[Acute disseminated lupus erythematosus. Diagnosis, course, principles of treatment].
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Acute Disease↗
Biomedical subjects
O Meyer
Publications and source records attributed to O Meyer.
Anti-HER2 immunoliposomes for targeted therapy of human tumors.
Anti-HER2 immunoliposomes (ILs) have been constructed by conjugation of Fab' fragments of recombinant humanized monoclonal antibody rhuMAbHER2 to small sterically stabilized unilamellar liposomes, to create a targeted drug delivery vehicle for the treatment of HER2 (c-erbB-2, neu)-overexpressing cancers. Parameters affecting in vitro binding and internalization of ILs include liposome composition, Fab' linkage site and Fab' density. Anti-HER2 ILs have been constructed to optimize intracellular drug delivery. Doxorubicin (dox)-loaded ILs are highly stable and exhibit prolonged circulation in rats. In nude mice bearing HER2-overexpressing tumor xenografts, anti-HER2 ILs administered i.v. resulted in efficient tumor localization, with penetration of the ILs throughout the tumor mass and accumulation within tumor cells. In contrast, non-targeted liposomes resulted in extracellular tumor accumulation only. In multiple HER2-overexpressing human breast tumor xenograft models, treatment with dox-loaded anti-HER2 ILs produces significantly increased antitumor cytotoxicity as compared to free dox or dox-loaded non-targeted liposomes and significantly less systemic toxicity than free dox. To explore further the intracellular delivery advantages of ILs, anti-HER2 ILs bearing cationic lipids are being developed for nucleic acid delivery. These cationic immunoliposomes mediate efficient and specific transfection of target cells with reporter genes, as well as intracellular delivery of labeled oligonucleotides. Thus, anti-HER2 ILs represent an efficient and feasible strategy to achieve targeted intracellular delivery of therapeutic agents.
Antibodies, Monoclonal↗
[Epidemiological aspects of osteoarticular tuberculosis in adults. Retrospective study of 206 cases diagnosed in the Paris area from 1980 to 1994].
OBJECTIVES: The aim of this study was to determine the epidemiologic features of bone and joint tuberculosis in the Paris area from 1980 to 1994. METHODS: This retrospective study included 206 cases of confirmed bone and joint tuberculosis (in situ specimen) diagnosed from 1980 to 1994 in 7 hospital units (mainly rheumatology clinics) in Paris and suburban areas. RESULTS: The number of cases increased by a mean 12 per year from 1980 to 1989 then by 17 cases per year from 1990 to 1994. In both 1993 and 1994 there were 21 cases per year. The percentage of immigrant patients was 53% from 1980 to 1989 then reached 74% for 1990-1994, predominantly in subjects from black Africa. Only one patient in the series had human immunodeficiency virus (HIV) infection. A favoring factor was found in 23% of the immigrant and in 45% of the native French patients. Mean age was 37 years in immigrants and 58 years in French patients. Compared with French patients, immigrants had a higher rate of multifocal bone and joint tuberculosis, peripheral osteitis and spondylitus. CONCLUSION: Our findings suggest that the incidence of bone and joint tuberculosis has increased in Paris in 1993 and 1994. Two populations are especially susceptible: the elderly and/or immunodepressed French population and immigrants coming from endemic zones. The role or HIV infection was minimal in this predominantly rheumatology series.
Adult↗
Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells.
