Also, increased apoptosis, together with ROS production and lipid peroxidation, has been observed in B lymphocytes isolated from diabetic mice [30]. In addition to affecting apoptosis, high

glucose affects cellular survival and proliferation progressively. For example, exposure of T and B lymphocytes to high glucose results in inhibition of DNA synthesis and proliferation [30, 38]. B cells, CSF-1R inhibitor together with other immune cells, are implicated in the pathogenesis and progression of atherosclerosis. Diabetic patients have an increased risk of developing atherosclerosis, and a disturbed function of B-1 cells as shown in this study could possibly mediate this. Previous studies have suggested that B-1a cells and natural IgM are atheroprotective [15], probably by the ability of these antibodies to compete with macrophages in binding OxLDL, thereby inhibiting foam cell formation [19]. In mice, absence of IgM leads to an increased propensity for atherosclerosis [12] and atherosclerosis development is inhibited if the amount

of oxidation-specific epitopes is increased, such as after immunization with the bacteria S. pneumoniae [13]. Clinical studies have shown that elevated circulating levels of IgM against OxLDL are associated with reduced ABT263 vascular risk in humans, but IgG antibodies show variable associations [16-18]. In conclusion, this study shows that diabetic db/db mice have lower proportion of peritoneal B-1a cells in the steady state and show a dampened response to TLR activation and immunization against S. pneumoniae, both stimuli that require a functional innate immune system. Moreover, culture of isolated peritoneal mouse B-1 cells Selleck Fludarabine in high glucose concentrations

led to reduced IgM secretion, decreased proliferation, and increased apoptosis. The results suggest that metabolic regulation of B-1 cells is of importance for the understanding of the role of this cell type in lifestyle-related conditions. This study was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, Sahlgrenska University Hospital, the Swedish Society of Medicine, the research foundations of Åke Wiberg, Syskonen Svensson, Fredrik and Ingrid Thuring, Magnus Bergvall and the Emelle Foundation. We thank Hannah Shaffer for excellent laboratory assistance. The authors declare no conflict of interest. “
“Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Arenaviruses. LASV causes hemorrhagic fever, whereas MOPV is not pathogenic. Both viruses display tropism for APCs such as DCs and macrophages. During viral infections, NK cells are involved in the clearance of infected cells and promote optimal immune responses by interacting with APCs. We used an in vitro model of human NK and APC coculture to study the role of NK cells and to characterize their interactions with APCs during LASV and MOPV infections.

B cells require B-cell-activating factor (BAFF) for normal B lymphocyte development. BAFF, also known as BLyS, TALL-1, zTNF4 and THANK, is a member of the tumour necrosis factor (TNF) superfamily (TNFSF13B), produced and secreted mainly by myeloid cells (macrophages, monocytes and dendritic cells), but also by non-lymphoid cell types (salivary gland epithelial cells, astrocytes and fibroblast-like synoviocytes) and epithelial cells including bronchial and nasal epithelial cells [2–4].

It is expressed as a type II transmembrane BGJ398 nmr protein (biologically active 17-kDa molecule), and levels of BAFF are upregulated by interferon (INF)-γ, interleukin (IL)-10 Small molecule library nmr and CD40 ligand produced during inflammation and/or chronic infections [5]. BAFF is an important regulator of peripheral B-cell survival, maturation, immunoglobulin production and immunoglobulin class-switch recombination (CSR) [2]. Increased release of BAFF

may lead to the emergence of autoreactivity, especially in those with genetic susceptibility. Thus, in animal models, overexpression of BAFF leads to B-cell hyperplasia, lymphoproliferation, hypergammaglobulinemia and symptoms of autoimmunity. Conversely, BAFF-deficient animals exhibit defects in peripheral B-cell maturation and decreased levels of immunoglobulins [4, 6]. Recently, BAFF has emerged as an important regulator of T-cell-mediated reactions as well [7, 8]. Although BAFF is supposed to play an important role in the pathogenesis of autoimmune diseases, high levels in other conditions such as allergic diseases, infections and malignancies suggest a role of BAFF also there (Table 1). BAFF activates IgG, IgA and IgE isotype switching in B cells. CSR is a biological mechanism by which activated B cells (plasma cells) change their antibody production from one isotype to another, for example, from IgM to IgG. Naive mature B

