Pyrocarbon proximal interphalangeal joint arthroplasty: a medium to long term follow-up of a single surgeon series.

We retrospectively reviewed a consecutive single surgeon series of 57 Ascension pyrocarbon proximal interphalangeal joint arthroplasties, with a mean follow-up of 7.1 years (range 2 years to 11 years 6 months). We assessed the ranges of motion, deformity, stability and pain of the operated joints, grip strength of the hand and patient satisfaction. Of the cases, 44 were for osteoarthritis, five for rheumatoid arthritis and eight for post-traumatic arthritis. The median post-operative active arc of motion was from 0° to 60°. The median post-operative visual analogue pain score was 0.3 out of ten. Thirty six of the joints had no complications; 14 had minor complications (squeak, slight swan neck); three required early reoperation (joint release, flexor tenodesis); and five required implant removal. A total of 69% of our patients would have the same operation if they had to make the decision again. The Kaplan-Meier survival method estimates the mean implant survival to be 10.7 years (95% confidence intervals 9.96-11.37 years). All five failures occurred during the first 2 years.Level of evidence 4 (Case-series).

Movement of newly assimilated 13C carbon in the grass Lolium perenne and its incorporation into rhizosphere microbial DNA.

One of the key processes that drives rhizosphere microbial activity is the exudation of soluble organic carbon (C) by plant roots. We describe an experiment designed to determine the impact of defoliation on the partitioning and movement of C in grass (Lolium perenne L.), soil and grass-sterile sand microcosms, using a (13)CO(2) pulse-labelling method. The pulse-derived (13)C in the shoots declined over time, but that of the roots remained stable throughout the experiment. There were peaks in the atom% (13)C of rhizosphere CO(2) in the first few hours after labelling probably due to root respiration, and again at around 100 h. The second peak was only seen in the soil microcosms and not in those with sterilised sand as the growth medium, indicating possible microbial activity. Incorporation of the (13)C label into the microbial biomass increased at 100 h when incorporation into replicating cells, as indicated by the amounts of the label in the microbial DNA, started to increase. These results indicate that the rhizosphere environment is conducive to bacterial growth and replication. The results also show that defoliation had no impact on the pattern of movement of (13)C from plant roots into the microbial population in the rhizosphere.

Nodules of fibrocollagenous scar tissue induced by subcutaneous insulin injections: a cause of poor diabetic control.

A 46 year old man with longstanding type 1 diabetes developed major weight loss and marked deterioration in diabetic control. He had been persistently injecting insulin into areas of abdominal lipohypertrophy within which hard collagenised fibrous tissue nodules had developed. Injecting insulin at different sites dramatically improved blood glucose control. Fibrocollagenous nodules induced by insulin injections have not been previously described. Examination of a further 73 type 1 patients revealed lipohypertrophy in 44% and hard subcutaneous nodules on two.

Crimean-Congo haemorrhagic fever virus: sequence analysis of the small RNA segments from a collection of viruses world wide.

Crimean-Congo haemorrhagic fever virus (CCHFv) is a member of the genus Nairovirus in the family Bunyaviridae. It possesses a tripartite, single stranded RNA genome of negative polarity consisting of large (L), medium (M) and small (S) segments. CCHF virus is enzootic in life stock and wild animals in many parts of the Middle East, Asia and Africa and is also recognised in Southeast Europe. Severe disease, manifest as haemorrhagic fever and high mortality rates (up to 50%), is only recognised in humans. We have determined the complete sequence of the small genomic RNA segment from several strains of CCHF virus from outbreaks in Pakistan 2000, Baghdad 1976 and Uzbekistan 1967. Phylogenetic analysis of three datasets of sequences from the small genomic RNA segment available from a range of strains indicates that they can be divided into seven subtypes. Superimposed on this pattern are links between distant geographic locations, pointing to the existence of a global reservoir of CCHFv. In some cases these links may originate from trade in livestock, and long-distance carriage of virus or infected ticks during bird migration.

