Biomedical subjects

Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 109 records · Page 6Linked to original sources

PubMed1997

Effects of various absorption enhancers on the intestinal absorption of water soluble drugs by in vitro Ussing chamber method: correlation with an in situ absorption experiment.

The effect of absorption enhancers on the small and large intestinal absorption of drug in rats was examined using an in vitro modified Ussing chamber method, and the results were compared with those from an in situ absorption experiment. Phenol red was chosen as a model drug, while the absorption enhancers used were sodium glycocholate (Na-GC), sodium taurocholate (Na-TC), sodium deoxycholate (Na-DC), EDTA, sodium salicylate (Na-Sal), sodium caprate (Na-Cap), diethyl maleate (DEM) and N-lauryl-beta-D-maltopyranoside (LM), all used at a concentration of 20 mM. This modified Ussing chamber method showed that Na-DC, EDTA and LM were the most effective absorption enhancers in the large intestine. A good correlation exists between the area under the curve (AUC) (in situ loop model) and the cumulative amount of phenol red absorbed (in vitro modified Ussing chamber method). These results indicated that the in vitro modified Ussing chamber method can be used to evaluate the effects of various absorption enhancers in the intestine.

Animals↗

PubMed1997

Signal transduction of granulocyte macrophage-colony stimulating factor in a human endothelium-derived cell line.

Granulocyte macrophage-colony stimulating factor (GM-CSF) regulates the growth and differentiation of hematopoietic cells and is also involved in angiogenesis. The induction of protein tyrosine phosphorylation is critical for cytokines and growth factor-mediated signal transduction. The protein tyrosine kinase (PTK), JAK2 is involved in signaling through a number of cytokine receptors, including GM-CSF receptors. In the present study, we investigated the effect of GM-CSF on the cell cycle and protein tyrosine phosphorylation in a human endothelial cell-derived cell line, EA.hy 926 cells. GM-CSF induced the cell cycle progression and tyrosine phosphorylation of cellular proteins including JAK2 kinase in EA.hy 926 cells. Herbimycin A, a PTK inhibitor, completely blocked the GM-CSF-induced cell cycle progression, protein tyrosine phosphorylation and JAK2 kinase activation in EA.hy 926 cells. Our results demonstrate that protein tyrosine phosphorylation and JAK2 kinase activation are closely related to the GM-CSF-mediated signal transduction and growth in vascular endothelial cells, and suggest the efficacy of herbimycin A in controlling angiogenesis.

Benzoquinones↗

PubMed1997

The use of bronchofiberscopy for diagnosis of allergic bronchopulmonary aspergillosis.

To assess the use of bronchofiberscopy for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA), we retrospectively analyzed bronchofiberscopic and pathologic findings of specimens obtained by bronchofiberscopy in 8 patients who met the British criteria for ABPA. Two of the 8 patients completely met Rosenberg's primary criteria for ABPA, while the remaining 6 lacked only 1 or 2 immunologic and radiographic conditions of the criteria. Bronchofiberscopic inspection revealed the presence of mucus plugs in all patients. Pathologic examination of plug specimens obtained by suction from 6 of 7 of these patients showed that the plugs consisted of allergic mucin containing fungal hyphae, diagnostic of ABPA. Bronchofiberscopy appears to be a useful tool in the diagnosis of ABPA, if immunologic and radiographic findings are not typical of ABPA. This bronchofiberscopic method is easily applicable for diagnosing allergic bronchopulmonary fungal disease (ABPFD) in addition to ABPA.

Adolescent↗

PubMed1997

[Tuberculosis in patients with human immunodeficiency virus infection].

Six men (mean age: 36.3 +/- 29 years) infected with the human immunodeficiency virus (HIV), four Japanese and two from Myammar, were admitted to our hospital for treatment of tuberculosis. In five, HIV positivity on serologic testing was first found when tuberculosis was diagnosed. The mean CD4 cell count was 37.3 +/- 29.6/microliters. Results of tuberculin skin tests were negative in 5 patients. One patient had pulmonary tuberculosis and 5 had miliary tuberculosis. Hilar and mediastinal lymphadenopathy was found on chest X-ray films in 4 patients and superficial lymphadenopathy was found in all patients. All patients had positive mycobacterial cultures of sputum and 2 patients had positive tests for acid-fast bacilli on smears of lymph-node aspirates. In one patient with tuberculosis meningitis, a culture of cerebrospinal fluid for acid-fast bacilli was positive. Epithelioid cell granulomas were found in samples of lung, liver, and bone marrow from 4 patients. Mycobacterium tuberculosis was isolated from all patients, and was not resistant to isoniazid, rifampicin, ethambutol, or streptomycin. Therefore all patients responded well to treatment of tuberculosis.

