Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6967680 | In vivo and in vitro effects of lithium on granulopoiesis in human neutropenic disorders. | 1980 | Studies have been cazrried out to determine the in vivo and in vitro effects of lithium carbonate in various neutropenic disorders. Addition of lithium to culture of bone marrow from patients with a variety of neutropenic disorders and ANLL in which normal or elevated serum and/or urinary CSA levels were present did not enhance granulocyte colony formation. Administration of lithium carbonate to patients with Felty's syndrome, in which serum and urinary CSA levels are reduced, enhanced peripheral blood neutrophil levels and serum and urinary CSA values. Lithium administration appears to be most beneficial in neutropenic patients in whom it can be demonstrated that CSA production is reduced. | |
| 7406414 | [The role of salivary gland scintigraphy in ear, nose and throat surgery (author's transl) | 1980 Apr | Scintigraphy of salivary glands might appear to be a relatively minor test in the study of the morphology of the salivary glands and especially tumours. However, with recent technical progress, it is an extremely useful test in th study of the function of the principal salivary glands. Changes in salivary secretion in certain severe facial paralyses could become an interesting prognostic test; on this subject, the simultaneous abnormalities in sub-maxillary and parotid salivary secretion in these cases of paralyses poses a physiological problem. The study of salivary junction is indispensable in the exploration of aptyalia (in particular in the Sjögren's syndrome), and in sialosis. | |
| 6153935 | Histopathological studies of the labial salivary glands in patients with Sjögren's syndro | 1980 Mar | The ultrastructural changes in the labial salivary glands, in which was demonstrated light microscopically the characteristic appearance of Sjögren's syndrome, were investigated in 12 cases. The significance of the following findings in this syndrome was discussed. The infiltrating cells were chiefly composed of small and medium sized lymphocytes and plasma cells. There were also found large lymphocytes with mitosis and morphologically regarded as T-lymphocytes. A small number of histiocytes and other mononuclear cells scattered among them. The remaining secretory cells were degenerated with disturbance of the secretory process. Degeneration, destruction, squamous metaplasia and proliferation of the duct epithelial cells were associated with mononuclear cell infiltration, and these changes were more conspicuous in the intercalated regions. The basal laminae of the acini and ducts were in part markedly thickened with high electron density. The epimyoepithelial islands in varying forms and sizes were composed of morphologically different kinds of cells which were probably derived from the duct cells. Only a few myoepithelial cells were located in the peripheral portion of the epimyoepithelial islands and there was no proliferation of myoepithelial cells. The hyaline-like substance, occasionally appearing in and around the epimyoepithelial islands, was an accumulation of fine fibrillar substance. Virus-like or tubuloreticular structures were found in the endothelial cells in 1 case. | |
| 6458737 | Immune complex glomerulonephritis in baboons (Papio cynocephalus) with indwelling intravas | 1981 Aug | Baboons with long term, indwelling, intravascular catheters developed clinical signs of renal and hepatic impairment. These included proteinuria and hypoalbuminemia without edema, and albumin to globulin ratios were reversed. Serum IgM, IgG, rheumatoid factor, and liver enzyme concentrations were above normal. Immunofluorescent staining of renal glomerular capillary loops was positive for IgG, IgM, B1c, and C4. Major microscopic lesions were membranoproliferative glomerulonephritis, chronic active hepatitis, degenerative arthritis, and chronic sialoadenitis. Electron microscopy of renal glomeruli demonstrated dense deposits in a variety of locations, mesangial cell interpositioning, and foot process fusion. These alterations, found in conjunction with the isolation of Staphylococcus aureus from the blood of affected baboons as well as the intravascular catheters, suggested that chronic bacterial infection was important in the pathogenesis of this disease. | |
