RESUMEN

Mycobacterium avium complex (MAC) was isolated and serotyped from 127 samples from 43 HIV-infected patients with disseminated disease in Sweden. Thirteen different serovars were observed. Serovar 6 was the most common, followed by 4, 9 and 11. Serovar 8 was rare. In 22 of the patients the same serovar was found in blood and at other sites. Clinical symptoms and outcome were compared in patients with different serovars. Analysis of patient records revealed no association between clinical picture and any specific serovar. The median survival time after MAC infection was 7 months. Somewhat shorter survival was observed in patients with serovar 4 than in those with serovar 6.

Asunto(s)

Asunto(s)

RESUMEN

15/60 subjects from one center, who all took part in a multicenter double-blind, placebo-controlled study to evaluate the effect of norfloxacin on acute enteritis, had norfloxacin sensitive strains of Campylobacter jejuni in pre-study stool specimens. Eight of the 15 subjects received active drug. In 3 of these 8, high-level quinolone resistant Campylobacter strains of the same serotype as in pre-treatment samples were isolated 4-90 days after the initiation of treatment.

Asunto(s)

Asunto(s)

RESUMEN

The influence of interferon (IFN) on cellular proliferation, blast transformation, and differentiation was studied in lymph node cells from 17 patients with B-cell lymphomas, one patient with T-cell lymphoma, and eight patients with enlarged, non-malignant lymph nodes. The effects of IFN on lymph node cells were compared with effects on mononuclear blood cells from chronic lymphocytic leukemia (CLL) patients and healthy donors. Natural IFN-alpha (nIFN-alpha) induced a proliferative response in cells from seven of 17 of the B-cell lymphomas, in two of eight of the non-malignant lymph nodes, and in lymphoid blood cells from two of 32 CLL patients. With few exceptions, the proliferating cells were B cells and the data suggest that IFN acts directly on the B cells. Proliferation was not induced with IFN in cells from the T-cell lymphoma or in mononuclear blood cells from 13 healthy donors. nIFN-alpha induced blast transformation in cells from ten of 14 of the B-cell lymphomas and in four of seven of the non-malignant lymph nodes. Also beta- and gamma-IFN were shown to induce proliferation and blast transformation in lymph node cells from some patients. No major effect on the expression of various differentiation markers could be observed following culture in the presence of nIFN-alpha. We conclude that IFNs can induce proliferation and blast transformation in malignant and non-malignant B cells from lymph nodes.

Asunto(s)

RESUMEN

alpha-Interferon (IFN-alpha) induces blast transformation of malignant B-cells from approximately 65% of chronic lymphocytic leukemia patients. We have shown previously that induction of blast transformation correlates with induction of 2'-5'-oligoadenylate synthetase. In this paper we address the question of whether low responsiveness to IFN-alpha is associated with a reduced expression of the IFN receptor. IFN-alpha receptor expression was studied by the binding of radioiodinated IFN-alpha to peripheral blood malignant B-cells from 20 chronic lymphocytic leukemia patients and to blood cells from 5 healthy donors. Chronic lymphocytic leukemia cells from all 20 patients displayed high affinity IFN-alpha receptors [mean Kd, 62 +/- 9 (SE) pM] ranging between 110 and 850 binding sites/cell [mean, 416 +/- 51]. Nonmalignant mononuclear blood cells showed similar binding data (411 +/- 105 binding sites/cell; Kd 66 +/- 20 pM). Receptor expression did not correlate with the degree of blast transformation or with induction of 2'-5'-oligoadenylate synthetase. We conclude that the deficiency of IFN sensitivity is localized somewhere between signal transduction from the receptor and induction of 2'-5'-oligoadenylate synthetase.

Asunto(s)

RESUMEN

The influence of interferon-alpha 2 (IFN-alpha 2) on the mRNA levels of cellular proto-oncogenes was studied in malignant cells from patients with chronic lymphocytic leukemia (CLL). These cells can be induced to blast transform, differentiate and, in some cases, proliferate upon exposure to IFN. Treatment with IFN-alpha enhanced the levels of c-myc mRNA in malignant cells from the patients, whereas the levels of c-myb mRNA decreased, as measured by slot blot hybridizations. In cells from some patients, an enhanced expression of c-fos and k-ras was observed following exposure to IFN-alpha. No major effect on the expression of c-raf or of enolase was observed in any of the patients following exposure to IFN-alpha, whereas the levels of beta 2-microglobulin mRNA increased. In contrast to the observed effects on oncogene expression in CLL cells, IFN had no major effect on the expression of any of the tested oncogenes in lymphocytes from healthy donors or in B-cells from three neoplastic cell lines (380, FL18, RS). We conclude that IFN-alpha can enhance or repress the expression of several oncogenes in nondividing primary malignant cells from patients with leukemia. We also show that the response of malignant cells from patients to IFN-alpha is different than that seen with neoplastic cell lines which represent a similar stage of B-cell differentiation.

