Infections and bacterial colonization during cytotoxic therapy in patients with acute leukemia.
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Acute Disease↗
Biomedical subjects
A Laatikainen
Publications and source records attributed to A Laatikainen.
Comparison of a new immunochromatographic rapid test with a commercial EIA for the detection of Puumala virus specific IgM antibodies.
BACKGROUND: Hantaviruses are associated with two human diseases: haemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS). Puumala virus (PUUV), which is one of the Hantaviruses, is a causative agent of nephropathia epidemica (NE), a mild form of HFRS. OBJECTIVE: a new 5 min rapid test, POC PUUMALA (Erilab Ltd, Finland), for detecting IgM antibodies to PUUV was evaluated and compared with the commercially available Hantavirus (Puumala) IgM ELISA test (Progen, Germany). Discrepant test results between the two tests were confirmed by a mu-capture reference EIA. STUDY DESIGN: Two hundred and thirty five serum samples, which had earlier been analyzed with the Progen IgM ELISA, were assayed with the POC PUUMALA rapid test. Five persons, without knowing the Progen IgM ELISA test results, interpreted independently the rapid test results. In addition, a panel of 48 serum samples was analyzed in parallel with the rapid test and the Progen IgM ELISA by one technician in daily routine diagnostics in a clinical microbiology laboratory. RESULTS: the agreement between the results of the five interpreters was 95%, and the congruence of the results between individual readers and commercial ELISA test varied from 93 to 96%. Diagnostic efficacy of the rapid test varied between 98 and 99% compared with 96% of the Progen IgM ELISA. The POC PUUMALA rapid test showed higher or similar sensitivity compared with the Progen IgM ELISA, whereas both the tests had similar levels of specificity. CONCLUSIONS: the analytical performance of the POC PUUMALA rapid test was found to be as good or even slightly better than the analytical performance of the Progen IgM ELISA. In addition, the rapid and straightforward procedure makes the POC PUUMALA a feasible tool for the diagnosis of the acute PUUV infection.
Antibodies, Viral↗
Effect of interferon gamma on the sensitivity of bovine-papilloma-virus(BPV1)-transformed cell lines to cell-mediated cytotoxicity.
The effect of interferon gamma (IFN gamma) on the immunogenicity and immunosensitivity of mouse cell lines transformed by bovine papillomavirus type 1 (BPV1) DNA was examined in a syngeneic mouse model. The overnight incubation of BPV1-transformed cell lines with 100 IU/ml IFN gamma did not affect their ability to induce the generation of cytotoxic effector cells but it clearly increased their sensitivity to lysis by interleukin-2-induced lymphokine-activated killer (LAK) cells and by non-specific LAK-type effector cells induced by BPV-1-transformed cell lines. The treatment of two allogeneic lymphoid tumour cell lines, P815X2 and YAC-1, with IFN gamma either decreased or had no effect on their sensitivity to LAK-cell-mediated lysis.
Animals↗
Tumorigenicity and H-2 expression of papillomavirus-transformed mouse cell lines.
Tumorigenicity in immunocompetent syngeneic mice and H-2 class I antigen expression of BPV1-transformed mouse cell lines had no correlation. H-2 expression was examined using monoclonal anti-(H-2Kb) and anti-(H-2Db) antibodies in immunofluorescence staining for flow cytometry analysis and by determining the sensitivity of the cells to cytolysis by allostimulated spleen cells. Nontumorigenic cell lines were as resistant as tumorigenic cell lines to natural killer activity. The results indicate that in our model defence by natural killer cells is not a decisive factor. The results also show that instead of or in addition to H-2 class I antigens other factors (e.g. the presence or absence of virus-specific antigens) are important in determining the tumorigenicity of BPV1-transformed cell lines.
Animals↗
Generation of cell-mediated cytotoxicity against bovine-papilloma-virus-transformed primary mouse cell lines.
The immunogenicity and immunosensitivity of primary mouse cell lines transformed by bovine papilloma virus 1 (BPV1) DNA were studied in a syngeneic mouse model by determining cell-mediated cytotoxicity in the spleens of mice immunized with the transformed cells. One of the cell lines induced the generation of cell-line-specific Thy1.2-positive cytotoxic effector cells. However, most of the cell lines tested induced the generation of Thy1.2-positive effector cells, which in addition to BPV1-transformed cells were able to lyse a syngeneic cell line transformed by methylcholanthrene. The lysis of BPV1- and methylcholanthrene-transformed cell lines was mediated by recognition of the same antigenic determinants expressed on these cells, and all the BPV1-transformed cell lines were sensitive to lysis by these nonspecific effector cells of the lymphokine-activated killer (LAK) type.
