Biomedical subjects
Publications and source records attributed to C A Holmberg.
Cell surface membrane characteristics of B and T lymphocytes were demonstrated on cells from canine malignant lymphoma, and the results were compared with cytologic classification. Lymphoma in 4 of 5 dogs was found to have one or more characteristics of B lymphocytes. Correlation between the cytologic classification and the presence of B- and T-lymphocyte characteristics was not apparent.
Peripheral blood lymphocytes from 37 healthy rhesus macaques (Macaca mulatta) and thymocytes from 10 fetal and neonatal rhesus macaques were studied for membrane characteristics. Spontaneous rosette formation with sheep erythrocytes, a characteristic of human T lymphocytes, was evaluated. The presence of membrane-bound immunoglobulin and surface receptors for fixed complement was measured, using fluorescent antibody techniques and erythrocyte-antibody-complement rosettes, respectively. The mean percentages +/- 1 standard error of the lymphocyte markers in the peripheral blood lymphocytes from the macaques were: spontaneous rosettes, 63 +/- 1.0; erythrocyte-antibody-complement rosettes, 14.9 +/- 1.2; and membrane immunoglobulin-positive cells, 21.9 +/- 2.2. These values are very similar to values reported for human beings.
Serum samples collected from clinically healthy rhesus macaques (Macaca mulatta) were compared with serums from animals diagnosed as having malignant lymphoma, atypical tuberculosis, progressive multifocal leukoencephalopathy, or more than 1 of these. Electrophoretic analyses of serum proteins (in grams per deciliter) indicated that mean values in a clinically normal group were as follows--total protein, 8.30; albumin, 4.07; alpha-globulin, 0.85; beta-globulin, 2.23; and gamma-globulin, 1.15. In macaques with malignant lymphoma, mean values were--total protein, 7.60; albumin, 2.72; alpha-globulin, 0.91; beta-globulin, 1.71; and gamma-globulin, 2.23. In macaques with atypical tuberculosis, these values were 8.47, 2.92, 0.84, 2.18, and 2.52, respectively, and those with progressive multifocal leukoencephalopathy, 9.06, 4.01, 6.71, 2.42, and 1.93. Where multiple serum samples were available from 1 macaque for analysis, gamma-globulin values were increased before clinical disease was apparent. Evaluation of serums from macaques may be used as a means of detecting preclinical lymphoproliferative disease.
The immunologic status of rhesus macaques (Macaca mulatta) with naturally occurring disease was evaluated by determining the percentages of B and T lymphocytes and mitogen responsiveness of lymphocytes in peripheral blood and lymph nodes. The B lymphocytes were identified by the presence of cell surface immunoglobulin and receptors for complement. The T lymphocytes were identified by their ability to form spontaneous rosettes with sheep red blood cells. Rhesus macaques with idiopathic or primary amyloidosis had normal lymphocyte characteristics. Peripheral blood lymphocytes from rhesus macaques with atypical tuberculosis had decreased percentages of spontaneous rosette-forming cells and depressed responses to concanavalin A, and those with chronic diarrhea or chronic arthritis were also found to have abnormal peripheral blood lymphocyte characteristics. The percentage of B and T lymphocytes in normal lymph nodes was variable, making simultaneous histologic examination necessary for evaluation of diseased animals.
