4c), when RA was added to CD19+ cells enriched from the PBMC of all individuals, the Selleck Epacadostat frequency of CD19+CD24+CD38+ cells was increased significantly after 3 days (Fig. 4c). This increase, however, was not due to proliferation, as the frequency and numbers of viable BrdU+ cells

that are represented in the CD19+CD24+CD38+ population were not statistically different among control and RA-treated cultures of CD19+ cells from two individuals (data not shown). In order to determine whether the iDC-induced proliferation of CD19+CD24+CD38+ B cells was due exclusively to RA, or if additional mechanisms are involved we co-cultured 2 × 105 iDC in the presence of an equal number of syngeneic CD19+ B cells enriched from thawed, viable PBMC in the presence or absence of 1 mM of ER-50891, a pan-RAR selective antagonist [48] for 72 h. In Fig. 4d we demonstrate that the frequency of CD19+CD24+CD38+ Bregs is significantly lower in iDC co-cultures in the presence of the RAR inhibitor. The inhibitor did not alter viability, as the % of live cells were statistically indistinguishable between inhibitor and control-treated cultures (data not shown). We have shown that administration into humans of autologous DC generated ex vivo under conditions promoting and stabilizing a tolerogenic state is safe and without any detectable side effects [31]. In the same study, we also discovered that administration

of autologous DC with tolerogenic ability generated under ‘conventional’ GM-CSF/IL-4 conditions resulted in an increased frequency of B220+CD11c– cells, Caspase inhibitor preferentially in iDC recipients. We also demonstrated the suppressive ability of B cells whose frequency increased in the DC recipients. The surface phenotype of these B cells, however, as assessed by flow cytometry, suggested that they were heterogeneous Thiamine-diphosphate kinase in character and thus could consist, in principle, of more

than one suppressive subpopulation. How tolerogenic DC could mobilize one or more populations of Bregs is the question we have begun to address. Herein, we demonstrate that the tolerogenic DC used in our Phase I trial, when co-cultured with freshly obtained PBMC, induce an increase in frequency of CD19+CD24+CD38+ B cells in vitro, which are suppressive in allogeneic MLC. By virtue of their surface phenotype these cells are most probably identical, if not related to the Bregs reported by Mauri and colleagues [32, 40]. The increase in their frequency appears to be due to proliferation of existing CD19+CD24+CD38+ Bregs as well as conversion of CD19+ B cells in PBMC into CD19+CD24+CD38+ Bregs. We also show that suppression of T cells in allogeneic MLC in vitro is conferred by the CD19+CD24+ constituent of the B220+CD11c– population from freshly obtained PBMC and more specifically by the known CD19+CD24+CD38+ Bregs. In the process of identifying mechanisms of how the tolerogenic DC could promote suppressive B cell activity, we have discovered that CD19+CD24+CD38+ Bregs express retinoic acid (RA) receptors.

Instead, immune responses contribute to the tissue damage.

However, this may depend on localization of infection in the upper conductive or in the peripheral respiratory zone. To study this we produced two distinct sizes of small alginate beads (SB) and large beads (LB) containing P. aeruginosa. In total, 175 BALB/c mice were infected with either SB or LB. At day 1 the quantitative bacteriology was higher in the SB group compared to the LB group (P < 0·003). For all time-points smaller biofilms were identified by Alcian blue staining in the SB group (P < 0·003). Similarly, the area of the airways in which biofilms were identified were smaller (P < 0·0001). A shift from exclusively endobronchial to both parenchymal IDH signaling pathway and endobronchial localization of inflammation from day 1 to days 2/3 (P < 0·05), as well as a faster resolution of inflammation at days 5/6, was observed in the SB group (P < 0·03). Finally, both the polymorphonuclear neutrophil leucocyte (PMN) mobilizer granulocyte colony-stimulating factor (G-CSF)

and chemoattractant macrophage inflammatory protein-2 (MIP-2) were increased at day 1 in the SB group (P < 0·0001). In conclusion, we have established a model enabling studies of host responses in different pulmonary zones. An effective recognition of and a more pronounced host response to infection in the peripheral zones, indicating that increased lung damage was demonstrated. buy Ibrutinib Therefore, treatment of the chronic P. aeruginosa lung infection should be directed primarily at the peripheral lung zone by combined intravenous and inhalation antibiotic treatment. Most patients