AIDS-Related Opportunistic Infections↗

PubMed1997

[An observation on tuberculosis associated with HIV infection in Japan].

OBJECTIVE: To observe the reported cases of tuberculosis (TB) with HIV infection in Japan, in terms of their main clinical features and related factors. METHODS: A voluntary reporting network has been organized by the authors who are specialists of TB or respiratory medicine in tuberculosis institutions located roughly all over the country. The members have been encouraged to report not only their own cases but cases seen by their friends or in other institutions. RESULTS: By the end of 1996, a total of 71 cases have been reported of which 59 were TB and 12 NTM cases. Nationality of the cases were; Japan 48, Other Asian countries 16, Others 7. All of the NTM cases were Japanese. 30% of the cases were aged less than 30 years, 24% were thirties, 24% forties, 17% fifties and 6% were those aged 60 years or older. The cases were clearly younger than the TB cases in the national TB registry, and older than HIV-infected persons as known from the HIV surveillance system. 97% of the TB cases were bacteriologically confirmed cases. Eight of NTM cases were positive for MAC, others for M.kansasii. 42% of the cases had extra-pulmonary disease, including disseminated infections seen among 19%. Of TB cases 25% were excreting bacilli resistant to any of the anti-TB drugs which was higher than in the case of general TB population (10-15%). 11% of TB cases had past history of TB treatment. The cases had severe immunological impairment, 79% of the cases having CD4+ cell count less than 100. The route of HIV infection were; 51% heterosexual, 13% homosexual, 13% through blood preparations, etc. DISCUSSION: Although there may be many cases not included in this observation, it is considered to well reflect the real situation of the problem of Japan. More attention should be paid to HIV infection of the patients in the clinical practice of TB in Japan.

AIDS-Related Opportunistic Infections↗

PubMed1996

Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2.

We show in this manuscript that expression of the mRNA for sterol regulatory element-binding protein-2 (SREBP-2) is regulated by the cellular sterol level in cultured HeLa cells. We have cloned the 5'-flanking region of the gene encoding human SREBP-2. Characterization of this region shows the minimum 50-base pair segment, which contains a 10-base pair sterol regulatory element 1 (SRE-1) identical to the one in the human LDL receptor promoter, confers sterol responsiveness when fused to the luciferase reporter gene. Enforced expression of the truncated SREBP-2 protein (amino acid residues 1-481) also shows that this upstream segment contains the information required for transcriptional activation. The luciferase assays using mutant versions of the reporter genes reveal that the sterol-dependent transcriptional regulation is mediated by two nearby motifs, the SRE-1 and the NF-Y binding site (the inverted CCAAT box, ATTGGC); the latter is reported to play a critical role in sterol-dependent regulation of 3-hydroxy-3-methylglutaryl-coenzyme A synthase and farnesyl diphosphate synthase genes (Jackson, S. M., Ericsson, J., Osborne, T. F., and Edwards, P. A. (1995) J. Biol. Chem. 270, 21445-21448). Gel mobility shift assays demonstrate that the transcription factor NF-Y truly binds to the ATTGGC sequence. These findings suggest that the activity of SREBP-2 is controlled not only post-translationally by proteolytic activation of the precursor protein but also transcriptionally by itself together with NF-Y.

Binding Sites↗

PubMed1996

Regulation of fatty acid synthase expression by cholesterol in human cultured cells.

The regulation of fatty acid synthase (FAS) expression by sterols in a cultured human hepatoblastoma cell line, Hep G2, was studied. When cells were treated with compactin in a medium containing lipoprotein deficient serum, FAS mRNA level increased 1.6-fold. A squalene synthase inhibitor, TAN1607A, decreased both free and esterified cholesterol contents in Hep G2 cells and increased mRNA levels for FAS, HMG-CoA reductase, squalene synthase and LDL receptor. However, for the increment of FAS mRNA, a 10-fold higher concentration of this inhibitor was needed. These results demonstrate that the concentration of cellular cholesterol which regulates FAS expression is necessarily lower than the levels which regulate other sterol sensitive genes. FAS mRNA was also increased by an inhibitor of SREBP degradation as well as chenodeoxycholic acid. These results indicate that FAS mRNA expression is regulated by cholesterol and is mediated through SREBPs. The implications of the different modes of sterol regulation of FAS and LDL receptor expression are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗

PubMed1996

Fas antigen expression on synovial cells was down-regulated by interleukin 1 beta.

