Of 352 patients with colorectal carcinoma followed for a minimum of 5 years after surgery, 39 cases (11.1%; median age 60 years) had mucinous adenocarcinoma, and 4 (1.1%; median age 62 years) had signet-ring cell carcinoma. Mucinous carcinomas were most frequently located in the rectum (61.5%) and in the sigmoid colon (15.3%) and presented with stage C and D disease in 41 and 15% of the cases, respectively. Disease recurrence was more frequently observed in patients with mucinous (51.7%) or signet-ring lesions (100%) as compared with adenocarcinomas. Five-year survival was 45 (median 48 months), 28 (median 27), and 0% (median 15 months) in patients with adenocarcinomas, mucinous adenocarcinomas, and signet-ring cell carcinomas, respectively (p < 0.05). Mucinous carcinomas of the rectum had had a significantly worse prognosis (5-year survival 17%, median 33 months) as compared with adenocarcinomas of the same site (5-year survival 34%, median 25 months; p < 0.05).

This study was designed to investigate the ability of bronchoalveolar and blood mononuclear cells to produce inflammatory mediators in vitro in pulmonary sarcoidosis. Seventeen patients with pulmonary sarcoidosis (stage I n=8; stage II/III n=9) and 10 normal controls were investigated. Bronchoalveolar and peripheral blood mononuclear cells were cultured in serum-free medium, without stimulant, for 24 h, and the supernatants analysed for concentrations of interleukin (IL)-1β (IL-1β), IL-2, IL-6, tumour necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and neopterin.Bronchoalveolar lavage cells (BALC) of sarcoid patients released significantly higher amounts of TNF-α, IL-6, IFN-γ and neopterin in comparison to normal controls. When smokers were excluded, there was also an increased release of IL-1β and GM-CSF. In the sarcoid group, the levels of IL-1β, IL-6, TNF-α and GM-CSF showed highly significant correlations between each other, but not with IL-2, IFN-γ or neopterin. Sarcoid patients whose BALC released more TNF-α or GM-CSF had higher percentage counts of alveolar macrophages but fewer lavage lymphocytes. In sarcoid patients, peripheral blood mononuclear cells (PBMNC) also released higher amounts of IL-1β, TNF-α, IL-6 and GM-CSF but less neopterin than normal controls. Patients whose PBMNC produced more IL-1β, IL-6 and GM-CSF had higher absolute and relative lavage neutrophil counts. No relationships were observed between cytokine release and radiographic or physiological markers of disease severity.We conclude from this study that sarcoid inflammation is associated with an increased and concerted release of monocyte/macrophage-derived cytokines not only in the lung but also in the peripheral blood. We speculate that the lymphokines, IFN-γ and IL-2, are not the primary triggers.

A monoclonal IgG-1 was produced by culture of a murine hybridoma (3.8.6) by three different methods, namely culture in ascites, in serum-free media and in serum-supplemented media. IgG-1 was purified to homogeneity (as judged by SDS/PAGE under reducing conditions) from each medium by ion-exchange chromatography and h.p.l.c. Protein A chromatography. Oligosaccharides were released from each IgG-1 preparation by hydrazinolysis and radiolabelled by reduction with alkaline sodium borotritide, and 'profile' analysis of the radiolabelled oligosaccharide alditols was performed by a combination of paper electrophoresis and gel-filtration chromatography. This analysis indicated clear and reproducible differences in the glycosylation patterns of the three IgG-1 preparations. Sequential exoglycosidase analysis of individual oligosaccharides derived from each IgG-1 preparation was used to define these differences. Ascites-derived material differed from serum-free-culture-derived material only with respect to the content of sialic acid. IgG-1 derived from culture in serum-containing media had an intermediate sialic acid content and a lower incidence of outer-arm galactosylation than the other two preparations. These differences in glycosylation could not be induced in any IgG-1 preparation by incubating purified IgG-1 with ascites or culture medium. It is concluded that the glycosylation pattern of a secreted monoclonal IgG is dependent on the culture method employed to obtain it.

