Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6808026 | Analysis of speckled fluorescent antinuclear antibody test antisera using electrofocused n | 1982 Aug | Antibodies to different components of the extractable nuclear antigen (ENA) have been thought to be serological markers for clinical subsets of rheumatic diseases. However, incomplete characterization and standardization of antigenic components such as ribonucleoprotein (RNP), Sm, and SS-B (Ha), and the multiplicity of autoantibodies produced by different patients have confounded correlations between autoantibody specificity and disease subsets. This study describes the preparative separation of the antigens Sm, RNP, and Ss-B (Ha) by electrofocusing and their use in a rocket electrophoretic assay that in one step identifies and quantifies the multiple reactivities of patient sera exhibiting the speckled FANA pattern. Preparative electrofocusing generates milligram quantities of these antigens with retention of their immunologic and biochemical characteristics, facilitating further study of their biological properties and relationships to disease subsets. | |
| 7190612 | Inhibition of human bone marrow-granulocyte precursors by serum from patients with Felty's | 1980 May | Eight of 19 patients with Felty's syndrome were shown to have a serum factor capable of inhibiting in vitro colony formation by human bone marrow-granulocyte precursors. These data raise the possibility that a serum factor may play a role in the induction of leukopenia in Felty's syndrome. | |
| 6653928 | Lactoferrin concentration in the parotid saliva of patients with chronic pancreatitis. | 1983 | Lactoferrin is present in pancreatic juice, and greatly increased concentrations are found in the pancreatic juice of patients with chronic pancreatitis. It is not known whether these high levels of lactoferrin represent a genetically determined defect predisposing to the later development of chronic pancreatitis or are simply a consequence of the disease. In view of the morphological and functional similarities between the pancreatic and parotid glands, we have measured the immunoreactive lactoferrin concentration in pure parotid saliva of 30 patients with chronic calcific pancreatitis, 26 controls, 5 patients with proven pancreatic cancer, 2 patients with Sjögren's disease and 2 patients with chronic recurrent parotitis. No difference in the lactoferrin concentration was detected between control subjects and patients with chronic pancreatitis or pancreatic cancer. Raised levels were found in the 4 patients with parotid gland disease. These findings suggest that increased lactoferrin secretion is confined to the exocrine pancreas in patients with chronic pancreatitis and is thus probably a phenomenon secondary to the disease. | |
| 787431 | Clinical presentations and mechanisms of necrotizing angitis of the skin. | 1976 Sep | Cutaneous necrotizing angiitis may be present as either palpable purpura or less commonly as recurrent urticaria, and each clinical presentation may be associated with hypocomplementemia or a normal complement system. A variety of mechanisms may be operative in the production of necrotic vascular skin lesions that appear as similar, recognizable morphologic lesions. These mechanisms include immune complexes, cellular-type hypersensitivity reactions, and initiation or modulation by mast cells. Two cellular patterns have been recognized in the skin of patients with cutaneous necrotizing angiitis that can be correlated with the involvement of the complement system in serum. In patients with hypocomplementemia, there is an infiltrate of neutrophils that is consistent with a process involving immune complexes; in patients with normocomplementemia there are lymphocytes and activated lymphocytes consistent with participation in part by cellular mechanisms. In both the hypocomplementemic and normocomplementemic forms and as well as in a unique patient in whom the mast cell may initiate the venular damage, the mast cell, which its content of chemical mediators, has the capacity to initiate as well as modulate subacute and chronic vascular damage. | |