Recent reports revealed that Fas antigen is functionally expressed on human synovial cells and apoptosis can be induced in these cells by anti-Fas antibody. We examined the effect of interleukin 1 beta (IL-1 beta) on Fas antigen-mediated apoptosis on human synovial cells in vitro. Using flowcytometric analysis, IL-1 beta inhibited Fas antigen expression on synovial cells in a dose-dependent fashion. No significant difference of Fas antigen gene expression between IL-1 beta-treated and untreated synovial cells was observed by RT-PCR analysis, suggesting that the inhibitory effect of Fas antigen expression by IL-1 beta is at posttranscriptional level. Apoptosis of synovial cells was easily induced by treatment of these cells with anti-Fas antibody. In contrast, pretreatment of synovial cells with IL-1 beta protected these cells against Fas antigen-mediated apoptosis. The expression of bcl-2 on synovial cells, known to interfere with the apoptotic process mediated by the Fas antigen, was not influenced by IL-1 beta. Our results suggest that IL-1 beta inhibits Fas antigen-mediated apoptosis of synovial cells and may perpetuate the hyperplasia of the synovium in patients with rheumatoid arthritis.

Apoptosis↗

PubMed1996

Inhibition of Fas antigen-mediated apoptosis of rheumatoid synovial cells in vitro by transforming growth factor beta 1.

OBJECTIVE: To investigate the mitogenic and anti-apoptotic effects of transforming growth factor beta 1 (TGF beta 1) on rheumatoid synovial cells in vitro. METHODS: Synovial cells were cultured with or without TGF beta 1. After incubation, the proliferative response of synovial cells and the expression of Fas antigen and bcl-2 on synovial cells were examined. Finally, Fas antigen-mediated apoptosis of synovial cells was investigated by the addition of anti-Fas antibody. RESULTS: TGF beta 1 enhanced the proliferation of synovial cells in a dose-dependent manner. In addition, Fas antigen expression on synovial cells was inhibited by the addition of TGF beta 1 with up-regulation of bcl-2 expression. The addition of anti-Fas antibody induced synovial cell apoptosis. However, stimulation of synovial cells with TGF beta 1 became markedly resistant to Fas antigen-mediated apoptosis. The results were not affected by the addition of a neutralizing antibody to platelet-derived growth factor type AA (PDGF-AA), which suggests that the effect of TGF beta 1 on synovial cells was promoted via PDGF-AA-independent mechanisms. CONCLUSION: Our results suggest that TGF beta 1 promotes synovial cell proliferation through its mitogenic effect on synovial cells and interference with the apoptotic process mediated by the Fas antigen, resulting in the perpetuation of the synovial hyperplasia in patients with rheumatoid arthritis.

Apoptosis↗

PubMed1996

Wegener's granulomatosis overlapped with Takayasu arteritis.

A 27-year-old woman presented with destructive scleritis of the left eye with subcutaneous haemorrhage and swelling of the lower eyelid. She had experienced recurrent nasal bleeding for the last six years, and chronic sinusitis resulting in the destruction of the nasal septum and left maxillary sinus. Nasal mucosal biopsies demonstrated granuloma formation with no evidence of vasculitis. The level of serum cytoplasmic anti-neutrophil cytoplasm antibody (c-ANCA) was significantly increased. Furthermore, multiple sites of complete occlusions were detected in the left subclavian and common carotid arteries by subtraction angiography and MRI. We describe a case of Wegener's granulomatosis overlapped with Takayasu arteritis, which, to our knowledge, has not been previously reported.

Adult↗

PubMed1996

Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells.