Spatial structure in soil chemical and microbiological properties in an upland grassland.

We characterised the spatial structure of soil microbial communities in an unimproved grazed upland grassland in the Scottish Borders. A range of soil chemical parameters, cultivable microbes, protozoa, nematodes, phospholipid fatty acid (PLFA) profiles, community-level physiological profiles (CLPP), intra-radical arbuscular mycorrhizal community structure, and eubacterial, actinomycete, pseudomonad and ammonia-oxidiser 16S rRNA gene profiles, assessed by denaturing gradient gel electrophoresis (DGGE) were quantified. The botanical composition of the vegetation associated with each soil sample was also determined. Geostatistical analysis of the data revealed a gamut of spatial dependency with diverse semivariograms being apparent, ranging from pure nugget, linear and non-linear forms. Spatial autocorrelation generally accounted for 40-60% of the total variance of those properties where such autocorrelation was apparent, but accounted for 97% in the case of nitrate-N. Geostatistical ranges extending from approximately 0.6-6 m were detected, dispersed throughout both chemical and biological properties. CLPP data tended to be associated with ranges greater than 4.5 m. There was no relationship between physical distance in the field and genetic similarity based on DGGE profiles. However, analysis of samples taken as close as 1 cm apart within a subset of cores suggested some spatial dependency in community DNA-DGGE parameters below an 8 cm scale. Spatial correlation between the properties was generally weak, with some exceptions such as between microbial biomass C and total N and C. There was evidence for scale-dependence in the relationships between properties. PLFA and CLPP profiling showed some association with vegetation composition, but DGGE profiling did not. There was considerably stronger association between notional sheep urine patches, denoted by soil nutrient status, and many of the properties. These data demonstrate extreme spatial variation in community-level microbiological properties in upland grasslands, and that despite considerable numeric ranges in the majority of properties, overarching controlling factors were not apparent.

TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS.

BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.

A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.

IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-alpha 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2-9) and is physically adjacent to IL-20Ralpha and IFN-gammaR1 on chromosome 6q23.3-24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses.

Recovery of atrazine, bromacil, chlorpyrifos, and metolachlor from water samples after concentration on solid-phase extraction disks: interlaboratory study.

An interlaboratory comparison was conducted in 1997 and 1998 to examine the feasibility of using C18 solid-phase extraction disks (Empore) to simultaneously determine the herbicides atrazine, bromacil, and metolachlor and the insecticide chlorpyrifos in water samples. A common fortification source and sample processing procedure were used to minimize variation in initial concentrations and operator inconsistencies. The protocol consisted of paired laboratories in different locations coordinating their activities and shipping fortified water samples (deionized or local surface water) or Empore disks on which the pesticides had been retained and then quantitating the analytes by a variety of gas chromatographic methods. Average recoveries from all laboratories were >80% for atrazine, bromacil, and metolachlor, and >70% for chlorpyrifos. Detection of bromacil was unachievable at some locations because of chromatographic problems. Shipping samples between cooperating laboratories did not affect the recovery of atrazine, chlorpyrifos, or metolachlor in either matrix. Recoveries tended to be higher from disks shipped to cooperating laboratories compared with those from fortified water. Shipping disks eliminated many problems associated with the shipment of water samples, such as bottle breakage, higher shipping cost, and possible pesticide degradation. Recoveries of bromacil and metolachlor were lower from fortified surface water samples than from fortified deionized water samples. This collaborative research demonstrated that pesticides in water samples can be concentrated on solid-phase extraction disks at one location and quantitated under diverse analytical conditions at another location. The extraction efficiencies of the disks were comparable with or better than the recoveries obtained from the shipped water samples, and the problems associated with shipping water samples were eliminated by using the disks.

Sociotechnical principles for system design.

