Biomedical subjects
Publications and source records attributed to I Turesson.
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A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-conjugated F(ab')2 fragments were prepared and further absorbed with normal peripheral blood leucocytes. The F(ab')2 fragments, studied in direct immunofluorescence, reacted with both normal and CLL B lymphocytes but not with T lymphocytes. Comparative studies with an HLA-DR antiserum showed that the antigen(s) detected by 7420 antiserum did not redistribute together with HLA-DR antigens in cocapping experiments, nor did the HLA-DR antiserum block the reaction of 7420 F(ab')2 fragments with B lymphocytes. The 7420 F(ab')2 fragments prcipitated detergent-solubilized B-cell membrane material with a molecular weight of around 40,000 and 150,000 daltons. The conclusion drawn is that the 7420 and HLA-DR antigens are different. The 7420 antigen was also shown to be different from classical HLA antigens, beta 2-microglobulin, surface immunoglobulin, the Fc receptor, and HC protein.
An IgM lambda M-component with a false Wasserman reaction and 'false' rheumatoid factor activity from a patient suffering from a well-differentiated lymphocytic lymphoma is presented. The monoclonal protein showed antibody activity against cardiolipin and cross-reacted with acryl particles, not with human IgG. Both these activities were found in the Fab fragment. The reduction of the 19S IgM to 7S IgM subunits was responsible for a strong decrease in activity. The importance of the IgM quaternary structure in determining antibody affinity is emphasized.
Nineteen patients with advanced lymphocytic or lymphocytic-histiocytic lymphomas were treated with Prednimustine (NSC-134087, Leo 1031). The median induction dose was 25 mg/m2 a day by mouth (range 11-42). Ten patients had previously received radiation or chemotherapy, or both. Four patients had a complete remission and eleven a partial remission. The median duration of remission was 12.5+ months for complete responders and 5 months for partial responders. Thirteen patients had a moderate myelosuppression. One patient had urticaria and pruritus and refused further treatment.
This report concerns six cases of multiple myeloma characterized by either no demonstrable monoclonal immunoglobulin in plasma or urine or by trace amounts (less than or equal to 0.1 g/l) of monoclonal kappa chains in the urine. In all cases there was an infiltration of the bone marrow by plasma cells containing kappa chains but no heavy chains. A retrospective analysis was made of 126 consecutive cases of Bence Jones myeloma. The number of kappa and lambda cases was approximately the same. All cases secreting less than or equal to 0.1 g light chains per 1 urine were of kappa type. This contrasts with a kappa/lambda ratio of 1.4-1.9 among reported series of M-components containing both heavy and light chains. A review of reported cases of non-secretory myeloma revealed a preserved capacity for Ig synthesis in the majority of cases and among these a preponderance of kappa chain producing clones. These observations might be explained by a higher tendency for kappa chain producing cells to mutate to low secretors or to cells producing abnormal light chains which are catabolized rapidly. The clinical data from our patients do not indicate a more pessimistic prognosis in non- or low-secretory myeloma, than in other cases of multiple myeloma.
Cell suspensions of bone marrow and lymphoid tissue from 85 patients with monoclonal gammapathy were investigated by a direct immunofluorescence procedure for the detection of intracellular immunoglobulin alpha, mu, gamma, kappa and lambda chains. Serum Ig levels were determined and daily syntheric rates estimated. In all cases the majority of Ig-containing bone marrow cells contained the same Ig class as that of the M-component in serum or urine indicating a diffuse distriubtion of these clones in the bone marrow. This was observed not only in myeloma but also in benign monoclonal gammapathy (BMG) and lymphoma with an M-component. The M-component producing clone could be traced to extramedullary lymphoid tissue in myeloma but usually not in BMG. A positive correlation was found between the calculated synthetic rate of the M-component and the number of Ig-containing cells in the bone marrow and some indication was found that the synthetic rate per cell might be lower in IgM and IgG than in IgA monoclonal gammapathy. The depressed level of polyclonal Ig in myeloma and to some extent in BMG was parallelled by a diminished number of Ig-containing cells in the bone marrow.
The surface expression of a recently described plasma glycoprotein called human complex-forming glycoprotein, hetergeneous in charge (protein HC) on a number of different human cell types was investigated. By means of direct and indirect immunofluorescence, protein HC was shown to be associated with the surface of virtually all cells of the investigated normal cell types including erythrocytes, peripheral blood B and T lymphocytes, and the human fibroblast lines HE 81, HE 31, and WI 38. When transformed and malignant cell populations were studied, it was found that some populations (e.g., the T cell line Molt-4) carried protein HC on the surfaces of very few cells, whereas other cell populations (e.g., chronic lymphocytic leukemia lymphocytes) carried the protein on most cells. Malignant cell populations with intermediary percentages of protein HC-positive cells were also found. Protein HC on the cell surface of normal peripheral blood lymphocytes could be redistributed by incubation of the cells with anti-protein HC-antiserum at 37 degrees C, and this reaction could be inhibited by sodium azide.