| 6297510 | Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxid | 1983 Jan | The effect of sodium aurothiomalate and triethylphosphine gold on the generation of superoxide radicals by chemotactic tripeptide-activated polymorphonuclear leukocytes has been investigated using a cytochrome C reduction technique. Neither gold compound inhibited the binding of the tripeptide to cells. Sodium aurothiomalate in concentrations ranging from 1 to 100 micrograms/ml produced mild, nonsignificant inhibition of the generation of superoxide radicals. In contrast, triethylphosphine gold at a concentration of 0.25 microgram/ml was associated with a mild enhancement of superoxide radical production, but the enhancement was not statistically significant. At concentrations of 1.25 micrograms/ml and above, there was a profound inhibition of superoxide radical production by these activated cells. Since the products of the respiratory burst, including superoxide, are thought to be inflammatory mediators, it is postulated that the inhibition of superoxide radical generation by gold compounds may be another mechanism by which the compounds modulate their antiinflammatory effects in patients with rheumatoid disease. | |
| 7385833 | Mixed connective tissue disease. | 1980 Apr | A study was done that involved 46 patients with high-titer serum antibody to ribonucleoprotein (RNP). Common cutaneous manifestations included swollen hands or sclerodactyly (50 percent), cutaneous lupus erythematosus (48 percent), periungual telangiectasia (46 percent), alopecia (46 percent), dyspigmentation (28 percent), photosensitivity (28 percent) and vasculitis (22 percent). Frequent systemic characteristics included Raynaud phenomenon (93 percent), arthritis or arthralgia (91 percent), adenopathy (43 percent), vascular headaches (35 percent), serositis (35 percent), hoarseness (28 percent), myositis (26 percent), sicca syndrome (24 percent), renal disease (17 percent) and central nervous system disease (9 percent). Associated laboratory findings included antinuclear antibodies (100 percent), epidermal nuclear lgG deposition (91 percent), hypergammaglobulinemia (78 percent), esophageal dysmotility (61 percent), abnormal pulmonary function (59 percent), rheumatoid factor (57 percent), lupus erythematosus cells (37 percent), positive lupus band test (34 percent), hypocomplementemia (28 percent) and elevated anti-nDNA (21 percent). It appears that patients with high-titer anti-RNP (without appreciable amounts of "anti-Sm") have a high prevalence of Raynaud phenomenon and a low prevalence of progressive renal insufficiency and severe central nervous system disease. | |
| 1087561 | [Immunosuppressive treatment of rheumatic diseases. Experimental bases of a rational conce | 1976 | For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the long-lived cells of the mouse as well, resulting in high immunosuppressive potency in both species. In the NZB mouse, a well-fitting model of human lupus erythomatodes, Cy is successful in prophylaxis and therapy. A similar therapeutic effect cannot be obtained with 6-MP. Neither of the two groups of substances revealed selective activity on circulating T- or B-cells. According to the literature available, lymphocytes in humans are predominantly long-lived, too. Accordingly, Cy possesses a good immunosuppressive potency in man, too. Its therapeutic success is paralleled by a reduction of small lymphocytes. In conclusion, a true basic immunosuppressive therapy of autoimmune diseases in humans will primarily be possible by aid of substances which act through a cytotoxic mechanism and are thus able to affect even the long-lived human lymphocytes. In contrast, a substance acting purely through interference with certain steps of cell proliferation will predominantly remain restricted to an antiphlogistic use. | |
| 697947 | Differential effects of propranolol on lymphocyte rosette formation and response to plant | 1978 Sep | The effects of propranolol on various lymphocyte functions were studied to gain a better understanding of the recently demonstrated suppressive effect of propranolol on rheumatoid factor production. D- and L-propranolol at a concentration of 1 X 10(-4)M inhibited the formation of human EA rosettes. The inhibition occurred within one minute of adding the compounds, was reversible, and did not affect cell viability. Addtion of propranolol to preformed EA rosettes failed to disaggregate them. Patching and capping of SIg by an Fab'2 anti-IgG were inhibited at 2.5 X 10(-5)M and above. Propranolol at 2.5 X 10(-5)M also inhibited lymphocyte response to phytohemagglutinin and pokeweed mitogen without evidence of cell toxicity by trypan blue staining or absolute numbers of surviving cells. Congeners of propranolol with mainly beta adrenergic blocking properties did not show inhibitory effects. The inhibitory activities of propranolol are interpreted in terms of propranolol's membrane stablizing effects and ability to interfere with membrane receptor movement. | |