OBJECTIVE: To assess the ability of anti-proteinase 3 (anti-PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis. METHODS: Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity-purified anti-PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control. RESULTS: TF activity was generated in anti-PR3-stimulated cells, as shown by a chromogenic test. This activity was inhibited by specific anti-TF antibodies. TF messenger RNA (mRNA) was found in anti-PR3-stimulated cells, as detected by reverse transcriptase-polymerase chain reaction, but not in cells stimulated with irrelevant human Igs or Igs from normal control sera. TF expression reached maximum levels 12 hours after exposure to the anti-PR3 cANCA, and did not require complement. TF mRNA expression was inhibited by cycloheximide, suggesting a requirement for protein synthesis. When added to the incubation medium, interleukin-1 (IL-1) receptor antagonist inhibited the induced TF mRNA expression, suggesting that cANCA-stimulated cells initiate IL-1 synthesis. Moreover, cANCA induced IL-1alpha mRNA before TF mRNA. CONCLUSION: This study showed that anti-PR3 treatment of HUVEC induces sequential expression of IL-1alpha mRNA and TF mRNA, as well as their corresponding proteins. Both proteins could have pathogenic roles in the vasculitic process, since TF is the main initiator of the coagulation cascade.
Antibodies, Antineutrophil Cytoplasmic↗
Laurdan solvatochromism: solvent dielectric relaxation and intramolecular excited-state reaction.
Absorption, steady-state, and time-resolved fluorescence measurements have been performed on laurdan dissolved either in white viscous apolar solvents or in ethanol as a function of temperature. The heterogeneity of the absorption spectra in white oils or in ethanol is consistent with semiempirical calculations performed previously on Prodan. From steady-state and time-resolved fluorescence measurements in apolar media, an excited state reaction is evidenced. The bimodal lifetime distribution determined from the maximum entropy method (MEM) analysis is attributed to the radiative deexcitation of a "locally excited" (LE) state and of a "charge transfer" (CT) state, whereas a very short component (20 ps), the sign and the amplitude of which depend on the emission wavelength, is attributed to the kinetics of the interconvertion reaction. The observation of an isoemissive point in the temperature range from -50 degrees C to -110 degrees C in ethanol suggests an interconvertion between two average excited-state populations: unrelaxed and solvent-relaxed CT states. A further decrease in temperature (-190 degrees C), leading to frozen ethanol, induces an additional and important blue shift. This low temperature spectrum is partly attributed to the radiative deexcitation of the LE state. Time-resolved emission spectra (TRES) measurements at -80 degrees C in the ethanol liquid phase show a large spectral shift of approximately 2500 cm(-1) (stabilization energy of the excited state: 7.1 kcal x M(-1)). The time-dependent fluorescence shift (TDFS) is described for its major part by a nanosecond time constant. The initial part of the spectral shift reveals, however, a subnanosecond process that can be due to fast internal solvent reorientation and/or to intramolecular excited-state reactions. These two relaxation times are also detected in the analysis of the fluorescence decays in the middle range of emission energy. The activation energy of the longest process is approximately 3 kcal x M(-1). At -190 degrees C, one subnanosecond and one nanosecond excited-state reactions are also evidenced. They are likely due to intramolecular rearrangements after the excitation, leading to the CT state and not to solvent relaxation, which is severely hindered in these temperature conditions. Therefore, both intramolecular and solvent relaxations are responsible for the large Stokes shift displayed by this probe as a function of solvent polarity. A possible scheme is proposed for the deexcitation pathway, taking into account the kinetics observed in these different solvents.
2-Naphthylamine↗
Solubilization and reconstitution of vesicular stomatitis virus envelope using octylglucoside.
Reconstituted vesicular stomatitis virus envelopes or virosomes are formed by detergent removal from solubilized intact virus. We have monitored the solubilization process of the intact vesicular stomatitis virus by the nonionic surfactant octylglucoside at various initial virus concentrations by employing turbidity measurements. This allowed us to determine the phase boundaries between the membrane and the mixed micelles domains. We have also characterized the lipid and protein content of the solubilized material and of the reconstituted envelope. Both G and M proteins and all of the lipids of the envelope were extracted by octylglucoside and recovered in the reconstituted envelope. Fusion activity of the virosomes tested either on Vero cells or on liposomes showed kinetics and pH dependence similar to those of the intact virus.
Animals↗
Imprecision of counting CFU-GM colonies and CD34-expressing cells.