This study was undertaken to investigate the immunomodulatory effect of clarithromycin against synovial fibroblast-like cells (synoviocytes). Synovial tissue obtained from rheumatoid arthritis (RA) or osteoarthritis (OA) patients was enzymatically digested to separate synoviocytes. The synoviocytes were cultured with or without cytokines in the presence of various concentrations of clarithromycin. The expression of costimulatory molecules was examined on the surface of the synoviocytes, using specific MoAbs and flow cytometry. The production of cytokines by synoviocytes was also measured using an immunoenzymatic assay. Finally, autologous T cells were stimulated by interferon-gamma (IFN-gamma)-treated synoviocytes in response to purified protein derivative (PPD). In some experiments, MoAbs specific for costimulatory molecules or clarithromycin were added and 3H-thymidine incorporation was counted. Intercellular adhesion molecule-1 (ICAM-1), LFA-3 and vascular cell adhesion molecule-1 (VCAM-1) were detected on the surface of both RA and OA synoviocytes. However, ICAM-2, B7-1 and B7-2 were not detected, and cytokines failed to induce these molecules. Both spontaneous and up-regulated expression of ICAM-1, LFA-3 and VCAM-1 by IFN-gamma, IL-1beta or 12-o-tetradecanoyl phorbol 13-acetate (TPA) were markedly suppressed by clarithromycin in a dose-dependent manner at concentrations between 0.1 and 10 microg/ml. The production of IL-1beta, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-1alpha and tumour necrosis factor-alpha (TNF-alpha) by synoviocytes was detected. Clarithromycin significantly suppressed the production of these cytokines, but did not enhance IL-10 production. Finally, autologous T cells were stimulated by IFN-gamma-treated synoviocytes in response to PPD. As clarithromycin suppressed HLA-DR and costimulatory molecule expression was enhanced by IFN-gamma, autologous T cell proliferation was markedly inhibited by clarithromycin. Clarithromycin has a considerable immunosuppressive effect on synoviocytes by inhibiting costimulatory molecule expression, cytokine production and antigen-specific T cell proliferation induced by synoviocytes.

Anti-Bacterial Agents↗

PubMed1996

The effects of the immunosuppressant rapamycin on the growth of rheumatoid arthritis (RA) synovial fibroblast.

RA is a chronic inflammatory disease characterized by mononuclear cell infiltration and the overgrowth of synovial fibroblast. This invasive growth of synovial tissues corresponds with the progressive destruction of articular cartilage and bone. Several immunosuppressive agents, such as cyclophosphamide, cyclosporin A and mizoribine, have been clinically used to control disease progression, though relatively little is known of their effects on rheumatoid synovium. Rapamycin exhibits a strong immunosuppressive activity by acting on T cell signalling pathways. In the present study we examined the effects of rapamycin on the growth of synovial fibroblast isolated from RA patients. Platelet-derived growth factor (PDGF) is a potent growth factor in synovial fibroblasts isolated from RA patients. PDGF and serum stimulation resulted in a rapid phosphorylation of tyrosine and activation of mitogen-activated protein kinase (MAP kinase), 70-kD-S6 kinase (P70S6k) and 90-kD-S6 kinase (P90rsk). Rapamycin, a macrolide immunosuppressant, inhibited completely growth factor-induced synovial fibroblast proliferation and P70S6k activation. In contrast, tyrosine phosphorylation and activation of MAP kinases and P90rsk were not influenced by rapamycin treatment. Our data demonstrate that growth factor-mediated P70S6k activation is closely related to the growth of synovial fibroblast, and suggest the efficacy of rapamycin for controlling synovial hyperplasia in RA.

Arthritis, Rheumatoid↗

PubMed1996

Staphylococcal enterotoxin B-specific adhesion of murine splenic T cells to a human endothelial cell line.

The presence of a putative autoantigen of autoimmune disorder in a target organ may cause accumulation of specific T cells in the inflammatory region. One of the mechanisms of such accumulation involves the migration of specific-circulating T cells through the endothelial cells into the target lesion. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific migration of circulating T cells to the target organ. We used a superantigen to investigate specific T-cell adhesion to endothelial cells, because it stimulates a large proportion of T cells with particular V beta elements and adhesion of T cells to the endothelium is a vital step in the migration process. Adhesion of murine T cells to the human endothelial cell line, EA.hy926, was specifically increased in the presence of staphylococcal enterotoxin B (SEB). The increase was interferon-gamma (IFN-gamma)-dependent, and consisted mainly of CD4+ T cells. V beta 8.1,2+ T cells preferentially adhered to endothelial cells in the presence of SEB compared with V beta 6+ T cells. Pretreatment of endothelial cells with SEB increased the adherence of V beta 8.1,2+ T cells, while anti-human leucocyte antigen (HLA)-DR and -DQ antibodies inhibited the increased adherence of V beta 8.1,2+ T cells. Our results demonstrate that increased T-cell adhesion to endothelial cells is SEB specific, and that the specificity is dependent on major histocompatibility complex (MHC) class II molecules expressed on endothelial cells and on the recognition of the SEB-MHC class II complex by V beta 8.1,2+ T cells.

