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ID PMID Title PublicationDate abstract
8098213 Regulation of the expression of intercellular adhesion molecule 1 in cultured human endoth 1993 May OBJECTIVE: To examine the regulation of intercellular adhesion molecule 1 (ICAM-1) in human synovial microvascular endothelial cells (HSE) and human umbilical vein endothelial cells (HUVE) upon exposure to a variety of agents. METHODS: Cultured endothelial cells were treated with various cytokines alone and in combination. The expression of ICAM-1 was evaluated at several levels, including an investigation of messenger RNA (mRNA) and surface protein expression. RESULTS: Treatment of HSE with interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor alpha (TNF alpha) resulted in minimal increases in ICAM-1 expression, in contrast to findings with HUVE. Incubation of HUVE or HSE with IL-1 or TNF in combination with interferon-gamma (IFN gamma) greatly potentiated the increase in ICAM-1 surface expression. The synergistic effect of IFN gamma and TNF was confirmed by several methods, including a cell-based enzyme-linked immunosorbent assay, fluorescence-activated cell sorting, immunofluorescence staining, and determination of mRNA levels. IFN gamma also augmented the actions of several other agonists on HSE, i.e., IL-4, lipopolysaccharide, and TNF beta/lymphotoxin. Immunoprecipitation of TNF alpha + IFN gamma-stimulated, 125I-labeled HSE cells with anti-ICAM-1 revealed a single 90-kd band, similar in size to ICAM-1 from HUVE treated in an identical manner. Unexpectedly, IFN gamma alone was a potent stimulus for HSE ICAM-1 mRNA synthesis, but was relatively ineffective in HUVE. CONCLUSION: These studies indicate that IFN gamma plays a critical synergistic role in the regulation of ICAM-1 expression in human synovial endothelial cells.
8655718 An unusual association of Felty syndrome and TCR gamma delta lymphocytosis. 1996 Apr Felty syndrome, comprised of neutropenia, rheumatoid arthritis and splenomegaly, occurs in approximately 1% of patients with rheumatoid arthritis. Up to one third of these patients have an increased number of large granular lymphocytes. The usual immunophenotype of these cells is CD3+, CD8+, CD57+, T cell receptor (TCR) alpha beta. A patient with Felty syndrome and large granular lymphocytosis, who had an unusual immunophenotype CD3+, CD4-, CD8-, TCR gamma delta, is described. Her neutropenia responded to treatment with granulocyte colony stimulating factor (G-CSF), which was given in order to raise her neutrophil count prior to bilateral knee replacement surgery. Thus, Felty syndrome with large granular lymphocytosis is a heterogeneous condition, one in which TCR gamma delta large granular lymphocytosis may be found, and also shows a response to treatment with G-CSF.
7572311 Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25-dihydroxyvitamin 1995 Jun This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone-derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or = 100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover.
8296162 Increased expression of VLA-5 adhesion molecules on synovial fluid T lymphocytes in chroni 1994 Feb This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against alpha-subunits of the VLA family. VLA-alpha 4 and VLA-alpha 5, but not VLA-alpha 1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-alpha 5-high and VLA-alpha 5-low, were found in resting peripheral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetate (PMA) and concanavalin A, most T cells became VLA-alpha 5-high. In patients with chronic polyarthritis, the expression of VLA-alpha 1 and VLA-alpha 5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.
8425377 Identification of species-specific, non-cross-reactive proteins of Borrelia burgdorferi. 1993 Jan The low specificity of diagnostic tests for Lyme disease is due to the fact that Borrelia burgdorferi possesses many antigenic proteins that are cross-reactive with other spirochetes and bacteria. The low sensitivity is a result of high (> or = 1:100) dilutions used for patient sera during testing to eliminate non-specific cross-reactivity. The present study was conducted to identify species-specific non-cross-reactive protein(s) of B. burgdorferi that might be used as antigen(s) in serologic tests. Whole-cell sonicates of B. burgdorferi were tested against pooled sera from patients with symptoms, signs, and serologic features diagnostic of Lyme disease (LD), rheumatoid arthritis, infectious mononucleosis, systemic lupus erythematosus, Rocky Mountain spotted fever, secondary syphilis, and from healthy individuals. Different LD pools were also tested against whole-cell sonicates of Treponema pallidum, Treponema phagedenis, Leptospira interrogans, and Escherichia coli. Comparison among patterns obtained by each serum pool revealed that IgM antibodies to species-specific 39-, 23-, and 22-kD proteins and IgG antibodies to 34- and 31-kD proteins were present only in the patients with LD and absent from patients with rheumatoid arthritis, infectious mononucleosis, systemic lupus erythematosus, Rocky Mountain spotted fever, secondary syphilis, and healthy individuals pools. These results suggest that 39-, 23-, and 22-kD proteins may be used in an IgM immunoassay for diagnosis of LD.