Determinations of committed haemopoietic progenitor cells, namely CFU-GM (colony-forming unit-granulocyte/macrophage) and of CD34-expression haemopoietic cells as assessed by multiparameter flow cytometry are routine diagnostic tools in haemopoietic cell therapy. Generally, the tests are used to optimise the timing and management of cytapheresis and to assess the engraftment potential of the harvested cells. Both measurements, however, are at best surrogate markers, as an adequate routine test which effectively assesses the short- and long-term repopulating haemopoietic cell is not available. Nonetheless, cell threshold doses have been established. Above these thresholds rapid engraftment is almost invariable but below these thresholds the outcome is variable. In this study we have focussed on the imprecision in counting haemopoietic cells, as assessed as CFU-GM and as CD34-expressing cells. The data on both tests have been analysed from six European institutions. The coefficient of variation in CFU-GM colony counting was about 30%, whereas the coefficient of variation in flow cytometric counting of CD34-expressing cells was about 10%. These data suggest that the technical imprecision in enumerating progenitor cells, particularly CFU-GM, at low levels, might make a major contribution to the clinical variability observed after transplantation of sub-threshold progenitor cell dose.
Antigens, CD34↗
Pulsed high-dose dexamethasone in chronic autoimmune haemolytic anaemia of warm type.
The management of patients with autoimmune haemolytic anaemia of warm type (AIHA) is often problematic. Recently, pulsed high-dose dexamethasone (HDD) has been shown to be effective in the treatment of autoimmune thrombocytopenic purpura (AITP). In this study we treated seven patients with AIHA with HDD. The regimen recommended for treatment of refractory AITP (40 mg dexamethasone for 4 d at the beginning of each 28 d cycle) was employed in almost all cases. Prior to dexamethasone administration, haemolysis was decompensated in all seven patients. HDD was well tolerated and led to an improvement of haemolysis in all cases.
Adult↗
Systemic sclerosis and sarcoidosis, a report of five cases.
We report on five cases of associated systemic sclerosis and sarcoidosis (associated connective tissue diseases). The special peculiarities of this association are emphasized with a review of the literature (14 other cases reported). The clinical aspects, the prognosis, the role of silica, the likelihood of a chance association and the need (in our opinion) to reconsider the name 'sarcoidosis' are discussed.
Adult↗
Antibodies to proteinase-3 mediate expression of intercellular adhesion molecule-1 (ICAM-1, CD 54).
We investigated the role of intercellular adhesion molecule-1 (ICAM-1) in the adhesion of polymorphonuclear neutrophils (PMN) to classic antineutrophil cytoplasmic antibody (C-ANCA)-treated endothelial cells, independently of cytokines. Human umbilical vein endothelial cells (HUVEC) grown to confluence in cytokine-free conditions were stimulated with C-ANCA sera and affinity-purified anti-proteinase 3 antibodies (PR3) from Wegener's granulomatosis (WG) patients. Non-activated PMN were added to treated HUVEC and adhesion was measured. In parallel experiments, treated HUVEC were fixed and ICAM-1 and E-selectin were assayed by cyto-ELISA; in other experiments anti-ELAM-1 and anti-ICAM-1 antibodies were assessed. In this in vitro model, adhesion of non-activated PMN to anti-PR3-stimulated HUVEC was enhanced. Adhesion was greater with anti-PR3 antibodies than with control and normal immunoglobulins, and correlated with the level of anti-PR3 antibodies. Neutralization of anti-PR3 antibodies by neutrophil azurophilic granule proteins abolished adhesion. This adhesion increased at the fourth hour after simulation, peaked at the twelfth hour and then decreased. This phenomenon occurred mainly through endothelial expression of ICAM-1 (the main counter-receptor for integrins, involved in firm PMN adhesion and migration) and E-selectin on HUVEC membranes. Anti-adhesion molecule antibodies inhibited this adhesion. This work supports the hypothesis of a direct effect of C-ANCA in endothelial stimulation, namely, on endothelium-PMN adhesion, and strengthens the major role of ICAM-1, directly involved in firm sticking of PMN to HUVEC, besides E-selectin. C-ANCA upregulate endothelial adhesiveness and thus participate in inflammatory reactions by providing endothelial adhesive structures for neutrophils. This might be one of the first steps leading to clinical expression of the disease. These results provide new insights into the pathogenesis of C-ANCA-related diseases.
