Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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4081594 | [Lysosomotropism and anti-inflammatory action of gold salts]. | 1985 Jul | Gold salts have been widely used in the past 70 years in the treatment of various connective tissue diseases and more particularly in rheumatoid arthritis. However their mechanism of action remains poorly understood. Gold salts are transported in the blood linked with several serum proteins including immunoglobulins. Methods of analytical electron microscopy (Castaing probe) have shown that gold is actively concentrated in the lysosomes of various cell types, including the proximal tubular cells of the kidney and certain bone marrow cells. These data, together with those provided by biochemical techniques, suggest that sodium aurothiopropanol sulfonate modifies the stability of lysosome membranes. In the present study it is shown that the stability of kidney lysosomes of treated rats was increased by 42.4 per cent after treatment for 3 days. This protective action was also seen when lysosomes were subjected to lysis by digitonin. The protective effect of gold salts on the lysosomal membrane may be explained by the formation of chemical complexes between gold and sulfhydryl groups present in the membrane, resulting in stable mercaptic bonds. These findings suggest that the increase in stability of lysosomal membranes plays a significant role in the anti-inflammatory action of gold salts. | |
6375688 | [Does the direct immunofluorescence examination of superficial temporal artery biopsies ha | 1984 Apr | The lesions in temporal arteritis (TA) are known to be often segmental and the pathologic study of involved temporal arteries may be falsely negative. Several reports suggest that direct immunofluorescence (IF) may be of value in the diagnosis of the disease. We have studied by IF 101 consecutive biopsies from 100 patients investigated during the last two years. Adjacent segments were processed for light and immunofluorescent microscopy. For the latter, tissues were immediately frozen in liquid nitrogen and stored at -- 70 degrees C. Cryostat sections were stained with anti-gamma, alpha, mu, C3, fibrinogen and albumin conjugates. A sister section was also stained with HE for light microscopy. Deposits of Ig and/or C were either granular (intra- or extra-cellular) or linear closely applied to internal elastic lamina. The 100 patients fall into 4 groups: Group I, (19 patients) with diagnosis ascertained upon typical clinical record and clear cut anatomic lesions by light microscopy; Group II (10 patients) with the clinical features of TA and a negative biopsy by light microscopy; Group III (29 patients) in whom the diagnostic criteria of polymyalgia rheumatica were fulfilled according to Forestier and Certonciny; Group IV (42 patients) affected with various diseases unrelated to T.A. (1 with polyarteritis nodosa, 5 with rheumatoid arthritis...). The following results were obtained by IF: in group I, deposits were found in 63% of the patients studied (linear in 11 and granular in 4 cases). They included Ig usually with C3 and fibrinogen. In group II, we observed linear deposits of IgG in one patient and granular C3 deposits in another case.(ABSTRACT TRUNCATED AT 250 WORDS) | |
6463200 | Are the causes and presentation of chronic hepatitis changing? An analysis of 104 cases ov | 1984 Spring | We describe the features at presentation of 104 patients with biopsy-proven chronic hepatitis who presented in Brisbane in the period 1968-32. The mean period of follow-up was 59 months. Sex ratio (female : male) was 70 : 34 and the mean age was 37 years (range 3-83). Eighty-five (82 per cent) were born in Australia. Serological evidence of hepatitis B (HBV) infection was present in 24 (23 per cent). Analysis of the HBV marker positive and negative (non-B) groups revealed that the clinical and laboratory features of HBsAg positive chronic hepatitis were much less florid than those of non-B patients. However, the disturbances seen in hepatic histopathology were similar in severity, and the mortality in the HBsAg positive group exceeded that in the non-B group. The relative risk calculated on an actuarial basis was higher in HBsAg positive patients. In contrast to the experience of others, severe chronic active hepatitis remains an important problem in Brisbane but some features of the disease are altering. Several changes may be attributable to the increasing incidence of HBV-associated disease, and in addition, patients aged under 20 with non-B chronic hepatitis are now rarely seen. This is of interest in view of recent reports of decreased incidence of another disease of disordered immune response, rheumatoid arthritis. | |