| 3874414 | IgG antibodies to SS-B (La), RNP/Sm and DNA are produced by PWM-stimulated normal human ly | 1985 | Peripheral blood lymphocytes from five healthy subjects and three patients with Sjögrens syndrome and systemic lupus erythematosus were stimulated with pokeweed mitogen to examine the effects of polyclonal activation on the secretion of autoantibodies in health and disease. Antibodies to SS-B (La), RNP/Sm and DNA were detected in supernatants from cultures from healthy controls, in some cases approaching levels secreted by the patients. All secreted autoantibodies were of IgG class and the antigen specificity of the secreted anti-SS-B was proven by cross-adsorption experiments. Our results extend the range of defined specificities of autoreactive B cells in healthy individuals. These data argue against a case for physiological deletion of autoreactive B cell clones and support theories of their active recruitment in autoimmunity. | |
| 6414079 | Human fibroblasts, a convenient nuclear substrate for detection of anti-nuclear antibodies | 1983 | Human fibroblast monolayers were applied as a nuclear substrate in indirect immunofluorescence for the detection of anti-nuclear antibodies (ANA). Comparison of the results obtained with this substrate and with conventional rat liver sections led to the conclusion that the application of human fibroblast monolayers as a substrate has the following advantages: 1) better recognition of the distinct nuclear staining patterns; 2) more convenient serum titrations, since a cryostat is not needed and twelve tests can be performed on one slide; 3) detection of significantly higher ANA titres in sera from patients with SLE and MCTD; 4) recognition of a type of ANA that was not detected on rat liver sections. These latter antibodies produced a discrete speckled pattern of fluorescence, which was completely lost after acid elution of the fibroblasts. Using HEp-2 cells in metaphase, it was shown that the antibodies were directed against the centromere regions of the chromosomes. These anti-centromere antibodies were detected in sera from patients with severe Raynaud's phenomenon. Underlying disorders were scleroderma (8 patients, 5 of them with CREST syndrome), Sjögren's syndrome (2 patients), and Raynaud's phenomenon in combination with a few symptoms of connective tissue diseases without fulfilling the criteria for a specific disease (5 patients). | |
| 6291883 | Speculations on potential anti-receptor autoimmune diseases. | 1982 | Many autoimmune disorders have a strong tendency to cluster in a single patient or type of patient. Therefore, in those cases in which anti-receptor antibodies are known to be responsible for one of the diseases in the cluster, it is logical to proceed investigatively on the presumption that the aetiology of other members of the cluster may also have an anti-receptor autoantibody basis. This logic is examined by considering examples of clustering in human diseases involving both organ-specific and non-organ-specific autoimmunities. The strong relationship between clustering among autoimmune diseases and the HLA-B8/DRw3 haplotype may provide a marker for anti-receptor autoimmune diseases. | |
| 6444308 | Immunoregulation in Sjögren's syndrome: influence of serum factors on T-cell subpopulatio | 1980 Feb | 21 patients with Sjögren's syndrome (sicca syndrome) with either glandular or extraglandular involvement, but without other connective tissue diseases, were studied with regard to immunoregulatory T-cell subpopulations, B-cell function, and suppressor cell capabilities. Patients with isolated glandular disease as well as patients with extraglandular disease had normal absolute numbers of total lymphocytes, T cells, and B cells. However, 9 of 11 patients with extraglandular disease and only 3 of 10 patients with glandular disease had decreased relative proportions of T cells bearing receptors for the Fc portion of immunoglobulin (Ig)G (T(G)) which was explained by a factor that blocked the expression of the IgG Fc receptor on T(G) cells. This blockage was reversible since the factor could be removed by trypsinizing the T cells before T(G) determination. Serum from patients with abnormal proportions of T(G) cells, but not serum from patients with normal proportions of T(G) cells, blocked the expression of the IgG Fc receptor on normal T cells. The serum factor upon fractionation over Bio-Gel A 1.5 columns as well as over staphylococcal protein A-Sepharose 4B columns was found diffusely within the IgG fraction, and not in the IgM fraction. Neither patients with glandular nor patients with extraglandular disease manifested increased numbers of in vivo-activated circulating lymphocytes as determined by spontaneous anti-trinitrophenyl (TNP) plaque-forming cells (PFC). However, patients with glandular disease had reduced numbers of pokeweed mitogen-induced anti-sheep erythrocyte PFC (P < 0.01) as compared with normals and patients with glandular disease. Of note was the fact that despite the modulation of T(G) subpopulation by the serum