7987619 Nonsteroidal antiinflammatory drugs and the gastrointestinal tract. 1994 Sep Nonsteroidal antiinflammatory drugs (NSAIDs) are used in large amounts for analgesic, antiinflammatory, and antithrombotic indications. This use is not without side effects on the gut and other organs, and some of these side effects may be serious and even lethal. No NSAID has been shown to be without side-effect potential. Use increases with age, and age poses additional risks to patients with side effects. The most serious side effects are perforation of peptic and gut ulcers and gastrointestinal (GI) bleeding, which NSAIDs, and especially acetylsalicylic acid (ASA; aspirin), may promote from both ulcer and nonulcer lesions of both the upper and lower GI tract (i.e., both acid- and nonacid-dependent). Upper GI mucosal lesions range from trivial--petechiae and superficial erosions--to significant and potentially serious deep (chronic) peptic ulcers, esophagitis, and, less commonly, small and large gut ulcers. Symptoms may occur independently of observable lesions, and serious lesions may occur without any prior symptoms. The risk of ulceration due to therapeutic doses of NSAIDs is estimated at 5- to 10-fold. NSAIDs also delay healing of conventional peptic ulcers. Moreover, ASA abuse, often surreptitious and discoverable by serum salicylate level measurement, may cause totally intractable gastric or duodenal ulceration. Surgery is contraindicated because relapse is inevitable and progressively more serious. The rational use of NSAIDs is discussed, and prophylactic and treatment strategies are proposed. None seems entirely satisfactory, and the best prophylaxis would be to avoid the use of NSAIDs except for proven indications. Until the mechanisms whereby NSAIDs both cause injury and provide therapeutic benefits can be separated, the problem of side effects and their prevention or treatment remains unresolvable.
8988401 Is local biotransformation the key to understanding the pharmacological activity of salicy 1996 Dec It is suggested that some drugs may be converted by inflammatory cells to yield active species. The transformation may be non-enzymatic, although being driven by the enzymatic production of highly reactive species which are normal products of activated leukocytes, such as singlet oxygen, hydrogen peroxide, hypochlorite, hydroxyl radical and nitric oxide. Drugs which may be transformed in this fashion are the anti-rheumatic gold complexes which may be converted either to aurocyanide or to Au(III) complexes by myeloperoxidase in polymorphonuclear leukocytes. Salicylate may also be activated by its oxidation to dihydroxybenzoates although evidence for its transformation is weaker than for the gold complexes.
8266016 Sulglycotide in the prevention of nonsteroidal anti-inflammatory drug-induced gastroduoden 1993 Oct The aim of this double-blind, randomized placebo-controlled trial was to evaluate whether sulglycotide prevents the onset of gastroduodenal mucosal injury in patients with rheumatic disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). One hundred patients, free from endoscopically detectable lesions of the gastroduodenal mucosa, affected either by rheumatoid arthritis or osteoarthritis, and candidates for NSAID therapy, were randomly allocated either to 200 mg sulglycotide three times daily (n = 50) or to an indistinguishable placebo (n = 50) for 4 weeks, together with standard NSAID administration (50 mg diclofenac three times daily (n = 50); 50 mg indomethacin three times daily (n = 50)). Upper gastrointestinal endoscopy was repeated at the end of the study. It was possible to evaluate 86 patients after treatment (sulglycotide = 42, placebo = 44); diclofenac = 45, indomethacin = 41). Six of 42 patients (14%) in the sulglycotide group and 15 of 44 (34%) in the placebo group had developed gastric or duodenal ulcerative lesions (p = 0.02). These data suggest that sulglycotide prophylaxis may be useful for the prevention of gastric and duodenal ulcer associated with NSAID therapy in rheumatic patients.