6625539 | Congenic autoimmune murine models of central nervous system disease in connective tissue d | 1983 Aug | Congenic mice of the MRL/Mp strain spontaneously develop an autoimmune connective tissue disease that shares immunological and histopathological features with systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. The autoimmune disorder in these mice is accelerated markedly by the recessive gene lpr. By 6 months of age, MRL/Mp-lpr/lpr mice developed prominent mononuclear cell infiltrates restricted to the choroid plexus and meninges, whereas congeneric MRL/Mp- +/+ mice (which lack the lpr gene) showed delayed but widespread inflammatory infiltrates involving cerebral vessels and meninges, with sparing of the choroid plexus. These distinctive patterns of cerebral inflammation, which are comparable in many respects to those seen in human connective tissue disease, provide some of the first animal models of relevant central nervous system histopathological processes associated with underlying connective tissue disease. | |
6642727 | Evaluation of the efficiency of a new hollow fiber plasmapheresis filter. | 1983 Jul | Plasma separation for plasma exchange or plasma treatment has, until now, been obtained prevalently by centrifugal separators. Recently, filters capable of continuously separating the plasma have been proposed. We have evaluated, both in vivo and ex vivo, the efficiency of a plasma separating filter (BT 900, Dideco, Mirandola, Italy) incorporating polypropylene hollow fibers with a pore size of 0.55 micron (PS 510 W, Membrana, Wuppertal, Germany) and an effective surface of 0.23 m2, using two hemodialysis blood pumps. Ex vivo, (bovine blood) at a blood flow (QB) of 100 ml/min, 47 +/- 2.8 ml/min of plasma were obtained in the first hour and 34 +/- 3.1 ml/min in the second hour. The Sieving coefficient was 100 for albumin and IgG, 98.4 for IgA and 92.3 for IgM. Neither hemolysis nor platelet contamination were observed. In vivo, 35 treatment were performer on 19 patients affected with mixed essential cryoglobulinemia, autoimmune glomerulonephritis, Wegener disease, thrombotic thrombocytopenic microangiopathy and rheumatoid arthritis. There were no clinical complications and the treatment was always well tolerated. A mean of 2064 +/- 400 ml of plasma was obtained in 103.7 +/- 29 minutes. The plasma flow was correlated (p less than 0.001) with the blood flow (13.4 ml/min at QB = 30 ml/min; 29 ml/min at QB = 100 ml/min). In some cases, immune complexes were found in the plasma removed by the filter (conglutinin method), confirming the membrane permeability to these high weight molecules. The use of hollow fibers to separate formed elements of blood from plasma has a brief history (1, 5).(ABSTRACT TRUNCATED AT 250 WORDS) | |
6340408 | Brain tissue immunoglobulins in adrenoleukodystrophy: a comparison with multiple sclerosis | 1983 | Immunoglobulin (Ig) concentrations were investigated in white matter samples of two adrenoleukodystrophy (ALD), three multiple sclerosis (MS), two systemic lupus erythematosus (SLE), one rheumatoid arthritis, and three control brains obtained at autopsy. "Free" Igs were extracted at pH 7.4; subsequently, bound Igs were extracted at pH 2.5 and 10.8, respectively. Igs were quantified by radial immunodiffusion. In ALD material there was an increase of free IgG and IgA, in one sample also of IgM, as compared to controls. No significant amounts of Igs were detected in the pH 2.5 and 10.8 extracts of ALD brain. Similarly to ALD, an increase of free IgG and IgA was a characteristic finding in MS brain; in contrast to ALD and control material, significant amounts of bound Igs (IgG) extractable at acid or alkaline pH, respectively, were present in MS tissue. In both SLE brains increase of free IgM was conspicuous. Preliminary studies on binding of Igs extracted at pH 7.4 from brain to frozen sections of normal human and bovine brain tissue revealed different binding properties of Igs from ALD, MS, SLE, and control brains. Immunochemical findings in ALD indicating pathologic accumulation of Igs in brain tissue were paralleled by immunocytochemical observations demonstrating accumulation of lymphoid cells staining for IgG, IgA, and IgM, respectively, mainly in areas of recent demyelination. Participation of Igs in the pathogenesis of ALD lesions may be considered but needs further confirmation. | |
6120251 | HLA and clinical manifestations in Takayasu disease. | 1982 Feb | In previous studies on HLA antigens in patients with Takayasu disease, we found a statistically high frequency of haplotype Bw52-Dw12. Clinico-pathological conditions of this disease observed for 85 +/- 3 months were compared between 29 patients with (positive group) and 39 patients without this haplotype (negative group), among 82 patients with Takayasu disease. Blood sedimentation rate and C-reactive protein exhibited statistically significant high figures in the positive group as compared with those in negative group, while no difference were seen in rheumatoid arthritis test, antistreptolysin-0 titer, anti-DNA antibody, levels of circulating immune complexes, platelet aggregation, although all revealed high levels in the positive group. Pulmonary disorders were more frequent in positive group. Fourteen patients (48%) in the positive group and 5 (13%) in the negative group had abnormalities in the aortic valve (p less than 0.01). In 14 patients in the positive (38%) and 5 in the negative (13%) groups, the systolic blood pressure was over 140 mmHg (p less than 0.01). Four patients in the positive (17%) and one in the negative groups (3%) were blind (p less than 0.01). These data suggest that in patients with a haplotype of Bw52-Dw12, there is a greater likelihood of an active inflammatory state and a rapid progression of these morbid conditions. | |