Cell suspensions of human bone marrow, spleen, lymph nodes and palatine tonsils have been investigated for the presence of intracellular immunoglobulins by a direct immunofluorescence technique, using monospecific antisera against human Ig heavy chains alpha, mu and gamma and light chains kappa and lambda. Serum Ig levels were determined and the number of positive cells was compared with the concentration and calculated synthetic rate of serum Ig in each individual. The 28 patients studied covered a wide range of diagnoses and included those with normal as well as pathologically decreased or increased serum Ig levels. There was a high correlation between the calculated synthetic rate of each Ig class and the percentage of cells positive for the same Ig class in the bone marrow but not in the spleen, lymph nodes or tonsils. The Ig-containing cells constituted a much larger proportion of the total lymphoid cell population in the bone marrow than in the peripheral lymphoid organs. The estimated total number of Ig-containing cells was also much larger in the bone marrow than in the other organs investigated. It is concluded that in man the bone marrow is the major site of serum Ig synthesis and that the average synthetic rate per cell is the same regardless which of the three major Ig classes is produced. The role played by different lymphoid organs in humoral immunity is discussed in the light of the present results and reported data regarding lymphocyte and plasma cell kinetics in mammals.
Indirect immunofluorescence was used to demonstrate the presence of protein HC on the surface of a large percentage of normal human peripheral blood lymphocytes. Protein HC is a recently described charge heterogeneous, complex-forming glycoprotein normally present in human plasma, urine and cerebrospinal fluid. The synthesis of protein HC by lymphocytes was indicated by the removal of the glycoprotein from the cell surfaces on trypsinization of the cells followed by the reappearance of the protein on continued cultivation of the cells.
Patients with breast cancer were irradiated postoperatively to bilateral parasternal fields. The validity of the Cumulative Radiation Effect (CRE) formula for treatment once a week and three times a day was analyzed, and both schedules were compared with treatment once a day (five times a week). The biological radiation effect on normal tissue was studied by reflectance spectrophotometry of skin erythema and pigmentation. Early skin reactions were identical after irradiation daily and once a week, respectively, but were found to be significantly more pronounced after irradiation three times a day than after treatment once a day, corresponding to an overexposure of 7-10%.
Different dose schedules prospectively calculated with the Cumulative Radiation Effect (CRE) formula were used for irradiation of inoperable breast carcinomas. Fractionation with 2 X 260 rad and 2 X 450 rad twice a week, and total doses corresponding to CRE levels 1900 to 2300, were compared. The results showed that prolonged fractionation increased the tolerance of normal skin and the therapeutic ration with respect to early radiation reactions. Late reactions could not be assessed as yet because their development requires several years. With the prolonged course of treatment and 2 X 260 rad per week, no moist desquamation developed despite dose levels between 6800 and 9400 rad. Skin reactions were milder than those in the rapidly treated areas, indicating that the CRE formula cannot exactly predict acute skin reactions for very prolonged treatment schedules. The tumor regressed continuously during the irradiation schedule.
In patients with mammary carcinoma, irradiated postoperatively on the parasternal regions, prospective dose calculations for different fractionation schedules have been performed with the CRE formula. The biologic radiation effect on normal tissue was recorded by reflectance spectrophotometry of skin erythema and pigmentation. The right side received 4 050 R in 25 days, the left side 4 390 R in 47 days with a gap of 3 weeks. A compensation for the gap with 8 per cent of the total exposure was found to be adequate. The smallest exposure difference that could be clearly discriminated visually and with spectrophotometry was recorded in a special series and was found to be 6 to 7 per cent.
By means of an immunofluorescent technique, we found factors promoting blood coagulation and platelet adhesion in the intima of retinal vessels. These factors coexisted with other agents causing the opposite process, fibrin dissolution. The components of this vascular hemostatic balance are possibly involved in the thrombotic occlusion of the retinal vessels, their canalization, and in the pathogenesis of diabetic retinopathy.
The cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) were studied with respect to the frequency of lymphocytes with intracellular immunoblobulins of different Ig classes as well as the relative frequency of B and T lymphocytes. An increased number of Ig-postive cells were found in CSF (mean, 0.52%) when compared with blood (mean 0.18%). In CSF there was a striking dominance of IgG-postive cells, very few IgA-postive cells, and almost no IgM-postive cells. The distribution in blood was approximately normal. The ratios between chi- and lambda-postive cells in CSF were all outside the range in blood. In CSF there were fewer B cells (mean, 4.7%) and more T cells (mean 74.2%) when compared with blood (mean, 11.5%) and 61.8%, respectively). The values for MS blood were approximately the same as for normal controls. The increased number of IgG-containing cells in the CSF are in agreement with earlier studies, which showed a local immunoglobulin synthesis. The increased proportion of T lymphocytes in CSF of MS patients may indicate that these cells play a role in the pathogenesis of MS.
The CRE formula was used for calculation of biologically equivalent radiation doses with different fractionation schedules. The early radiation effects, skin erythema and pigmentation were measured with a reflectance spectrophotometer at wavelengths 578 and 660 nm. The course and maximum for both erythema and pigmentation agreed well with the two types of fractionation. The results seem to justify further use of this simple formula.