This paper offers a set of sociotechnical principles to guide system design, and some consideration of the role of principles of this kind. The principles extend earlier formulations by Cherns (1976, Human Relations, 29, 783-792; 1987, Human Relations, 40, 153-162). They are intended to apply to the design of new systems, including those incorporating new information technologies and a range of modern management practices and ways of working. They attempt to provide a more integrated perspective than is apparent in existing formulations. The principles are of three broad types: meta, content and process, though they are highly interrelated. They are for use by system managers, users and designers, and by technologists and social scientists. They offer ideas for debate and provide devices through which detailed design discussions can be elaborated. The principles are most likely to be effective if they are relatively freestanding, but supported by relevant methods and tools. The principles are necessary but not sufficient to make a substantial contribution to design practice.

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease.

B cells are important in the development of autoimmune disorders by mechanisms involving dysregulated polyclonal B-cell activation, production of pathogenic antibodies, and co-stimulation of autoreactive T cells. zTNF4 (BLyS, BAFF, TALL-1, THANK) is a member of the tumour necrosis factor (TNF) ligand family that is a potent co-activator of B cells in vitro and in vivo. Here we identify two receptors for zTNF4 and demonstrate a relationship between zTNF4 and autoimmune disease. Transgenic animals overexpressing zTNF4 in lymphoid cells develop symptoms characteristic of systemic lupus erythaematosus (SLE) and expand a rare population of splenic B-Ia lymphocytes. In addition, circulating zTNF4 is more abundant in NZBWF1 and MRL-lpr/lpr mice during the onset and progression of SLE. We have identified two TNF receptor family members, TACI and BCMA, that bind zTNF4. Treatment of NZBWF1 mice with soluble TACI-Ig fusion protein inhibits the development of proteinuria and prolongs survival of the animals. These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI-Ig as a promising treatment of autoimmune disease in humans.

Regulation of extrathymic T cell development and turnover by oncostatin M.

Chronic exposure to oncostatin M (OM) has been shown to stimulate extrathymic T cell development. The present work shows that in OM transgenic mice, 1) massive extrathymic T cell development takes place exclusively the lymph nodes (LNs) and not in the bone marrow, liver, intestines, or spleen; and 2) LNs are the sole site where the size of the mature CD4+ and CD8+ T cell pool is increased (6- to 7-fold). Moreover, when injected into OM transgenic mice, both transgenic and nontransgenic CD4+ and CD8+ T cells preferentially migrated to the LNs rather than the spleen. Studies of athymic recipients of fetal liver grafts showed that lymphopoietic pathway modulated by OM was truly thymus independent, and that nontransgenic progenitors could generate extrathymic CD4+CD8+ cells as well as mature T cells under the paracrine influence of OM. The progeny of the thymic-independent differentiation pathway regulated by OM was polyclonal in terms of Vbeta usage, exhibited a phenotype associated with previous TCR ligation, and displayed a rapid turnover rate (5-bromo-2'-deoxyuridine pulse-chase assays). This work suggests that chronic exposure to OM 1) discloses a unique ability of LNs to sustain extrathymic T cell development, and 2) increases the number and/or function of LN niches able to support seeding of recirculating mature T cells. Regulation of the lymphopoietic pathway discovered in OM transgenic mice could be of therapeutic interest for individuals with thymic hypoplasia or deficient peripheral T cell niches.

Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study.

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.

Oncostatin M transforms lymphoid tissue function in transgenic mice by stimulating lymph node T-cell development and thymus autoantibody production.