Animals↗
Local immune reaction in syngeneic mice against tumorigenic and nontumorigenic BPV-transformed mouse cell lines.
The role of cytotoxic T cells in immune response to Bovine Papillomavirus type 1 (BPV1)-transformed mouse cell lines was assessed. The chromium release assay was used to follow the induction of cytotoxicity in local lymph nodes of syngeneic C57BL/6J (B6) mice after injection of BPV1-transformed cell lines tumorigenic in nude mice but tumorigenic or nontumorigenic in B6 mice. The nontumorigenic cell line B6B31.C-NuT.A induced cell line-specific cytotoxicity with a maximal activity on day 7 after subcutaneous inoculation of one million B6B31.C-NuT.A cells. After injection of nontumorigenic B6B31.J or tumorigenic B6B31.J-NuT.A or B6B31.A cell lines, only low levels of nonspecific cytotoxicity were observed. These results suggest a role for cytotoxic T cells only in rejection of B6B31.C-NuT.A cells. One reason for the poor immunogenicity could be the lack of transformation-induced/virus-specific antigens on most of the present BPV1-transformed cell lines. However, in a transplantation rejection experiment, protection was induced in B6 mice against a challenge of the highly tumorigenic B6B31.A-B6T.1 line by repeated injections of BPV1-transformed cells. These results suggest the expression of common transplantation rejection antigens on the three BPV1-transformed cell lines used in the immunization experiments.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. VI. Histamine-induced suppression of in vitro generation of tumour-specific cytotoxic T cells.
Histamine was shown to suppress the in vitro generation of secondary syngeneic tumour-specific Ly-2+, L3T4- cytotoxic T cells from Ly-2+, L3T4- precursor cells. The sensitivity of the spleen cells from P815X2 mastocytoma-bearing DBA/2 mice to histamine-induced suppression changed during tumour progression; by the time of cytotoxic peak reaction (between days 12 and 16 after P815X2 inoculation), the spleen cells were more resistant to histamine than the spleen cells obtained from mice a few days before or a few days after maximal cytotoxicity. Histamine had no effect on the effector function of in-vitro-generated cytotoxicity. The results suggest histamine-induced modulation of cytotoxic T-cell reactions in P815X2-bearing mice.
Animals↗
Tumorigenicity of primary mouse fibroblasts transformed by bovine papillomavirus type 1.
Cell lines transformed by bovine papillomavirus type 1 DNA were established from transfected primary fibroblast cultures of C57BL/6 mice. Southern blot analysis revealed that most of the viral DNA in the cells was in episomal oligomeric form. These cell lines were tested for tumorigenicity in nude mice in comparison to properties associated with malignant transformation including growth in low-serum medium, focus formation in agar, and resistance to natural killer cells. Two of the 5 cell lines were highly tumorigenic, producing spindle cell sarcomas in all animals. Metastatic spreading to local lymph nodes was also observed. The same cell lines also showed anchorage-independent growth in agar, but no correlation was observed between natural killer cell resistance and tumorigenicity. Viral transcripts were detected in two nontumorigenic and in two tumorigenic cell lines.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. III. Morphometric assessment of the dynamic changes in post-capillary venules as regulatory elements of lymphocyte recirculation in tumor-draining lymph nodes.
To evaluate the dynamics of lymphocyte recirculation in tumor-bearing mice, the post-capillary venules (PCV) were subjected to quantitative measurements in the regional (RLN) and nonregional (NRLN) lymph nodes during the progression of P815X2 mastocytoma in syngeneic DBA/2 mice. Mice were sacrificed at two-day intervals, and RLNs and NRLNs were analysed for their content of B- and T-lymphocytes and their subsets, demonstrated by immunoperoxidase technique using monoclonal antibodies; Anti-Thy 1.2 (T cells), Anti-Lyt 1 (T-helper cells), Anti-Lyt 2 (T-suppressor cells), and Anti-I-Ad (B cell) antigens, separately in the B- and T-cell compartments. In the PCVs, migration index (MI) and endothelial height (Hend) were measured. There was a biphasic elevation of MI in the RLNs, as compared with only a late rise in the NRLNs, reaching the peak (1.54) on day 14. In RLNs, there was a sharp reduction in Hend starting from the values (6.37 microns) on day 2, down to 4.79 microns on day 8. This is followed by rapid elevation close to the second-day values, e.g. 6.07 on day 10. The changes in MI paralleled the early influx of B cells, as evidenced by the decrease of Thy 1.2+/I-Ad+ cell ratio and a late recruitment of T cells as indicated by the elevation of that ratio as well as the Hend values in both the RLNs and NRLNs. The present experiment shows that morphology of PCVs in the RLNs and in NRLNs of P815X2-bearing mice is subjected to alterations reflecting the dynamics of lymphocyte recruitment into these organs. When combined with lymphocyte subset enumeration using monoclonal antibodies, the quantitative analysis of the PCVs permits predictions to be made on the recirculatory activity of these cell populations during the tumor progression.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. IV. Lymph node immunoreactivity and cell-mediated cytotoxicity.