Antibodies↗
The ability of two cooked food mutagens to induce aberrant crypt foci in mice.
The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet. In the present study two food-borne initiators, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used. To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses. Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP. Two additional groups were given azoxymethane (AOM) (5 mg/kg body weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCl) (20 mg/kg body weight), respectively, one dose a week for two weeks. Animals were killed after four and 10 weeks. After four weeks only the mice dosed with IQ and PhIP had aberrant crypt foci. A much higher number of aberrant crypt foci were found in the IQ mice (31.8 +/- 5.2) than in the PhIP mice (0.5 +/- 0.3). After 10 weeks aberrant crypt foci were found in all dosed groups. The IQ mice had significantly more (P < or = 0.001) small and total aberrant crypt foci than the other groups. AOM and DMH induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ. The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens. If cooked food mutagens such as IQ or PhIP are to be used as initiators in the aberrant crypt foci test, the use of rats may be preferable.
Analysis of Variance↗
Purification and molecular characterization of the H2 uptake membrane-bound NiFe-hydrogenase from the carboxidotrophic bacterium Oligotropha carboxidovorans.
The membrane-bound hydrogenase of Oligotropha carboxidovorans was solubilized with n-dodecyl-beta-D-maltoside and purified 28-fold with a yield of 29% and a specific activity of 173 to 178 micromol of H2 x min(-1) x mg(-1). It is the first hydrogenase studied in a carboxidotrophic bacterium. The enzyme acts on artificial electron-accepting dyes, such as methylene blue, but is ineffective with pyridine nucleotides or other soluble physiological electron acceptors. Hydrogenase of O. carboxidovorans belongs to class I of hydrogenases and is a heterodimeric 101,692-Da NiFe-protein composed of the polypeptides HoxL and HoxS. Molecular cloning data revealed, that HoxL comprises 604 amino acid residues and has a molecular mass of 67,163 Da. Pre-HoxS comprises 360 amino acid residues and is synthesized as a precursor protein which is cleaved after alanine at position 45, thus producing a mature HoxS of 33,767 Da. The leader sequence corresponds to the signal peptide of small subunits of hydrogenases. The hydropathy plots of HoxL and HoxS were indicative for the absence of transmembranous helices. HoxZ has four transmembranous helices and is considered the potential membrane anchor of hydrogenase in O. carboxidovorans. Hydrogenase genes show the transcriptional order 5' hoxV --> hoxS --> hoxL --> hoxZ 3'. The hox gene cluster as well as the clustered CO dehydrogenase (cox) and Calvin cycle (cbb) genes are arranged within a 30-kb DNA segment of the 128-kb megaplasmid pHCG3 of O. carboxidovorans.
Amino Acid Sequence↗
Autoantibodies predicting the outcome of rheumatoid arthritis: evaluation in two subsets of patients according to severity of radiographic damage.
OBJECTIVE: Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA). PATIENTS AND METHODS: Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined. RESULTS: Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage. CONCLUSION: These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.
Adolescent↗
Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity.
