Search

Chromatofocusing of proteins in a microcolumn format (750 μm i.d.) was evaluated with slurry-packed Mono P anion-exchanger beads (10 μm bead size) as chromatographic matrix. Evaluation was performed with three standard proteins in terms of flow rate, Polybuffer 96–acetic acid, pH 6.0, concentration (eluent buffer strength), and detection limit. A column with the dimension 750 μm i.d. × 50 mm length, a flow rate of 20 μL min−1, and a 1:10–1:20 Polybuffer 96-acetic acid aqueous dilution showed the best resolution between the proteins. Detection limits were 3 μg mL−1 for carbonic anhydrase I and 6 μg mL−1 for myoglobin A employing UV-detection at 280 nm. [ABSTRACT FROM AUTHOR]

A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumoun For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m[sup -2] Cisplatin and 250 mg m[sup -2] decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 10[sup 7] IU IFN-α2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of I I tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells; however, its exact immunological pathomechanism(s) remain to be established. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of biochemotherapy in metastatic malignant melanoma still carries a low remission rate, but with some durable responses. It would therefore be of considerable importance if patients with a high probability of responding could be identified using predictive tests. The response to interferon-alpha (IFN-α) correlates with the occurrence of CD4[SUP+] lymphocytes identified by fine-needle aspirates from melanoma metastases (Håkansson et al, 1996). The present investigation studies a possible correlation between tumour-infiltrating CD4[SUP+] lymphocytes in malignant melanoma metastases and the therapeutic effect of biochemotherapy. A total of 25 patients with systemic and 16 with regional metastatic melanoma were analysed before initiation of biochemotherapy (cis-platinum 30 mg/m[SUP2] d.1-3, DTIC 250 mg/m[SUP2] d.1-3 i.v. and IFN-α2b 10 million IU s.c. 3 days a week, q. 28d.). A monoclonal antibody, anti-CD4, was used to identify tumour-infiltrating lymphocytes in fine-needle aspirates before start of treatment. The presence of these lymphocytes was correlated to response, time to progression and overall survival. A statistically significant correlation (P = 0.01) was found between the occurrence of CD4[SUP+] lymphocytes and tumour regression during biochemotherapy in patients with systemic disease. Out of 14 patients with moderate to high numbers of infiltrating CD4[SUP+] lymphocytes, 12 achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, 8 out of 11 had progressive disease. We also found a significantly longer time to progression (P < 0.003) and overall survival (P < 0.01) among patients with moderate to high numbers of these cells compared to patients with low numbers of these cells before initiation of biochemotherapy. Furthermore, in patients with regional disease, we found a significantly longer time to progression (P = 0.01) and a trend toward a longer... [ABSTRACT FROM AUTHOR]

Twenty patients with palmoplantar pustulosis (PPP) and 21 patients with psoriasis were compared with respect to the chemotactic response and random migration of their neutrophils (PMNs) and to the chemotactic and chemokinetic activities of their serum. The Boyden chamber technique was used. Compared with the reference group, the PPP neutrophils showed a significant decrease in random migration ( p=0.036) and chemotactic response to casein ( p=0.031), but not to zymosan-activated serum. The psoriasis PMNs had normal chemotactic response, but decreased random migration ( p=0.001). The chemokinetic effects of serum from PPP and psoriatic patients on normal neutrophils were increased (for PPP, p=0.019 and for psoriasis p=0.024). The chemokinetic activity of the heated sera was decreased and inversely correlated to the serum level of IgA in both disorders (PPP, p=0.021; psoriasis, p=0.013). The chemotactic activity of serum on normal PMNs was decreased in both conditions (PPP, p=0.001; psoriasis, p=0.047); this was due to the presence of chemotactic factor inhibitors in 34% of the sera. It seems likely that the high chemokinetic effect of serum both from the PPP and from the psoriasis patients compensates for the slightly low or normal migratory activity of neutrophils from these patients. [ABSTRACT FROM AUTHOR]

The relationship between psoriasis and palmoplantar pustulosis (PPP) is uncertain, as is the role of the neutrophil granulocyte in these conditions. In a previous comparative study of the rate of polymorphonuclear leucocyte (PMN) phagocytosis of IGG- and IgG-C3b-coated particles, an increased uptake rate was found in both diseases. Further information on the in vivo activity of PMNs in these conditions may be obtainable by determining the level of lactoferrin (LF) in serum from such patients, since LF serves as a specific marker of the turnover and activity of the circulating pool of neutrophils. In this study on 19 patients with psoriasis and 20 patients with PPP, elevated levels of LF were found in both conditions. In contrast, the levels of lysozyme and β-microglobulin, which are markers of monocyte-macrophage and lymphocyte activity, respectively, were normal. This suggests the selective activation of neutrophils in these disorders. LF was significantly correlated ( P<0.05 and 0.001, respectively) to the rates of phagocytosis of IgG- and IgG-C3b-coated particles, but not to the chemotaxis of isolated PMNs. There was no correlation between the severity of the disease and the levels of serum LF. The data suggest the increased in vivo activity of neutrophils in psoriasis and PPP. [ABSTRACT FROM AUTHOR]

Seventy-eight patients with advanced non-Hodgkin's lymphomas were randomized for treatment with predni mus tine (Sterecyt) in two different schedules: either receiving continuous treatment at a dosage of 60 mg daily, or intermittent two-week courses with 200 mg daily for five days. The aim of the study was to compare efficacy and side effects of the two different schedules. Forty patients received continuous, and 38 patients intermittent treatment. Objective response was achieved in 66% of 71 evaluable patients, equally distributed between the two treatment arms. The 10-year survival rate was 20% (SE = 6%; continuous treatment) and 11% (SE = 5%; intermittent treatment), respectively (logrank p = 0. 26). Median time to response, duration of response and time to progression showed no significant difference between the treatment groups. Median time on treatment was longer for patients treated continuously, probably due to more easily performed dose adjustments in such patients. There was a significant decrease of the white blood cell counts in patients who received prednimustine continuously compared with those treated according to the intermittent schedule ( p = 0. 02). No significant differences were found regarding the thrombocyte levels. The response rate was closely related to haematological toxicity ( p = 0. 01). Our results suggest that prednimustine in non-Hodgkin's lymphomas has similar effectiveness both in daily treatment and in a two-weekly intermittent schedule. Continuously given treatment may be easier to govern and, thereby, allow for higher treatment intensity. With respect to toxicity, daily doses of approximately 30-40 mg in previously untreated patients may be recommended. [ABSTRACT FROM AUTHOR]

Neutrophil and eosinophil chemotactic activities (NCA and ECA) were measured in serum from twenty-two patients with urticaria pigmentosa or systemic mastocytosis. NCA was also measured after heating serum to 56°C (heat-stable NCA). Although these factors were increased in about half of the patients there was no correlation with histamine release as estimated by the excretion of the main histamine metabolite methylimidazoleacetic acid (MelmAA) in urine. A significant increase in heat-stable NCA, however, was found in patients with pruritus and abnormal high values of MelmAA. It is concluded that only heat-stable NCA is a specific mast cell mediator, but that the heat-labile NCA and ECA are dependent on mast cells for their production by a different cell, tentatively identified as the macrophage. [ABSTRACT FROM AUTHOR]