A fungal growth model fitted to carbon-limited dynamics of Rhizoctonia solani.

Here, a quasi-steady-state approximation was used to simplify a mathematical model for fungal growth in carbon-limiting systems, and this was fitted to growth dynamics of the soil-borne plant pathogen and saprotroph Rhizoctonia solani. The model identified a criterion for invasion into carbon-limited environments with two characteristics driving fungal growth, namely the carbon decomposition rate and a measure of carbon use efficiency. The dynamics of fungal spread through a population of sites with either low (0.0074 mg) or high (0.016 mg) carbon content were well described by the simplified model with faster colonization for the carbon-rich environment. Rhizoctonia solani responded to a lower carbon availability by increasing the carbon use efficiency and the carbon decomposition rate following colonization. The results are discussed in relation to fungal invasion thresholds in terms of carbon nutrition.

Quasi-steady state approximation to a fungal growth model.

In a previous paper, we proposed a fungal growth model (Lamour et al., 2001 IMA J. Math. Appl. Med. Biol., 17, 329-346), describing the colonization and decomposition of substrate, subsequent uptake of nutrients, and incorporation into fungal biomass, and performed an overall-steady-state analysis. In this paper we assume that where nutrient dynamics are much faster than the dynamics of fungal biomass and substrate, the system will reach a quasi-steady-state relatively quickly. We show how the quasi-steady-state approximation is a simplification of the full fungal growth model. We then derive an explicit fungal invasion criterion, which was not possible for the full model, and characterize parameter domains for invasion and extinction. Importantly, the fungal invasion criterion takes two forms: one for systems where carbon is limiting, another for systems where nitrogen is limiting. We focus attention on what happens in the short term immediately following the introduction of a fungus to a fungal-free system by analysing the stability of the trivial steady state, and then check numerically whether the fungus is able to persist. The derived invasion criterion was found to be valid also for the full model. Knowledge of the factors that determine invasion is essential to an understanding of fungal dynamics. The simplified model allows the invasion criterion to be tested with experimental data.

Modelling the growth of soil-borne fungi in response to carbon and nitrogen.

Growth of soil-borne fungi is poorly described and understood, largely because non-destructive observations on hyphae in soil are difficult to make. Mathematical modelling can help in the understanding of fungal growth. Except for a model by Paustian & Schnürer (1987a), fungal growth models do not consider carbon and nitrogen contents of the supplied substrate, although these nutrients have considerable effects on hyphal extension in soil. We introduce a fungal growth model in relation to soil organic matter decomposition dealing with the detailed dynamics of carbon and nitrogen. Substrate with a certain carbon : nitrogen ratio is supplied at a constant rate, broken down and then taken up by fungal mycelium. The nutrients are first stored internally in metabolic pools and then incorporated into structural fungal biomass. Standard mathematical procedures were used to obtain overall-steady states of the variables (implicitly from a cubic equation) and the conditions for existence. Numerical computations for a wide range of parameter combinations show that at most one solution for the steady state is biologically meaningful, specified by the conditions for existence. These conditions specify a constraint, namely that the 'energy' (in terms of carbon) invested in breakdown of substrate should be less than the 'energy' resulting from breakdown of substrate, leading to a positive carbon balance. The biological interpretation of the conditions for existence is that for growth the 'energy' necessary for production of structural fungal biomass and for maintenance should be less than the mentioned positive carbon balance in the situation where all substrate is colonized. In summary, the analysis of this complicated fungal growth model gave results with a clear biological interpretation.

Modelling the growth of soil-borne fungi in response to carbon and nitrogen.

Growth of soil-borne fungi is poorly described and understood, largely because non-destructive observations on hyphae in soil are difficult to make. Mathematical modelling can help in the understanding of fungal growth. Except for a model by Paustian & Sch urer (1987a), fungal growth models do not consider carbon and nitrogen contents of the supplied substrate, although these nutrients have considerable effects on hyphal extension in soil. We introduce a fungal growth model in relation to soil organic matter decomposition dealing with the detailed dynamics of carbon and nitrogen. Substrate with a certain carbon : nitrogen ratio is supplied at a constant rate, broken down and then taken up by fungal mycelium. The nutrients are first stored internally in metabolic pools and then incorporated into structural fungal biomass. Standard mathematical procedures were used to obtain overall-steady states of the variables (implicitly from a cubic equation) and the conditions for existence. Numerical computations for a wide range of parameter combinations show that at most one solution for the steady state is biologically meaningful, specified by the conditions for existence. These conditions specify a constraint, namely that the 'energy' (in terms of carbon) invested in breakdown of substrate should be less than the 'energy' resulting from breakdown of substrate, leading to a positive carbon balance. The biological interpretation of the conditions for existence is that for growth the 'energy' necessary for production of structural fungal biomass and for maintenance should be less than the mentioned positive carbon balance in the situation where all substrate is colonized. In summary, the analysis of this complicated fungal growth model gave results with a clear biological interpretation.

Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société de Rhumatologie de l'Ouest.

OBJECTIVE: To document the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in Brittany, France. METHODS: (1) Members of rheumatism self-help groups screened cases using questionnaires. (2) Rheumatologists in our unit contacted persons who had possible inflammatory rheumatic diseases and persons who refused the first interview. (3) When diagnosis remained unknown or discordant with the questionnaire, the general practitioner or the rheumatologist of these patients was interviewed. (4) Patients without diagnosis and who had not had a rheumatological examination were examined without charge by a rheumatologist. RESULTS: An overall prevalence rate of 0.62% (0.33-0.91) and 0.47% (0.22-0.72) was found for RA and for SpA, respectively. The prevalence of RA and SpA was 0.86 (0.39-1.33) and 0.53 (0.16-0.9) in women and 0.32 (0.01-0.63) and 0.41 (0.05-0.77) in men. The minimum prevalence of RA and SpA calculated on the estimated initial group (3189 persons) was 0.53 (0.28-0.78) and 0.41 (0.18-0.63), respectively. CONCLUSION: Our telephone survey revealed that the prevalences of RA and SpA are nearly similar among our population and that SpA is as common in women as in men.

Novel enzyme-linked immunosorbent assays for the detection of anti-Fc gamma receptor autoantibodies.

There is a substantial interest in the role of antineutrophil antibodies since Fc gamma receptors (Fc gamma Rs) have been identified as the target for the majority of such autoantibodies. Antineutrophil antibodies have long been detected by an indirect immunofluorescence technique. Following optimization of the flow cytometric method of detection, we developed three enzyme-linked immunosorbent assays (ELISAs), each specific for autoantibodies against one of the three classes of human Fc gamma R. Fc gamma RI and Fc gamma RII were purified from cultured cells, and Fc gamma RIII was produced as a recombinant molecule. These were then used as capture agents in the respective ELISAs. When applied in parallel to a sizeable group of patients with primary Sjögren's syndrome, both methods established that anti-Fc gamma R autoantibodies were heterogeneous. This finding indicates that different populations of partly cross-reactive antibodies are detectable by these two methods.

Anti-Fc gamma receptor autoantibodies from patients with Sjögren's syndrome do not react with native receptor on human polymorphonuclear leukocytes.

Sera from patients with primary Sjögren's syndrome (pSS) have been examined for the presence of cell-free Fc-gamma receptor (Fc gamma R) IIIb, which is expressed in polymorphonuclear leukocytes (PMN), and the production of related autoantibody. Sera from 66 patients with pSS were evaluated by an ELISA using recombinant human Fc gamma RIIIb as the substrate and by flow cytometry. Cell-free Fc gamma RIIIb was also detected by an ELISA. The fine specificity of autoantibodies was established by inhibition with a preparation of Fc gamma RI plus Fc gamma RII, and two ELISAs using Fc gamma RI and Fc gamma RII as the substrates respectively. Anti-Fc gamma RIIIb activity was found in 30 patients (45%), but 25 of them did not react with autologous PMN, whereas they bound to Fc gamma RIIIb eluted from the same PMN in ELISA and Western blotting. Autoantibodies from one serum recognized the three receptors, six with Fc gamma RII in addition to Fc gamma RIII, and three sera were specific for the latter receptor. None of these reacted with Fc gamma RI- and Fc gamma RII-carrying cells. Cell-free Fc gamma RIIIb, but negligible amounts of Fc gamma RIIIa, were detectable in the patient sera. The membrane expression of CD15, an early activation marker, was diminished, while that of three PMN late activation markers was markedly enhanced. Taken together, these results suggest that autoantibodies are produced following the shedding of Fc gamma RIIIb upon PMN activation. A credible candidate for this activation is IgG-containing immune complexes.

Spondylarthropathy with distal joint involvement.