with the inherited disease cystic fibrosis (CF) acquire a chronic lung infection with Pseudomonas aeruginosa. Once chronic P. aeruginosa lung infection is established it is almost impossible to eradicate, despite relevant antibiotic treatment and substantial innate and adaptive host responses. The background for the tolerance of the chronic P. aeruginosa Glycogen branching enzyme lung infection to antibiotics and host responses is the formation of biofilms, where the bacteria are organized in micro colonies surrounded by an extracellular matrix. Because the infection remains in the lungs, continuous induction of pulmonary inflammation and stimulation of the adaptive immune response is the result. In fact, both parts of the host immune response contribute to the lung pathophysiology. The constantly recruited polymorphonuclear neutrophil leucocytes (PMNs) contribute by release of exoproteases, reactive oxygen and nitrogen species, and the induced T helper type 2 (Th2)-dominated response contributes by induction of a pronounced antibody response resulting in immune complex disease [1]. The activation and recruitment of the host response is, however, not uniform throughout the lung.

These findings led to experiments designed to assess infection of human skin in a controlled study of live spirochetes infecting full thickness human skin explants (keratomes). Blinded analysis of low power fields Erlotinib assessed the number of CD1 expressing cells within the dermis and epidermis. There were no significant changes in the number, apparent brightness or size of CD1a expressing Langerhans cells (LCs) in the epidermis, when comparing infected or sham-treated

keratomes (Fig. 1B and C). The number of CD1a expressing cells in the dermis (4.1% of all cells) increased slightly after infection (6.1%) but did not reach statistical significance (p=0.34). However, the number of CD1b (p<0.0027) or CD1c (p<0.0086) expressing cells showed a significant increase after infection (Fig. 1C). Also, we observed marked increases in brightness of staining in each of three experiments. Although PS341 CD1d could be detected at very low levels in flow cytometry experiments

(Fig. 2), CD1d staining was not seen at levels higher that isotype-matched staining control samples (Fig. 1C). We conclude that evaluation of CD1a induction was limited by constitutively positive LCs, but increased CD1b and CD1c expression is induced during B. burgdorferi infection of human skin. To study the cellular mechanisms of CD1 induction by B. burgdorferi, we measured CD1 expression on human monocytes in culture. To determine whether the events seen ex vivo could be modeled in vitro, we first measured CD1 expression on monocytes after infection with live bacteria or by treatment of cells with lipids extracted from bacteria with chloroform and methanol. Fresh monocytes and control monocytes sham treated with medium for 3 days did not detectably express CD1a, CD1b or CD1c proteins at the surface, but CD1d was detected at low density on some cells (Fig. 2A and data not shown). Ex vivo infection with live spirochetes (data not shown) or cell wall lipids (Fig. 2A) increased cell surface expression of CD1a, CD1b and CD1c proteins to high levels. CD1a surface density increased

in a dose-dependent fashion (Fig. 2B). The resultant CD1a cell surface expression of was sufficient to activate a CD1a autoreactive T-cell line (Fig. 2C). The low levels of baseline expression of CD1d were unaltered or slightly decreased, so that they were undetectable (Fig. 2A). These results confirm that B. burgdorferi potently activates group 1 CD1 expression on monocyte-derived DCs in a model that mimics many aspects of the in vivo observations. In particular, these data show selective upregulation of group 1 CD1 proteins over 3 days. Activation of myeloid cells by B. burgdorferi lipoproteins is mediated through TLR-2 29. Also, a synthetic TLR-2 agonist triacyl-CSK4, which mimics the structure of the N-terminus of a borrelial lipoprotein, can induce CD1 expression 30.

58 Following vasectomy reversal, pregnancy rates are reduced when these ASA are present in the seminal fluid or detected on spermatozoa. However, this occurs relatively infrequently when men who have had vasectomy reversal are studied. Meinertz and colleagues studied a group of 216 men following vasovasostomy with mixed antiglobulin reaction (MAR) for IgG, IgA, and IgA U0126 mouse secretory antibodies bound to sperm. ASA in serum and seminal plasma were detected by agglutination tests.59 In the subgroup with a pure IgG