cells produce both IgM and IgD, which contain the Methocarbamol first two heavy chain segments of the immunoglobulins. For making a new isotype of antibody by CSR, B cells require 2 signals. The first signal normally comes through T-cell cytokines (IL-4, IL-10, IL-13 and TGF-β), while the second is delivered by engagement of CD40 on B cells [9]. In addition, BAFF impacts on this process by one of its specific receptors, called TACI [9, 10]. To produce IgG, IgA or IgE antibodies, the constant region of the immunoglobulin heavy chain changes while the variable regions, and therefore antigen specificity, stay the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1 and IgG2).

Nonetheless, the absence of HAX1 did not lead to a complete block of B-cell development, as mature B cells were present. However, HAX1 was not required for splenic B-cell proliferation under the stimulation conditions used in vitro and immunoglobulin levels of naïve Hax1−/− mice resembled those selleck products from WT littermates. These

experimental facts, from our point of view, indicate that the developmental impairment of HAX1-deficient B lymphocytes can most probably be explained by migration defects. Importantly, the observed phenotypes were also not restricted to 10-wk-old Hax−/− mice, which is near their end of life. FACS analysis of B-cell maturation in the bone marrow and spleen of 6-wk-old mice showed a comparable lymphocyte loss (Supporting Information Fig. 1). Thus, B lymphopoiesis is also affected selleck chemicals llc early in life and the decline is not due to systemic poor health. A characteristic feature of B-cell development in the bone marrow is the migration of developing precursors from early stages nearest the endosteum layer to latter stages progressively closer to the central arteriole, the site of exiting 32. This migration is likely due to differential expression of specific adhesion molecules and chemokine receptors. A critical chemokine in this process is SDF1 (CXCL12), found on bone marrow stromal cells, and its receptor CXCR4 22, expressed by hematopoietic

precursors and B-cell progenitors. Deletion of either the receptor or ligand leads to impairments in B-cell development probably because of failure to retain precursors in the bone marrow 33, 34. Therefore, we analysed Hax1−/− and WT splenic B cells for CXCR4 expression by a real time PCR. Interestingly, compared to Thymidine kinase WT B cells, CXCR4 expression was reduced by approximately 70%. However, this fact had no effect on the formation of follicular structures or distributions of B or T cells within these follicles. Nevertheless, migration defects of Hax−/− B cells could

partially be responsible for the observed defects in B-cell development. In parallel, we also tried to analyse the expression of CXCL12 in B- and T-cell-depleted bone marrow cells (data not shown). However, CXCL12 expression even in WT mice was too low to significantly evaluate the amplification products. Alternatively, we speculated about a possible function of the receptor for B-cell-activating factor (BAFFR) because signals through the BAFFR have a significant role in promoting B-cell survival and homeostatic proliferation 23. Signalling through the BCR provides a cell intrinsic measure of B-cell fitness, whereas BAFFR-mediated survival is linked to the cell-extrinsic parameter of primary B-cell population size, i.e. the amount of available BAFF (also known as BlyS) is a measure of unfilled “space” in the B-cell compartment 35, 36.