To study whether the presence of distal joint involvement in spondylarthropathy corresponds to a particular set of the disease, one hundred and twenty six patients with spondylarthropathy were included in a retrospective study. Two groups of patients were defined according to the presence or the absence of distal joint involvement and their clinical, radiological, and biological features were compared. The patients with distal joint involvement had a later onset of spondylarthropathy and showed higher levels of biological markers of inflammation in their peripheral blood. However, no great difference appeared between the two groups of patients. Spondylarthropathy with distal joint involvement cannot be separated from spondylarthropathy without distal joint involvement and appears to be the same disease.

The presence of anti-Fc gamma receptor autoantibodies is related to the clinical presentation of primary Sjögren's syndrome.

OBJECTIVE: Fc gamma receptor III (Fc gamma RIII) is one of the 3 structurally distinct families of receptors for the Fc domain of IgG, and its Fc gamma RIIIb isoform is exclusively expressed in polymorphonuclear (PMN) cells. We sought to detect anti-Fc gamma RIII autoantibodies in serum from patients with primary Sjögren's syndrome (SS). METHODS: Sixty-six patients with SS and 44 healthy controls were enrolled in the study. ELISA were developed. RESULTS: IgG and IgM autoantibodies were found in 16 (10 IgG+ IgM+ and 6 IgG+ IgM-) and 24 patients (10 IgG+ IgM+ and 14 IgG- IgM+) respectively. Their frequency was higher in patients with nonerosive arthritis (p < 0.02), Raynaud's phenomenon (p < 0.003), and lung involvement (p < 0.02) than in patients without such complications. The levels of IgM and IgG antibody (p < 0.05) correlated with the content of IgA without the circulating immune complex (IC), while there was no relationship between anti-Fc gamma RIII activity and the PMN count. CONCLUSION: Anti-Fc gamma RIII autoantibodies may act as an acquired additional factor further compromising IC handling in individuals who share HLA-DR3 alloantigen.

Heterogeneity of neutrophil antibodies in patients with primary Sjögren's syndrome.

Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjögren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of positivity for the two assays: IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be Fc gamma RIII, and this may partly account for the dysfunction in Fc gamma R-mediated clearance by the reticuloendothelial system reported in these patients.

Impaired binding capacity of asialyl and agalactosyl IgG to Fc gamma receptors.

OBJECTIVE: Autoimmunity in rheumatoid arthritis has been associated with deficient glycosylation of serum and synovial IgG which could potentially be mediated through the binding of the Fc portion of the molecule to its cognate receptor. METHODS: Normal IgG1 and IgG3 were affinity-purified, and sialic acid and galactose were clipped off using neuraminidase and beta-galactosidase, respectively. The binding of these sugar-depleted IgG to the Fc gamma receptors (Fc gamma R)IIIb on polymorphonuclear leukocytes (PMN) was assessed by flow cytometry. RESULTS: The binding of both asialyl and agactosyl IgG1 and IgG3 to PMN was significantly lower than that of the native IgG1 and IgG3. CONCLUSION: These data indicate that agalactosyl and, to a lesser degree, asialyl IgG, do not bind as efficiently as native IgG to Fc gamma R. Such a reduction in the perspective of the heterogeneity of the PMN Fc gamma RIIIb.

Anti-Fc gamma receptor III autoantibody is associated with soluble receptor in rheumatoid arthritis serum and synovial fluid.

We sought to detect anti-Fc gamma receptor (Fc gamma R) autoantibodies and soluble Fc gamma R in the serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and to correlate these serological abnormalities to the polymorphonuclear cell (PMN) activation state. Paired samples of blood and SF were obtained from 33 RA patients as well as blood from 25 normal adults from SF from 20 non-RA patients. Anti-Fc gamma R autoantibodies were assessed by an enzyme-linked immunosorbent assay (ELISA) using recombinant human Fc gamma R as the substrate. Soluble Fc gamma RIII was determined by an ELISA based on the combination of two monoclonal antibodies (MAb). The mean fluorescence intensity (MFI) of complement receptor 1 (CD35) and 3 (CD11b) and Fc gamma RIII (CD16) was evaluated by flow cytometry on the membrane of PMN. IgM anti-Fc gamma RIII activity was present in seven RA sera and five SF, and IgG in eight RA sera and six SF. The average concentration of soluble Fc gamma RIII was 1.80 +/- 3.50 micrograms/ml in RA patients and 0.33 +/- 0.06 micrograms/ml in normal adults (P < 0.05). This was elevated in the SF of 15 RA, while normal in that of all the non-RA patients. There was an inverse correlation between the CD16 MFI on the PMN and the serum/SF soluble Fc gamma RIII level, whereas the density of CD35 and CD11b was markedly augmented. Anti-Fc gamma RIII activity exists in RA patients, associated with soluble Fc gamma RIII. PMN activation could be due to these autoantibodies and thereby obviate the clearance of immune complexes.

