Increased suppressor- and normal helper T-cell activity in patients with B-cell chronic lymphatic leukaemia (B-CLL)
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Biomedical subjects
Publications and source records attributed to F Herrmann.
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Macrophage- and T-cell-depleted mononuclear cells from 36 patients with B cell lymphoma and 12 healthy individuals were investigated by indirect immunofluorescence with the monoclonal antibodies NEI-011 (7.2) and NEI-015 (10.2). The monoclonal antibody NEI-011 (7.2) recognized the Ia antigen and identified almost all B cells in the peripheral blood of healthy individuals. Furthermore, neoplastic B cells from all patients except those with plasma cell proliferation were found to react with this antibody. NEI-015 (10.2), a monoclonal antibody known to react with both T cells and B-CLL cells, did not react with normal circulating B cells. However, this antibody did identify neoplastic B cells except in cases of plasma cell proliferation and lymphoblastic lymphoma.
Functional properties were studied in the purified T cell fraction of patients with chronic lymphocytic leukaemia of the B cell type (B-CLL). This analysis included the evaluation of T suppressor activity when investigated patients' T cells were co-cultured together with allogenic normal B and OKT4 enriched T cells in the presence of pokeweed mitogen (PWM). The Ig secreting cells (ISC) were assessed in a reverse haemolytic plaque assay (RHPA). Antibody-dependent cytotoxicity (ADCC) and natural killer activity (NK) were determined in a 51Cr release assay. Furthermore, purified T cells reactive with the monoclonal antibody HNK1, known to recognize most effector cells in ADCC and NK, were enumerated using an indirect immunofluorescence. Our results revealed increased T suppressor cell activity and markedly deficient NK activity in peripheral blood lymphocytes (PBL), T cell and T gamma cell fractions from B-CLL patients, whereas ADCC potential was only increased in T cells and T gamma cells. Accordingly, T cells were recognized by HNK1 in greater numbers in B-CLL patients than in healthy subjects. Our data suggest that there may be a link between our findings and the hypogammaglobulinaemia as well as the increased incidence of second neoplasias reported in CLL.
Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B1-chronic lymphocytic leukemia (CLL), one patient with B2-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B1- and B2-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B1-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.
Certain markers for B lymphocytes (SIg, EAIgG, EAIgMC3b, EAIgMC3d, M-R) and T lymphocytes (E-R, EAIgG, EAIgM) were applied in order to characterize circulating neoplastic cells in non-Hodgkin lymphomas (NHL) of low and intermediate malignancy. In all cases, the diagnoses were based on the histological examination of lymph nodes, bone marrow, or skin biopsies. According to the Kiel classification, the diagnoses were as follows: chronic lymphocytic leukemia (CLL) n = 145. Immunocytoma (Ic) n = 39. Centrocytic (Cc) and centroblastic/centrocytic lymphoma (Cb/Cc) n = 17. Hairy-cell leukemia (HCL) n = 10. Prolymphocytic leukemia (PLL) n = 6 and Sézary's syndrome n = 3. In only 8 of the 220 cases did the leukemia cells show T characteristics. In leukemic B-cell lymphoma, a uniform phenotype was observed for B-CLL, characterized by a weak SIgM staining with or without SIgD, the presence of C3d-receptors and a high percentage of M-R. This phenotype was also detected in one third of the cases of immunocytoma. The cells of B-PLL and leukemic CC and CB/CC were characterized by a stronger SIg staining, a variable formation of complement receptors and, in most cases, absence of M-R. In all cases of B-cell lymphoma, the monoclonality of the cell proliferation could be confirmed by the restriction to a single L-chain type. This also applies to the 10 cases of HCL, although in the majority of these cases, several heavy-chain classes could be detected at the malignant cells.
T cell enriched mononuclear cells from the peripheral blood of 20 patients with histologically and immunologically defined chronic lymphocytic leukaemia of the B cell type (B-CLL) and 20 healthy individuals of various ages were investigated with T cell-specific monoclonal antibodies (OKT 4 and OKT 8) with regard to their subpopulation distribution. In B-CLL, a significant increase of lymphocytes reacting with OKT 8 could be demonstrated. Whereas there was a ratio of OKT 4 to OKT 8 of 1 X 72 in the control group, an OKT 4 to OKT 8 ratio of 0 X 67 was found in the B-CLL as a whole. With increasing clinical stage in accordance with the Rai scheme (Rai et al., 1975), a further displacement of this ratio in favour of OKT 8 positive cells was found. These results clearly show that, in peripheral blood of patients with B-CLL, an abnormal distribution pattern of circulating T cell subpopulations is present and that this also has prognostic relevance.
