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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 379 records · Page 21Linked to original sources
PubMed1980

Immunocytological studies of lymph nodes in rheumatoid arthritis and malignant lymphoma.

Lymph nodes obtained from 9 patients with active rheumatoid arthritis were stained by immunological techniques permitting identification of B and T cell areas within the nodes. The lymph nodes were also compared with those obtained from patients with lymphoma. The rheumatoid lymph nodes showed prominent B cell staining in the follicular centres by the EAC and fluoresceinated immunoglobulin techniques. Interfollicular areas were intensely stained with anti-theta globulin. In contrast, lymphoma nodes stained less intensely with fluoresceinated immunoglobulins but stained like benign nodes with EAC. The difference in staining may reflect the degree of disorganisation of the neoplastic follicle and/or the different sensitivity of these 2 methods in the detection of B cells. The differences in staining are helpful in distinguishing the benign changes associated with chronic inflammation from neoplastic B cell proliferative changes seen in lymph nodes.

Arthritis, Rheumatoid↗
PubMed1980

Lymphocyte antigens in systemic lupus erythematosus: studies with heterologous antisera.

Rabbit antisera were produced against pooled living lymphocytes from 25 patients with active systemic lupus erythematosus (SLE). Lymphocytes collected at plasmapheresis or venipuncture were frozen in liquid nitrogen and later coated with rabbit antibody to normal human tonsils and normal thymocytes immediately before intravenous immunization of rabbits. Antisera were subsequently extensively absorbed with normal human tonsillar cells, thymocytes, peripheral blood lymphocytes, erythrocytes, and leukocytes from patients with myelogeneous and lymphatic leukemia until residual base-line immunofluorescent staining of normal human lymphocytes using F(ab)2' of whole antisera averaged less than 5%. Absorbed pepsin-digested antisera detected membrane antigens which were markedly increased (mean 32%) on lymphocytes from patients with active SLE (P less than 0.05). Membrane antigens reacting with absorbed, pepsin-digested antisera were present on both T and B cells but, in most instances, predominated on T cells. Control observations using absorbed pepsin-digested antisera to normal human lymphocytes or peripheral blood lymphocytes from patients with rheumatoid arthritis showed no similar specificity. SLE patients treated with moderate or high dose corticosteroids or immunosuppressive agents (cytoxan or azathioprine) appeared to lose lymphocyte antigens detected by these reagents. Control studies with other connective tissue disease patients, miscellaneous hospitalized subjects, or normal controls showed low levels of reactivity (2-5%). SLE lymphocyte membrane antigens uniquely increased during active disease; this may represent neoantigens or alterations associated with the disease itself.

Adult↗
PubMed1980

Studies of T- and B-cell interactions in adult patients with combined immunodeficiency.

Cellular interactions involved in the pathogenesis of hypogammaglobulinemia were studied in six patients with common variable immunodeficiency. Amounts of immunoglobulin (Ig)G and IgM in the supernate of pokeweed mitogen-stimulated cocultures of normal and immunodeficient mononuclear cells were measured by radioimmunoassays. Mononuclear cells from three of six patients inhibited Ig production of normal B cells (P < 0.005). When purified patient and normal T cells were added to B cells in various autologous or allogeneic combinations, it was observed that immunodeficient T cells (AT) from four patients suppressed normal IgM synthesis. Allogeneic normal T cells did not provide help for B cells from these same immunodeficient patients. In two patients, autologous T cells were able to help autologous B-cell IgM synthesis in vitro. In five patients, AT cells inhibited normal B-cell IgG synthesis. Removal of T cells bearing Ia determinants or T cells with Fc-IgG receptors did not diminish the suppressive effect of AT cells on normal B-cell Ig synthesis. Addition of indomethacin, a prostaglandin synthetase inhibitor, did not abrogate the suppressive effect of immunodeficient mononuclear cells. Addition of hydrocortisone succinate (10 muM) did reverse the suppressive effect of AT cells on IgM production in one patient; however, no in vitro reversal of suppressor cell effect was recorded in five. Suppression by immune-deficient T cells was eliminated by 2,000 rad of x-ray irradiation in three patients. After x-ray irradiation immunedeficient T cells could function as helpers of normal B cells.

Adult↗
PubMed1980

Studies on the pharmacologic manipulation of suppressor cells associated with impaired immunoglobulin production.

Several agents were tested for their potential to reverse the suppression of normal IgG and IgM production mediatd by human cord T cells and cells from patients with agammaglobulinemia. No reversal of suppression was observed with in vitro incubation of co-cultured normal and immune-deficiency suppressor cells with cimetidine, lithium, or levamisole. Allogeneic helper factor prepared from normal mononuclear cells was able to overcome the suppression of normal IgG production mediated by cord T cells but did not overcome suppression of IgG or IgM production mediated by suppressor cells from agammaglobulinemic patients.

Agammaglobulinemia↗
PubMed1980

Suppressor leukocytes in anergic patients with solid tumors.

