[Clinical and immunopathologic study on 100 cases of rheumatoid arthritis].
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Biomedical subjects
Publications and source records attributed to W C Wang.
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Antibodies that bind to human platelet membrane glycoproteins IIb and IIIa were used to develop methods for analyzing platelet membrane components by flow cytometry. Platelets were tentatively identified by their low-intensity light scatter profiles in whole blood or platelet-rich plasma preparations. Identification of this cell population as platelets was verified by using platelet-specific antibodies and fluorescein-conjugated antiimmunoglobulin. Two-parameter analysis of light scatter versus fluorescence intensity identified greater than 98% of the cells in the "platelet" light scatter profile as platelets due to their acquired fluorescence. Both platelet-rich plasma and whole blood were used to study platelet membrane glycoproteins IIb and IIIa on a single cell basis in an unwashed system. Prostacycline was included in these preparations as a precautionary step to inhibit platelet aggregation during analysis. Flow cytometry is a successful technique for rapid detection of platelet membrane defects such as Glanzmann's thrombasthenia. Platelets from Glanzmann's thrombasthenic individuals were readily distinguished from platelets with normal levels of glycoprotein IIb and IIIa and from platelets with glycoprotein levels characteristic of heterozygote carriers of this disorder. This technique provides a sensitive tool for investigating platelet functional defects due to altered expression or deficiency of platelet surface proteins.
Chronic T-cell lymphocytosis with neutropenia has primarily been reported in adults. We have cared for a 14-year-old patient with this condition for over five years. This patient consistently had greater than 90% lymphocytes in his differential cell count. The majority of these cells had the OKT8 phenotype. Serologic studies demonstrated evidence for a chronic Epstein-Barr infection with elevated antibody titers to both early antigen and to the viral capsid antigen. Patients presenting with this condition should be carefully evaluated for possible viral infection.
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Serial bone marrow cell culture studies, with cytogenetic characterization, were performed in an 18-month-old boy with monosomy 7 syndrome--a condition that usually converts to nonlymphoblastic leukemia. Over a 12-month course, his marrow demonstrated: decreased colony formation and increased cluster formation in vitro with disease progression (consistent with preleukemia); persistence of only the monosomy 7 karyotype in direct marrow studies; and in contrast, proliferation of both 46,XY and monosomy 7 cells in in vitro marrow cultures. The findings indicate that certain dormant marrow cell populations may be expressed under in vitro culture conditions and suggest the need for determining factors which would allow their expression in vivo.
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The ultrastructure of neutrophils from two brothers with cyclic neutropenia was studied at various time intervals of the neutrophil cycle, which varied from 15 to 21 days. During the nonneutropenic portion (middle third) of the cycle, when the blood neutrophil counts approached normal, the majority of blood and marrow segmented neutrophils appeared morphologically normal, whereas marrow promyelocytes demonstrated increased autophagy with decreased condensation of primary granules. During the early neutropenic portion of the cycle (first third), increased autophagy and granule abnormalities persisted in promyelocytes, myelocytes, and the few segmented neutrophils present. During the late neutropenic portion (last third) of the cycle, which preceded neutrophil recovery, most promyelocytes appeared morphologically normal, whereas the few segmented neutrophils present frequently contained increased autophagic and/or heterophagic vacuoles and decreased cytoplasmic granules. Abundant neutrophil debris was present in marrow macrophages consistent with dysgranulopoiesis and intramedullary destruction of abnormal myeloid cells. Similar changes were not observed in monocytes, eosinophils, or basophils. These results demonstrate a cyclic insult which has its initial morphologic impact on the promyelocyte of patients with cyclic neutropenia.
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An eight-point diagnostic criteria for SLE was proposed and evaluated at the Veterans General Hospital (VGH), Taipei. It consists of 8 points and 12 items, 3 points being required for an accurate diagnosis. All of 94 cases of SLE whether they could or could not be diagnosed with the ARA criteria fulfilled 3 or more points of the VGH criteria. None of the 17 cases of rheumatoid arthritis fulfilled 3 or more points of the VGH criteria.
Forty-eight cases of systemic lupus erythematosus (SLE) were studied for lymphocyte subpopulations, and 42 cases were studied for lymphocyte response to mitogen stimulation. A decreased percentage of thymus-derived cells (T cells) and an increased percentage of bursa-equivalent derived cells (B cells), null cells (N cells), double labelled cells (D cells) were found in non-treated cases of SLE. There was no significant difference in these lymphocyte subpopulations in the treated cases in comparison with the normal control. There was an inverted linear relationship between T cells and N cells (p less than 0.001). No such relationship was found between B cells and N cells. The lymphocyte transformation in response to phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (Con A) was expressed in three ways: (1) the net count of transformed data, (2) the difference between the square roots of the isotope incorporation in the stimulated and the non-stimulated cultures (Dsq), and (3) the stimulation index (SI). There were significantly decreased lymphocyte transformation in response to PHA, PWM stimulation in both the non-treated and the treated cases of SLE when results were expressed as net count and Dsq. But decreased counts in response to Con A was only found in non-treated cases. In contrast, no significantly lowered response to all three mitogens was found when data were expressed as stimulation index. Simultaneous study of the percentages of T cells, B cells, N cells, and D cells might be helpful in assessing the clinical activity of SLE and monitoring the effect of therapy. In the study of lymphocyte response to mitogen stimulation, Con A response was a more sensitive indicator of disease activity. The stimulation index was not a good method to demonstrate the result of lymphocyte response to mitogen stimulation in cases of SLE.
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The Winn assay was used for the study of effector (tumor-inhibiting) and enhancing (tumor-promoting) lymphoid cells in BALB/c mice bearing MOPC-104E plasmacytomas. Kinetic studies with thymus, lymphnode, spleen and bone-marrow cells revealed that spleen, lymph node and to a lesser extent bone-marrow cells from 7- and 10-day tumor-bearers inhibited MOPC-104E growth, while at day 13 all three cell populations enhanced tumor growth. However, at day 16 strong tumor inhibition was observed again by spleen cells and to a lesser extent by lymph-node cells and thymocytes. Peritoneal cells from normal and tumor-bearing (7 and 10 days) animals enhanced tumor growth significantly. Separation of spleen cells on nylon wool columns showed that at 10 days the effector cells were T lymphocytes, but at a later stage (35 days) a different effector mechanism was present in the spleen. Treatment of MOPC-104E recipients with carrageenan or silica had little influence on tumor growth, but marked tumor inhibition occurred after lethal irradiation and bone-marrow reconstitution. This latter observation, together with the finding that bone-marrow, lymph node and peritoneal cells from normal donors enhanced tumor growth in several experiments, suggests that this plasmacytoma, like hormone-dependent tumors, requires lymphocyte-derived growth factors.
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