7304721 | Ear anomalies in an infant with Potter's syndrome. | 1981 Oct | Microdissection and scanning electron microscopy were used to study temporal bone specimens from a newborn infant with Potter's syndrome. The 34-year-old mother of the infant had juvenile-onset rheumatoid arthritis and she took prostaglandin inhibitors (aspirin, indomethacin, and Clinoril) during pregnancy. Autopsy findings included bilateral renal dysgenesis, pulmonary hypoplasia, abnormal facies with low-set ears, and bilateral cataracts. The infant's left external ear canal was stenotic and the left tympanic anulus was narrowed. Otherwise, both middle ears, as well as the sensory structures of the cochleae and semicircular canals, were normal. The saccular and utricular muculae on the right were entirely devoid of otoconia, although they were covered by gelatinous otoconial membranes which appeared normal. On the left, the maculae were covered by thin layers of flat, lenticular crystals 2 to 10 mu in diameter. X-ray powder diffraction analysis showed these aberrant otoconia to be composed of calcium carbonate in the form of vaterite. No abnormalities of the neuroepithelia or macular nerve supply were found in either ear. | |
4085153 | 65-70 kD protein identified by immunoblotting as the presumptive gastric microsomal autoan | 1985 Dec | Sera from 20 of 24 patients with pernicious anaemia reacted by immunoblotting with a 65-70 kD protein in canine and rodent gastric mucosal cells enriched for 80-90% parietal cells, and in microsomal preparations derived from these cells. All 20 reactive sera were positive for parietal cell microsomal antibody demonstrated by immunofluorescence. Eighteen parietal cell microsomal antibody-positive sera from patients with unconfirmed pernicious anaemia also reacted with the same 65-70 kD protein. Serum reactivity with the same 65-70 kD protein was not seen with canine and rodent liver cells or with microsomal preparations derived from these cells. Sera from 10 patients with chronic active hepatitis, 10 with scleroderma and 10 with rheumatoid arthritis and 22 healthy persons did not react with the 65-70 kD protein. These results suggest that the 65-70 kD protein is probably the parietal cell microsomal autoantigen. A second antigen of 85-90 kD mol. wt. present only in canine gastric mucosal preparations also correlates with the presence of parietal cell microsomal antibody. However, the contribution of this second antigen to parietal cell microsomal antibody reactivity remains uncertain. | |
6226816 | Effect of N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA) on the inductio | 1983 Aug | Keyhole lympet hemocyanin (KLH)-specific suppressor T (Ts) cells that suppress the in vitro secondary anti-trinitrophenyl (TNP) PFC response to TNP-KLH could be induced when murine spleen cells were precultured with KLH. N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt (CCA) at 1-100 micrograms/ml augmented the in vitro induction of Ts cells when the cells were precultured with a suboptimal dose of KLH (10 micrograms/ml). Ts cell-induction was, however, rather slightly inhibited by the same concentrations of CCA when the lymphocytes were precultured with an optimal amount of KLH (100 micrograms/ml). In the in vivo experiments, the daily administration of 10 mg/kg CCA for 4 weeks augmented or inhibited Ts cell-induction when mice were immunized with a suboptimal (30 micrograms/body) or an optimal (100 micrograms/body) amount of KLH, respectively. However, CCA had no effect on the induction of Ts cells by concanavalin A in vivo. On the other hand, CCA augmented the induction of helper T (Th) cells both in vitro and in vivo when Th cells were induced with a suboptimal amount of antigens. In contrast, the augmentative effect was no longer observed when Th cells were induced by an optimal amount of antigens. These results suggest that CCA is a compound showing immunomodulating properties that affect Ts and Th cell-induction depending on immunological conditions. These immunopharmacological profiles are discussed in connection with its clinical application to an autoimmune disease like rheumatoid arthritis. | |
6602291 | Muscle function in rheumatic disease patients treated with corticosteroids. | 1983 Feb | Clinical and experimental data indicate that long-term corticosteroid use leads to atrophy of the type 2 muscle fibers. The purpose of this study was to characterize and quantify the nature of muscle function in rheumatic disease patients who have been on long-term corticosteroid therapy. Quadriceps function (i.e., peak torque and power) in 19 patients (11 with rheumatoid arthritis, five with systemic lupus erythematosis, and 3 other) and 11 age- and activity-matched normal controls was measured with an isokinetic dynamometer (Cybex II), during four constant velocity movements. Power was significantly lower for the patients at all speeds. At the higher speeds the patients' deficit in power production increased as indicated by a difference in the slopes of power-velocity regression lines. Measures of peak torque could not be consistently used to differentiate the groups. Patients with rheumatic diseases receiving corticosteroids have a decreased ability to generate muscle power. The method described allows for quantification of these deficits in a clinical setting. | |
