Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca.
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Adult↗
Biomedical subjects
R I Fox
Publications and source records attributed to R I Fox.
Elevation of von Willebrand factor is independent of erythrocyte sedimentation rate and persists after glucocorticoid treatment in giant cell arteritis.
Von Willebrand factor (vWF) antigen levels were measured in 39 patients with biopsy-proven giant cell arteritis (GCA), 16 patients with polymyalgia rheumatica (PMR), 12 patients with Sjögren's syndrome, and 7 with choroiditis, as well as in 20 age- and sex-matched controls. Among GCA patients, 31 (group A) had clinically inactive disease and were taking low-dose glucocorticoids for at least 1 year; their vWF levels were high even in the presence of a normalized erythrocyte sedimentation rate (ESR). When the ESR and vWF were analyzed in another 8 GCA patients (group B) before and after treatment with glucocorticoids, vWF remained elevated even though the ESR returned to normal. Among the highest levels of vWF were those of 3 GCA patients who presented with ocular symptoms and positive temporal artery biopsies, but normal ESR. The presence of elevated vWF was not specific for GCA since elevated levels were also found in patients with PMR, Sjögren's syndrome, and choroiditis. The levels of vWF in GCA were significantly higher (P less than 0.01) than in these other conditions associated with myalgias and eye symptoms. Elevation of vWF levels may help in the differential diagnosis of GCA, particularly when the ESR is normal and ocular symptoms are present.
Aged↗
Decreased T cell ecto-5'-nucleotidase activity in agammaglobulinemia patients is not due to altered proportions of helper and suppressor T cells as defined by the monoclonal antibodies OKT4 and OKT8.
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5'-Nucleotidase↗
Primary Sjogren syndrome: clinical and immunopathologic features.
Primary Sjogren syndrome is an autoimmune condition in which dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) result from lymphocytic infiltration of lacrimal and salivary glands. Clinical and laboratory features of 60 primary Sjogren syndrome patients seen at our clinic during the past three years are presented. These patients illustrate the wide spectrum of extraglandular features that may occur as a result of lymphoid infiltration of lung, kidney, skin, stomach, liver, and muscle. They further emphasize the difficulty in classifying a patient as primary or secondary Sjogren syndrome (ie, sicca symptoms associated with systemic lupus erythematosus, rheumatoid arthritis, or scleroderma), particularly early in the disease course. As an initial step in understanding the pathogenesis, the lymphocytes that infiltrate the salivary glands and lymph nodes were characterized by using monoclonal antibodies that recognize distinct lymphocyte subsets and by using in vitro functional assays. These studies have demonstrated that affected tissues have infiltrates of T cells with helper/inducer activity and with a high frequency of "activation antigens." The immunohistologic techniques are useful in differentiating "benign" and "pseudolymphoma" lesions (both due predominantly to T cells) from non-Hodgkin lymphoma (usually due to B-cell infiltrates). Although there is no "cure" for primary Sjogren syndrome patient's symptoms may be significantly improved by measures aimed at prevention of ocular and dental complications and by the recognition of extraglandular features that may be amenable to specific treatment.
Adolescent↗
Evaluation of hospital care in one trauma care system.
To evaluate the effectiveness of the trauma care system in the Hudson Valley Emergency Medical Services (EMS) Region, (with no designated regional trauma care center) 421 consecutive trauma autopsy reports for 1979-80 were analyzed. Of the 421 trauma patients, 194 died at the scene (DAS), most from vehicular accidents. The remaining 227 patients were triaged into the EMS system. Ninety-five were dead on arrival (DOA) at medical facilities; of 132 (31 per cent) who arrived alive at hospitals, 35 died in emergency rooms and 97 died later as inpatients. Nearly 60 per cent of the deaths involved brain injuries. A panel of five physician-evaluators examined the pathologist's analysis of those deaths considered to have been possibly preventable and concluded that 10 deaths (7.6 per cent) of in-hospital cases were preventable. The study showed the need for primary prevention of accidents to decrease the number of victims (46 per cent) who died at the scene and those (23 per cent) who were dead on arrival at hospitals.