Animals↗

PubMed1996

TNF-alpha-mediated expression of membrane-type matrix metalloproteinase in rheumatoid synovial fibroblasts.

Degradation of the extracellular matrix plays an important role in rheumatoid articular destruction. Rheumatoid synovial fibroblasts secrete a large amount of matrix-degrading metalloproteinases (MMPs), which initiate tissue damage by proteolytic degradation of collagens and proteoglycans. Cytokines, such as interleukin-1 alpha, -1 beta or tumour necrosis factor (TNF)-alpha, are potent inducers of MMPs in rheumatoid synovial fibroblasts, MMPs are synthesized and secreted as latent pro-enzymes and their activation is achieved by proteolytic cleavage or the propeptide domain at the N-terminus of the molecule. Thus, the interaction of the pro-enzymes with specific activators determines the enzymatic activity in the extracellular space. In the present study, we identified a novel mechanism for the activation of pro-MMP-2, which can be achieved through the interaction of the inflammatory cytokine, TNF-alpha, with synovial fibroblasts. Although MMP-2 is constitutively secreted by synovial fibroblasts as a pro-enzyme, stimulation of fibroblasts by TNF-alpha-induced secretion of MMP-2 in an active form. In support of this result, TNF-alpha stimulation-induced membrane-type matrix metalloproteinase (MT-MMP), a newly identified MMP-2-specific activator on synovial fibroblasts. Cycloheximide analysis demonstrated that protein synthesis may be required for TNF-alpha-mediated MT-MMP expression on synovial fibroblasts. Our results suggest that TNF-alpha induces MMP-2 activation in part by up-regulating MT-MMP expression, thus representing a new mechanism for cytokine-mediated articular destruction in rheumatoid arthritis (RA).

Arthritis, Rheumatoid↗

PubMed1996

Cytokine production by endothelial cells infected with human T cell lymphotropic virus type I.

OBJECTIVE: To investigate the ability of human T cell lymphotropic virus type I (HTLV-I) to infect endothelial cells and induce cytokine production by these cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were cocultured with HTLV-I infected T cell line (MT-2 cells) or uninfected T cell line (CEM cells). RESULTS: Following coculture with MT-2 cells, endothelial cells expressed HTLV-I specific core antigens. Endothelial cells cocultured with MT-2 cells produced significant amounts of several cytokines, including interleukin (IL)-1 alpha, IL-6, granulocyte colony stimulating factor (G-CSF), and granulocyte/macrophage colony stimulating factor (GM-CSF), compared with endothelial cells cocultured with CEM cells. Coculturing of endothelial cells with MT-2 and CEM cells failed to produce detectable amounts of IL-1 beta and tumour necrosis factor alpha (TNF-alpha). The production of cytokines by endothelial cells cocultured with MT-2 cells was more persistent than that by endothelial cells cocultured with CEM cells after several passages. Furthermore, the production was blocked by cocultivation of endothelial cells and MT-2 cells using the Millicell system. Finally, after cocultivation of endothelial cells and MT-2 cells, endothelial cells positive for HTLV-I antigen were stained by anti-GM-CSF antibody. CONCLUSIONS: HTLV-I can infect endothelial cells, resulting in their active production of several cytokines, such as IL-1 alpha, IL-6, G-CSF, and GM-CSF. These findings strongly suggest that the excess production of these cytokines by HTLV-I infected endothelial cells may be involved in the pathogenesis of HTLV-I associated inflammatory diseases.

Cell Line↗

PubMed1996

Thyroid-stimulating hormone inhibits Fas antigen-mediated apoptosis of human thyrocytes in vitro.