response, the conception rate reached 85.7%, whereas only 42.9% of men who also had IgA on their sperm achieved a pregnancy. When 100% of the spermatozoa were coated with IgA, the conception rate was reduced to 21.7%. Isahakia et al.60 have shown, in baboons, that new antigens are expressed on developing spermatocytes and spermatids after initiation of spermatogenesis. Three monoclonal antibodies (Mabs) raised in mice immunized with baboon sperm were used to study the stage-specific expression of sperm-associated antigens on intratesticular sperm. One of these Mab’s recognized a moiety on the sperm tail and the other over the anterior acrosomal region of the sperm. The tail antigen was absent in 2- and 3-year-old baboon testes, first appearing in spermatids located close to

the lumen of the seminiferous tubules at CH5424802 solubility dmso about 4 years of age. The acrosomal antigen was recognized in late pachytene spermatocytes and round spermatids in a 3-year-old animal, but failed to be demonstrated in a 2-year-old juvenile baboon. These antigens, to which the immune system may not be tolerant, could play a role in the genesis of autoimmunity sperm. As men with acquired sperm obstruction (secondary to vasectomy) develop autoimmunity to sperm, we asked whether men with cystic fibrosis, the majority of whom exhibit obstructive azoospermia due to congenital absence of the body & tail of the epididymis, the vas deferens,

and seminal vesicles, exhibited ASA in their serum. We also wanted to determine whether there was a relationship between puberty (at which time filipin spermatogenesis becomes active) and the development of autoimmunity to sperm. We studied 15 males, using an Immunobead binding assay, to detect the presence of ASA in their serum.61 Six of 7 post-pubertal males (ages 18-33) were found to possess ASA in their serum. These men were judged post-pubertal by their testes volume and serum testosterone levels. Conversely, none of 8 pre-pubertal (ages 9–11) were found to have autoimmunity to sperm. An additional control consisted of 16 diabetic post-pubertal males, one of whom was found to exhibit ASA. There is increasing evidence that the blood–testes barrier in itself is not sufficient to prevent autoimmunity to sperm.

6A). In E-Btk-2 and EY-Btk-5 mice IgM serum levels were increased (Fig. 6B), consistent with the presence of increased numbers of IgM ASC in the long-lived compartment in the BM. The E-Btk-2 and EY-Btk-5 mice did not

show an increase in ASC of other subclasses (data not shown), and accordingly serum levels were either decreased or in the WT ranges (Fig. 6B). To investigate mature B-cell functionality, we analyzed the immune response to the T-cell independent type II (TI-II) antigen, TNP-Ficoll and the T-cell dependent (TD) antigen, TNP-KLH. Consistent with previous reports 8, 23 Btk-deficient mice did not show TI-II IgM or IgG3 responses (Fig. 6). Similarly, click here E-Btk-2 mice were unresponsive to TNP-Ficoll immunization, whereas EY-Btk-5 mice responded similarly to WT mice (Fig. 6C). The response to the TD

antigen TNP-KLH was assessed 1 wk after immunization (IgM) and 1 wk after booster immunization (IgG). WT and Btk-deficient mice had similar primary IgM and secondary IgG1 responses (Fig. 6D), but these were severely reduced in E-Btk-2 and EY-Btk-5 mice. Consistent with defective TD responses, clusters of PNA+ germinal center B cells were not detectable (E-Btk-2) or severely reduced (EY-Btk-5) in immunohistochemical analyses (data not shown). In summary, these findings demonstrate that both E-Btk2 and EY-Btk5 Tg efficiently drive IgM+ plasma cell differentiation, but this is not associated with increased functional TI-II responses. Moreover, TD responses and germinal center

formation were oxyclozanide significantly affected by the presence of constitutive active Btk. As the E-Btk-2 and EY-Btk-5 B cells were spontaneously driven into germinal center-independent Tipifarnib cell line plasma cell differentiation, the Btk Tg mice may have lost self-tolerance. In serum of 9–12 wk old animals we found that anti-nucleosome-specific IgM was increased in E-Btk-2, but not in EY-Btk-5 mice, to levels that were similar to those found in autoimmune MRL/lpr control mice (Fig. 7A). No anti-nucleosome IgG was detectable in WT or Btk Tg mice. Serum analysis of ∼35 wk old mice revealed that total IgM levels increased with age and that IgM serum levels in E-Btk-2 and EY-Btk-5 mice remained dramatically elevated compared with values in WT mice (Fig. 7B). Strikingly, E-Btk-2 mice had developed dramatically increased anti-nucleosome IgM, which was at least >15 times the level found in MRL/lpr mice (Fig. 7C). Also in YE-Btk-5 mice anti-nucleosome activity was detectable, but concentrations were lower. Overexpression of unmutated human Btk (in Btk-2 mice, also under the control of the CD19 promoter 28) or high-level expression of E41K-Btk (in E-Btk-3 mice) did not induce anti-nucleosome IgM (Fig. 7C). Although immunohistochemical stainings of kidneys revealed the presence of enlarged glomeruli containing IgM deposition in E-Btk-2 Tg mice (Fig. 7D), we did not find evidence for autoimmune disease, such as proteinuria or glomerular inflammation.