Accidents, Traffic↗
Thoracic duct drainage in rheumatoid arthritis.
Thoracic duct drainage (TDD) led to major improvement of disease in two of five patients with severe rheumatoid arthritis and lesser improvement in two others. This improvement was maintained as long as 10 months, but reassertion of disease activity was seen despite use of azathioprine in standard immunosuppressive doses. A consistent fall in the mitogen-induced proliferative responses of blood lymphocytes occurred during TDD, along with a shift in the ratio of OKT4/T8 to a higher proportion of OKT8. However, there was minimal effect on B cell function and no demonstrable influence on complement activating events in the disease, and there was an inverse relationship between responsiveness to TDD and the degree to which in vivo complement activation was occurring. We suggest that it may be important to assess the candidacy of RA patients for given apheresis procedures by sensitive measures of the degree of activation of complement proteins.
Adult↗
Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors.
Two monoclonal antibodies (LN-1, LN-2) reactive with B lymphocytes in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by utilizing cell extracts from pokeweed mitogen-stimulated peripheral blood lymphocytes and diffuse histiocytic lymphoma SU-DHL-4 cells, respectively. Both monoclonal antibodies were initially identified by indirect immunofluorescence screening techniques on paraformaldehyde-acetone-fixed cell preparations. Specificity screens with 36 well-characterized human lymphoma and leukemia cell lines showed that both LN-1 and LN-2 stained cell lines of B cell lineage but were unreactive with those of T cell or, with one exception, myeloid derivation. Null cell acute lymphoblastic leukemia cell lines were found to be LN-2+ but LN-1-. The B cell specificity of these reagents was confirmed on 15 lymphoma and 17 leukemia biopsy specimens by using indirect immunofluorescence techniques. Immunoperoxidase staining of sections from B5-fixed, paraffin-embedded human lymphoid tissues showed that LN-1 bound to the cell membrane and cytoplasm of germinal center cells whereas LN-2 stained the nuclear membrane and cytoplasm of germinal center and mantle zone B lymphocytes as well as interfollicular histiocytes and thymic medullary dendritic cells. Both monoclonal antibodies failed to stain cortical thymocytes, lymph node T cells, and peripheral blood T and myeloid cells. Immunoperoxidase staining of 20 nonlymphoid human organs and tissues revealed that LN-1 reacted positively with red blood cell precursors of the bone marrow, ciliated epithelial cells of the bronchus, distal tubular cells of the kidney, and ductal cells from several organs including the breast and prostate. In contrast, LN-2 was unreactive with all human nonlymphoid organs and tissues including the bone marrow. Indirect immunofluorescence staining of a panel of 26 solid tumor cells lines showed that LN-1 was reactive with the majority of epithelium-derived cell lines, glioblastomas, and astrocytomas but was unreactive with neuroblastomas, small cell carcinoma of the lung, and sarcomas. LN-2 was unreactive with 25 of 26 of the solid tumor cell lines by these techniques. Immunobiochemical studies have shown that LN-1 recognizes a cell surface sialoantigen whereas LN-2 is directed against a 35,000 dalton nuclear membrane protein. Because of their high specificity for B cell tumors and their ability to stain B5-fixed, paraffin-embedded tissues, LN-1 and LN-2 are useful reagents for the diagnosis and classification of the human lymphomas and leukemias.
Antibodies, Monoclonal↗
Characterization of recirculating lymphocytes in rheumatoid arthritis patients: selective deficiency of natural killer cells in thoracic duct lymph.