Oncostatin M (OM) is a member of the IL-6 subfamily of cytokines that is expressed in primary lymphoid tissues such as bone marrow and thymus, as well as in secondary lymphoid tissues and activated leukocytes. We produced transgenic mice that overexpressed the human, bovine, or mouse OM genes and compared their relative ability to modulate lymphopoiesis. Each species of cytokine induced a similar extrathymic pathway of T-cell development involving the accumulation of immature T cells within lymph nodes. Reconstitution experiments utilizing lethally irradiated athymic mice indicated that OM had caused hematopoietic precursors within fetal liver and bone marrow to initiate lymph node T-cell development in the absence of a thymic environment. Breeding experiments with IL6-/- and IL-7r(alpha)-/- deficient mice, indicated that induction of this extrathymic pathway by the OM transgene occurred in the absence of IL-6, but was strictly dependent on IL-7 receptor signaling. Separately, OM stimulated the accumulation of immature B cells within the transgenic thymus and caused the subcapsular regions of the thymus to expand with mature B and T cells. This thymus conversion to secondary lymphoid tissue was responsible for a lethal autoimmune-like disease marked by high titers of circulating autoantibodies, proteinuria, and glomerulonephritis. The conserved phenotypes elicited by these three forms of OM indicate that this potent hematopoietic cytokine can regulate lymphoid tissue function and morphogenesis.

In vitro positive selection and anergy induction of class II-restricted TCR transgenic thymocytes by a cortical thymic epithelial cell line.

Thymic epithelial cell lines isolated from hyperplastic thymi of transgenic mice over-expressing human papilloma viral oncogenes E6 and E7 constitutively displayed a phenotype consistent with a cortical origin. Exposure to IFN-gamma induced class II MHC and ICAM-1 expression, and up-regulated expression of VCAM-1 and class I MHC molecules. CD40 expression was maximally induced by a combination of IFN-gamma and IL-1, with lower levels of induction observed with a mixture of IFN-gamma and tumor necrosis factor (TNF)-alpha or TNF-alpha alone. B7-1 or B7-2 was not expressed constitutively or in response to cytokines. These stromal cells supported the development of CD4 single-positive (SP) cells in reaggregate co-cultures with CD4+ CD8+ thymocytes from TCR transgenic mice, but did not stimulate class II MHC-restricted, moth cytochrome c (MCC)-reactive T cells in vitro. The behavior of the culture system was consistent with positive selection, i.e. increased numbers of CD4 SP cells, gain of antigen responsiveness, and requirement for epithelial class II MHC products. Some variants of these stromal cell lines required exogenous MCC peptide in the reaggregation cultures (RC) for positive selection to occur. While a low concentration of MCC peptide (0.01-0.1 microM) significantly enhanced the accumulation of CD4 SP cells, higher concentrations of peptide (1-10 microM) resulted in recovery of predominantly CD4- CD8- and CD4(low) CD8- cells. Thymocytes recovered from RC containing low, but not high concentrations of peptide responded to MCC peptide in secondary cultures with splenic antigen-presenting cells.

Multiple epsilon-promoter elements participate in the developmental control of epsilon-globin genes in transgenic mice.

To delineate the regulation of the human epsilon-globin gene, we investigated epsilon-gene expression during the development of transgenic mice carrying constructs with epsilon-promoter truncations linked to a micro-locus control region (microLCR). Expression levels were compared with those of microLCR epsilon mice carrying a 2 kilobase epsilon-promoter and betaYAC controls. epsilon mRNA in the embryonic cells of microLCR (-179)epsilon mice were as high as in microLCR epsilon mice suggesting that the proximal epsilon-promoter contains most elements required for epsilon-gene activation. epsilon mRNA in adult microLCR (-179) epsilon mice was significantly lower than in the embryonic cells indicating that elements involved in epsilon-gene silencing are contained in the proximal epsilon-promoter. Extension of the promoter sequence to -463 epsilon decreased epsilon-gene expression in the definitive erythroid cells, supporting previous evidence that the -179 to -463epsilon region contains an epsilon-gene silencer. However, the epsilon-gene of the microLCR(-463)epsilon mice was not silenced in the definitive cells of fetal and adult erythropoiesis indicating that additional silencing elements are located upstream of position -463epsilon. These results provide in vivo evidence that multiple elements of the distal as well as the proximal promoter contribute to epsilon-gene silencing.