Clinical data of 116 patients with chronic lymphocytic leukaemia (CLL) and of 114 patients with lymphoplasmacytic/lymphoplasmacytoid lymphoma (synonym: LP immunocytoma, IC) as diagnosed according to the Kiel classification were compared. This interim evaluation of a prospective multicenter study of the Kiel Lymphoma Study Group characterizes IC the less favorable lymphoma entity as evidenced by a more rapid lymph node enlargement, by a higher incidence of constitutional symptoms and of marked anaemia, and by a higher percentage of patients requiring early treatment. In addition, in IC autoimmune haemolytic anaemia was detected in 11.2% of investigated patients as compared to none of the patients with CLL, and monoclonal gammopathy was disclosed in 34.2% of investigated patients as compared to only three patients with CLL who could be, however, unrecognized cases of IC. Actuarial survival data after a follow-up period of 40 months are in favor of an overall better prognosis of patients with CLL than of patients with IC.
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The anaemia in rheumatoid arthritis is apparently of complex origin, in which case an increased accumulation of iron in the RES and the decreased utilisation of storage iron play the quantitatively most important role. According to literary data megaloblastic anaemias shall not appear frequently in rheumatoid arthritis. The frequency of the anaemia is rheumatoid arthritis is clearly depending on the composition of the collective of patients. In our patients anaemia and hypoferraemia do not correlate with the actual activity of the disease, however with the extension of the affection of the joints and the progressing of the basic disease. Anaemia and hypoferraemia may, therefore, be valuated as prognostically unfavourable signs. We could prove decreased vitamin B12-levels in 11.6%. There was no statistically significant relation to the course of the disease. An inhibition of the resportion of vitamin B12 by means of a long-term therapy is discussed.
The effect of furosemide (Lasix) therapy on a standardized experimental cerebral edema, induced in rats by applying a cooling stamp to the right side of the skull over the right coronal suture by means of a stereotactic instrument, was examined. The hemispherically separated water and electrolyte contents of the brain were analyzed after 24 h. Following furosemide therapy, the behavior of these edema parameters was compared statistically with dexamethasone, glycerol and albumin. An increase of the water and sodium content, and a decrease of potassium was observed 24 h after the trauma, especially in the right hemisphere. Furosemide did not improve either the water content or the electrolyte balance. By contrast, the administration of dexamethasone, glycerol and albumin was followed by a significant improvement of the edema. In experiments with cats, the course of the edema and the effect of furosemide on the cold brain injury of the right hemisphere were observed by measuring the intracranial pressure (ICP) values, and by continuous monitoring of the EEG. The ventricular CSF pressure and epidural pressures were also recorded. The electrical brain activity was continuously compared with the course of the ICP by means of computer analysis. In addition, the blood osmolality and diuresis were monitored. The ICP increased rapidly after the trauma, establishing considerable pressure gradients, and the EEG power intensities decreased markedly on the right side. Histologically, there was an extended edema of the white matter of both hemispheres. The ICP was not lowered by single injections or high dose infusions of furosemide, and the EEG power intensities also did not improve. Infusions of large volumes of furosemide even resulted in an increase of ICP, but infusion of 40% sorbitol effected a rapid decrease of ICP and EEG recovery over the left hemisphere. Sorbitol infusion also caused a marked rise in the blood osmolality, whereas furosemide had no such effect. The results raise considerable doubts as to the propriety of the exclusive use of furosemide for cases of acute cerebral edema with raised ICP. The diuretic effect is insufficient to establish an osmotic gradient, and its general dehydrating effect does not acutely influence the ICP. The absence of effect on the experimental tissue edema would not appear to commend furosemide as basic therapy for cases of traumatic cerebral edema.
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We conducted comparative biochemical and electron-microscopic studies of several types of plastome and nuclear mutants of Antirrhinum majus and Pelargonium zonale. It was shown that specific blocking of the photosynthetic reaction occurs in plastome mutants of A. majus; Photosystem II was found to be damaged in the en:alba-1 mutant and photo-system I was affected in the en:viridis-1 mutant. The plastid mutations in these mutants caused loss of certain soluble lamellar proteins and pigment--protein complexes or a reduction in their content, which led to disappearance of photosynthetic activity. When the content of high-molecular ribosomal RNA in the leaves of normal and mutant P. zonale plants was compared, the normal plants were found to have four types of RNA: two types of cytoplasmic-ribosome RNA and two types of plastid-ribosome RNA. No plastid-ribosome RNA was detected in the mutant. These results were confirmed by electron-microscopic examination: no ribosomes were detected in the mutant plastids. Thus, use of plastome mutants made it possible to establish that the genetic information concentrated in the plastid DNA controls formation of ribosomes and lamellae in the chloroplasts and thus affects chloroplast photosynthetic function.
1. Samples of cutaneous sebum were taken from different skin regions, according to the method of Herrmann and Prose. 2. Some samples were removed from the skin using diethyl ether, while others were removed under similar conditions, with cyclohexane. 3. As a rule, thin-layer chromatography revealed darker, clearer and more numerous bands after the use of diethyl ether, than after the use of cyclohexane. However, some exceptions were seen. 4. The chromatograms showed individual differences while the differences between the samples taken from different skin regions of one and the same person were less considerable. 5. Despite the individual differences, the samples taken from persons without skin diseases showed some characteristic features.
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