The majority of Fc gamma RIII-positive gamma delta T cells do not express HLA-DR in patients with primary Sjögren's syndrome.

The percentages of circulating gamma delta T cells and the proportions of these expressing Fc gamma RIII (CD16) or HLA-DR in patients with primary Sjögren's syndrome (pSS) and controls were determined using monoclonal antibodies and flow cytometry. There was no significant difference in the percentages of gamma delta T cells in the pSS patients compared with controls. There was, however, a significant increase in the proportions of both CD16+ and HLA-DR+ gamma delta T cells in pSS patients. A 3-colour immunofluorescence technique demonstrated that these two markers were mutually exclusive and therefore may identify either subpopulations of gamma delta T cells or different stages of the activation process.

Some nutritional parameters in patients with rheumatoid arthritis.

Its was our aim to appreciate the respective influence of age, sex, duration of disease, inflammatory status and treatment on protein markers in patients with rheumatoid arthritis (RA). Serum albumin (SA), thyroxin-binding prealbumin (TBPA), transferrin and retinol-binding protein (RBP) were determined in 155 RA patients. Since the cut off, levels of these proteins are highly dependent on sex and age, several groups of sex- and age-matched normal controls were evaluated. The levels of SA (p < 0.03) and RBP (p < 0.002) were reduced in the women under 45 years of age. SA and RBP reached a nadir following one year of evolution. There were inverse correlations between SA and Lee's index (p < 0.01) and TBPA and Lee's (p < 0.05) and Ritchie's index (p < 0.01). Sa correlated inversely with the inflammatory status. The complex challenge of nutritional evaluation in RA patients is thus impossible to adequately portray and results should be interpreted with caution.

Selective expression of V beta families by T cells in the blood and salivary gland infiltrate of patients with primary Sjögren's syndrome.

OBJECTIVE: The T cell infiltration of the salivary gland of patients with Sjögren's syndrome (SS) has been implicated in the pathogenic process of the disease. We examined the representation of V beta subsets in the blood and salivary tissue of patients with SS. METHODS: Circulating T cells from 12 patients and paired samples of blood and labial salivary glands obtained from 8 patients were studied. A panel of monoclonal antibodies directed against the variable region of the T cell receptor was used to enumerate the cells expressing V beta families in the peripheral blood by flow cytometry, and in tissue sections by immunofluorescence. RESULTS: We found an increase of cells bearing V beta 2 family gene products in the circulation, and an increase in both V beta 2 and V beta 8 in the salivary gland infiltrate of patients with SS. No significant difference was noted between the 5 DR3+ patients and 7 DR3- patients studied with regard to the V beta families seen. CONCLUSION: Our data are consistent with a role for specific T cell families in the pathogenesis of SS.

Lack of relationship between the Epstein-Barr virus and the antiperinuclear factor/'perinuclear antigen' system in rheumatoid arthritis.

Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-positive and 50 APF-negative sera from RA patients were examined for the presence of antibodies to six different EBV antigens. APF was tested in the serum of 40 patients with acute infectious mononucleosis (IM), 48 PNA-expressing donors and 29 non-PNA-expressing donors. The EBV genome was sought in the saliva and buccal cells of both types of donors. The targeted granules of cells from a PNA-expressing donor were studied by electron-microscopy. The prevalence of anti-EBV antibodies was similar in RA patients with and without APF, whereas the APF-positive sera was elevated in acute IM. The titres of anti-EBV antibodies did not correlate to the expression of PNA in the buccal cells of the donors. There was no relationship between this expression and the presence of the EBV genome in the material obtained from 'positive' donors, relative to 'negative' donors. No virus-like particles could be detected inside the granules by electron microscopy. These results indicate that there are no direct relationships between EBV and the APF/PNA system, although APF was present in a number of patients with IM.

Cell-free Fc-gamma receptor III in sera from patients with systemic lupus erythematosus: correlation with clinical and biological features.

Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA based upon a sandwich of two monoclonal antibodies. The standard curve was obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25 microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be lower in 11 patients with renal involvement than in those without. For the biological parameters, we observed that the 27 patients who presented lymphopenia also had a lower level of cell-free Fc gamma RIII when compared to the 23 patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by presumably activated polymorphonuclear cells.