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability.

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis -acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.

Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion.

The human beta-globin locus control region (LCR) consists of five erythroid-lineage-specific DNase I-hypersensitive sites (HSs) and is required for activation of the beta-globin locus chromatin domain and globin gene expression. Each DNase I-HS of the LCR consists of a highly conserved core element and flanking sequences. To analyze the functional role of the core elements of the HSs, we deleted a 234-bp fragment encompassing the core of HS3 (HS3c) from a beta-globin locus residing on a 248-kb beta-locus yeast artificial chromosome and analyzed its function in F2 progeny of transgenic mice. Human epsilon-globin gene expression was absent at day 10 and severely reduced in the day 12 embryonic erythropoiesis of mice lacking HS3c. In contrast, gamma-globin gene expression was normal in embryonic erythropoiesis but it was absent in definitive erythropoiesis in the fetal liver. These results indicate that the core element of HS3 is necessary for epsilon-globin gene transcription in embryonic cells and for gamma-globin gene transcription in definitive cells. Normal gamma-globin gene expression in embryonic cells and the absence of gamma-globin gene expression in definitive cells show that different HSs interact with gamma-globin gene promoters in these two stages of development. Such results provide direct evidence for developmental stage specificity of the interactions between the core elements of HSs and the promoters of the globin genes.

Broad-scale analysis of soil microbial community DNA from Upland grasslands.

We have applied a broad-scale approach to the analysis of DNA extracted from soils which support characteristic grasslands at an upland site in the UK. To test for the degree of coherence between microbial and vascular communities, grasslands were characterised as 'improved', 'semi-improved', or 'unimproved', according to the degree of management they had received and consequent botanical composition. Microbial DNA was extracted directly from the grassland soils and analysed by three techniques: (i) thermal denaturation, which profiles the guanine and cytosine (G + C) base distribution within the community; (ii) cross hybridisation of the DNA which measures the degree of similarity between the samples; (iii) measurement of reassociation kinetics of denatured DNA, which provides a measure of the complexity of the DNA. Thermal denaturation revealed significant differences in the %G + C composition of the communities. DNA from the improved soil had the highest median %G + C value, whilst that from the unimproved soil had the lowest. The relative distribution of G + C bases also differed significantly between the samples from the three grasslands. Cross hybridisation of DNA from the different soils also indicated significant differences in the degree of similarity between the DNA from the grasslands, with unimproved showing 59% similarity to improved. Indices from the cross hybridisation assay suggested that, in terms of complexity, the samples ranked unimproved > semi-improved > improved. Reassociation kinetics supported this conclusion, but the rates of reassociation were such that less than 40% reassociation occurred over a 31-day period, thus preventing calculation of C(o)t1/2.

Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease.

Oncostatin M (OM), a member of the IL-6 gene family, stimulates a variety of functions implicated in wound repair. Transgenic mice that express this cytokine in islet beta-cells develop a connective tissue disorder that typifies excessive healing with severe fibrosis and lymphocytic infiltration. To compare this phenotype with the normal progression of connective tissue disease, we measured the expression patterns of genes encoding proinflammatory cytokines, fibrogenic cytokines, and ECM components by in situ hybridization. To test whether the OM effect was caused by its ability to regulate IL-6, we crossed the OM transgene into IL-6-deficient mice. Our data suggest that the fibrosis in these animals is not a secondary consequence of inflammation, or IL-6 expression, but is a direct effect by OM on extracellular matrix production. In a separate experiment, we observed that OM could regulate vasoactive intestinal peptide gene expression in the neurons that innervate the transgenic pancreas. This nerve healing response, in combination with its fibrogenic activity, suggests that OM functions downstream of inflammation in the wound repair cascade. These transgenic mice represent a useful model in which the fibroproliferative phase of connective tissue disease is uncoupled from inflammation.