Cultured "hairy cells" infected with Epstein-Barr virus: evidence for B-lymphocyte origin.
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Biomedical subjects
Publications and source records attributed to P D Utsinger.
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The influence of patterns of usage on the structure and function of the hands was formally tested. Three groups of female textile workers, each employed in a distinct and defined, atraumatic, repetitive, stereotyped manual task for at least 20 years, were identified in a single rural mill. Replicate data were obtained for the following measures of structure and function: range of motion, a score for the degree of radiographic degenerative changes at each hand joint, malalignment at digital joints determined radiographically, and a quantitative measure of osteophyte formation. Significant and consistent differences in the right hand when compared to the left were detected. Furthermore, highly significant task-related differences were demonstrated. These task-related differences in the structure and function of the hands were consistent with the pattern of usage. Therefore these three patterns of usage influence hand structure and function in the population studied.
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The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
The terms erosive or inflammatory osteoarthritis refer to an inflammatory condition of the interphalangeal joints of the hand. In this report, observations of 15 patients with erosive osteoarthritis are described. The principal clinical features are symmetrical synovitis of the interphalangeal joints of the hand, the knees, and the first carpometacarpal, interphalangeal, and metacarpophalangeal joints. The principal roentgenographic features are productive and destructive osseous changes. These changes, found particularly at the interphalangeal joints of the hand, consist of both central and peripheral articular erosions and cysts associated with adjacent osteophyte formation. Serologic abnormalities commonly found in rheumatoid arthritis are rarely encountered. In two thirds of the patients, the synovial fluid is noninflammatory; in the remainder, it is mildly to severely inflammatory. The injection of intra-articular corticosteroids predictably results in decreased synovitis but does not seem to affect the subsequent development of erosions.
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The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements.
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Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.
THE PHYTOHEMAGGLUTININ (PHA) RESPONSE OF LYMPHOCYTES FROM UNTREATED PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) WAS STUDIED USING HIGHLY PURIFIED SUBPOPULATIONS OF CELLS INVOLVED IN THE TRANSFORMATION RESPONSE: T lymphocytes, B lymphocytes, and monocytes. Cell transformation was quantitated using both tritiated thymidine ([(3)H]-TdR) incorporation into DNA and cytofluorographic determination of cellular DNA content. Dose-response curves using six concentrations of PHA and five concentrations of cells over 0-5 days revealed a decrease in [(3)H]TdR by stimulated lymphocytes from some SLE patients. This decrease in [(3)H]TdR was paralleled by a decreased percentage of cells in S, G(2), and M phases of the cell cycle. However, abnormal response occurred entirely in those SLE patients who were hypocomplementemic. The etiology of the impaired response was further examined. Lymphocyte receptors for concanavalin A were studied using cytofluorography of lymphocytes stained with fluorescein-conjugated concanavalin A. The frequency distribution of concanavalin A receptors was similar in the normocomplementemic and hypocomplementemic lupus patients and in normals. The latex phagocytic activity of lupus macrophages was similar to normals when allogeneic normal plasma was used in the culture medium. Phagocytic activity became abnormal in the presence of SLE plasma. However, there was no difference in the [(3)H]TdR response or the percentage of cells in S, G(2), and M phases when T lymphocytes from the hypocomplementemic patients were stimulated on either autologous or normal allogeneic monocyte monolayers. Likewise, normal lymphocytes incorporated similar amounts of [(3)H]TdR and had similar percentages of cells in S, G(2), and M phases whether their T lymphocytes were stimulated on autologous or SLE monocyte monolayers. Highly purified subpopulations of B and T lymphocytes were obtained by density sedimentation or Fenwal Leuko-Pak passage of lymphocyte populations. The response to PHA by lymphocytes from the hypocomplementemic lupus patients could be seen to involve at least two abnormalities. One, in reference to normal lymphocytes, SLE T lymphocytes plus monocytes had an impaired response; two, SLE B lymphocytes plus SLE T lymphocytes plus SLE monocytes had an impaired response. Two patients in the hypocomplementemic group were treated with steroids. 5 days after steroid treatment was initiated, the percentage of cells in S, G(2), and M phases and the [(3)H]TdR response of PHA-stimulated lymphocytes returned to normal. The normalization of the [(3)H]TdR response was explained both by a return of purified T cells plus monocytes, purified B cells plus monocytes, and whole lymphocyte populations to normal responsiveness. These studies suggest that a steroid-correctable defect exists in T and B lymphocytes in SLE.
The diagnosis of hairy cell leukemia was made in three patients by phase-contrast microscopy and histochemistry of the abnormal peripheral blood cells. Both IgM and IgD surface immunoglobulins were resynthesized after these cells were trypsinized and cultured. Aggregate or Fc receptors were demonstrated on hairy cells. The ability to phagocytose latex was also a property of hairy cells; however, these cells did not demonstrate nonspecific esterase activity. Stimulation by phytohemagglutinin resulted in very low incorporation of tritiated thymidine. Cytofluorographic analysis of the phytohemagglutinin-stimulated cell population revealed less than 9% of the cells in an interploid or tetraploid state. The abnormal mitogen response was largely restored when purified T lymphocytes obtained from the peripheral blood of the patients were cultured with phytohemagglutinin. Hairy cells cultured with normal allogeneic mononuclear cells did not undergo blast transformation. These data strongly suggest that the cells of at least some patients with hairy cell leukemia are B lymphocytes with phagocytic capabilities.