| 3874723 | Electrophoresis of serum protein to detect alpha 1-antitrypsin deficiency: five illustrati | 1985 Aug | We describe five cases of severe alpha 1-antitrypsin (AAT) deficiency to illustrate the importance of visual inspection of electrophoretic patterns of serum proteins. In four patients the diagnosis of AAT deficiency was clinically unsuspected; in the other patient, the electrophoretic pattern was the first clue to confirm the diagnosis. Densitometric scanning of these patterns invariably overestimated the concentration of alpha 1-globulin. By visually inspecting electrophoretic strips instead of relying on densitometry, clinical chemists can help detect AAT deficiency earlier. | |
| 6215195 | An increase in peripheral blood Ia-positive T cells in Sjögren's syndrome correlates with | 1982 Jul | The defective autologous MLR was studied in Sjögren's syndrome (SS) in relation to Ia+ cells as determined by reactivity with a monoclonal anti-human Ia antibody. By indirect immunofluorescence, the percentage of Ia+ T lymphocytes was increased in nine of 15 patients. There was no correlation with clinical features or drugs. The percentage of Ia+ T cells in the non-T cell preparations was normal. An inverse correlation was found between the percentage of Ia+ T cells and the proliferative response to autologous non-T cells. Removal of Ia+ T cells enhanced both the autologous MLR and the allogeneic MLR. Thus Ia+ T cells contain suppressor cells in the MLR, but this may not be the sole explanation for the defective autologous MLR. | |
| 6368058 | Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis. | 1984 Mar | The presence of autoantibodies in the serum of 110 patients with primary biliary cirrhosis (PBC), 50 with HBsAg negative chronic active hepatitis (HBsAg- CAH) and 30 with HBsAg positive chronic active hepatitis (HBsAg+ CAH) was assessed using two methods: indirect immunofluorescence on cells grown in tissue culture (HEp-2 cell line) or standard mouse tissue sections, and counter immunoelectrophoresis (CIE) with soluble tissue extracts. Anti-nuclear antibodies (ANA) were found in 38% of sera from patients with PBC using HEp-2 cells compared with 10% using mouse tissue. A variety of staining patterns were detected including a pattern of multiple nuclear dots. In contrast, ANA was detected in 70% of sera from patients with HBsAg- CAH and 27% with HBsAg+ CAH. Using CIE four distinct antibody antigen systems were detected: Ro (SS-A), La (SS-B) and two new systems, designated XH and XR, reacting with extracts of human spleen and rabbit thymus, respectively. Correlation of the presence of antibody with clinical conditions confirmed the close association between anti-centromere antibody and sclerodactyly in patients with PBC and indicated an association between 'multiple nuclear dot' staining and the sicca syndrome in PBC. No association was found between the presence of either Ro or La antibody and the sicca syndrome in patients with PBC. | |
| 6398163 | Presence of intracytoplasmic IgG in the lymphocytic infiltrates of the minor salivary glan | 1983 Jul | The nature of the minor salivary gland B cell infiltrates in 13 patients with primary Sjögren's syndrome was studied utilizing an immunoperoxidase staining technique. A group of 6 patients without primary Sjögren's syndrome undergoing lip biopsy for evaluation of dry mouth served as controls. The patients with primary Sjögren's syndrome, in contrast to the control group, were found to have a large percentage of cells containing intracytoplasmic IgG. This finding points to the minor salivary gland as a site of localization of the activated B cell in patients with primary Sjögren's syndrome. | |
| 6620714 | Studies of human tear proteins--2. Analysis by crossed immunoelectrophoresis of tears from | 1983 | By filter paper strips, tears were collected from patients with diseases in the anterior ocular segment and analysed by crossed immunoelectrophoresis. Their crossed immunoelectrophoretic patterns were compared with those of normal subjects. Tear proteins from Sjögren's syndrome. Mikulicz's disease and tumor of the lacrimal gland showed abnormal patterns by crossed immunoelectrophoresis. Tears were collected from patients with lacrimal gland tumor after resection of the tumors. Ten tear-specific proteins were more decreased in these patients than in normal subjects. Serum proteins in the tears of these patients were increased, but secretory