OBJECTIVE: To investigate the difference in acute phase protein responses between patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and spondyloarthropathies (SpA). METHODS: Circulating levels of cytokines inducing the production of acute phase proteins such as interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF)-alpha, and of cytokine inhibitors such as TNF soluble receptors (TNF-sR55 and TNF-sR75) and IL-1 receptor antagonist (IL-1ra), were measured in 2 cohorts of patients. The first cohort included 52 patients with SLE and 22 with RA, and the second included 21 with SLE, 20 with RA, and 18 with SpA. An examination at the time of blood collection and the Systemic Lupus Activity Measure (SLAM) index were used to assess disease activity in patients with SLE. Serum levels of IL-6 were measured using a biological assay, and concentrations of IL-1 beta, TNF-alpha, TNF-sR55, TNF-sR75, and IL-1ra were assessed by immunoassays. RESULTS: Although C-reactive protein (CRP) levels were significantly lower in SLE than in RA or SpA, the concentrations of circulating IL-6 or TNF-alpha were higher in SLE. The most striking observation was that TNF-sR levels were significantly higher in SLE than in RA or SpA. The TNF-alpha: TNF-sR ratio was also significantly lower in SLE than in RA. TNF-sR55 and TNF-sR75 levels correlated with disease activity in SLE. CONCLUSION: The weak acute phase protein response in SLE may be explained by a decreased ratio between inducing cytokines and their inhibitors. In addition, TNF-sR may prove a useful biological marker for the followup of SLE, where acute phase protein response is generally low during disease exacerbations.
Acute-Phase Proteins↗
The prevalence of Paget's disease in 1994 in a rheumatology department of a Paris hospital.
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Hospital Departments↗
Thromboangiitis obliterans with inaugural rheumatic manifestations. A report of three cases.
Thromboangiitis obliterans, or Buerger's disease, is a segmental occlusive inflammatory disorder of the small- and medium-sized arteries and veins seen in young adults and associated with cigarette smoking. The lesions are most marked in the distal limbs. We report three cases in which the first manifestations were rheumatic, consisting in polyarthritis in two cases and carpal tunnel syndrome in one. Rheumatic manifestations are infrequent and rarely inaugural in thromboangiitis obliterans, although they are probably underdiagnosed. Their pathogenesis is unclear but may involve autoimmunity. Heightened awareness of the possibility that rheumatic manifestations can inaugurate thromboangiitis obliterans may allow an earlier diagnosis of this disease, which may improve the functional prognosis. However, recovery can be achieved only if the patient stops smoking.
Adult↗
Role of HLA-DR-DR and DR-DQ associations in the expression of extraarticular manifestations and rheumatoid factor in rheumatoid arthritis.
OBJECTIVE: To investigate the role of HLA-DRB1 genotypes and HLA-DRB1*0401-DQB1*03 haplotypes in the expression of extraarticular manifestations and rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: 189 patients with RA were classified according to the presence of vasculitis and seropositivity for RF. IgM RF were determined by at least 2 of the following methods: standard latex agglutination, the Waaler-Rose test, and nephelometry. HLA genotyping was performed by reverse dot blot hybridization for DRB1 alleles and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DQB1 alleles. RESULTS: The QKRAA susceptibility sequence, which characterizes the HLA-DRB1*0401 allele, was observed in 71.5% of the 21 patients with vasculitis and 57.6% of the 158 RF positive patients. The influence of a 2nd allele within the major histocompatibility complex was observed but the allele differed according to the clinical features examined. Higher risk for vasculitis was observed in patients who carried 2 DRB1 susceptibility alleles, one characterized by the QKRAA sequence and the other by the QRRAA sequence (OR = 3). Conversely, the higher risk for IgM RF positivity was observed in patients who carried the QKRAA sequence of the DRB1 alleles with the DQB1*0301 alleles of the DQ region (OR = 4.7). CONCLUSION: Our data suggest that a distinct immunogenetic association is involved in the extraarticular manifestations of RA and in the expression of RF.
Adult↗
Polyarthritis with cutaneous mucinosis and intrasynovial mucin deposits.
We report the first case of cutaneous and articular mucinosis with presence of mucin deposits within the synovium in an HIV-positive patients. Presentation was asymmetric polyarthritis, and subcutaneous nodules developed two months later. Treatment was with hydroxychloroquine. The outcome of both the skin and joint lesions was favourable.
Adult↗