Such delays are of particular importance, as the risk of death from HAE has been shown to be three- to ninefold higher in undiagnosed patients [8]. Complement C3 and C4 levels were generally performed at clinic visits or annually, and 78% (40 of 51) of normal C4 results were from patients on either attenuated androgens or, in one case, C1INH prophylaxis. This leaves a small overall percentage of patients (3%) who were not on attenuated androgens and had a normal C4 recorded. Liver function tests were measured

in the majority and lipids in a lower proportion, probably reflecting the use of attenuated androgens. Autoantibody testing was not routine; testing revealed positive anti-nuclear antibodies (ANA) in eight patients, thyroid peroxidase antibodies in five patients, Ensartinib datasheet with individual patients positive for adrenal antibodies, glutamic acid decarboxylase

(GAD) antibodies and anti-neutrophil cytoplasmic antibodies [with a perinuclear indirect immunofluorescence pattern (pANCA) on a background of Crohn's disease]. Hepatitis serology testing was variable and incomplete. Information on acute treatment on 343 patients CHIR99021 (Fig. 5a) showed that the majority, 62%, had C1INH available at home, with 8% receiving prophylactic C1INH and 30% attending accident and emergency departments for C1INH acute treatment. Small numbers of patients (6%) were given icatibant, due perhaps to its relatively recent availability, and the majority of these also had access to C1INH. Treatment with oral agents for long-term prophylaxis demonstrates a clear and expected difference in the use of this form of medication between adults (total 335 patients) and children (total 37 patients)

(Fig. 5b,c). Children were less likely to need long-term prophylaxis and attenuated androgens are contraindicated, except in exceptional circumstances. The majority of children check details (73%) were on no regular medication and those who required therapy were treated with tranexamic acid. Sixty-seven per cent of adults received long-term prophylaxis with oral medication, the majority taking attenuated androgens. Data on attack frequency were available for 323 patients; overall analysis showed that peripheral attacks are the most frequent form of attack in HAE and constitute 58% of all swellings. There was considerable variability in the numbers of peripheral attacks per year between patients, with an overall mean of eight peripheral swellings annually (Fig. 6a). Patients have, on average, 5 attacks of abdominal pain per year, and these constitute 38% of all attacks. The huge variability in mean annual attack frequency is again highlighted (Fig. 6b). Attacks affecting the airway are the least frequent, at 4% of all attacks; however, 19% of patients (n = 62) experienced an airway attack during the 12 previous months, with some having up to two per month (Fig. 6c). Figure 6d shows the average annual attack frequency at the three main sites of swelling.

The level of AOPP was independently associated with IHD only in HD patients. “
“Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of chronic proteinuric renal disease. AN is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a number of loci that alter both risk and severity of renal injury induced by Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to be modulated by both non-immune and immune factors, and has facilitated further study of mechanisms

of tubulointerstitial injury. This review will outline the pharmacological behaviour of selleck screening library Adriamycin, and describe in find more detail the model of AN, including its key structural characteristics, genetic susceptibility and pathogenesis. Most types of chronic kidney disease (CKD) are characterized by the development of glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Adriamycin® (Pfizer, Sydney, Australia) (doxorubicin) is a well-known inducer of renal injury in rodents, which mirrors that seen in human CKD due to primary focal segmental glomerulosclerosis.

The first published record of anthracyclines causing renal injury was in 1970 by Sternberg.1 The first description of Adriamycin inducing renal injury was in 1976 in rats,2 and 1998 in mice.3 In 1977, Burke and colleagues4 described a case of a 78-year-old man developing renal failure after the administration of doxorubicin. Since then, Adriamycin nephropathy (AN) in rodents has been extensively studied and

has enabled a greater understanding of the processes underlying the progression of renal injury. Adriamycin nephropathy has several strengths as an experimental model of kidney disease. It is a highly reproducible model of renal injury. It is also a ‘robust’ model in that the degree of tissue injury is severe while associated with acceptable mortality (<5%) and morbidity (weight loss). Because the model is characterized by the induction of renal injury within a few days of drug administration, the timing of injury is consistent and predictable. The severity and timing of renal injury means that it is a model those suitable for testing interventions that either worsen or protect against renal injury. The type of structural and functional injury is very similar to that of chronic proteinuric renal disease in humans (see below). Last but not least, this model is similar in rats and mice. Rodent models are extremely useful in the study of disease. Rodents are characterized by their short reproduction period, easy (and cheap) availability of animals and reagents, and amenability to genetic manipulation.5 There are also limitations in the use of AN as an experimental model.