factor in patients with extra-glandular disease, these patients manifested normal concanavalin A-generated suppressor cells of pokeweed mitogen-induced PFC responses in allogeneic co-cultures. This was unlike the suppressor cell defect previously described in this system with systemic lupus erythematosus patients. The discrepancy was attributed both to the fact that the T(G) defect was reversible and to the fact that concanavalin A-generated suppressor cells are not limited to the T(G) subset. Thus, these studies have demonstrated reversible abnormalities in T(G) cells in patients with extraglandular Sjögren's syndrome which are not associated with suppressor cell defects. The discrepancy between these findings and the immuno-regulatory defects demonstrated in systemic lupus erythematosus may explain the difference in severity of the autoimmune expression in these diseases. | |
| 373382 | Incidence and titres of smooth-muscle antibodies in human sera. | 1979 Feb | By means of the indirect immunofluorescence method smooth-muscle antibodies (SMA) were determined in 182 patients with various diseases and the findings were compared with those of 7 patients with chronic active hepatitis (CAH) and 580 normal controls. IgG-SMA were found in 85.7% of the patients with CAH, titres above 80 occurred only in Hepatitis B-associated antigen (HBAg)-negative CAH, but IgG-SMA in low titres were also found with increased incidence in syphilis (16.7%) and in infections of the central nervous system (19%). In other diseases (Sjøgren's syndrome, ulcerative colitis, regional enteritis, myasthenia gravis, progressive muscular dystrophy, atopic dermatitis and mycoplasma pneumoniae infection) the prevalence did not differ from that of controls (3.6%). IgM-SMA were found more often in CAH (28.6%), in infections of the central nervous system (14.3%) and in the mycoplasma pneumoniae infections (13%) than in controls (2.6%), but titres above 20 occurred only in controls. IgA-SMA were detected only in a patient with syphilis. Demonstration of IgG-SMA titres above 80 seems to support the diagnosis of HBAg-negative CAH, while the demonstration of IgA- and IgM-SMA seems to be without diagnostic value in chronic hepatitis. | |
| 3923102 | Salivary gland lymphocytes in primary Sjogren's syndrome lack lymphocyte subsets defined b | 1985 Jul | Primary Sjogren's Syndrome (SS) is an autoimmune disease characterized by dry eyes and dry mouth due to lymphocytic infiltration of lacrimal and salivary glands. Biopsies of their salivary glands provided an opportunity to characterize the phenotypic and functional properties of inflammatory site lymphocytes. We found that the salivary gland lymphocytes (SGL) of SS patients differed from the peripheral blood lymphocytes of the same patients because: a) SGL lacked lymphocytes reactive with anti-Leu-7 and anti-Leu-11 monoclonal antibodies; b) SGL lacked natural killer (NK) activity; and c) SGL lacked the ability to suppress polyclonal B cell responses in the presence of complement fragment C3a, a function that requires the presence of Leu-7+ cells. These studies also showed that the SGL of SS patients differed from tonsillar lymph node (LN) lymphocytes of immunologically normal individuals because tonsillar LN contained Leu-7+ T cells, and tonsillar LN could suppress polyclonal B cell responses in the presence of the complement fragment C3a. The absence of this regulatory subset in the salivary glands of SS patients may contribute to pathogenesis, because these cells may be important in the suppression of polyclonal antibody synthesis and in the elimination of neoplastic or viral infected cells. | |
| 4056315 | [Ocular complications of Lyell's syndrome: recent concepts apropos of 26 cases]. | 1985 | Acute ocular lesions are usual during Toxic Epidermal Necrolysis (T.E.N.) and may induce persistent alterations. These were thought to be of cicatricial nature. 26 patients recovering from TEN had a systematic ophthalmological follow-up of at least six months after the acute stage (mean: 3 years). 11 of 26 patients (42%) exhibited a dry eye, associated in 7 with decreased salivary flow. The sicca syndrome appeared during the acute phase of TEN or, more often, a few weeks later. The reduction of the lacrymal flow induced corneal lesions in all 11 patients and 6 patients suffered permanent visual impairment. Biopsies of labial accessory salivary glands showed a lymphocytic infiltration of the glandular tissue in 5 of 7 cases. In 2 cases the lymphocytic infiltrate was nodular, grade III of Chisholm's classification, considered as pathognomonic of Sjogren's syndrome. The occurrence of Sjogren-like syndrome in patients recovering from TEN suggests an auto-immune pathogenesis for TEN, and is one more analogy between TEN and graft-versus-host disease. | |
