Ultrastructural distribution of surface immunoglobulin determinants on mouse lymphoid cells.
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Biomedical subjects
Publications and source records attributed to A D Bankhurst.
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A microradioimmunoassay technique is described for detecting carcinoembryonic antigen (CEA) in whole serum. It differs from previous methods in being performed on 0·025 ml of whole serum instead of 5 ml of serum extracted with perchloric acid. The present assay was sufficiently sensitive to detect 85% of carcinomata, localized to the colon, but positive results occurred also with certain non-gastrointestinal cancers, chiefly lung and breast, and certain non-malignant diseases. Many of the latter sera, with the general exception of alcoholic cirrhosis and pancreatitis, gave negative results after extraction with perchloric acid. It is suggested that a direct assay for CEA in whole serum may permit testing of large numbers of sera by laboratories with facilities for radioimmunoassays.
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Lymphoid cells from thymus, thoracic duct lymph (TDL), and thoracic duct lymph in irradiated animals reconstituted with allogeneic thymus cells (TTDL) were labeled with radioiodinated anti-immunoglobulins using radioautographic techniques. Thymus and TTDL were labeled (14.4 and 37.0%, respectively) with anti-light chain protein after prolonged exposures (30-60 days). No labeling was observed on thymus and TTDL with anti-polyheavy chain globulin. In contrast 18.5-19.0% of TDL labeled on short exposure (6 days) with anti-polyheavy chain and anti-light chain materials. It is proposed that the difference between the labeling observed on short exposures versus long exposures can be related to the difference in surface density of immunoglobulins between nonthymus-derived (B) and thymus-derived (T) cells. The distribution of labeled cells in the thymus was preferentially among the larger cells (greater than 10 micro diameter). The TTDL population was mostly composed of a larger, blast-like population and the distribution of label was independent of size. As the thymus and TTDL preparations contain almost exclusively T cells, this represents a direct demonstration of surface immunoglobulin light chains on T lymphoid cells.
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Lymphocyte-dependent antibody cytotoxicity (LDAC) was studied using peripheral blood and in some instances synovial fluid cells from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). No difference from normal controls was observed with peripheral blood lymphocytes from either RA or SLE. Marked decrement in LDAC effector cell activity was present particularly with RA synovial fluid cells. Sera from patients with RA or SLE as well as RA synovial fluids markedly inhibited LDAC.
Synovial tissues from 5 patients with rheumatoid arthritis (RA) were examined with immunofluorescence microscopy for the presence of lymphocytes with either bone marrow-derived (B) or thymus-derived (T) surface markers. Five synovial tissues with severe to mild lymphocytic infiltrations by bright field microscopy were examined in parallel with immunofluorescence. B cells were identified with a pepsin-digested fluoresceinated anti-F (ab')2 antiserum and T cells were detected with a specific rabbit anti-T lymphocyte antiserum. By these techniques 75-90% of the lymphocytes in these frozen sections were identified as T cells. Cell suspensions were also prepared by collagenase digestion of two of the five synovial tissues. The lymphocytes in these cell suspensions were predominantly T lymphocytes (78-85%) as shown by their ability to form spontaneous rosettes with sheep erythrocytes (E rosettes).
125I-labeled protein A was utilized to detect lymphocyte binding of IgG at 37 degrees C in 50 sera from patients with SLE. IgG binding was partially inhibited by preincubation of test cells with immune complexes in 50% of sera. In 10%, cytophilic Ig was increased by immune complex preincubation, and in 40% no appreciable change was recorded. With purified preparations of T and B cells, binding of SLE IgG at 37 degrees C was equal for both cell populations.
Because of reports that acquired immune deficiency syndrome (AIDS) might be transmissible by blood transfusion, we studied potential surrogate tests that could be used for screening donors. Male donors at one volunteer blood center and two plasma centers were screened for total lymphocyte count, OKT3, OKT4, OKT8, OKT11, LEU-7, LEU-M2, antibodies to hepatitis B core (anti-HBc), cytomegalovirus (CMV), and herpes and circulating immune complexes. Total lymphocyte counts and the OKT11 were significantly lower in one plasma center. No significant differences were found for the other lymphocyte or monocyte tests. Low T4/T8 ratios, found in 20 percent of donors, did not correlate with other abnormalities. A small percentage (3.3%) of volunteer donors, 15.4 percent at one plasma center and 20.8 percent at a second plasma center, and 38.5 percent of the male homosexual donors were positive for anti-HBc (significant when comparing the male homosexuals to the volunteers at p = 0.032). Positive CMV and herpes titers were similar in the groups. Circulating immune complex levels greater than two standard deviations above the mean were found in 20 percent of the volunteer donors, 7.7 percent at one plasma center and 8.3 percent at the second plasma center, and none in the male homosexual population. Pearson product moment correlations showed reasonably good agreement among the lymphocyte tests. However, the anti-HBc, CMV, and herpes antibodies and circulating immune complex levels did not correlate with any of the other tests. Surrogate tests for AIDS are nonspecific and unlikely to be helpful in screening blood donor units.
Tumor necrosis factor (TNF) is a major proinflammatory cytokine in the rheumatoid joint. TNF activity can be neutralized by administration of a recombinant version of its soluble p75 TNF receptor linked to the Fc portion of human immunoglobulin IgG1 (etanercept). The present study examined the combination of etanercept with methotrexate (MTX) in a group of patients with rheumatoid arthritis (RA) who had persistent activity despite monotherapy with MTX. The etanercept-MTX group had a significantly better outcome than the placebo-MTX group using American College of Rheumatology (ACR) criteria. At 6 months, 71% of the patients in the etanercept-MTX group had an ACR 20% response (versus 27% in the placebo-MTX group). In the etanercept-MTX group, 39% had an ACR 50% response (versus 3% in the placebo-MTX group), and 15% in the etanercept-MTX group versus 0% in the placebo-MTX group met the robust ACR 70% response. The present study indicates that etanercept is a novel and robust drug in combination with MTX for the treatment of RA.
Infectious parotitis as a complication of the sicca syndrome has rarely been reported. A patient with bilateral parotitis due to H. influenza in reported and the literature regarding this rare complication of the sicca syndrome is reviewed. The host defense mechanisms which ordinarily protect normal individuals or patients with Sjögren's syndrome against purulent parotitis are discussed.
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We report a case of definite rheumatoid arthritis (RA) by ARA criteria with a high titer rheumatoid factor and coexisting gout as demonstrated by biopsy-proven monosodium urate crystals. Two other cases meeting ARA criteria for RA who probably had gout as their sole disease are described. Criteria for the definition of coexistent RA and gout are proposed.
Natural killer (NK) cell tumoricidal and antimicrobial activities can be rapidly modulated by molecules that interact with membrane receptors. The discovery of NK cell depolarization induced by steroid-like Na+ channel agonists prompted a study of purified human NK cell excitability to a variety of steroids. Progesterone, but not estrogen, depolarized NK cells with concentration and time dependency. Excitability was measured by using flow cytometry and the anionic voltage-sensitive dye oxonol. Preincubation with the Na+ channel antagonist tetrodotoxin or removal of the extracellular Na+ blocked the response. Progesterone may rapidly change membrane potential, and eventually function, by acting on putative NK plasma membrane receptors coupled to Na+ conductances.