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Biomedical subjects

R G Miller

Publications and source records attributed to R G Miller.

At least 361 records · Page 20Linked to original sources
PubMed1975

Membrane particles on fracture faces of frozen myelin.

Freeze-fracture electron microscopy reveals constant and widespread presence of membrane particles on the fracture faces of frozen myelin. In unfixed myelin frozen shortly after dissection the distribution of the particles is uniform. In glutaraldehyde-fixed and/or glycerol-impregnated myelin the particles frequently occupy a network interspersed with circumscribed particle-free areas of variable dimension. In these membranes the network of particles is propagated radially across many lamellae. Particle-rich areas are closely apposed and contrast with frequent delamination of adjacent particle-free regions. We propose that, as in other plasma membranes, the particles of myelin represent protein-containing structures intercalated across the hydrophobic matrix of a membrane with bilayer organization. Our results indicate that these structures contain sites which mutually interact at the surface of apposed membranes and may be important in maintaining the organizational integrity of myelin.

Animals↗
PubMed1975

Characterization of immunoglobulin-bearing and other small lymphocytes in mouse bone marrow by sedimentation and electrophoresis.

125I-antiglobulin binding and radioautography have been used to define the sedimentation and electrophoretic properties of immunoglobulin-bearing and other small lymphocytes in bone marrow. Bone marrow cell suspensions from CBA mice were exposed to 125I-labeled rabbit anti-mouse immunoglobulin for 30 min at 0 degrees C. Cell fractions were collected after either sedimentation at unit gravity or continuous free-buffer film preparative electrophoresis. The sedimentation profiles of labeled, antiglobulin-binding small lymphocytes and of unlabeled small lymphocytes were identical, peaking at 2.6 mm/hr, except for 5% of the labeled small lymphocytes which sedimented at 3.8 to 4.1 mm/hr. In electrophoretic fractions most labeled small lymphocytes were contained in a peak of low mobility and unlabeled small lymphocytes were of intermediate mobility, but high mobility fractions also contained small numbers of labeled and unlabeled small lymphocytes. Small lymphocytes comprised 80 to 85% of all nucleated bone marrow cells in fractions taken at the peak of the small lymphocyte distribution profile after either sedimentation or electrophoresis, accompanied mainly by either erythroid or granulocytic precursor cells, respectively. The results demonstrate that small lymphocytes with readily detectable surface immunoglobulin in the bone marrow closely resemble those in peripheral lymphoid tissues with respect to their sedimentation and electrophoretic properties. The possibility is raised that the rapidly sedimenting immunoglobulin-bearing small lymphocytes in bone marrow are a functionally distinct group of potential precursor cells. Non-antiglobulin-binding small lymphocytes in bone marrow resemble electrophoretically the double negative (immunoglobulin -and theta -negative) small lymphocytes in other lymphoid tissues. Small lymphocytes of high electrophoretic mobility, prominent in the theta- bearing lymphocyte populations of peripheral lymphoid tissues, are few in bone marrow. Lymphocyte-rich suspensions, containing either high or low proportions of immunoglobulin-bearing small lymphocytes, can be separated from bone marrow by electrophoresis

Animals↗
PubMed1975

Development of B lymphocytes-1,2.

A rough outline of the development pathway of stem cells to B lymphocytes in mammals is beginning to emerge. The stem cell is most probably either identical to or closely related to the spleen colony-forming unit or hemopoietic stem cell. The stem cell appears not to be specificity-restricted and to lack Ig surface receptors. Whether part of B-cell development in mammals takes place in a specialized lymphoid environment, analogous to the bursa of Fabricius in birds, is still unresolved. The bone marrow does not form such an environment. The bone marrow and spleen, but not the lymph nodes, of mice contain a nondividing B-cell precursor population at an intermediate stage of development between the stem cell and B cell. This population has Ig surface receptors and is specificity-restricted. It cannot be initiated into differentiating into antibody-producing cells. However, under appropriate conditions it can give rise to functional B cells within 3 days. Newly-formed B cells (designated B1) are physically different from mature B cells (designated B2) and appear to be a dividing population of cells differentiating from the B-cell precursor to B2 nondividing cell populations.

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PubMed1973

Inhibition of the immune response by 7S antibody mechanism and site of action.

A cell culture system was used to investigate the mechanism of action of the feedback inhibition caused by specific 7S antibody. It was found that preincubation of spleen cells with specific 7S antibody led to a marked reduction in the in vitro response of the treated spleen cells to the antigen used to prepare the antibody. The inhibition was not caused by a carry-over of free antibody nor by the release of 7S antibody from the cells. Rather, the preincubation appeared to specifically inactivate one of the cells required for initiation of an in vitro response. Since the suppression could be reversed by addition of untreated cells, it was possible to characterize the properties of the reconstituting cell. This cell is identified as the nonlymphoid accessory cell (A cell) by several criteria. (a) Suppression can be demonstrated only in assay systems requiring functional A cells. (b) The most active sources for reconstitution are also good sources for A cells. (c) The sedimentation velocity of the reconstituting cell is identical with that for A cells. (d) Like A cells, the reconstituting cell is resistant to high doses of ionizing radiation. (e) The reconstituting ability is not affected by anti-theta antibody. Of the three cells required for the initiation of an immune response, A cells, bone marrow-derived cells, and thymus-derived cells, the data are only compatible with the reconstituting cell being an A cell. Additional experiments suggest that the Fc portion of 7S antibody binds to the surface of A cells. Thus, fluorescein isothiocyanate-labeled 7S antibody binds specifically to cells with properties similar to those described above, and F(ab')(2) fragments, lacking Fc portion, are unable to cause immunosuppression when they are preincubated with spleen cells. It is possible that this binding is related to the specific suppression caused by 7S antibody molecules.

Animals↗
PubMed1973

Restriction of specificity in the precursors of bone marrow-associated lymphocytes.

Previous work has shown that the immediate precursor of B lymphocytes (PB cell) has many properties that distinguish it from both B lymphoctes and hemopoietic stem cells. Size, density, tissue distribution, and sensitivity to cytotoxic antisera differ for each type of cell. The work described here was designed to study three aspects of the differentiation of PB cells. First, since PB cells probably have immunoglobulin surface receptors, fluorescein-labeled anti-immunoglobulin antiserum was used in an attempt to investigate directly the physical properties of PB cells. The use of this labeled antiserum revealed a population of cells with properties similar to the PB cells defined by the functional assays. Second, the differentiative potential of PB cells was studied by comparing the size of the total population of PB cells, as determined with fluorescein-labeled anti-immunoglobulin antiserum, to the size of the population of PB cells responding in a functional assay with a specific antigen. The cells responding in the functional assay represent only 0.1% of the total population of PB cells. This observation suggests that PB cells are not pluripotent stem cells of the immune system. Finally, the kinetics of the differentiation of PB cells to B lymphocytes was studied. The differentiation to mature lymphocytes involves at least one intermediate stage in which cells larger than mature B cells are active in a functional assay for B cells. These large B cells are present in irradiated mice soon after transplantation of PB cells, but by 20 days the majority of the B cells are typical small lymphocytes.

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