The aim of this study was to evaluate serum levels of the lymphokine interferon-gamma (IFNg) in patients with chronic pulmonary sarcoidosis, and to investigate its value as a predictive marker of clinical response to corticosteroid therapy. Twenty-five patients and 28 age-matched control subjects were studied. All the patients had parenchymal shadows (Stage II or Stage III) and none had clinical evidence of extrathoracic disease. Before therapy, serum IFNg levels were significantly higher in the patient group (p less than 0.001), and 20 (80%) had values above the normal range. After oral treatment with corticosteroids for a median 13 months (range, 3 to 49 months) the levels decreased significantly (p less than 0.01). However, the falls were less pronounced in patients who had a better outcome in terms of achieving complete radiographic resolution and in those who improved in forced vital capacity by greater than or equal to 10%. The prognostic value of the pretreatment serum IFNg was explored, and a significant relationship was found between higher pretreatment levels and lower grades or radiographic abnormality assessed 3 yr after commencement of treatment (p less than 0.01). In addition, the patients who had cleared completely while receiving steroids and remained in remission had significantly higher pretreatment serum IFNg levels than did those with incomplete resolution of parenchymal shadows or radiographic relapses (p less than 0.05). We conclude that elevated levels of circulating IFNg are detectable in most untreated patients with Stage II/III pulmonary sarcoidosis and that patients with the highest levels appear to have a better chance of achieving complete resolution with corticosteroid therapy.

No abstract

A novel mass-spectrometric technique is described that permits the identification of the C-terminal peptide of a protein. The technique involves the incorporation of 18O into all alpha-carboxy groups liberated during enzyme-catalysed partial hydrolysis of the protein, followed by mass spectrometry to identify as the C-terminal peptide the only peptide that did not incorporate any 18O. The technique has been used to identify the true C-terminal tryptic peptide of a bacterially produced gamma-interferon and to distinguish it from a peptide produced by anomalous tryptic cleavage. It was found that a closely similar sequence segment of bacterially produced alpha 2-interferon undergoes an analogous cleavage. The technique was also used to identify the C-terminus of a clipped gamma-interferon that retains full antiviral activity.

SUMMARY The in vivo role of interferons in the development of fibrosis is not fully understood but it is known that interferons can suppress fibroblast proliferation and collagen synthesis in vitro. We have recently demonstrated that in a group of patients with sarcoidosis having predominant pulmonary involvement, patients with the highest levels of circulating interferon‐gamma (IFN‐y) more frequently resolved on corticosteroids, suggesting that they had a less‘fibrotic’ component to their disease. We now report that in two other diseases, where the tendency to develop pulmonary fibrosis is greater than in sarcoidosis, namely cryptogenic fibrosing alveolitis (CFA) and fibrosing alveolitis associated with the systemic connective tissue disease progressive systemic sclerosis (FA + PSS), very few patients have elevations in IFN‐γ in their serum. However, as in sarcoidosis, those with the highest levels responded to corticosteroids (P < 0·05). Attempts to measure IFN‐γ levels in the lungs, using cell‐free bronchoalveolar lavage (BAL) fluid supernatants, were negative in all the study groups, suggesting that these samples may be inadequate for such studies. To investigate whether there might be an intrinsic defect in T lymphocyte function associated with predisposition to fibrosing lung diseases, we then investigated the in vitro production of IFN‐y by lymphocytes separated from the blood of 18 untreated patients (six with CFA, six with FA + PSS and six with sarcoidosis). IFN‐γ production was impaired in 10 (56%) (two with CFA, four with FA + PSS and four with sarcoidosis). A higher proportion of the fibrosing alveolitis patients (CFA or FA + PSS) with impaired IFN‐γ production have subsequently shown spontaneous lung functional deterioration. These findings suggest that impaired IFN‐γ release might be a potentiating factor in the pathogenesis of these fibrosing lung diseases.

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.