Five patients with rheumatoid arthritis (RA), who were treated by lymphocyte depletion by using thoracic duct drainage (TDD), provided an opportunity to characterize the phenotype and function of their recirculating lymphocytes. We found that: a) thoracic duct lymphocytes (TDL) were similar in their proportion of T cells (83% +/- 6 OKT3+), OKT4+ subset (65% +/- 8), and OKT8+ subset (22% +/- 6) to peripheral blood lymphocytes (PBL): b) fewer natural killer-like cells were present in TDL (5% +/- 4 Leu-7+; 2% +/- 2 Leu-11+: 8% +/- 2 OKM -1+) than in PBL (20% +/- 10 Leu-7+: 11% +/- 6 Leu-11+; 18% +/- 5 OKM -1) (p less than 0.01); c) TDL differed from synovial fluid lymphocytes ( SFL ) and synovial membrane lymphocytes ( SML ) in that TDL lacked a high percentage of activated lymphocytes (T cells bearing Ia antigen, OKT10 , and transferrin receptor): d) immature T cells (expressing either OKT6 antigen or reactive with peanut agglutinin) were not found in TDL even late in the course of TDD: and e) in vitro functional studies demonstrated that TDL were similar to PBL in their ability to synthesize immunoglobulin after mitogen stimulation and to generate cytotoxic T lymphocytes capable of lysing autologous EBV-transformed B cells. However, natural killer activity, as measured by lysis of K562 cells was significantly lower in TDL than PBL (p less than 0.05). These results demonstrate that natural killer cells defined by phenotype and function are excluded from thoracic duct lymph and thus have a circulation pattern different from most T cells.
Adult↗
Ecto-5'-nucleotidase activity in human T cell subsets. Decreased numbers of ecto-5'-nucleotidase positive cells from both OKT4+ and OKT8+ cells in patients with hypogammaglobulinemia.
T lymphocytes from control subjects were separated into subsets using monoclonal antibodies of the OKT series and complement lysis and analyzed for ecto-5'-nucleotidase activity both by quantitative radiochemical assay and a histochemical stain. T cells from 15 control subjects contained 54+/-4% OKT4(+) (helper/inducer) cells and 32+/-3% OKT8(+) (cytotoxic/suppressor) cells. Total T cell ecto-5'-nucleotidase activity was 10.9+/-2.1 nmol/h per 10(6) cells with 25+/-7% positive by histochemical stain. Ecto-5'-nucleotidase activity in OKT4-enriched populations was 5.43+/-1.8 nmol/h per 10(6) cells with 14+/-2% positive by histochemical stain; that in OKT8-enriched populations was 17.1+/-5.9 nmol/h per 10(6) cells with 35+/-8% positive by histochemical stain. Two of four patients with congenital agammaglobulinemia and four of seven patients with common variable immunodeficiency had decreased proportions of OKT4(+) T cells with corresponding increases in the proportions of OKT8(+) T cells (OKT4/OKT8 = 0.60 to 1.0 as compared with 1.7+/-0.2 for control subjects). All four patients with congenital agammaglobulinemia, and three of seven patients with common variable immunodeficiency also had low T cell ecto-5'-nucleotidase activity (<5.5 nmol/h per 10(6) cells). Ecto-5'-nucleotidase activity in OKT4- enriched populations isolated from four patients with low total T cell activity was 2.85+/-0.90 nmol/h per 10(6) cells with 10+/-4% positive by histochemical stain; that in OKT8-enriched populations was 6.82+/-1.7 nmol/h per 10(6) cells with 7.5+/-3% positive by histochemical stain. Thus, the number of ecto-5'-nucleotidase positive cells is decreased, especially in the OKT8(+) subpopulation, and the low total T cell ecto-5'-nucleotidase activity seen in these patients is due to fewer positive cells rather than to substantially less activity per cell. Our data indicate that ecto-5'-nucleotidase activity defines two subpopulations of T lymphocytes (ecto-5'-nucleotidase positive and negative), the proportions of which are markedly altered in many patients with hypogammaglobulinemia. In preliminary studies with seven patients, increased numbers of ecto-5'-nucleotidase negative T cells appeared to correlate with increased suppressor T cell activity toward in vitro immunoglobulin synthesis. Therefore, ecto-5'-nucleotidase may be a useful cell surface marker in the study of imbalances of regulatory T cell subsets in patients with antibody synthesis disorders.
Adenosine Deaminase↗
Lymphocyte phenotype and function in pseudolymphoma associated with Sjögren's syndrome.
