurrence. There is probably no connection between the hyper-IgE syndrome and the development of a malignant non-Hodgkin lymphoma, judging by the results of immunological and immunoelectrophoretic findings.

Prognostic factors were obtained by retrospective analysis of data on 44 patients (34 men and ten women; average age 64 +/- 13 years) with a primary myelodysplastic syndrome. The most important factors for a poor prognosis were the presence of more than 5% blast cells in the bone marrow (P = 0.001), serum platelet count of less than 150,000/microliters (P = 0.05), serum white cell count less than 3000/microliters (not significant) and serum lactate dehydrogenase concentration greater than 240 U/l (P = 0.05). Protein electrophoresis revealed a polyclonal hypergammaglobulinaemia in 15 of 38 patients; in eight of 17 patients with partly normal curve pattern at protein electrophoresis, a monoclonal gammopathy was demonstrated (monoclonal gradient 3.5 g/dl) by immunoelectrophoresis or immunofixation. No prognostic significance could be established for these gammopathies.

Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids.

An in vitro lymphocyte-mediated cytotoxicity assay using [3H]proline-labeled target cells is described. The assay, modified from an original procedure of Bean et al., assesses the release of [3-H]proline by filtering the total culture fluid containing both trypsinized tumor cells and effector cells. Filtration is performed with a semiautomatic harvesting device using low suction pressure and large-diameter glass filters. Pretreatment of filters with whole serum diminishes adsorption of cell-free radioactive material considerably and thus increases the sensitivity of the assay. Nearly 100% of the radioactivity could be recovered with this harvesting device. The technique allowed the detection of cytolytic activities of lymphocytes after 6 h of incubation. Lymphocytes from patients with primary malignant melanoma showed a significantly higher cytolytic reactivity (P less than 0.001) than normal donors' lymphocytes against three different melanoma cell lines. In a series of parallel experiments on 36 patients and 18 normal donors, this modification of the [3H]proline test was compared with three different assays: the conventional microcytotoxicity test of Takasugi and Klein, the original [3H]proline microcytotoxicity test of Bean et al., and the viability count of tumor cells.

In connective tissue diseases, the differentiation of disease-related hematological aberrations from drug-induced cytotoxic or allergic blood-cell dyscrasias is often difficult. In this paper we report on the positive identification of an indoprofen-induced severe pancytopenia in a multi-drug-treated patient with active systemic lupus erythematosus by use of a drug-specific lymphocyte transformation test.

Synovial membranes of patients with osteoarthritis--a disease with unaltered immunoregulation--and rheumatoid arthritis were immunostained for the different immunoglobulin isotypes using the PAP-method and a two-layer alkaline phosphatase technique. Randomly selected plasma cells with positive immunostaining were measured by plug photometry. The average extinction of the single plasma cell is considered to be indicative of the immunoglobulin synthesis of the measured plasma cell and the isotype under study. When we compared both disease entities, patients with rheumatoid arthritis were characterized (i) by higher average extinction values for all Ig-isotypes except IgG (ii) by a higher rate of high producer plasma cells. From this data, we conclude that immunophotometry is a new in vivo method for discriminating two types of synovitis (i) one without increased Ig-synthesis at the single cell level and (ii) a second one with increased Ig-synthesis.

Lysozyme-producing cells were analysed by enzyme histochemistry in paraffin sections of synovial tissue of 60 patients with rheumatoid arthritis (RA) and 20 patients with osteoarthritis (OA). For lysozyme detection three enzyme histochemical systems - peroxidase-anti-peroxidase, alkaline phosphatase and biotin-avidin - were used in parallel experiments. Lysozyme was found to be produced by polymorphonuclear cells, mononuclear phagocytes and part of synovial lining cells. All types of lysozyme-producing cells were increased in RA compared with OA. Subgrouping of RA synovitis according to histomorphological criteria allowed the demonstration of an inverse relationship between the number of lysozyme-producing cells and the grade of proliferation of fibroblasts, called mesenchymoid transformation by Fassbender [19]. The different methods of lysozyme detection differed in specificity and sensitivity. The immunoenzymatic staining of lysozyme allows specific and quantitative evaluation of phagocytizing cells in RA and OA.