The in vitro cytotoxicity assay and the morphological in vivo analysis were used to follow the T cell reaction in tumor draining lymph nodes from DBA/2 mice bearing subcutaneously developing P815X2 mastocytoma. Mononuclear cells separated from local lymph nodes between days 8 and 14 following tumor inoculation were able to kill P815X2 cells in vitro. The maximal tumor-specific cytotoxicity was measured on day 10. Changes in lymph node morphology and in cellular contents of individual lymph node compartments were seen from day 12 onwards. The extensive expansion of the paracortex and the enlargement of the whole lymph node reached the peak on day 14. On days 12 and 14, a slight increase was also observed in the proportion of T lymphocytes. The results indicate that the tumor-specific cytotoxicity was detectable in tumor draining lymph nodes four days earlier than the morphological and cellular changes. The maximal cytotoxicity preceded the morphological peak reactions by two to four days.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. V. Spleen immunoreactivity and cell mediated cytotoxicity.
The in vitro cytotoxicity assay and the histological in vivo analysis were used to study cell-mediated immunity in the spleen of DBA/2 mice bearing subcutaneously developing P815X2 mastocytoma. Mononuclear cells separated from the spleen showed P815X2 specific cytotoxic activity between days 10 (12) and 16 following tumor inoculation. Maximal cytotoxicity was detected on days 13 and 14. In the T cell area of the spleen white pulp (C-PALS), an increase in the proportions of T lymphocytes and mononuclear phagocytes was observed on days 10 and 12 after the injection of P815X2 cells. On day 14, the T cell level in C-PALS dropped below control values, and the cellular density in the T cell area was reduced. Tumor metastases were seen in the spleen from day 14 onwards. The results indicate, that the T cell reaction in vivo was detectable in C-PALS one to two days earlier than the in vitro cytotoxicity of the spleen cells. By the time of maximal cytotoxic activity, the in vivo reaction had disappeared.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. I. Morphometric assessment of lymph node immunoreactivity and analysis of circulating antibodies.
To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the lymph nodes with the functional assays measuring cytotoxic and tumor cell membrane-bound antibodies in mouse sera. Regional and non-regional (RLN, NRLN) lymph nodes, were subjected to stereological analysis to determine the volume fractions (Vv) of the cortex (C), the paracortex (PCA), the germinal centers (GC), and the medulla (M), using a computerized analysis system (IBAS I, Kontron). In both RLN:s and NRLN:s, lymphocyte subsets were identified and their ratios determined using the ABC (avidin-biotin peroxidase complex) technique and following monoclonal antibodies; Anti-Thy 1.2, Anti-Lyt 1, Anti-Lyt 2, and Anti-I-Ad. The 51Cr release assay was used to test the mouse sera for cytotoxic antibodies, and an indirect immunofluorescence (IF) technique to assess the sera for tumor cell membrane-bound antibodies. There was a marked enlargement of the RLN:s reaching the peak on day 12, due to increase of the Vv of the B-zone as well as of the T-zone. Evidence of distinct B-cell stimulation by the growing of P815X2 was provided by an early decrease of Thy1.2+/I-Ad+ cell ratio both in the RLN:s and in NRLN:s. This activation of B-cells seems to be parallel to the elevation of Lyt1+/Lyt2+ ratio in T-cell region on day 6. The IF-tests for or the presence of tumor cell membrane-bound antibodies were almost invariably negative. With exception of two sera, the 51Cr-release assay for cytotoxic antibodies against P815X2 targets was negative. The present study confirms the previous observations on failure to find circulating cytotoxic or cell membrane-bound antibodies in DBA/2 mice bearing P815X2 mastocytoma, despite the morphologically well definable activation in RLN:s and in NRLN:s of the B-cell areas. This is in alignment with the findings in the majority of human tumors, where B-cell predominance in RLN:s does not represent a favourable prognostic sign.