Lymph node (LNL) and salivary gland lymphocytes (SGL) from three patients with pseudolymphoma and primary Sjögren's syndrome (1(0)SS) were characterized with monoclonal antibodies to demonstrate (a) a predominance of T cells (greater than 80%) reactive with anti-T cell antibodies OKT4 (greater than 70%) and OKT8 (less than 20%); (b) a high prevalence of activation antigens (greater than 50% of cells reactive with antibody OKT10 and anti-Ia antibody); (c) polyclonal B cells (8-15% of all cells expressing kappa or lambda); and (d) a specific B cell subset defined by reactivity with antibody B532 that was not present in their peripheral blood. In vitro functional studies showed that both SGL and LNL provided T helper activity for immunoglobulin synthesis and that this activity could be abolished by treatment with antibody OKT4 plus complement. The SGL and LNL exhibited little natural killer, antibody-dependent cellular cytotoxicity, or cytotoxic T cell activity. Normal karyotype was observed in SGL, LNL, and peripheral blood lymphocytes (PBL) from these patients. These findings indicate that pseudolymphoma in 1(0)SS results from the infiltration of salivary glands and extraglandular tissues by nonneoplastic T helper cells. Monoclonal antibodies provide an important tool to distinguish pseudolymphoma from non-Hodgkins (B cell) lymphomas that have a markedly elevated incidence in 1(0)SS patients. Our finding of T helper cells in pseudolymphoma tissues supports the hypothesis that chronic stimulation of B cells by helper T cells leads to eventual escape of a malignant B cell clone.
Aged↗
Characterization of the phenotype and function of lymphocytes infiltrating the salivary gland in patients with primary Sjogren syndrome.
Monoclonal antibodies directed against T-cell subsets, B-cell subsets, and monocytes were used to characterize the cells infiltrating the salivary glands of patients with primary Sjogren syndrome (1 degree SS). Analysis of stained frozen tissue sections and lymphocyte suspensions derived from salivary glands revealed the majority of infiltrating cells to be T cells (reactive with antibodies SC1 and Leu 4) of the Leu 3a+ subset (greater than 70% reactive). Of particular interest, a high frequency of Ia+ T cells (up to 50% of T cells) and B cells reactive with antibody B532 (5-15% of infiltrating cells) were found in salivary gland lymphocytes (SGL) but not in peripheral blood lymphocytes (PBL) of the same patients. Our finding that the phenotype of SGL was significantly different from PBL emphasizes the need to characterize lymphocytes at the site of tissue destruction. In vitro functional assays demonstrated that the OKT4+ SGL exhibited T-helper activity but not natural killer, antibody-dependent cellular cytotoxicity, or cytotoxic T-lymphocyte activity. Of note, rheumatoid factor (IgM anti-IgG) was produced by SGL but not by the corresponding PBL. Our studies on SG-lymphocyte function represent an early step in elucidating the cellular and subcellular events responsible for this autoimmune disease.
Antibodies, Monoclonal↗
Immunohistologic analysis of lymphoid infiltrates in primary Sjogren's syndrome using monoclonal antibodies.
The characterization of lymphocytes infiltrating salivary glands in patients with primary Sjogren's syndrome (1 degree SS) yields insights to disease pathogenesis that are not revealed by studies of the corresponding peripheral blood lymphocytes (PBL) alone. We analyzed salivary gland lymphocytes (SGL) and PBL in 14 patients with untreated 1 degree SS using monoclonal antibodies that detect T cells, T cell subsets, B cells, and antigens associated with lymphocyte activation. A four-step biotin-avidin immunoperoxidase technique was used for salivary gland frozen sections; cell suspensions and PBL were stained cytofluorographically. A predominance of T cells (Leu 1 = L17F12; Leu 4 = OKT3) was found in SGL (greater than 75%) and PBL (76 +/- 9%) with the majority belonging to the Leu 3a (OKT4) subset. A minority of B cells (anti-delta, -kappa, -lambda) was present in both SGL and PBL; however, a subset of B cells defined by monoclonal antibody B532 was present in SGL (5 to 20%) but was absent from PBL. An increased prevalence of activation antigens (Ia; OKT10) was found on SGL T cells (greater than 50% positive) compared to PBL T cells (less than 15% positive). These studies demonstrate that specific antigenic markers on lymphocytes at the site of inflammation in 1 degree SS differ significantly from those of the corresponding PBL. These differences emphasize that theories of disease pathogenesis of 1 degree SS must include studies on SGL.