8352249 Clinical significance of antineutrophil cytoplasmic autoantibodies with specificity for la 1993 Aug The prevalence and clinical significance of antineutrophil cytoplasmic antibodies with specificity for lactoferrin was determined in patients with renal diseases. Antilactoferrin antibodies were found in only 12 of 920 patients (1.3%). These patients had either "pauci-immune" necrotizing crescentic glomerulonephritis (three cases) or lupus nephritis (nine cases). To verify whether antilactoferrin antibodies were specific for patients with systemic lupus erythematosus (SLE) and renal involvement, we studied 61 additional lupus patients, 40 with active lupus nephritis and 21 with active SLE and no renal involvement. Antilactoferrin antibodies were found in approximately 15% to 20% of patients with SLE, irrespective of the presence of renal involvement. We conclude that antineutrophil cytoplasmic antibodies with specificity for lactoferrin are only sporadically found in patients with renal diseases; these patients have either necrotizing crescentic glomerulonephritis or lupus nephritis. However, antilactoferrin antibodies are not a marker for renal involvement in SLE.
8306821 The RNA polymerase I-specific transcription initiation factor UBF is associated with trans 1993 Nov We have characterized an anti-NOR (nucleolar organizer region) serum (P419) from a patient with rheumatoid arthritis and show that it contains antibodies directed against the RNA polymerase I-specific transcription initiation factor UBF. This serum reacts with UBF from a variety of vertebrate cells as revealed both by immunoblotting and by indirect immunofluorescence. We have used the P419 serum to study the intracellular localization of this transcription factor at the light and electron microscopic level. In interphase cells, UBF exhibits a pronounced punctate pattern and is found to be associated with necklace-like structures, which appear to reflect the transcriptionally active state of the nucleolus. Inhibition of rRNA synthetic activity caused either by nutritional starvation or by actinomycin D treatment resulted in a marked decrease in the number and in a significant increase in the size of UBF-positive granules. Under all experimental conditions applied, UBF was exclusively found within the nucleolus and was not released into the nucleoplasm or cytoplasm. During mitosis, UBF was found to be concentrated at the chromosomal NOR indicating that a significant quantity, if not all, of this factor remains bound to the ribosomal transcription units. From this we conclude that UBF is associated both with transcriptionally active and inactive rRNA genes and, therefore, changes in the intracellular localization of UBF are very likely not involved in rDNA transcription regulation.
8894345 Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of d 1996 Oct Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.
7869026 Activation of monocyte effector genes and STAT family transcription factors by inflammator 1995 Mar 1 Activated monocytes play an important role in the pathogenesis of inflammatory arthritis. Blood monocytes which enter the inflamed joint become activated upon adherence to extracellular matrix and exposure to a complex inflammatory environment. We have analyzed the mechanism of monocyte activation by soluble factors present in inflammatory synovial fluid (SF). Greater than 75% of inflammatory SFs tested (a total of 22 fluids to date) increased cell surface expression and dramatically increased mRNA levels of monocyte activation markers Fc gamma RI, Fc gamma RIII, and HLA-DRA. This induction was not triggered by adherence, a known activating stimulus, and several lines of evidence showed that induction was not dependent upon interferon gamma (IFN-gamma). Induction was not prevented by neutralizing anti-IFN-gamma antibodies and IFN-gamma was not detected in the SFs using a sensitive enzyme-linked immunosorbent assay. The SFs also were not able to activate the IFN-gamma-activated transcription factor Stat1, thus providing further support for the absence of IFN-gamma. SFs did activate a related signal transducer and activator of transcription (STAT) family factor, termed Stat-SF, which bound specifically to the IFN-gamma response region (GRR), a well-characterized transcription element in the Fc gamma RI promoter. Based upon DNA-binding specificity and mobilities in gel shift assays, and reactivity with specific antisera, Stat-SF likely contains Stat3, or a closely related STAT family member. Neutralization of interleukin 6, a cytokine present in SFs which is known to activate Stat3, abolished the activation of Stat-SF and inhibited the induction of Fc gamma RI expression by SFs. These results demonstrate the activation of monocytes by inflammatory SF and suggest that monocyte activation at an inflammatory site may occur in the absence of IFN-gamma through the triggering of signal transduction pathways that activate STAT transcription factors.