Anergic patients with solid tumors were studied for the presence of suppressor cells which could be responsible for their significantly impaired phytohemagglutinin induced lymphocyte proliferation. Three types of suppressor cell assays were measured. First, no increased activity of prostaglandin producing suppressor cells was found in 10 cancer patients. Second, 5 cancer patients did not have significantly increased activity of short-lived suppressor cells in comparison with normal subjects. Third, no enhanced activity of concanavalin A induced suppressor cells was seen in 6 patients. This study emphasizes that the in vitro T cell immunodeficiency in this group of cancer patients was not due to suppressor cells as measured by conventional in vitro assays and emphasizes the potential importance of a loss of responder cells or other suppressor mechanisms in immune deficient patients with solid tumors.

Adult↗
PubMed1980

Ia antigen on the surface of a subfraction of T cells that bear Fc receptors for IgG.

Human peripheral blood T cells and T cell subpopulations were studied for the presence of Ia-like antigen, by using indirect immunofluorescence with heterologous rabbit anti-Ia antisera. In 13 normal subjects the percentage of T cells staining with the anti-Ia reagent was 2 to 5% and appeared limited to the T gamma subfraction. After concanavalin A (Con A) or phytohemagglutinin (PHA) activation, the proportion of Ia(+) T cells increased due to an increase in the percentage of T gamma cells bearing Ia-like antigen as well as an increase in the proportion of T gamma cells in the T cell fraction.

Animals↗
PubMed1980

T-lymphocyte subpopulations in peripheral blood and tissues of cancer patients.

Patients with cancer often show impaired immune functions; however, the basis of this suppression is still not understood. In several experimental systems, human T-cells with receptors for Fc of immunoglobulin G may function as suppressors, and those with receptors for Fc of immunoglobulin M may function as helpers. Peripheral blood as well as tumor tissue infiltrates were examined for proportions and numbers of T gamma, T mu, or Ia-positive T-cells. Forty-five untreated patients with solid tumors and 24 patients with lymphomas were studied. An increase in the percentage of peripheral blood T gamma cells (p < 0.001) and a decrease in T mu cells (p < 0.0005) were recorded in all tumor patients when compared with 30 normal controls. Percentages and absolute numbers of peripheral blood Ia-positive T-cells were decreased (p < 0.001 and < 0.00001) in solid-tumor patients; by contrast, the proportion of peripheral blood Ia-positive T-cells was elevated (p < 0.005) in lymphoma subjects. Studies of cancer tissues from 46 untreated patients using immunofluorescence and mouse hybridoma antibody specific for T-cells showed that tumor lymphocytic infiltrates were composed mainly of T-cells. Double staining with fluorescein-conjugated specific anti-T gamma and Ia-positive T-cells within solid-tumor lymphoid infiltrates. A comparison of peripheral blood and tumor lymphocyte T-cell profiles revealed that, in some patients, low proportions of Ia-positive T-cells in blood were paralleled by a high percentage of such cells in tumor lymphoid infiltrates.

Antigens, Surface↗
PubMed1980

T lymphocyte subpopulations and Ia-positive T cells in patients with immunodeficiency.

T lymphocyte subpopulations (T gamma and Tmu) were studied in a group of 36 adult patients with immunodeficiency. Proportions and numbers of Ia(+) T cells were also studied in comparison to 46 normal adult controls. Values for per cent and total numbers of T gamma and Tmu cells indicated no uniform abnormality. Mean normal percentage of Ia(+) T cells was 2.4% whereas 16 to 29 immunodeficient patients showed elevated proportions and absolute numbers of Ia(+) T cells. Striking fluctuation in proportions of Ia(+) T cells was noted in serial studies of five immunodeficient subjects in contrast to similar analyses of normal controls. A correlation (P less than 0.01) was recorded between absolute numbers of Ia(+) T cells in immune deficiency patients and numbers of T mu cells. Depletion of T gamma cells by EA rosetting in patients with late-onset primary acquired hypogammaglobulinaemia did not result in significant change in IgG or IgM synthesis with T gamma-depleted T cells were co-cultured with normal B cells. Depletion of Ia(+) T cells likewise did not significantly influence Ig synthesis in co-culture with normal or immune-deficient B cells. These studies emphasize the complexity of defects present among any large group of patients with immune deficiency.

Adult↗
PubMed1980

Lymphocytes binding C-reactive protein and streptococcal membranes in acute rheumatic fever.

Peripheral blood lymphocytes binding CRP and streptococcal membrane antigens were studied in 19 patients with ARF with the use of a number of paired analyses for cell surface markers. A small fraction (6.9%) of T cells showed binding to streptococcal membrane. A large degree of overlap (38% to 46%) occurred in membrane-binding T cells and those with identifiable CRP. One third of T gamma cells showed CRP bindings, and approximately one quarter to T gamma cells in both ARF patients and normal controls showed membrane la antigen. A considerable concordance (50% to 75%) was noted between T cells binding streptococcal membrane and cells positive for la antigen. In contrast to T cells, B cells bearing CRP showed less overlap (mean 11%) with cells binding streptococcal membrane. Since B cells with concomitant surface immunoglobulin and la antigen constituted the major lymphocyte subpopulation binding streptococcal membrane antigens, relative exclusion of streptococcal membrane binding by B cells with surface CRP may represent natural protective modulation whereby proportions of potential antigen-binding B cells are defused by lymphocyte membrane CRP.