IgA (s-IgA) showed no change. A patient with symblepharon showed a marked decrease of both tear-specific proteins and s-IgA. Tears from patients wit epidemic keratoconjunctivitis (EKC), vernal conjunctivitis, herpes simplex keratitis (HSK) and adult inclusion conjunctivitis were analyzed. No remarkable change in tear-specific proteins could be noticed between tears from a case with an early stage of EKC or slight inflammation of the conjunctivitis and tears from the fellow unaffected eye. However, an increase was noted in serum proteins of the diseased eye. The tears collected from a case with severe EKC showed a decrease of tear-specific proteins, but an increase of serum proteins; especially s-IgA showed a significant increase. Tears from patients with EKC, HSK, vernal conjunctivitis and adult inclusion conjunctivitis showed differences in the immunoelectrophoretic patterns of tear proteins according to the severity and duration of the inflammation, as well as the amount of tears secreted. After due consideration of the analysis of tear proteins from some diseases of the anterior ocular segment, the following secretory sites of tear proteins under normal conditions were projected. The 10 tear-specific proteins reported in the previous paper are thought to be largely secreted from the main lacrimal gland. s-IgA is mainly secreted through the excretory ducts of the main lacrimal gland. Serum proteins in the tears are thought to come through the conjunctiva. | |
| 4604204 | Changes in the oral flora in Sjögren's syndrome. | 1974 May | The oral flora of 10 patients with Sjögren's syndrome was compared with that of 10 healthy control subjects. Significantly greater numbers of Candida albicans, Staphylococcus aureus, and coliform bacilli were present in the Sjögren's group. Possible reasons for these changes are discussed. | |
| 7310170 | IgA-associated inhibition of polymorphonuclear leukocyte chemotaxis in neutrophilic dermat | 1981 Dec | The chemotactic activity of normal human polymorphonuclear leukocytes (PMNs) confronted with heat inactivated sera from patients with psoriasis as well as various chronic proliferative diseases was determined using modified Boyden chambers. By the addition of phorbol myristate acetate (PMA) at a concentration of 1 ng/ml the chemoattractant activities of the sera were greatly potentiated. However, the chemotactic migration of normal PMNs was strongly inhibited by sera from patients with long standing and wide spread psoriasis, pyoderma gangrenosum, severe acne conglobata, Sweet syndrome, and some patients with chronic arthritis following rheumatoid fever. In acute guttate psoriasis and atopic dermatitis increased migratory activities were seen. The inhibition of chemotaxis correlated with increased serum IgA levels as determined by radial immuno diffusion. Column chromatography (Sephacryl S-300) revealed serum fractions of strong inhibitory potency at a molecular weight near 200,000 Dalton. These inhibitory fractions were seen in patients with long standing neutrophil related diseases and could not be detected in normal control sera. It appears that inhibition of PMN chemotaxis is a secondary phenomenon and may play an autoregulatory role in PMN related inflammation. | |
| 6838674 | Connective tissue activation. XXV. Regulation of proteoglycan synthesis in human synovial | 1983 Apr | In this study, virtually all sulfated glycosaminoglycan (GAG) synthesized and secreted by human synovial cells, both normal and rheumatoid, was detected in the form of proteoglycans of monomeric size. Enzyme hydrolysis studies that were performed demonstrated dermatan sulfate to be the dominant GAG in the proteoglycan, with lesser amounts of chondroitin 4/6 sulfate. Exposure to beta-xyloside, used as a false "core protein," resulted in marked enhancement of GAG chain formation, suggesting that the synthesis of the sulfated carbohydrate chain itself was not rate limiting. Proteoglycan synthesis and secretion were stimulated by several types of connective tissue activating peptides (CTAP); CTAP-III stimulation of incremental core protein and glycosaminoglycan was shown to be of a similar magnitude. Since chain synthesis was not rate limiting, it is suggested that stimulated proteoglycan formation caused by the CTAP peptides may be primarily modulated through increased formation of core protein. | |