Complement, determined by hemolytic assay, and the third component of complement (C3), determined by radial immunodiffusion assay, were measured in nine nonhuman primate species. The species studied were the titi (Callicebus mollach). The sooty mangabey (Cercocebus atys), the thick-tailed galago or bushbaby (Galago crassicaudatus panganiensis), the crab-eating monkey (Macaca fascicularis), the rhesus monkey (Macaca mulatta), the bonnet monkey (Macaca radiata), the stumptailed macaque (Macaca speciosa), the yellow baboon (Papio cynocephalus), and the black-and-red tamarin (Saguinus nigricollis). Both sheep and bovine erythrocytes were used in the hemolytic complement assays. With the sheep erythrocyte system, sera from four species (yellow baboon, sooty mangabey, bonnet monkey, black-and-red tamarin) had similar titers with both antibody sensitized and non-sensitized erythrocytes. In contrast, the titers obtained using sensitized bovine erythrocytes was always higher than the values obtained using non-sensitized bovine erythrocytes. In all species, the titers for non-sensitized sheep erythrocytes was higher than the titer for non-sensitized bovine erythrocytes. When the species were compared for cross reactivity using the radial immunodiffusion assay for human C3, the rhesus monkey showed the strongest cross reaction; the thick-tailed galago, a prosimian, showed no detectable cross reactivity; and the other species examined showed intermediate degrees of reactivity.
Twenty-three canine malignant lymphomas were studied to correlate morphologic and immunologic properties of the neoplastic cells. Morphotologic characterization included histologic classification of cell type and growth pattern, anatomic distribution of lesions, and transmission electron microscopic examination. Parameters examined to indicate B- or T-cell nature of lymphoma cells included demonstration of mitogen responsiveness, cell-surface Ig, spontaneous rosette formation with human red blood cells, and scanning electron microscope (SEM) examination of cell-surface features. Results indicated that the cells from histiocytic lymphomas were lymphocytes rather than histiocytes or macrophages. Most cells from lymphomas examined possessed cell-surface ig, indicating B-cell nature. The cell types represented by the different Ig-positive lymphomas were compatible with maturation arrest at different stages in normal lymphocyte differentiation. For the two most common histiologic cell types, nitogen responsiveness and the presence of cell-surface Ig indicated that diffuse, poorly differentiated lymphocytic cases were biologically heterogenous, whereas nodular histiocytic lymphomas were biologically homogenous. Most canine lymphomas had a multicentric anatomic distribution; however, one thymic and two alimentary forms were observed. Lymphomas with a nodular pattern in lymph nodes had multifocal splenic involvement centered on small arteries, whereas lymphomas with a diffuse pattern in lymph nodes had diffuse involvement of splenic white pulp. The cells of Ig-positive and Ig-negative neoplasms examined by SEM were predominantly of the smooth-cell type.
In a study on the primary humoral response of calves vaccinated against infectious bovine rhinotracheitis (IBR) and simultaneously given levamisole, mild but consistent suppression of the group's geometric mean serum-neutralization titer to IBR virus occurred between 12 and 59 days later. The quantitative determination of circulating immunoglobulins (Ig) over the same period indicated a slight decrease in the IgG concentrations from an initial geometric mean concentration of 18.28 mg/ml before calves were vaccinated to 15.29 mg/ml after vaccination, and the control calves (vaccinated and given saline solution only) maintained their prevaccination IgG geometric mean concentration of 20.92 mg/ml. Difference was not observed in the circulating IgM values of the 2 groups. Levamisole had no apparent effect on the circulating Ig-bearing lymphocyte values when compared with control calves during the 24 hours of treatment. It was concluded that a single treatment of levamisole may mildly suppress the primary humoral response to IBR vaccination in calves, but it is unlikely that this would affect the animal's capability to recover from, or maintain resistance to, IBR infection.
Lymphoid cell populations from various hematopoietic tissues of normal cats (n = 22) and from cats with malignant lymphoma (n = 14 cats) were examined simultaneously for morphologic and immunologic features. Scanning electron microscopy and mitogen stimulation studies were not useful in identifying the B or T cell nature of malignant lymphomas. Cell markers successfully used to identify B cells were the presence of surface immunoglobulin by fluorescent-immunoglobulin staining procedures and the presence of complement receptors by EAC (erythrocyte, antibody, complement) rosette formation. The formation of rosettes with guinea pig erythrocytes was used to identify T cells. Using these cell surface markers, thymic lymphomas were found to be composed of T cells and alimentary lymphomas were found to be composed of B cells. The multicentric lymphomas lacked B or T cell surface markers. Classification by cytologic type of cell did not show any correlation with other values.