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Biomedical subjects

C Gabay

Publications and source records attributed to C Gabay.

At least 55 records · Page 3Linked to original sources

Corticosteroid therapy for the treatment of acute attacks of crystal-induced arthritis: an effective alternative to nonsteroidal antiinflammatory drugs.

To evaluate glucocorticoids as an alternative to nonsteroidal antiinflammatory drugs in patients with crystal-induced arthritis, a study was conducted in 27 patients with acute attacks of gout or chondrocalcinosis. Patients with contraindications to nonsteroidal antiinflammatory drug therapy were given either a single intramuscular injection of 7 mg betamethasone (group B, n = 10) or, if they were receiving anticoagulant therapy, a single intravenous injection of 125 mg methylprednisolone (group C, n = 7). The remaining patients (group A, n = 10) were given diclofenac in a dosage of 150 mg per day for three days then 75 mg per day for three days. Efficacy was evaluated based on the self-evaluated subjective improvement (%) and on the severity of joint swelling on days 1, 3, and 6. Both parameters improved promptly in all three groups. C-reactive protein decreased between baseline and day 6. Few patients had relapses. Glucocorticoid therapy was well tolerated. Our data show that a single intramuscular or intravenous injection of a glucocorticoid is safe and effective in patients with crystal-induced arthritis and risk factors for intolerance to nonsteroidal antiinflammatory drugs.

Administration, Oral↗

Adult seronegative arthritis with antinuclear antibodies: a distinct group of patients with a different immunogenetic pattern from seropositive rheumatoid arthritis and a good outcome.

To determine whether patients with rheumatoid factor (RF)-negative, antinuclear antibody (ANA)-positive oligo/polyarthritis are clinically and immunogenetically distinct from RF-positive rheumatoid arthritis (RA) and whether this subset of patients is the adult counterpart of early-onset pauciarticular juvenile chronic arthritis (EOPA JCA), we retrospectively studied 20 adult patients with RF-negative, ANA-positive arthritis. After a median duration of 3.25 years, only half of our patients had active synovitis. Seventy-five per cent were completely or reasonably self-sufficient according to the HAQ index. In contrast to the results in a group of 30 RF-positive RA patients, the percentage of patients having at least one of the susceptibility alleles (HLA DR1 or HLA-DR4) was not significantly higher in patients with RF-negative, ANA-positive arthritis than in controls. Furthermore, none of our RF-negative, ANA-positive patients had two susceptibility alleles, whereas 16.5% of RF-positive RA patients had both DR1 and DR4 or DR4 homozygosity. In conclusion, our results show that patients with RF-negative, ANA-positive oligo/polyarthritis are immunogenetically distinct from RF-positive RA and tend to have a better articular prognosis. The absence of typical ocular features and of the characteristic HLA-DR markers suggests that these patients cannot be considered as the adult counterpart of EOPA JCA.

Adult↗

Soluble interleukin-6 receptor strongly increases the production of acute-phase protein by hepatoma cells but exerts minimal changes on human primary hepatocytes.

Interleukin-6 (IL-6) interacts with a system of receptors, which include a 80-kDa IL-6-binding subunit (IL-6R) and a transducing element (gp130). The soluble form of IL-6R (sIL-6R) can bind its ligand and induce cellular responses by association with gp130, thus acting as an IL-6 agonist. We and others have previously shown that the responsiveness to IL-6 is different in hepatoma and human primary hepatocytes. We therefore compared the effects of sIL-6R on the two types of cells, and on the B9 hybridoma, another IL-6-sensitive cell line. Human primary hepatocytes, hepatoma cells PLC/PRF/5, and B9 cells were incubated with different concentrations of IL-6, sIL-6-R, or both. The hepatocyte culture supernatants were tested for their content of acute-phase proteins (APP). The proliferation of B9 cells was assessed by a colorimetric method. Results showed that sIL-6R alone markedly increased the production of APP by hepatoma cells in a dose-dependent manner, but affects only minimally primary hepatocytes and the proliferation of B9 cells. The combinations of IL-6R and its ligand enhanced the effects of Il-6 alone in both PLC/PRF/5 and B9 cells, but had no effect on primary hepatocytes. An immunohistochemical study indicated that the cell-surface expression of IL-6R was dramatically lower in hepatoma cells than in primary hepatocytes. In conclusion, our results show that the expression of IL-6R is low in the hepatoma cell PLC/PRF/5 when compared with primary hepatocytes and that this difference can, at least partly, explain their deficient responsiveness to IL-6. On the other hand, it appears that IL-6R expression by primary hepatocytes is sufficient and that circulating sIL-6R is unlikely to play a significant role in the modulation of IL6 effects.