61%). RCM seems to be useful for microscopic evaluation of mycelium features and may have a scientific value in study of superficial cutaneous fungal infections. “
“This report presents

a rare case of tinea capitis caused by Trichophyton soudanense and Microsporum audouinii in a 31-year-old woman from Senegal. The patient showed atrophic skin lesions causing cicatricial alopecia, scarring being caused by two aetiological agents uncommon in Spain. “
“Undetected tinea pedis selleck chemicals in a patient with diabetes can lead to serious bacterial infections with potentially serious consequences, such as foot amputations. Here we report on a 60-year-old patient with diabetes presenting with pain, severe pruritus, and malodour in the foot’s interdigital area, and subsequently, diagnosed with inflammatory tinea Selleck HDAC inhibitor pedis with bacterial superinfection. The patient was successfully treated with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%; marked improvement occurred within 5 days. “
“Invasive aspergillosis (IA) is a major cause of death among patients with chronic granulomatous disease (CGD). Few cases of cardiac aspergillosis have been published on CGD patients. Diagnosis of IA in CGD patients can be hampered by lack of characteristic symptoms and clinical signs and the serum galactomannan assay

is often negative. We report the first CGD patient with IA presenting as pericarditis where combined antifungal therapy resulted in a successful outcome. “
“Phaeohyphomycosis is a distinct mycotic infection of the skin or internal organs caused by darkly pigmented (dematiaceous) fungi, which are widely distributed in the environment. Phaeohyphomycosis is most frequently an opportunistic infection in immunosuppressed patients (HIV, corticotherapy, transplant patients) or is frequently associated with chronic diseases and diabetes. The spectrum of the disease

is broad and includes superficial infections, onychomycosis, subcutaneous ADP ribosylation factor infections, keratitis, allergic disease, pneumonia, brain abscesses and disseminated disease. Rarely, immunocompetent patients may be affected. We describe two new cases of subcutaneous phaeohyphomycosis in immunocompetent patients: in the first patient, the causative agent was Exophiala jeanselmei, a common cause of phaeohyphomycosis; and in the second, Cladophialophora carrionii, which could be identified by culture. Cladophialophora carrionii is mainly the aetiological agent of chromoblastomycosis and only rarely the cause of phaeohyphomycosis. The first patient was treated with surgical excision and oral itraconazole, and the second patient responded to oral itraconazole only. Lesions improved in both patients and no recurrence was observed at follow-up visits. “
“Superficial fungal infections are expected to be more prevalent in renal transplant recipients because of graft-preserving immunosuppressive therapy.

The PI3K Inhibitor Library present data reveal a possible role that IL-9+IL-10+ T cells may attract Mϕ to the local tissue and the latter contribute further to inflammation. The data support the hypothesis; a portion of Mo is F4/80+ Mϕ. Our results are in line with other investigations reported previously that also observed that the levels of MIP1, together with other proinflammatory cytokines, were elevated in patients with chronic allergic asthma [15], chronic atopic dermatitis [16] or animal studies [17]. The present results reveal that in allergic reactions, a portion of IL-9+IL-10+ T cells extravasate into

local tissue such as the intestine. As MIP1 plays an important role in inflammation, the source of MIP1 is of significance to be understood. Our results indicate that, upon antigen-induced TCR activation, IL-9+IL-10+ T cells produce MIP1 that has the capacity to attract Mϕ; the latter may be responsible for further