| 7237912 | A prospective survey of radiological bone and joint changes in primary biliary cirrhosis. | 1981 May | A prospective survey of radiological bone and joint changes was undertaken in 42 patients with primary biliary cirrhosis (PBC) and 23 patients with alcoholic or cyptogenic cirrhosis who formed a control population. PBC patients were commonly found to have hypertrophic osteoarthropathy (38%), joint erosions (31%) and osteoporosis, these results being significantly different from the control group. Hypertrophic osteoarthropathy most frequently affected the first metacarpal and was rarely associated with finger clubbing or clinical symptoms. Joint erosions were most evident in the hands, often associated with a positive rheumatoid factor but only accompanied by symptomatic arthritis in four cases. Patients with PBC show a high prevalence of symptomless bone and joint changes which may become manifest clinically only as the disease progresses; radiography of the hands is recommended as a screening test for these changes. | |
| 2410122 | Analysis of "early" thymidine/inosine protection as an adjunct to methotrexate therapy. | 1985 Jul | The feasibility of "early" thymidine and inosine protection of methotrexate (MTX) toxicity is evaluated in this paper. This approach is based on the proposition that the most vulnerable period for susceptible host cells to MTX toxicity is an interval following a pulse of MTX when the MTX monoglutamate level is high. In contrast, tumor cells that accumulate active MTX polyglutamyl derivatives are exposed to the cytotoxic effects of MTX, not only when the monoglutamate levels are high, but also over the much longer interval during which polyglutamyl derivatives are retained within these cells. The protecting agents employed, thymidine and inosine, circumvent the antipurine and antipyrimidine effects of MTX, but neither agent inhibits the transport or the polyglutamylation of MTX. Nucleoside protection given over 6 hours after MTX markedly decreased toxicity to normal BDF1 mice at MTX doses up to 150 mg/kg/day for 3 consecutive days. The LD10 for unprotected mice was 14 mg/kg/day, while the LD10 for the protected mice was 114 mg/kg/day, a greater than eightfold increase in the drug dose delivered. MTX with early nucleoside protection produced a 50% increase in median life span in tumor-bearing mice at doses of drug that were toxic to unprotected mice. Flow cytometric analyses indicated that consecutive daily pulses of MTX with early nucleoside protection alter the cell cycle distribution. By 24 hours after the last of three daily pulses of MTX, the G1 component was maximal (80% of the cell population), with less than 2% of the cells in G2M and 17% of the cells in S phase. This distribution persisted for 24 hours, after which a normal pattern emerged, a process that was accelerated by neither thymidine/inosine nor leucovorin. These studies support the concept that toxicity to the host is initiated largely in the interval shortly after MTX administration. The data indicate that early nucleoside protection permits the repetitive administration of much higher doses of MTX than can be given with MTX alone. This approach may be useful not only in the treatment of human neoplasms but in the treatment of other disorders, such as rheumatoid arthritis, psoriatic arthritis, or psoriasis. Finally, this paper considers the potential advantages of early thymidine/inosine protection in comparison to leucovorin rescue with the administration of low or moderate doses of MTX. | |
| 2578825 | A solid-phase immunosorbent assay to determine the proteinase binding capacity of alpha 2- | 1985 Mar 8 | Hyperimmune sera against human alpha 2 macroglobulin were raised in rabbits following immunization with 's' alpha 2-macroglobulin over half a year. Immunoglobulins were prepared by DEAE-Sephacel anion exchange chromatography. The immunoglobulin preparations showed a remarkably high and equal titer for 's' and 'f' alpha 2-macroglobulin (plasma alpha 2-macroglobulin fully saturated with pig pancreas trypsin), which amounted to 6.4 X 10(-6) as revealed by passive hemagglutination. Immunoimmobilization experiments revealed that at equilibrium, 's' alpha 2-macroglobulin