The mechanisms of TSH-induced growth stimulation of thyrocytes in vivo have yet to be elucidated. We examined the antiapoptotic effect of TSH toward Fas antigen-mediated apoptosis of thyrocytes. Fas antigen was expressed on approximately 40% of unstimulated thyrocytes, and the expression was significantly inhibited by the addition of TSH in a dose-dependent manner. Treatment of thyrocytes with 8-bromo-cAMP mimicked the effect of TSH, suggesting that the inhibitory effect of TSH on Fas antigen expression was mediated by activating protein kinase A. In contrast, treatment of thyrocytes with either interleukin-1 beta (IL-1 beta) or interferon- gamma (IFN gamma) markedly increased Fas antigen expression on thyrocytes, and these effects were inhibited in the presence of TSH. The expression of the protooncogene product Bcl-2 did not change after the addition of TSH, 8-bromo-cAMP, IL-1 beta, IFN gamma, or a combination of TSH and IL-1 beta or IFN gamma. When thyrocytes stimulated with either IL-1 beta or IFN gamma were treated with anti-Fas IgM mAb, the cells were committed to apoptosis, whereas this apoptotic process was significantly inhibited by the addition of TSH. These results indicate that the Fas antigen is functionally expressed on the surface of thyrocytes, and TSH inhibits Fas antigen-mediated apoptosis of thyrocytes through the inhibitory effect of Fas antigen expression, resulting in the promotion of growth of the thyroid gland.

Antibodies, Monoclonal↗

PubMed1996

[Untoward effects of low dose methotrexate therapy in rheumatoid arthritis].

Sixty patients with rheumatoid arthritis who were administered weekly low dose methotrexate (MTX) were retrospectively analyzed for their untoward effects of MTX by interviewing to the patients and by the medical records. Cough and sputa were the most frequent symptoms (23.3%) and gastrointestinal symptoms were the next (20%). Five of 60 patients (8.2%) showed liver function test abnormalities, and four (6.7%) exhibited transient exacerbation of arthralgia for several hours to a few days after MTX administration. Three patients (5%) suffered from interstitial pneumonitis. Hair loss was seen in 3 patients (5%), and headache, leucocytepenia, fever, skin eruption, abnormal taste, hemorrhagic cystitis, and flashing were experienced in a patient, respectively. Three (5%) suffered from fungal infection, and herpes zoster, sepsis, and osteomyelitis were experienced in each one patient, respectively. MTX was withdrawn in three patients (5%) because of cough and sputa the drug was withdrawn in other three patients because of the interstitial pneumonia, and was drawn in another three patients because of transient exacerbation of arthralgia. The drug was withdrawn in each one patient, because of nausea and vomiting, skin eruption, osteomyelitis, and sepsis, respectively. Overall, MTX were withdrawn in 21 patients (35%), and, of those, 13 patients (21.7%) because of untoward effects and 8 patients (13.3%) because of the lack of efficacy.

Adult↗

PubMed1996

Increased circulating serum amyloid A protein derivatives in rheumatoid arthritis patients with secondary amyloidosis.

Secondary amyloidosis, a serious complication of chronic inflammatory diseases, is caused by the deposition of amyloid fibrils in various organs. The major component of amyloid fibrils is derived from serum amyloid A protein (SAA) by proteolysis. To explore the mechanisms of amyloidogenesis, we measured SAA concentrations in the sera of 38 patients with rheumatoid arthritis (RA) without secondary amyloidosis and in the sera of 18 RA patients with secondary amyloidosis, using the latex agglutination immunoassay. We also determined whether SAA was present as a full-length protein in the sera of RA patients by immunoblotting. Although SAA concentrations were elevated in the sera, there were no significant differences in these concentrations between RA patients without amyloidosis (128.2 +/- 145.4 micrograms/ml) and RA patients with amyloidosis (165.0 +/- 162.9 micrograms/ml). To test for qualitative abnormalities of SAA, the isolated SAA proteins from individual RA patients were analyzed by anti-SAA immunoblot. In addition to full-length SAA protein, 6-kd and 4.5-kd SAA-derived fragments were detected in the sera of RA patients, and the ratio of these fragments to total SAA proteins was significantly higher in RA patients with amyloidosis (37.0% +/- 0.7%) compared with that of RA patients without amyloidosis (15.0% +/- 5.5%). Although a high serum level of SAA is a predisposing condition for amyloid formation in RA patients, our data suggest that the increased circulating proteolytic cleavage of SAA may potentially contribute to the development of AA-amyloid deposition.

Adult↗