Acute-Phase Proteins↗

The genomic region of rbcLS in Synechococcus sp. PCC 7942 contains genes involved in the ability to grow under low CO2 concentration and in chlorophyll biosynthesis.

Several genes involved in the ability of Synechococcus sp. PCC 7942 to grow under different CO2 concentrations were mapped in the genomic region of rbcLS (the operon encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase). Insertion of a cartridge encoding kanamycin resistance within open reading frame (ORF) 78, designated ccmJ, located 7 kb upstream of rbcLS, resulted in a kanamycin-resistant, high-CO2-requiring mutant, M3, which does not contain normal carboxysomes. ccmJ shows significant homology to csoS1 encoding a carboxysomal shell polypeptide in Thiobacillus neopolitanus. Analysis of the polypeptide pattern of a carboxysome-enriched fraction indicated several differences between the wild type and the mutant. The amount of the ribulose-1,5-bisphosphate carboxylase/oxygenase subunits was considerably smaller in the carboxysomal fraction of the mutant when compared to the wild type. On the basis of the sequence analyses, ORF286 and ORF466, located downstream of ccmJ, were identified as chlL and chlN, respectively, which are involved in chlorophyll biosynthesis in the dark.

Algal Proteins↗

IL-1 receptor antagonist (IL-1Ra) does not inhibit the production of C-reactive protein or serum amyloid A protein by human primary hepatocytes. Differential regulation in normal and tumour cells.

The synthesis of some class 1 acute-phase proteins (APP), including C-reactive protein (CRP) and serum amyloid A (SAA) protein is completely blocked by the IL-1 receptor antagonist (IL-1Ra), whereas the production of fibrinogen, a class 2 APP, is increased by IL-1Ra in hepatoma cells, but this has never been tested in human hepatocytes in primary culture. Since previous studies on the contributions of cytokine inhibitors in connective tissues diseases suggested that IL-1 and tumour necrosis factor-alpha (TNF-alpha) might play an important role in the regulation of CRP, we decided to examine in more detail the respective roles of IL-1 beta, IL-6, and TNF-alpha and their inhibitors in the production of APP by human primary hepatocytes versus the hepatoma cell line PLC/PRF/5. In the hepatoma cell line, IL-1 beta and/or TNF-alpha had synergistic effects with IL-6 on the production of CRP and SAA. In contrast, these cytokines were devoid of effect in normal hepatocytes. The production of fibrinogen was increased by IL-6 and decreased by IL-1 (and TNF-alpha) in both cell types. The secretion of CRP and SAA by primary hepatocytes incubated with a cytokine-rich mononuclear cell-conditioned medium was totally unaffected by IL-1Ra or anti-TNF-alpha antibodies. In contrast, the addition of IL-1Ra increased the production of fibrinogen by both hepatoma cells and primary hepatocytes incubated with the mononuclear cell-conditioned medium. We therefore conclude that IL-1 beta and TNF-alpha do not exert any significant effect on the synthesis of CRP and SAA by human primary hepatocytes.

C-Reactive Protein↗

Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response.

OBJECTIVE: To determine whether the lack of acute-phase protein (APP) response in numerous patients with polymyositis/dermatomyositis (PM/DM) is related to an imbalance between cytokines and cytokine inhibitors. METHODS: Levels of C-reactive protein (CRP), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), IL-6, IL-1 receptor antagonist (IL-1ra), TNF soluble receptor 55 kd (sTNFR 55 kd), and sTNFR 75 kd were tested in the serum of 15 patients with PM/DM, 14 patients with spondylarthropathies (SPA), and 12 healthy blood donors. Serum IL-1 beta, TNF alpha, IL-6, IL-1ra, sTNFR were measured by specific immunoassays. RESULTS: Serum levels of CRP were lower in PM/DM patients than in SPA patients. Normal or slightly elevated CRP values were found in 10 of the 15 PM/DM patients, 7 of whom had active myositis. Serum IL-6 levels were significantly higher in SPA patients than in PM/DM patients, whereas serum IL-1ra and sTNFR levels were significantly higher in PM/DM than in SPA patients. IL-1ra levels were particularly elevated in patients with active myositis and decreased in response to treatment. CONCLUSION: These differences in cytokine levels, particularly IL-1ra, between PM/DM and SPA patients are indicative of distinct pathogenic mechanisms. High levels of IL-1ra may account for the weak APP response in some PM/DM patients. Our results suggest that measurement of IL-1ra, together with clinical examination, may provide useful information for the followup of PM/DM patients.