THYMUS-DERIVED (T) lymphocytes from animals immunised with syngeneic or allogeneic tumour cells are well known to kill specifically target cells in vitro1. The as yet unidentified antigen recognition structure on T lymphocytes is not deemed to be a conventional type of immunoglobulin. In contrast to this kind of cell-mediated cytolysis another cellular killing mechanism has been described, called antibody-dependent cell-mediated cytolysis (ADCC), in which cells bearing the Fc receptor (FcR) cooperate with humoral antibody in the cytolytic action2,3. The nature of the main lymphoid effector cells (K cells) involved in the latter system is still ill-defined. They are supposed not to be T lymphocytes. Recently however, Lamon et al. reported on mouse thymocytes which were able to lyse MSV-induced tumour cells using IgM antibodies4. In this report we present evidence that human lymphocytes bearing the T marker in collaboration with homologous or autologous antibodies can efficiently kill tumour cells in vitro.

A simple system of synovitis classification is proposed based on histomorphological evaluation of 400 random specimens of synovial tissue. It discriminates between two types of diagnosis: 1) one with a high degree of information, being called C-synovitis (synovitis with a characteristic or diagnostic histomorphological pattern), where the clinical diagnosis can be predicted on the basis of the histomorphological pattern, 2) a second type of diagnosis with a lower degree of information, being called NC-synovitis (synovitis with non-characteristic or non-diagnostic morphological findings in the synovial membrane). We subdivided NC-synovitis into 4 subgroups and determined the RA-probability of each subgroup in order to permit clinical use of the proposed histomorphological classification. In addition, by using immunoperoxidase staining methods for immunoglobulins the subgroups were shown to have different quantities of extravasally deposited immunoglobulins in the synovial membrane. The subgroup with the highest RA-probability also turned out to have the highest amount of extravasally deposited immunoglobulins.

Mast cells are demonstrated in synovial membranes of patients with osteo-arthritis and rheumatoid arthritis using a new staining principle based on interaction of heparin in mast cell granules with peroxidase labeled avidin. It was found that mast cell numbers in the subsynovial layer of patients with rheumatoid arthritis were significantly lower than those in patients suffering from osteo-arthritis. This decrease can be mainly attributed to patients with rheumatoid arthritis whose synovitis was characterized by a distinct histomorphological pattern consisting of lining cell ulcers and granulation tissue. However, when mast cell numbers in rheumatoid arthritis and osteo-arthritis patients were compared without respect to mast cell distribution in the subsynovial layer or the stratum fibrosum, no statistical differences between the diseases could be observed.

Inflammatory mediators originating at the limbus seem to play an important role in the pathogenesis of peripheral corneal ulcers. In this paper, the immunohistological results of conjunctival biopsies of patients with corneal ulcers are reported. The most important result was that an abnormal HLA class II expression was found. The expression of HLA-DR was stronger than that of HLA-DQ and HLA-DP. A model of ulcer formation involving T-cells and lymphokines is presented.

Five by five patients with rheumatoid arthritis were treated with gold salts, D-penicillamine and cyclophosphamide. The T-lymphocyte subpopulations were measured. In patients, treated with gold salts or D-penicillamine, we did not find alterations of the number of TG- and TM-lymphocytes. The daily treatment with 100 mg cyclophosphamide will result in a significant reduction of TG-lymphocytes.