Adolescent↗
The instructor cell for the human procoagulant monocyte response to bacterial lipopolysaccharide is a Leu-3a+ T cell by fluorescence-activated cell sorting.
A variety of responses of cells of the lymphoid system are associated with acquisition of the capacity to initiate the coagulation protease pathways. The initiating or procoagulant molecules are produced by the monocyte; however, a number of studies have indicated that lymphocyte collaboration is required. The induction of human monocyte procoagulant activity (PCA) by the model stimulus bacterial lipopolysaccharide (LPS) was examined in the present study by using relatively highly purified monocyte and lymphocyte populations in reconstitution experiments. Consistent with prior studies, the PCA response could not be generated by highly purified monocytes alone after exposure to LPS. The ability to generate PCA was restored to these monocyte populations by the addition of fibronectin-gelatin nonadherent lymphocytes, nylon wool effluent T cells, or Leu-3a+ inducer/helper T cells selected by fluorescence-activated cell sorting. T cells added to monocytes at a ratio of 8:1 or higher, and Leu-3a+ cells added at a ratio of 6:1 or higher, provided a maximal collaboration for monocyte PCA induction by LPS. These results substantiate further previous suggestions of an absolute requirement for collaborating T cells and demonstrate that these instructor cells carry a marker for the inducer/helper subset.
Blood Coagulation↗
A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states.
Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.
Animals↗
Molecular interactions in human T-cell-mediated cytotoxicity to Epstein-Barr virus. I. Blocking of effector cell function by monoclonal antibody OKT3.
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Antibodies, Monoclonal↗
Use of monoclonal antibodies to analyze peripheral blood and salivary gland lymphocyte subsets in Sjögren's syndrome.
Using monoclonal antibodies to cell surface antigens, we studied lymphocyte subsets in 15 patients with primary Sjögren's syndrome. The absolute number of OKT8-positive cells (reactive with T suppressor/cytotoxic cells) was significantly decreased in such patients (353 +/- 186/mm3) compared to age-matched controls (631 +/- 150/mm3) (P less than 0.001). The number of OKT4-positive cells (reactive with T helper/inducer cells) was comparable in both groups (932 +/- 588/mm3 versus 1.073 +/- 290/mm3). The ratio of OKT4/OKT8-reactive peripheral blood lymphocytes was increased (greater than 2.4) in 67% of these patients and ranged from 1.0 to 6.4 (normal = 1.8 +/- 0.3). OKT4-positive cells were the predominant subset in lip biopsy specimens stained with immunofluorescence or immunoperoxidase techniques; the OKT4/OKT8 ratio exceeded 3.0 in all 5 patients examined. In 1 patient with pseudolymphoma, a lymph node biopsy specimen contained 80% T cells with an OKT4/OKT8 ratio of 3.2. Thus, OKT4-positive cells predominated in the peripheral blood lymphocytes as well as in sites of inflammation in primary Sjögren's syndrome. The decreased number of OKT8-positive cells in primary Sjögren's syndrome was probably not caused by circulating autoantibody, since patients' sera did not react with normal OKT8-positive cells. Functional studies using pokeweed mitogen demonstrated that T helper cell activity for immunoglobulin synthesis was contained in the OKT4-positive subset in both normal and patients' peripheral blood lymphocytes. Removal of OKT8-positive cells by complement-mediated lysis did not lead to increased immunoglobulin synthesis or production of rheumatoid factor. The identification of peripheral blood lymphocyte subsets by use of monoclonal antibodies and the relationship of these subsets to tissue infiltrates and autoantibody production provide further insight into the pathogenesis of primary Sjögren's syndrome.
Adolescent↗
Lysis of autologous Epstein-Barr virus-infected B cells by cytotoxic T lymphocytes of rheumatoid arthritis patients.
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Antibodies, Monoclonal↗
Structural characterization of the human T cell surface antigen (p67) isolated from normal and neoplastic lymphocytes.
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Animals↗