and both 'f' alpha 2-macroglobulins (27 and 82% saturation of 's' alpha 2-macroglobulin with trypsin) had been bound to the same degree from the fluid phase to the monospecific antibodies that had been adsorbed to polystyrene tubes. Comparison of quantitative gel scans for disappearance of the intact alpha 2-macroglobulin subunit (Mr 182000) with 125I-labeled trypsin binding capacity of immunoimmobilized alpha 2-macroglobulin-trypsin complexes showed conspicuous agreement. Rocket immunoelectrophoresis did not give significant differences between 's' alpha 2-macroglobulin and 'f' alpha 2-macroglobulin. In the fluid phase, a binding ratio of 2.4 mol trypsin/mol alpha 2-macroglobulin was observed. Saturation of solid phase immunoimmobilized 's' alpha 2-macroglobulin with trypsin could be accomplished by incubation with a 100-200-fold molar excess of enzyme for 10 min. The solid-phase experiments showed a binding ratio of 2.0 mol trypsin/mol alpha 2-macroglobulin. The high molar excess of trypsin needed to saturate solid-phase immunoimmobilized alpha 2-macroglobulin, which binds 20% less trypsin than in the liquid phase, is partially explained by an enhancement of the negative cooperativity of trypsin binding to alpha 2-macroglobulin found in the liquid-phase system. Assessment of the trypsin-binding capacity of alpha 2-macroglobulin immunoadsorbed from synovial fluids (n = 19) of patients with seropositive rheumatoid arthritis yielded an inactive alpha 2-macroglobulin of 0-53% when compared to the trypsin-binding capacity of normal plasma alpha 2-macroglobulin. | |
| 7048180 | Immunosuppressive therapy for progressive ocular cicatricial pemphigoid. | 1982 Apr | In a controlled, nonrandomized, longitudinal cohort study, we studied the efficacy of systemic immunosuppression in treatment of progressive cicatricial pemphigoid affecting the eyes. Twenty-six patients were studied; 18 received systemic immunosuppressive drugs, and eight received conventional therapy. Three patients who received cytotoxic agents withdrew from the study with intolerable gastrointestinal distress. Fourteen of the 15 patients who were immunosuppressed successfully for prolonged periods experienced a cessation of their episodic ocular inflammation and a halting of their progressive conjunctival cicatrization. They maintained vision at least as good as that present when disease activity was brought under control; in two patients vision improved. The one patient who was adequately immunosuppressed and successfully maintained in such a state for two years but who had progressive ocular surface pathology with eventual blindness had concomitant rheumatoid arthritis and severe sicca syndrome. The three patients who withdrew from immunosuppressive therapy and the eight concomitant controls all showed continued episodic conjunctival inflammation and conjunctival cicatrization with development of severe keratopathy and profound visual loss. Complications in this series included alopecia (100%), anemia (78%), gastrointestinal distress (22%), hemorrhagic cystitis (11.1%), and severe leukopenia (5.5%). These results support the notion that abnormal immunoregulatory mechanisms are involved in the progressive disease activity in cicatricial pemphigoid and that systemic immunosuppression may have an appropriate role in the treatment of this disease. | |
| 12338027 | OCs: international experts discuss state-of-the-art. | 1981 Nov | ||
| 7336255 | [Modern methods of regulating generative function]. | 1981 | ||
| 6965944 | Inhibition of human helper T cell function in vitro by D-penicillamine and CuSO4. | 1980 May | The effect of d-penicillamine (Pen) and mixtures of Pen and copper sulfate on the capacity of normal human peripheral blood mononuclear cells (PBM) to generate immunoglobulin-secreting cells (ISC) in response to the T-cell-dependent polyclonal B-cell activators pokeweed mitogen (PWM) and staphylococcal protein A (SPA) was examined. PBM obtained from normal individuals were incubated for 1-2 h at 37 degrees C with medium alone, Pen, CuSO(4), or a mixture of Pen and CuSO(4). After washing, the cells were incubated for 6-7 d with PWM or SPA and then, with a reverse hemolytic plaque assay, assayed for the number of ISC generated. Preincubation of PBM with either Pen (100 mug/ml) or