The activities of acid phosphatases (AP) were measured in leukocytes from patients with chronic myelocytic leukemia (CML), macrophages, granulocytes, in the fractionated mononuclear cells of patients with CML and with hairy-cell-leukemia (HCL) and in the cells from patients with acute leukemia (AL). The lowest activities were found in lymphocytes of normal subjects and of patients with chronic lymphatic leukemia (CLL) and in thrombocytes. Isoenzyme (IsE) 1 was characteristic for thymocytes, IsE 2 for granulocytes, IsE 3 for pathologic blast-cells, lymphocytes and thrombocytes, IsE 4 for macrophages, IsE 5 with components a and b for the mononuclear fraction of patients with HCL. In addition IsE 5 was detected in lymphocytes, macrophages and CLL-cells. In 4 patients with HCL the relative percentage of IsE-5-fraction was slightly greater than the percentage of tartrate resistant cells. In two patients with questionable HCL well marked IsE-5-fractions were recognized but no tartrate resistant cells. In one patient with HCL a relatively high percentage of tartrate resistant hairy-cells and in comparison an inadaquate low IsE-5-fraction was found. These different relations were explained with the more sensitive method of gelelectrophoresis and different affinity of substrates to AP.

In peripheral blood of SLE-patients fluctuating patterns of Fc-gamma-receptor bearing T-lymphocytes have been observed, when long term monitoring has been performed. No influence of disease activity and corticoid treatment on number of Fc-gamma-receptor bearing lymphocytes was seen.

In 52 patients with severe rheumatoid arthritis the therapeutic efficacy of 600 mg/die of D-penicillamine was evaluated for two years in a prospective trial. Patients were included in the study only if the duration of their disease exceeded 6 months (upper limit 12 months), and there was involvement of 6 or more joints and an elevated erythrocyte sedimentation rate (1 hour values greater than or equal to 25 mm). In 26 patients (50%) a decline in the activity index could be observed, but 18 of these subjects had a deterioration of findings as assessed by X-ray. The increase of the activity index indicated no therapeutic benefit in 26 patients (50%), which could be confirmed in 23 subjects by X-rays.

In four patients with hairy cell leukemia the expression of surface immunoglobulins and Fc-receptors on the leukemic cells as well as the stimulation of the leukemic cells by various T- and B-cell mitogens was studied. Using a combined cytochemical radioautographic method the tartrate resistant isoenzyme of the acid phosphatase and immunological markers could be demonstrated simultaneously on single cells. Surface immunoglobulins were detected by 125I-labelled (Fab')2-fragments of monospecific anti-heavy-chain-antibodies. In two patients only mu- and delta-determinants were found on the isoenzyme-positive hairy cells; in one patient 86% and in the other 44% of these cells carried both heavy chains on the same cell. Another patient showed both gamma- and delta-chains on the isoenzyme-positive cells and the fourth patient gamma-chains only. When the hairy cells of one patient were cultured in vitro in human serum-free medium for 14 days, mu- and delta-determinants were found just as on freshly isolated cells suggesting that hairy cells synthesize immunoglobulins. By indirect immunofluorescence the surface-Ig on hairy cells was shown to be capped very rapidly at room temperature. The concentrated surface-Ig was found over that cytoplasmic area where most of the ingested latex particles were located. In addition, using 125I-labelled aggregated human IgG (M.W. 5-15 X 10(6)), Fc-receptors were found on virtually all of the isoenzyme-containing hairy cells in all four patients. Furthermore, a distinct, low-degree stimulation of the isoenzyme-positive hairy cells could be demonstrated when the cells were cultured in the presence of pokeweed mitogen or Lima-bean lectin (B- and T-cell-mitogens), whereas no stimulation was observed by phytohemagglutinin and concanavalin A (T-cell-mitogens). In three patients studied, isoenzyme-positive hairy cells were negative with regard to rosette formation with sheep erythrocytes.

The neoplastic cells of a patient with hairy cell leukemia were found to express a high Fc-receptor actitivy on their surface. When the Fc-receptors were determined quantitatively by measuring the uptake of 125I-labelled aggregated IgG under saturation conditions, it was found that the hariy cells bound approximately 3 times more aggregated IgG than normal adherent mononuclear cells. The bound 125I-Agg. IgG was evenly distributed on the cell surface when the cells were labelled at 4 degrees C and was rapidly redistributed in form of a cap at one cell pole during incubation at 20 degrees C.