Acute Disease↗
PubMed1979

Application of an automated extractor/concentrator to the analysis of anticonvulsant drugs in blood serum by high-performance liquid chromatography.

An automated extractor/concentrator has been used to extract a variety of anticonvulsant drugs from blood serum in a concentration range from 0.075 to 80 microgram/ml. The volume of serum required varies from 0.1 to 2.0 ml, depending on the concentration of drug. The average absolute extraction recovery is 90% larger; recoveries relative to an internal standard are greater than 95%. The serum extracts were analyzed by high-performance liquid chromatography on a reversed-phase column with an acetonitrile and phosphate buffer mobile phase. Comparison of results with gas chromatographic and immunoassay techniques was excellent.

Anticonvulsants↗
PubMed1979

Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes.

Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions.

Binding Sites↗
PubMed1979

Separation of tubulin from microtubule-associated proteins on phosphocellulose. Accompanying alterations in concentrations of buffer components.

Tubulin can be conveniently separated from the microtubule-associated proteins by chromatography on phosphocellulose [Weingarten, M. D., Lockwood, A. H., Hwo, S.-Y., & Kirschner, M. W. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 1858]. Concentrations of Mg2+, GTP, GDP, and glycerol were measured in the various fractions collected during several such separations. The phosphocellulose was found to sequester Mg2+ under the conditions employed for the separation and to retard GTP, GDP, and glycerol relative to tubulin. Polymerization of the resulting phosphocellulose-tubulin was found to be inhibited by this Mg2+ depletion. The composition of the buffer in which tubulin emerges from the chromatographic column was found to depend in a sensitive way upon the retardation of the other components of the buffer and to be a sensitive function of the width of the pooled tubulin peak and of the ratio of the volume of the chromatographic column to that of the column load. The bearing of these findings on interpretation of existing literature is briefly discussed. Efficient separation of tubulin from microtubule-associated proteins can also be obtained on phosphocellulose columns that have been saturated with Mg2+. Such saturation of the column, or addition of Mg2+ to the collected fractions, followed by equilibration of the tubulin with known buffer, is suggested as an improvement to the preparative scheme.

Chromatography, Ion Exchange↗
PubMed1979

Identification of the major 68,000-dalton protein of microtubule preparations as a 10-nm filament protein and its effects on microtubule assembly in vitro.

The major 68,000-dalton protein present in cycled microtubule preparations from bovine brain can be isolated in a rapidly sedimenting fraction consisting of filaments 10 nm in diameter. This 68,000-dalton protein remains in the filament fraction after gel filtration, phosphocellulose chromatography, or salt extraction of microtubule protein. Microtubule protein devoid of 10-nm filaments contains ring structures under depolymerizing conditions, and it polymerizes into microtubules with a characteristically low critical concentration, although all of the 68,000-dalton protein has been removed from it. When cycled microtubule protein is subjected to chromatography on phosphocellulose, the tubulin fraction (PC-tubulin) assembles into microtubules only at concentrations greater than 2 mg/mL. The other fraction, eluted from phosphocellulose at high ionic strength, contains the major 68,000-dalton protein and can be further resolved into two components by centrifugation. The supernatant, which consists mainly of high molecular weight microtubule-associated proteins, stimulates low concentrations of PC-tubulin to assemble. The pellet contains all of the 68,000-dalton protein, consists of 10-nm filaments, and does not stimulate assembly of PC-tublin. Boiling of purified filaments, however, releases several proteins, including the 68,000-dalton protein, and these released proteins stimulate the assembly of PC-tubulin. The morphology and protein composition of the filaments isolated from microtubule preparations by these techniques are very similar to those of mammalian neurofilaments. These results suggest that the major 68,000-dalton protein in cycled microtubule preparations, which may correspond to tubulin assembly protein [Lockwood, A.H. (1978) Cell 13, 613--627], is a constituent of neurofilaments.

Animals↗
PubMed1979

Inhibition of human eosinophil chemotaxis by IgA paraproteins.

Sera from patients with IgA myeloma inhibit normal human eosinophil chemotaxis. No correlation was noted between inhibition and the absolute concentration of IgA or lambda-K light-chain type. Eosinophil chemotactic inhibitory activity was associated with isolated IgA paraproteins and was found to be cell directed and stable at 56 degrees C. Pepsin digestion of IgA paraproteins resulted in loss of both IgA Fc fragment and eosinophil chemotactic inhibitory activity. Polymeric IgA accounted for most of the inhibitory activity as evidenced by sucrose density gradient centrifugation studies and a loss of inhibitory activity following dithiothrietol reduction and iodoacetamide alkylation which converted polymeric IgA to monomeric IgA. Comparative studies with neutrophils showed that both neutrophil and eosinophil chemotaxis and chemokinesis were effectively inhibited by IgA paraproteins. The mechanisms of suppression of eosinophil and neutrophil chemotaxis by IgA paraproteins appear to be similar and possibly may involve a membrane receptor for IgA.

Chemotaxis, Leukocyte↗