8004060 Cytokine expression by inflammatory neutrophils. 1994 Mar Bloodstream neutrophils do not express mRNA for interleukin-1 beta (IL-1 beta), but transcripts for this cytokine are rapidly induced following exposure to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) in vitro. Levels of IL-1 beta mRNA reach maximal values 1 h after exposure to rGM-CSF and then decline to near basal levels by 4 h. Similarly, rGM-CSF treatment of blood neutrophils in vitro induced increases in levels of mRNA for IL-6 and tumour necrosis factor-alpha (TNF-alpha). RNA extracted from neutrophils isolated from the synovial fluid of patients with rheumatoid arthritis expressed low, but significant levels of IL-1 beta mRNA that were between 0.5 and 3% of the levels that could be maximally induced by rGM-CSF treatment of blood neutrophils. However, transcripts for TNF-alpha and IL-6 were not detected in these synovial fluid neutrophils. mRNA for transforming growth factor-beta (TGF-beta) was constitutively expressed in blood and synovial fluid neutrophils and transcripts for this cytokine were not altered by rGM-CSF exposure. Because of the transient nature of IL-1 beta expression by activated neutrophils, we propose that the low levels of expression of mRNA for this cytokine in the synovial fluid neutrophils represents expression by a small, perhaps newly-recruited and activated, sub-population of cells. IL-1 beta expression by this sub-population may thus contribute to the pathogenesis of rheumatoid disease.
8672021 Increased serum concentrations of pro-gastrin-releasing peptide in patients with renal dys 1996 Jul BACKGROUND: Gastrin-releasing peptide has a prominent role as a tumour marker in the diagnosis of small-cell lung carcinoma. This study was designed to assess the validity of a newly developed enzyme-linked immunosorbent assay (ELISA) for pro-gastrin-releasing peptide in patients with renal and systemic diseases. METHODS: Pro-gastrin-releasing peptide concentrations in sera from normal subjects and patients with small-cell lung carcinoma, diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, chronic glomerulonephritis, or undialysed or dialysed chronic renal failure were measured with the TND-4 Kit, a newly developed ELISA for pro-gastrin-releasing peptide. RESULTS: All of the patients with normal renal function, whether they had diabetes mellitus (n=16), rheumatoid arthritis (n=10), systemic lupus erythematosus (n=12) or chronic glomerulonephritis (n=14), had serum pro-gastrin-releasing peptide concentrations less than 46 ng/l, the upper limit in normal subjects. In contrast, 14 or 16 patients (88%) with small-cell lung carcinoma, who had normal renal function, and 25 of 26 (96%) patients with chronic renal failure on haemodialysis had serum pro-gastrin-releasing peptide concentrations greater than 46 ng/l. The highest serum pro-gastrin-releasing peptide levels in patients with chronic renal failure, before and after initiating haemodialysis were 183 and 290 ng/l respectively. Ten of 16 (63%) small-cell lung carcinoma patients had serum pro-gastrin-releasing peptide concentrations greater than 290 ng/l, the highest level in haemodialysed patients. Serum pro-gastrin-releasing peptide concentrations were also elevated in patients with chronic glomerulonephritis or diabetes mellitus when their serum creatinine concentrations were greater than 120 micromol/l. And, there was a significant correlation, y=23.5+0.15x(n=22, r=0.82, P<0.001),between serum pro-gastrin-releasing peptide (y, in ng/l) and serum creatine (x in micromol/l) concentrations in those patients with renal dysfunction. The correlation between serum pro-gastrin-releasing peptide and serum urea nitrogen concentrations was likewise significant. CONCLUSIONS: The evaluation of patients as to their renal functional state may be mandatory when serum pro-gastrin-releasing peptide levels are to be applied as one of the diagnostic tools for small-cell lung carcinoma or as a marker monitoring their clinical course.
8212757 [Nizatidine in therapy and prevention of non-steroidal anti-rheumatic drug-induced ulcers 1993 Jun 269 patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least three weeks, were enrolled in this randomised double-blind multicenter trial. Entry criteria were both the presence of an ulcer in gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) as well as dyspeptic symptoms. The patients had been treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine. All patients continued to take their original NSAID-medication. The three nizatidine-groups had been well matched with respect to important patient characteristics. After 8 weeks of treatment more than 90% of gastric and duodenal ulcers had been healed under all three nizatidine-dosages. There was a tendency for higher healing rates in case of gastric ulcers after 4 weeks following the higher dose of nizatidine. Erosions in stomach and duodenum as well as esophagitis had been improved to a similar degree with all nizatidine doses. The same holds with respect to improvement of clinical symptoms such as epigastric pain, heartburn etc. Consumption of additional antacids was similar in all three groups. In the subsequent prophylactic trial 237/221 patients had been followed for 3/6 months. 116/107 received in addition to their continued antirheumatic medication nizatidine 150 mg nocte and 121/114 patients 2 x 150 mg nizatidine daily. The cumulative relapse rates within 6 months averaged 5.5% in the low and 1.8% in the high dose group (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
7921152 NSAID--induced gastroduodenal ulcers: exploring the silent dilemma. 1994 Jul Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications and are very commonly prescribed. They are used by a large proportion of elderly persons who are most prone to adverse events. NSAID gastropathy is the commonest side effect. The relative risk of adverse events is high, but the absolute risk for any individual patient is low. Individualizing the risk/benefit ratio would lead to cost effective care.