In 34 patients with severe rheumatoid arthritis the therapeutic efficacy of 600 mg/die of D-penicillamine was evaluated for five years. Patients were included in the study only if the duration of their disease exceeded 6 months (upper limit 12 months), and there was involvement of 6 or more joints and an elevated erythrocyte sedimentation rate (1 Hour values greater than or equal to 25 mm). In 9 patients (26%) a decline in the activity index could be observed, but 7 of these subjects had a deterioration of findings as assessed by x-ray. The increase of the activity index indicated no therapeutic benefit in 25 patients (74%), which could be confirmed in all subjects by x-ray.

In this review, three patients with severe inflammatory acne accompanied by a distinct rheumatologic syndrome are discussed together with 44 similar cases reported in the literature. This syndrome, here referred to as "acne-associated arthritis (AAA)" usually involves male teenagers and twins. The most characteristic clinical findings relate to the axial skeleton as well as the sterno-costo-clavicular region. Although no association with HLA-B27 has been found, AAA shares a number of clinical, radiological and histomorphological features with seronegative spondylarthropathies. Furthermore, nosological connections seem to exist with a number of ill-defined "hyperostotic osteoarthropathies." Similar characteristics are known from other "pustulotic or neutrophilic dermatosis." The hypothesis of an infectious etiology of AAA has not been substantiated. Responses to systemic antibiotics are generally disappointing, whereas steroids have been shown to exhibit some therapeutic efficacy.

In ten patients with systemic lupus erythematosus lymphocyte suppressor cell function was repeatedly monitored over a period of nine months. The method used is based on the finding that in vitro addition of ConA to PWM-stimulated lymphocytes activates suppressor T cells which in turn inhibit immunoglobulin synthesis. Nine of ten SLE patients exhibited significant impairment of IgG suppression but no correlation was found between the outcome of the IgG suppressor cell assay and disease activity or the treatment protocol applied.

The expression of acid phosphatases is cytochemically one of the most important features in permanent growing B-cell-lines. In few cell lines acid phosphatase is resistant against tartrate. Tartrate resistant isoenzyme 5 with components a and b can be demonstrated in monocytes, lymphocytes, chronic lymphatic leucemic cells and especially in hairy cells as well as in cell lines derived from a healthy donor. Fractionation of acid phosphatase by gelelectrophoresis in separated lymphocytes demonstrates especially isoenzyme 3, in separated macrophages isoenzyme 4. Isoenzyme 4 could not be detected in several cell lines. It is therefore concluded that these cell lines are probably derived from lymphocytic precursors. Cell lines with isoenzyme 4 may be the result of a facultative hybridisation between lymphocytes and monocytes. Profiles of acid phosphatases in virus-negative cell lines (Ramos, BJAB) were not significantly altered by conversion with EBV.

We describe an improvement of the immunogold technique, which is based on the colour development of silver-intensified immunogold signals. This method (referred to as the coloured-SIG technique) was found to be as sensitive as the silver-intensified immunogold method and more sensitive (in two of the three tested systems) than immunoenzymatic procedures, such as the peroxidase/antiperoxidase technique or the avidin-biotin system. The coloured SIG-method results in either a magneta-red or a cyan-blue final reaction product. Therefore, this new improvement of the immunogold technique should be useful in (1) double-staining methods, (2) immunoblot methods and (3) conventional immunostaining methods.

We report on a 39-year-old male patient suffering from seropositive rheumatoid arthritis who developed severe colitis during oral gold (Auranofin) therapy. So far, two further cases of colitis during oral, and 28 cases of enterocolitis during parenteral chrysotherapy have been described. The pathomechanism has not been identified. Symptomatic therapy was applied, under which our patient recovered from intestinal discomfort in a few weeks. In differential diagnosis gold induced colitis has to be distinguished both from loose stools occurring during oral gold therapy, most probably caused by an inhibition of NA+K+ ATPase, and from colitis induced by concomitant application of nonsteroidal anti-inflammatory drugs.