Asunto(s)

RESUMEN

Interferon (IFN) can induce blast transformation and differentiation of malignant cells from patients with chronic lymphocytic leukemia (CLL). In this work the capacity of IFN to induce 2',5'-oligoadenylate synthetase (2',5'-A synthetase) in lymphoid cells from patients with CLL was investigated, and the results were related to the induction of blast transformation. IFN induced enhanced levels of 2',5'-A synthetase in unseparated lymphoid cells from 18 of 24 patients with CLL. In a control group of 11 healthy donors, 2',5'-A synthetase was induced in all cases tested. There was a close correlation between induction of 2',5'-A synthetase and induction of blast transformation by IFN. Thus, transformation occurred in clones expressing enhanced levels of 2',5'-A synthetase, but not in those showing no increase in 2',5'-A synthetase. An enhancement of 2',5'-A synthetase was observed in the IFN-sensitive cells following exposure to concentrations as low as 0.5 IFN units/ml. For induction of blast transformation, 10-1000 times more IFN was required. One h of pretreatment was sufficient for induction of 2',5'-A synthetase, whereas 20 h of pretreatment were required for induction of transformation by IFN. The finding that induction of 2',5'-A synthetase parallels interferon-induced blast transformation indicates that the reason why some CLL clones do not differentiate following exposure to IFN is a resistance of these cells to the action of IFN. The resistance to IFN in some CLL clones may be due to a defect in the 2',5'-A synthetase system of the cells, but it could also be at an early stage of the interaction between IFN and the cell, for instance at the receptor level.

Asunto(s)

RESUMEN

3H-thymidine incorporation following stimulation with interferon (IFN) in vitro was investigated in cell cultures from peripheral blood of patients with chronic lymphocytic leukemia (CLL), spleens from necro-kidney transplants and healthy blood donors. It was demonstrated, that IFN can induce a proliferative response in some normal as well as leukemic B lymphocyte subsets. The responses were not T-cell dependent. The results indicate, that B-cell subsets that proliferate in the presence of IFN, are present in higher proportions in spleen than in peripheral blood, and that they constitute a portion of the leukemic blood lymphocyte pool in some patients with CLL. We have previously demonstrated, that IFN induces varying degrees of transformation and differentiation in blood lymphocytes from a majority of CLL patients. The functional characteristics of different B-cell subsets, and their heterogeneous distribution in leukemia, may be important for the results of IFN treatment in various malignant B-cell disorders.

Asunto(s)

RESUMEN

The ability of interferon (IFN) to induce proliferation and differentiation in malignant B cells from 29 patients with chronic lymphocytic leukemia (CLL) and in lymphoid cells from 11 healthy donors was investigated. IFN induced transformation and plasmacytoid differentiation in B cells from 19 of 29 CLL patients. The transformed cells belonged to the malignant clone as indicated by the immunoglobulin (lg) light chain restriction. Cells exposed to IFN expressed intracellular lg to a varying degree, which was correlated to the level of plasmacytoid differentiation. IFN gave rise to proliferative responses in cells from three patients. Cytogenetic studies on lymphoid cells from one patient showed that proliferation occurred in the malignant B cells. Induction of proliferation and differentiation was observed with various alpha-IFN and gamma-IFN preparations, as well as with a completely pure beta-IFN, showing that IFN and not contaminants in the preparations were responsible for the observed effects. Maximal transformation and proliferation usually occurred after four days of incubation at an IFN concentration of 500 to 5,000 U/mL. The ability of IFN to induce differentiation in CLL cells may be of importance for the reported antitumoral effects observed in some B cell malignancies during IFN therapy.

Asunto(s)

RESUMEN

The influence of interferon-alpha (IFN-alpha) on the differentiation of malignant cells from six patients with chronic lymphocytic leukaemia was studied in vitro. IFN induced differentiation in the leukaemic cells from four of the patients. In cells from two of these patients, IFN also induced proliferation. When tested by immunofluorescence, the clonality of the differentiating cells was established by the presence of intracellular light chains of one type only.

Asunto(s)

Asunto(s)

RESUMEN

The moving aperture and the moving random mask are two methods suggested for speckle reduction in recording images of diffuse objects with coherent light. An analysis is given that shows that these methods are equivalent to a two-step recording process: (1) recording the image with the full pupil in coherent light and (2) reimaging and recording this speckled image in incoherent light with the aperture or random mask in a fixed position. The two-step process makes it easy to understand the filtering effect and can be physically implemented to offer short exposure time in the coherent step and a wider choice of filtering functions in the speckle reduction step. Experimental results to support the analysis are presented.

Asunto(s)

Asunto(s)