The technique of flow cytofluorometry has been employed to assess the response of unfractionated and highly purified human lymphocyte subpopulations to phytohemagglutinin (PHA) and pokeweed mitogen. Normal values for cytofluorometric responses were established and compared to the uptake of tritiated thymidine in simultaneous experiments. Cytofluorometric analysis offered the advantages of increased sensitivity and direct measurement of DNA content per cell, and provided percentages and absolute numbers of responding cells. B-cell responses to pokeweed mitogen were absent, but brisk T-cell responses were noted. Between 4% and 8% of highly purified human B cells were found to respond to PHA by increasing their DNA content; modest but significant uptake of tritiated thymidine by B cells following PHA stimulation was also observed.
Of the many associations between histocompatibility antigens and human diseases a prominent one is that between HLA-B27 and inflammatory arthropathies. Hypotheses to explain this association include the B27 gene being linked to a specific immune-response gene required for disease expression and the B27 antigen acting via molecular mimicry with a microorganism or as a microorganism receptor. Alternatively, the HLA-B27 gene might be closely related to a gene which influences bone formation. The finding of a significant association between B27 and Forestier's disease, a disease characterised by abundant new bone formation, supports such a hypothesis.
A patient with allopurinol hypersensitivity, manifested by fever, lymphadenopathy and a severe erythematous, morbilliform, maculopapular rash was studied. On immunofluorescent staining of the patient's skin, heavy granular deposits of immunoglobulin M (IgM) were found at the dermal-epidermal junction. Transformation of the patient's lymphocytes could not be effected by a variety of combinations of allopurinol, allopurinol metabolites and serum. These data suggested that the hypersensitivity reaction caused by allopurinol had immune complex deposition as the central feature in pathogenesis. The predominance of IgM may provide a distinctive feature from the deposits generally seen in systemic and discoid lupus erythematosus.
Forty lymphoblast cell lines derived from normal subjects, patients with infectious mononucleosis, leukemia, and Burkitt's lymphoma have been studied for surface receptors including surface Ig, complement receptors by the EAC rosette and fluorescent (Raji cell) techniques, and Fc (aggregate) receptor by direct and indirect immunofluorescence. Because of the B-cell tropism of the Epstein-Barr virus (EBV), an effort was made to correlate the expresion of various surface properties of lymphoblastoid cell lines with the content of EBV viral DNA as determined by complementary RNA-DNA (cNRA-DNA) hybridization on membrane filters or by DNA-DNA renaturation kinetic analysis. The only correlation established was with the Fc receptor determined by direct immunofluorescence. No correlation of EBV genome equivalents per cell with complement receptor or surface Ig was noted, suggesting that the expression of these receptors is not influenced by EBV viral DNA content. Subgroups of lymphoblastoid cell lines were on the basis of variable expression of surface receptors, designated B1, B2, B3, B4, and T. The distribution of lymphoblastoid cell lines into these subgroups were in the ratio of 14:4:1:4:1. The B1, B2, and B4 cell lines (except Molt 4F) were found to contain EBV. The B3 subgroup, for wich cell line 698 was the sole example, expressed surface immunoglobulins but no other B-cell characteristics, and H.S.B., a T-cell line, lacked detectable EBV.
Peripheral blood lymphocyte subpopulations determined in 40 patients with systemic lupus erythematosus, revealed significant lymphopenia in comparison to normal controls. The lymphopenia was caused by decreases in the absolute numbers of both T cells and surface immunoglobulin bearing (SIg) cells. There were significant percentage decreases in T cells and normal percentages of SIg cells, resulting in an increased percentage of "null" cells. The lymphopenia was significantly greater in patients considered to have active disease on the basis of clinical parameters, and was strongly correlated with lymphocytotoxic antibodies, DNA antibodies, and hypocomplementemia. The lymphocytotoxic antibodies were reactive with both T and B lymphocytes from normal and ill donors, human organs, and various lymphoblastoid cell lines. In 30 patients who were followed for up to 22 months, the lymphopenia was clearly seen to develop during, but not before, periods of clinical disease activity, independent of changes in therapy.
Lymphocyte subpopulation studies in 21 patients with Sjögren's syndrome and rheumatoid arthritis revealed an absolute lymphopenia and a normal percentage of T- and SIg-cells. In one patient, a large percentage of lymphocytes bore both IgG and IgM; after cell trypsinization only IgM was resynthesized. This surface IgM was capable of binding human IgG, suggesting that the presence of multiple classes of immunoglobulins on the surface of these lymphocytes was due to surface rheumatoid factor activity. Profound lymphopenia was associated with high concentrations of cryoglobulins and the presence of lymphocytotoxic antibodies. These antibodies were broadly reactive, causing cytotoxicity of T- and SIg-cells from normal subjects, from viral and lymphoproliferative disease subjects, from different organs, and SIg-cells from human lymphoblastoid cell lines. Lymphocyte transformation after phytohemagglutinin and pokeweed mitogen stimulation was impaired in comparison to normal subjects. Warm washing of the lymphocytes and purification to greater than 80 per cent T-cells did not restore mitogen responsiveness to normal, suggesting that cell coating by an antibody and diminished responder cell number were inadequate explanations for the impaired transformation.