Adult↗

A case of scurvy presenting with cutaneous and articular signs.

This report is on a patient, who presented purpura and hemarthrosis in a context of vitamin C deficiency. This case gives us the opportunity to discuss the differential diagnosis, the clinical features, the pathogenicity and the treatment of this rare condition.

Ascorbic Acid↗

High CO2 concentration alleviates the block in photosynthetic electron transport in an ndhB-inactivated mutant of Synechococcus sp. PCC 7942.

The high-concentration CO2-requiring mutant N5 of Synechococcus sp. PCC 7942 was obtained by the insertion of a kanamycin-resistant gene at the EcoRI site, 12.4 kb upstream of rbc. The mutant is unable to accumulate inorganic carbon internally and exhibits very low apparent photosynthetic affinity for inorganic carbon but a photosynthetic Vmax similar to that of the wild type. Sequence and northern analyses showed that the insertion inactivated a gene highly homologous to ndhB, encoding subunit II of NADH dehydrogenase in Synechocystis sp. PCC 6803 (T. Ogawa [1991] Proc Natl Acad Sci USA 88: 4275-4279). When the mutant and the wild-type cells were exposed to 5% CO2 in air, their photosynthetic electron transfer capabilities, as revealed by fluorescence and thermoluminescence measurements, were similar. On the other hand, a significant decrease in variable fluorescence was observed when the mutant (but not the wild-type) cells were exposed to low CO2 under continuous light. The same treatment also resulted in a shift (from 38-27 degrees C) in the temperature at which the maximal thermoluminescence emission signal was obtained in the mutant but not in the wild type. These results may indicate that subunit II of NADH dehydrogenase is essential for the functional operation of the photosynthetic electron transport in Synechococcus under low but not high levels of CO2. We suggest that the inability to accumulate inorganic carbon under air conditions stems from disrupture of electron transport in this mutant.

Amino Acid Sequence↗

Occurrence of antiperinuclear, antikeratin, and anti-RA 33 antibodies in juvenile chronic arthritis.

OBJECTIVES: Antiperinuclear factor (APF), antikeratin antibodies (AKA), and anti-RA 33 antibodies are currently considered to be good markers for the diagnosis of adult rheumatoid arthritis with or without rheumatoid factor (RF). The prevalence of these markers was retrospectively reviewed in children with juvenile chronic arthritis (JCA) to determine whether they were associated with specific features. METHODS: One hundred and twenty-four patients with JCA participated in this study. Controls included 28 patients with juvenile systemic lupus erythematosus and 21 healthy children. Antiperinuclear factor and AKA were determined by indirect immunofluorescence on buccal mucosal cells and oesophagus sections respectively. Anti-RA 33 antibodies were detected using a Western blot technique on HeLa cell nuclear extract. RESULTS: Antiperinuclear factor was virtually absent in all the tested subgroups and anti-RA 33 antibodies were detected only in a subset of patients with RF positive polyarticular onset. Antikeratin antibodies were found in 27% of all children with JCA and in 42% of those with RF negative polyarticular onset. These results were statistically significant compared with healthy controls, but the presence of AKA was not specific to any patient subgroup. Moreover, in contrast with previous studies in adult RA, no relation was found between the presence of AKA and disease severity or activity. CONCLUSION: These data suggest that APF, AKA, and anti-RA 33 antibodies are not useful for the diagnosis or classification of JCA.

Antibodies, Antinuclear↗

Bone mineral density in patients with end-stage renal failure.

Renal osteodystrophy is a well-recognized complication of chronic renal failure (CRF) and is associated with a marked morbidity. Bone mineral density (BMD) has been shown to be the best predictor of fracture risk in different circumstances. In this cross-sectional study, we measured BMD using dual photon absorptiometry at three skeletal sites of functional importance such as the lumbar spine (LS), the femoral shaft (FS) and the femoral neck (FN) in 106 patients with end-stage renal failure (11 predialysis patients and 95 patients on maintenance dialysis). These skeletal sites are characterized by various relative amounts of trabecular and cortical bone. The results indicate that decreased bone mass was detectable in all skeletal sites before the beginning of dialysis and that BMD was negatively related to dialysis duration in LS and FS. Nevertheless, the deleterious effects of renal osteodystrophy were more pronounced at the FS level, where cortical bone is predominant. A separate analysis of BMD in both sexes revealed that females presented a more important bone loss in both cortical and trabecular bone than males. We did not find any significant difference in BMD at the three measured sites between patients on continuous ambulatory peritoneal dialysis and on regular hemodialysis. This study emphasizes the need to pay more attention to the prevention of bone loss in patients on CRF before the start of dialysis therapy, and to the fact that the female population might display a more pronounced susceptibility to bone loss.