Animals↗
Immune response against P815X2 mastocytoma growing in syngeneic DBA/2 mice. II. Morphometric assessment of immunoreactivity in the thymus and spleen related to lymphocyte subsets in peripheral blood.
To assess the significance of humoral immune mechanisms in host reactivity against the P815X2 mastocytoma grown in syngeneic DBA/2 mice, an approach was made to correlate immunomorphology of the thymus and spleen with the functional assays measuring cytotoxic (51Cr-release assay) and tumor cell membrane-bound antibodies (IF test) as well as phenotyping (with monoclonal antibodies Anti-Thy1.2, Anti-Lyt1, Anti-Lyt2, and Anti-I-Ad) the lymphocyte subsets in peripheral blood. The volume fractions (Vv) of the cortex (C), and medulla (M) of the thymus, as well as central (C-PALS) and peripheral periarteriolar lymphoid sheath (P-PALS) in the spleen were determined morphometrically. There was a steady increase of the C/M ratio from the control levels until day 8, not accompanied by any major fluctuations in the percentages of Thy1.2+ or I-Ad+ cells in C and M. In M, two significant peaks were found in Lyt1+/Lyt2+ cell ratio. In the spleen P-PALS, Thy1.2+/I-Ad+ cell ratio was subject to major early elevation, followed by a rapid and permanent decline to levels below the controls. Two high peaks of Lyt1+/Lyt2+ ratio were found in P-PALS, on day 10 and 16. In the C-PALS, a marked decline in Thy1.2+/I-Ad+ ratio was observed throughout the experiment. As determined by Vv, there was a marked early enlargement of P-PALS reaching the peak on day 4, and followed by a steady reduction reaching the control values on day 10. In peripheral blood, there was an initial increase of T-cells, leading to elevated Thy1.2+/I-Ad+ ratio and a subsequent elevation of Lyt1+/Lyt2+ ratio on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Direct action of cyclosporin A on human B-lymphocytes with regard to immunoglobulin production.
Highly purified preparations of human B-lymphocytes were cultured with or without cyclosporin A (CyA; 1 microgram/ml) for 8 days with pokeweed mitogen (PWM) in the presence of helper factors or with Epstein-Barr virus (EBV). The amounts of IgG, IgM, IgA and IgE produced in cultures were measured by radioimmunoassays or by reverse hemolytic plaque-forming cell assays. The results demonstrate that whereas CyA had a strong suppressive effect on the production of immunoglobulins (Ig) by PWM-activated B-cells, it had an enhancing effect on EBV-activated B-cells. It is concluded that CyA has a direct effect on human B-lymphocytes and that it may suppress or enhance their activation depending on the stimulant employed to trigger the cells.
B-Lymphocytes↗
Spontaneous lymphokine production by human B lymphocytes.
When human blood lymphocytes are cultured in vitro without any intended stimulus, they produce activities in the supernatant resembling lymphokine. This phenomenon was further investigated in the present study, where it has been demonstrated by physicochemical characterization and inhibition experiments that leukocyte migration inhibitory activity in the supernatants is due to leukocyte inhibitory factor (LIF). When T and B lymphocytes were purified by carbonyl iron and SRBC-rosette sedimentation, only B cells produced LIF and leukocyte chemotactic lymphokine(s) in subsequent cultures. B cells elaborated lymphokines without the help of T cells. the need for co-operation of monocytes was also unlikely. T cells were inactive even when reconstituted with monocytes and platelets.
B-Lymphocytes↗
Leukocyte chemotactic activity in cultures of unstimulated human lymphocytes.
We have shown earlier that unstimulated human lymphocytes in in vitro cultures produce migration inhibitory factor into the supernatant. The evidence of spontaneous lymphokine synthesis is strengthened further by this study, which demonstrates leukocyte chemotactic activity in these culture supernatants. The factor has a molecular weight of more than 5000 daltons, it resisted heating for 15 min at 100 degrees C, and showed maximum activity at dilution 1:4-1:8 of the supernatants.
Cells, Cultured↗
[Lymphokines--immunological agitators].
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Animals↗
A simple technique for measuring leucocyte chemotaxis in reversible Boyden chambers.
A technique for assay of leucocyte chemotaxis in Boyden chambers is described. A set of up to 12 closed chambers with 2 compartments is formed from commercially available migration plates. The set can be turned during the incubation and thus the detachment of cells from the filter, a major source of variation in classical type of chambers, can be prevented. The technique is simple and so inexpensive that it allows the use of the material as disposable if preferred.
Chemotaxis, Leukocyte↗