pathological changes in local tissue. It is well documented that Mos extravasate in allergic hypersensitivity reactions [18,19]. The present data are in line with these published data by revealing abundant Mos in the intestine Selleckchem Hydroxychloroquine after antigen challenge, as shown by flow cytometry and histology studies. Furthermore, we have shown that these Mos express high levels of MIP2γ, indicating that they have the capacity to attract neutrophils to local tissue. Meanwhile, we also observed an increase in neutrophils in the intestine during LPR. A link between the extravasation of Mos and neutrophils has been noted in the present study. Thus, we may envisage a scenario that TCR activation induces IL-9+IL-10+ T cells to express MIP1; MIP1 attracts Mϕ to local tissue; Mϕ-derived MIP2γ attracts neutrophils to extravasate in the intestine to release proinflammatory molecules, such as MPO (Fig. 3),

that may damage intestinal tissue and induce inflammation, as shown by the present study as well as by other investigators [9]. Allergic hypersensitivity RG7420 plays an important role in the induction of pathological changes in chronic allergic inflammation [20]. A skewed cellular response is proposed to play a major role in the inflammatory process [21]. These results are in line with previous reports [19,21] showing that the cellular elements in local tissue (the intestine) include eosinophils, mast cells, Mos and neutrophils. The data demonstrate that the extravasation of eosinophils and mast cells occurs mainly in early allergic responses; the frequency of these cells declines gradually after antigen challenge. At 48 h after antigen challenge, neutrophil becomes the major inflammatory cellular element together with a portion of Mo; the latter has been reduced markedly compared to cell counts at 2 h after antigen challenge. Neutrophil contains several enzymes, such as MPO, that essentially function to fight against invaded microbes as well as to damage local tissue and to cause inflammation such as inflammatory bowel disease.

Subsequent 16S rRNA gene analysis later revealed

the good biofilm formers to be strains of S. epidermidis, while the poor biofilm formers (C116 and C191) were identified as Staphylococcus lugdunensis and Staphylococcus warneri, respectively. To study the effects of P. aeruginosa on the ability of S. epidermidis to form biofilms, equal numbers of S. epidermidis (strains C103 or C121) and P. aeruginosa cells (strains 14:2 or 15159) were inoculated into the flow cells and maintained for 6 h. Image analysis showed the level of surface coverage by the P. aeruginosa strains in the dual-species biofilms to be in the same range as that seen for the mono-species ones (Fig. 2g and h). The presence BTK inhibitor of P. aeruginosa strain 14:2 in the biofilms caused large reductions in colonization NVP-BKM120 cost by S. epidermidis strains: 88% for strain C103 (Fig. 2b) and 86% for strain C121 (Fig. 2e) compared with their respective controls (Fig. 2a and d). However, the presence of the P. aeruginosa strain 15159 reduced biofilm-formation by the S. epidermidis strains C103 (Fig. 2c) and C121 (Fig. 2f) by only 34% and 38%, respectively, over the control (the equivalent mono-species levels) (Fig. 2a and d). Thus, although both the P. aeruginosa strains cause some degree of inhibition of biofilm formation by S. epidermidis, the effect is much greater for strain 14:2 than 15159. The effects of all the different strains of P. aeruginosa

(PAO1, NCTC 6750, 14:2, 23:1, 27:1 or 15159) on the ability Org 27569 of S. epidermidis (Mia, C103 or C121) to form biofilms were also studied as above. For the

Mia strain, even after 6 h of co-culture in biofilms, the presence of all the P. aeruginosa strains reduced colonization compared with the control and the effect was significant (P<0.05) for strains PAO1 and 23:1 (Fig. 3). For S. epidermidis strains C103 and C121, a significant reduction in colonization (P<0.05) was seen when strain 14:2 was present in the dual-species biofilms. The S. epidermidis strain C121 appeared to be generally more resistant to the effect of P. aeruginosa than the other two (Fig. 3) and an increase in surface coverage was seen in the presence of NCTC 6750. In summary, of the P. aeruginosa strains studied here, 14:2 had the greatest effect in inhibiting biofilm formation by S. epidermidis, giving rise to a 50% reduction for strain Mia and a >85% reduction for strains C103 and C121. Staphylococcus epidermidis strain C121 differed somewhat from the other two in that it was more resistant to P. aeruginosa. Established 6-h biofilms of the three S. epidermidis strains (Mia, C103 or C121) corresponding to a total area of 0.8 mm2 were exposed to biofilm supernatants from P. aeruginosa strains (PAO1, NCTC 6750, 14:2, 23:1, 27:1 or 15159) or TH medium (control) for 1 h. Cells remaining in the biofilms were then visualized using 16S rRNA FISH. The results for S. epidermidis strain C121 are shown in Fig. 4. Supernatants of all the P.