8216402 Detection of human T lymphotropic virus type I tax gene in salivary gland epithelium from 1993 Oct OBJECTIVE: To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjögren's syndrome (SS). METHODS: Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present. RESULTS: Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients. CONCLUSION: None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.
8185700 Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of 1994 May OBJECTIVE: To determine the content of two crosslinks, pyridinoline (a mature crosslink) and pentosidine (a senescent crosslink), in human articular cartilage, and to examine the effect of bone and joint disorders on the content of those crosslinks in articular cartilage. METHODS: After pretreatment with SP-Sephadex C-25, high-performance liquid chromatography was conducted on a hydrolysate of human articular cartilage from 53 patients with one of the following diseases: osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, femoral head necrosis, and renal osteodystrophy (ROD). RESULTS: Pyridinoline levels were either unchanged with age or were slightly decreased in elderly patients. Pentosidine levels increased with age in the entire patient population. There was no significant difference in the pyridinoline content among the study groups, but there was a significant difference in pentosidine content (P < 0.001). ROD patients had the highest mean level of pentosidine (407 mumoles/mole of hydroxyproline), and RA patients had a higher mean level than age-matched OA patients (214 versus 103 mumoles/mole of hydroxyproline). CONCLUSION: Bone and joint disorders do not affect the pyridinoline content in articular cartilage, but they do not affect the pentosidine content.
8235913 [Immunoglobulin decrease accompanying adverse reactions with bucillamine]. 1993 Aug Forty-two RA patients treated with Bucillamine (B) were divided into two groups with (n = 26) and without (n = 16) adverse reactions, and IgG, M, A and total protein concentration x globulin ratio (Ig) before and after B were compared. IgG did not differ before B administration, but was significantly lower in the adverse reactions group after B, and in each group it was significantly lower after B treatment with a much greater decrease demonstrated in the adverse reactions group. IgA before B did not differ either between the two groups or between before and after B administration in the non-adverse reaction group, but was significantly lower only after B in the adverse reaction group. IgM did not differ either before or after B treatment between the two groups, and was significantly lower following B administration in both groups. Ig showed results similar to IgA. In the adverse reaction group, IgG, A, M and Ig recovered following suspension of administration. It is concluded that the adverse reaction brought on by B administration might occur with the decrease in immunoglobulin.
8062449 Changes in rheumatoid factor and monoclonal IgG antibody specificity after site-specific m 1994 Sep Antigenic epitopes on the SKDWSFY region (positions 57-63) of human beta 2-microglobulin (beta 2m) reacting in ELISA with polyclonal and monoclonal human IgM rheumatoid factors (RF) as well as with monoclonal mouse IgG anti-beta 2m antibodies were studied after site-specific mutation of single or double beta 2m amino acid residues. Single site-specific mutations at lysine 58 and serine 61 produced a major decrease (50-100%) in reactivity of polyclonal IgM RF with beta 2m. Mutations at serine 57, tryptophane 60, and phenylalanine 62 also induced substantial decrements (25-49%) in IgM RF reactivity. beta 2m mutants containing double amino acid mutations including one residue outside the SKDWSFY region along with four different mutations at tryptophane 60 also often showed marked decrements in IgM RF anti-beta 2m reactivity. Site-specific mutations at virtually all residues within the SKDWSFY beta 2m region produced a major decrease in reactivity of two of three monoclonal human IgM RF. Results with nine murine IgG anti-beta 2m mAbs often showed an entirely different profile. Site-specific mutation of aspartic acid at position 59 produced a 50-100% decrease in binding of nine mAbs. Serine at position 61 and tyrosine at 63 also appeared to represent important residues for antigenic determinants reacting with anti-beta 2m mAbs. Results of mapping discrete epitopes using glycine substitution within overlapping 7-mers of beta 2m linear sequence compared with site-specific mutation of single beta 2m residues were similar in many instances, but also often showed marked differences. A marked change in antigenic contribution of single amino acid residues to beta 2m antigenic epitopes frequently depended on what residues were mutated to. Our findings emphasize that single residues within a small seven amino acid, solvent-accessible antigenic stretch of primary beta 2m sequence vary considerably in their contribution to the reactive antigenic structures for IgM RF as well as monoclonal IgG antibodies.