7117506 | The noncontraceptive health benefits from oral contraceptive use. | 1982 Jul | ||
6291123 | Serum protease inhibitory capacity. (Recent knowledge on alpha 1-antitrypsin deficiency). | 1982 Jul | The molecular structure and the serum levels of alpha 1-antitrypsin, the major antiprotease of human serum, are controlled by a series of codominant alleles at a single chromosomal locus, known as the Pi(protease-inhibitor) locus. The congenital deficiency of this inhibitor is known to be associated with the development of lung emphysema in early adulthood and chronic liver disease in childhood. Less frequent associations have been reported, such as rheumatoid arthritis, membranoproliferative glomerulonephritis and mosaicism for sex chromosomes. The identification of several suballeles of the Pi system, which was accomplished by means of a refinement of the isoelectric focusing technique, has promoted research concerning their possible pathogenic implications. The studies so far performed have often led to contradictory results, but nevertheless they strongly ascribe the property of controlling the quantitative levels of alpha 1-antitrypsin to certain M subtypes. Intermediate M3 subtype has recently been associated with the development of chronic obstructive lung disease in adulthood. Should this finding be confirmed by further evidence, a new approach to the prevention of lung disease could be considered, given that 30% of the individuals are carriers of the M3 suballele. In Italy, the incidence of congenital deficiency of alpha 1-trypsin appears to be greater in the northern regions, where 15-20 out of every 100,000 individuals are affected by the severe (ZZ) form of the deficiency. | |
7067004 | [Steroidal contraceptives and the immune system]. | 1982 Mar | ||
6784583 | Application of polyethylene glycol turbidity assay to detection of circulating immune comp | 1981 Apr | A rapid, reproducible immune complex screening assay was used to quantitate levels of circulating immune complexes in the sera of normal subjects, patients with documented increases in immune complexes from rheumatoid arthritis, patients with clinically or microbiologically documented infections, and patients with cancer. Although wide variations in individual values within the groups were noted and the concurrent elevation of polyethylene glycol-circulating immune complex levels by infection was documented as expected, significant differences were found in the values in patients with cancer compared with those in normal subjects. The overall clinical application of polyethylene glycol-circulating immune complex screening is discussed and current application of screening of serial sera samples from individual patients for correlation with measurable tumor volume is proposed. | |
6153183 | Lymphocyte antigens in systemic lupus erythematosus: studies with heterologous antisera. | 1980 Feb | Rabbit antisera were produced against pooled living lymphocytes from 25 patients with active systemic lupus erythematosus (SLE). Lymphocytes collected at plasmapheresis or venipuncture were frozen in liquid nitrogen and later coated with rabbit antibody to normal human tonsils and normal thymocytes immediately before intravenous immunization of rabbits. Antisera were subsequently extensively absorbed with normal human tonsillar cells, thymocytes, peripheral blood lymphocytes, erythrocytes, and leukocytes from patients with myelogeneous and lymphatic leukemia until residual base-line immunofluorescent staining of normal human lymphocytes using F(ab)2' of whole antisera averaged less than 5%. Absorbed pepsin-digested antisera detected membrane antigens which were markedly increased (mean 32%) on lymphocytes from patients with active SLE (P less than 0.05). Membrane antigens reacting with absorbed, pepsin-digested antisera were present on both T and B cells but, in most instances, predominated on T cells. Control observations using absorbed pepsin-digested antisera to normal human lymphocytes or peripheral blood lymphocytes from patients with rheumatoid arthritis showed no similar specificity. SLE patients treated with moderate or high dose corticosteroids or immunosuppressive agents (cytoxan or azathioprine) appeared to lose lymphocyte antigens detected by these reagents. Control studies with other connective tissue disease patients, miscellaneous hospitalized subjects, or normal controls showed low levels of reactivity (2-5%). SLE lymphocyte membrane antigens uniquely increased during active disease; this may represent neoantigens or alterations associated with the disease itself. | |
213163 | Sensory action potentials and biopsy of the sural nerve in neuropathy. | 1978 Sep | In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy ("proportionate slowing"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres ("disproportionate slowing"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver. | |