Absorptiometry, Photon↗

Palindromic syndrome: appearance of chondrocalcinosis after 47 years of evolution.

We describe a case with a very long history of recurrent episodes of arthritis without radiological articular damage. After 47 years of followup, he developed chondrocalcinosis located only in previously affected joints. Our patient illustrates the heterogeneity of palindromic rheumatism, which should more appropriately be considered as a clinical syndrome. Our case gives us the opportunity to discuss the nosologic situation of palindromic rheumatism and the role of primary joint damage in the articular deposition of calcium pyrophosphate dihydrate.

Arthritis↗

Absence of correlation between interleukin 6 and C-reactive protein blood levels in systemic lupus erythematosus compared with rheumatoid arthritis.

To investigate if the low C-reactive protein (CRP) response frequently observed in systemic lupus erythematosus (SLE) is related to an impaired expression of interleukin 6 (IL-6), considered its main inducer, we studied serum IL-6 and CRP levels in 37 patients with SLE and 22 with rheumatoid arthritis (RA). Results show that in contrast to CRP, IL-6 levels are significantly higher in SLE than in RA. A linear regression analysis shows a positive correlation between levels of these 2 molecules in RA but not in SLE. Similarly, levels of fibrinogen, another acute phase protein mainly induced by IL-6, did not correlate with IL-6 in SLE. Our results suggest an impairment of part of the acute phase response to IL-6 that might play a role in the pathogenesis of SLE.

Antibodies↗

[Male-type scleroderma: the role of occupational exposure].

A number of occupational exposure risks have been suspected as potential causes of scleroderma (systemic sclerosis), particularly in males. These include silica dust and numerous organic chemicals. With particular reference to the type of employment, we have reviewed the charts of male scleroderma patients receiving treatment in our Rheumatology Department since 1976. Of 39 patients, 25 could be included in the present study. Among these, 14 (56%) had an occupational activity which put them at risk: 11 were exposed to silica dust, one to organic chemicals and two to both silica dust and chemicals. Mean exposure time was 14.5 years (range 4-33 years); and the interval between the beginning of exposure and the onset of scleroderma averaged 24.4 years (range 4-45 years). Considering these 14 cases as silica- or chemically-induced scleroderma, we found that, except for the absence of muscular involvement, the clinical features and prognosis were similar to those of "idiopathic" scleroderma patients. Antinuclear antibodies and autoantibodies directed against Scl-70 were also found in both occupationally induced and idiopathic scleroderma. Our results emphasize the unusually high frequency of occupational exposure in scleroderma in males. Hence, a detailed professional history should be taken for all scleroderma patients. Our results also suggest that, in certain cases, scleroderma should be classified as an occupational disease.

Adult↗

[Lumbosacral spina bifida associated with an intraspinal lipoma].

Spina bifida is a congenital malformation which occurs during the first weeks after conception. The association with intraspinal tumours, usually lipomas, is well known. During evaluation of back pain, we observed a case of occult spina bifida associated with extra- and intradural lipoma. Simultaneously the patient exhibited cutaneous, orthopedic and neurological signs. The clinical symptoms of lipoma are due to compression and elongation of the spinal cord causing tethered cord syndrome. The onset of neurological symptoms usually occurs in childhood. Late occurrences in adults are often associated with sphincter problems. CT scan and, in particular, magnetic resonance imaging (MRI) provide good visualization of intraspinal lipoma. Treatment is surgical.

Child↗

[The association of dermatomyositis with cancer: myth or reality?].

We present the case of a 56-year-old woman with proven dermatomyositis associated with an adenocarcinoma of the gallbladder. The association of dermatomyositis-polymyositis and cancer has been known for many years but is still controverted. The search for a malignancy in a patient with DM-PM should not be systematic but guided by abnormal history, physical examination and laboratory results.

Adenocarcinoma↗