| 896201 | Salivary gland involvement in systemic diseases. | 1977 Jun | The salivary glands participate in systemic illnesses because they are secretory structures allied with the gastrointestinal tract. Thus they are involved in systemic inflammatory, allergic, and neoplastic conditions. Perhaps the most common condition is that of mumps in the acute phase. Of the chronic diseases, Mikulicz's disease or Sjögren's syndrome is most frequently noted. In most instances of systemic involvement, the salivary gland enlargement is the rule, with the gland being tense, soft, and enlarged, and with progressive growth over a period of time. Usually all glands are involved. The diagnosis should be suspected from the history and the physical examination, noting that all the glands are equally involved by the enlargement. If there is any question, a biopsy should be performed. In the case of Sjögren's syndrome, the biopsy specimen may be taken either from a major salivary gland or from one of the minor ones, or the nasal mucous membrane or oral cavity. In general, definitive therapy is unsuccessful for the systemic illness involving the salivary glands, and in most instances has to be supportive. | |
| 6348956 | The hematopoietic effects of lithium. | 1983 Apr | The observation that patients treated with Li for manic-depressive illnesses develop an associated leukocytosis has led to a series of experimental and clinical studies of the hematopoietic effects of this simple molecule. Increases in blood neutrophils, eosinophils and perhaps monocytes are observed routinely when persons with an apparently normal hematopoietic system are exposed to "therapeutic" doses of the drug. Blood platelets tend to be increased, but lymphocytes and erythrocytes are unaffected. Neutrophilia reflects a true increase in the total number of mature neutrophils in all body compartments and is due to increased production. Neutrophil function generally is unaffected by Li. In man or in other mammals, certain classes of hematopoietic stem cells are increased by Li administration. Extensive studies of the effect of Li have been carried out in cultures of cells producing colonies of neutrophils and macrophages (CFUNM) in semisolid media. The colony-forming cell itself is little affected by Li. Cells which produce the factor essential for production of normal CFUNM (CSF) are stimulated to produce more CSF by the presence of Li. Studies of changes in vivo in CSF levels yield somewhat conflicting results; serum CSF being increased in some but not in others. Thus, it is not clear if the effect of Li on cell production in vivo reflects a direct effect on granulocytic precursors, including stem cells, or is mediated by stimulation of a feed-back loop (or both). A number of trials of Li therapy designed to modify induced neutropenia or to correct existing neutropenia are reviewed. Although many of these are very difficult to interpret, there is some reason to be optimistic concerning an eventual role for Li therapy of certain diseases associated with hematologic abnormalities. | |
| 714380 | A clinical study of slow-releasing artificial tears. | 1978 Aug | The slow-releasing artificial tear (SR-AT) is a soluble polymer in solid form. Placed in the inferior cul-de-sac and allowed to dissolve, it is used to treat dry-eye patients. The SR-AT was studied in two phases. The short-term cross-over study of 40 patients was completed in October 1976. The long-term open study is still in progress. Of 37 patients who started the long-term study, 18 are still using the inserts-a study retention of 49%. | |
| 742516 | Salivary immunoglobulins in diseases affecting salivary glands. | 1978 | Inflammatory disorders of the salivary glands cause marked abnormalities in secretion of immunoglobulins. The changes are reversible, however, in a relatively short period of time. More subtle changes in immunoglobulin transport are present in such diseases as Sjogren's syndrome and diabetes. No changes are discernable in alcoholic cirrhosis. Apparently salivary gland basement membranes are much more resistant to derangement than plasma membranes and the secretory IgA system can continue to operate in the face of numerous affronts. If nothing else these findings suggest that vaccination procedures in the region of the salivary glands may produce an inflammatory response, but it would be readily reversible. In addition, one could anticipate a functioning s-IgA system even in salivary glands with alterations in electrolyte transport. It is difficult to anticipate the situation in immunologically compromised patients, such as those on hemodialysis. Fortunately these patients represent a small population and for them at least, caries is a relatively minor concern. | |
| 12263973 | Statement on steroidal oral contraceptives. | 1981 Dec |