3930337 | Antibody to liver-specific lipoprotein in acute and chronic liver diseases. Its quantitati | 1985 Jun | A double-antibody radioimmunoassay was developed to detect antibody to human liver-specific membrane lipoprotein (anti-LSP antibody) in patients' serum. Anti-human LSP monoclonal antibody was labeled with 125I and anti-anti-LSP antiserum raised in rabbits was used as the first antibody in the assay. Anti-LSP antibody level was quantitatively measured and the assay was shown to be specific. Anti-LSP antibody was found in 5/8 patients with type B acute viral hepatitis (AVH), 3/7 patients with type A AVH, 1/6 patients with non-A, non-B AVH, 10/17 patients with chronic active hepatitis (CAH), 6/16 patients with chronic persistent hepatitis, 13/16 patients with active cirrhosis of the liver and 7/19 patients with primary nonhepatic autoimmune diseases such as glomerulonephritis, systemic lupus erythematosus and rheumatoid arthritis. The mean levels of anti-LSP were increased in patients with cirrhosis of the liver (p less than 0.01), CAH (p less than 0.05) and AVH (p less than 0.05) when compared with that of normal individuals. However, the frequencies of anti-LSP did not depend on HBsAg status. The data showed that anti-LSP antibody can be detected without the use of LSP preparation although it is also found in patients with primary nonhepatic autoimmune diseases. | |
6676400 | [Acoustical analysis of joint-sound through passive motion--with special reference to dege | 1983 Dec | Sounds from the joints are still in the mysterious zone. It seems to be important to study the sound which occurs on motions. Here, a new analysing method and its clinical application are presented and discussed. The joint which is studied, is moved in some ranges for four seconds in the unechoic chamber, and a special microphone is kept to touch on the pan-articular skin manually throughout the motion. These collected sounds are analyzed with a narrow band spectrum analyzer (Br uel & Kjaer Co., 2031 Type) and a computer. In the unechoic chamber, it may diminished the background noises. The narrow band spectrum analyzer made it possible not to use the magnetic tape which usually induced much noise. Furthermore, as the computer system is utilized, it become easy to compile the data of each frequency analysis and to obtain over all value, with which the sound volume can be compared with each other. The over all value means an integrated volume of each joint sound. In this paper, joint sound were obtained from normal and pathological human joints. In the normal cases, the frequency analysis data showed almost flat spectrum curves, and the total over all values (0.5 kHz to 5 kHz) were usually less than 80 dB. On the other hand, in the pathological joints which had bony changes affected by rheumatoid arthritis, degenerative osteoarthritis, fracture, and others, the frequency analysis showed elevated curves in range from 0.5 kHz to 4.0 kHz, and the total over all value increased in each pathological joint. In 85 cases of osteoarthrosis of the knee joints, the total over all values were a wide dispersion from 76 to 104 dB. And these values and radiological grading (by Swanson) correlated to each other. The over all values at each 0.5 kHz interval, especially from 0.5 to 1.5 kHz, were maximum ones in each radiological gradings. It is concluded that these results in osteoarthrosis cases, are related to with radiological gradings. | |
6623355 | Increased risk of malignancy and uterine disease following perimenarchal hospitalization: | 1983 Oct | The estrogen window hypothesis postulates that tumor induction by environmental carcinogens is facilitated by the endocrine effects of incomplete ovarian maturation at menarche. To determine if illness and operation at or near menarche might modify ovarian maturation and thus increase cancer risk, we studied the subsequent reproductive, surgical, and malignancy history of 125 women who were aged 10 to 15 years when admitted for possible appendicitis during 1945 to 1951. Total operative experience and cholecystectomy rates were within expectation, but excess rates for dilatation and curettage (98 versus 57 expected, P less than 0.001) and hysterectomy (41 versus 23 expected, P less than 0.0006) suggest disturbed endocrine maturation. In addition, one patient developed Cushing's syndrome and five patients developed rheumatoid arthritis. Eight malignancies were observed (twice the expected rate of 3.4, P = 0.047); six occurred before age 40 years (versus 1.54 expected, P = 0.001). Tumors and age at diagnosis were: lymphoma (20), ovarian (28), breast (32), thyroid (34), lung (36), cervix (39), endometrium (48), and colon (50). Compared with standard rates, the peak incidence in those who were menarchal at hospitalization was 20 times the expected incidence; in those who were premenarchal the rate was five times the expected incidence, and in those who were postmenarchal the rate was as expected. The results of this study support the validity of the estrogen window hypothesis and indicate the serious consequences of perimenarchal illness. Enteric disease requiring hospitalization at or near menarche appears to define a group of women at risk for gynecologic disease and malignancy; further study is needed to determine if there is an appropriate prophylactic therapy to reduce that risk. |