CuSO(4) (2 mug/ml) did not alter the subsequent capacity of the cells to generate ISC in response to PWM or SPA. In contrast, responsiveness to both mitogens was nearly abolished when PBM were similarly preincubated with a mixture of Pen and CuSO(4). Inhibition of responsiveness could not be ascribed to cell death, carry-over of the inhibitors, or an alteration in the concentration of PWM or the length of incubation yielding maximum responses. Co-culture experiments demonstrated that Pen and CuSO(4) preincubation had not caused augmented suppressor cell function. Experiments in which PBM were separated into adherent and nonadherent populations indicated that Pen and CuSO(4) preincubation inhibited the responsiveness of the nonadherent cells but did not alter the accessory cell function of monocytes. To determine whether Pen and CuSO(4) preincubation effected T- or B-cell function, PBM were separated into B- and T-cell-enriched populations, individually preincubated with Pen and CuSO(4), and then co-cultured with PWM. The results indicated that Pen and CuSO(4) markedly inhibited helper T-cell function and had little effect on the capacity of B cells to generate ISC. The observation that in the presence of CuSO(4) Pen inhibits helper T-cell activity may, in part, explain the therapeutic efficacy of Pen in rheumatoid arthritis and especially the capacity of Pen therapy to decrease antiglobulin titers in treated patients. | |
| 300179 | Peripheral lymphocyte count and suppopulations of T and B lymphocytes in benign and malign | 1977 Mar | It is well known that there are many independent and inter-related clinical and pathologic factors which influence the prognosis of patients with benign and malignant conditions. Lymphocyte level is an index of cell-mediated immunity which is important in host defense against cancer. But it is surprising that a simple test such as peripheral lymphocyte count could be correlated with clinical stages and survival results in patients with Hodgkin's disease, non-Hodgkin's lymphoma and non-lymphomatous solid tumors. Regarding the latter, lymphocyte count had prognostic values in patients with cancer of the bone, Ewing's sarcoma; breast; colon; kidney, neuroblastoma; uterine cervix, and other sites. In general, higher lymphocyte counts before therapy correlated with longer survival. Using newer immunologic techniques, T and B lymphocytes can be identified and the different subtypes of leukemia, immunodeficiency and lymphoproliferative diseases have been studied intensively. Chronic lymphocytic leukemia represents a proliferation of B cells, while the Sezary syndrome represents that of T lymphocytes. There is a qualitative and quantitative disturbance of Blymphocytes in patients with multiple myeloma. In Hodgkin's disease, there is hyperactivity of the B cells and functional defect of the T cells. Finally, the nodular non-Hodgkin's lymphoma resulted from neoplastic transformation of the B lymphocytes. In several nonmalignant autoimmune conditions, abnormality of T-cell or B-cell counts has been reported. For example, T cells were reported to be decreased in patients with ulcerative or granulomatous colitis and in patients with rheumatoid arthritis, However, it needs to be pointed out that, in 1973, Farid and associates (44) reported a significant increase in T and a proportionate reduction of B rosette in 17 patients with untreated Grave's disease and 16 with Hashimoto's thyroiditis as compared with 24 normal and eight goiter controls. In 1975, six publications later, they (143) had to announce a retraction because further studies by them and by other investigators could not repeat the earlier results. Despite variations and lack of standardization of the test systems, some consistent deviations of T-lymphocyte and B-lymphocyte counts have been reported. T lymphocytes were quantitatively decreased in patients with carcinoma of the brain, breast, head and neck, liver, lung and urologic organs and with malignant melanoma. In general, there is a marked decrease of T cells with increasing stage of disease and a return of T cells to normal level after successful therapy. Cellular immunity is depressed, often lasting for years after localized radiation therapy, whether or not the thymus is included in the treatment field... |