As Foxp3 specifically defines mouse CD4+ Tregs 24, we next assessed if induced CD8+Foxp3+ T cells display expression of bona

fide Treg markers. Therefore, induced CD8+GFP+, activated CD8+GFP− and naïve CD8+Foxp3− T cells were obtained from DEREG×Rag1−/−×OTI ABC294640 order mice. CD4+GFP+ nTregs sorted from DEREG mice served as the positive control. The expression of various markers was assessed by quantitative real-time PCR. As expected, CD8+GFP+ T cells and CD4+GFP+ nTregs expressed high levels of Foxp3, whereas only marginal Foxp3 expression was detected in CD8+GFP− T cells, confirming that Foxp3 is not substantially induced by sole T-cell activation in mice (Fig. 4B). CD8+GFP+ T cells expressed CD25 and CTLA4 to equal or higher levels compared with nTregs; however, those markers were also induced in CD8+GFP− T cells (Fig. 4B), consistent Decitabine ic50 with their expression upon activation. Interestingly, CD73 was highly expressed by both nTregs and induced CD8+GFP+ T cells,

whereas activated T cells lacked CD73 mRNA. In contrast, the nTreg-associated marker folate receptor 4 (Folr4) showed low expression in both CD8+GFP+ and CD8+GFP− T cells (Fig. 4B). CD103 was expressed at low levels in CD8+GFP−-activated T cells, whereas induced CD8+GFP+ T cells and nTregs showed signals above untreated CD8+Foxp3− T cells (Fig. 4B), the majority of which express CD103 protein (Fig. 4C). Notably, granzyme B mRNA was induced in CD8+GFP−-activated T cells but was low in CD8+GFP+ T cells and nTregs (Fig. 4B). We next

performed FACS analysis of CD8+ Rag1−/−×OTI T cells similarly cultured in vitro. Additionally, DEREG and WT mice were used for ex vivo characterization of CD8+ T-cell populations. The expression of various markers of Foxp3+ and Foxp3− cell populations was compared. CD4+Foxp3+ Tregs (nTregs) served as the positive control. As expected, the vast majority of induced CD8+Foxp3+ T cells and CD4+Foxp3+ nTregs co-expressed GFP ADAMTS5 due to the Foxp3 promoter-driven DEREG transgene, whereas GFP expression was absent in CD8+Foxp3− T-cell populations (Fig. 4C). We found high expression of the classical Treg markers CD25, CTLA4 and GITR on both Foxp3+ and Foxp3− in vitro activated CD8+ T cells, whereas their constitutive high expression ex vivo was selective for the Foxp3+ subset, similar to CD4+Foxp3+ Tregs (Fig. 4C). CD103 and CD73 were selectively expressed on the CD8+Foxp3+ subset in vitro, whereas significant yet lower expression was also detected on CD8+Foxp3− populations ex vivo when compared with the CD8+Foxp3+ subset (Fig. 4C). Of note, the expression of CD25, CD103 and GITR was predominantly independent of functional Foxp3 as demonstrated using cells from DEREG×Rag−/−×OTI×Sf mice (Supporting Information Fig. 3C). CD122 expression and lack of CD28 expression were previously used to define naturally occurring CD8+ Treg populations 7, 8.

All selected patients reported the use of cigarettes for more than 20 years, and TAO was diagnosed at a mean age of 40 years. Ninety per cent of the patients exhibited evidence of critical limb ischaemia and 60% presented leg amputations (below- or above-knee amputation) in the contralateral leg. Thus, the patients were classified into two groups: (i) TAO former smokers with clinical remission (n = 11) and (ii) TAO active smokers with clinical exacerbation (n = 9); selleck products the control groups included normal

volunteer non-smokers (n = 10), former smokers (n = 10) and active smokers (n = 10). All smokers analysed in this study (control and TAO) had used cigarettes for at least 3 years and smoked a minimum of 10 cigarettes per day. All the subjects classified as TAO former smokers were ex-smokers who had quit 10 years before or even earlier. Patients presenting with anti-phospholipid syndrome were excluded. Standard treatment was applied to all TAO patients, including anti-platelet treatment with aspirin (100 mg/day), pain management (orally 5–7 days) with anti-inflammatory (ibuprofen 400 mg thrice-daily) Etoposide and opioid drugs (tramadol 100 mg thrice-daily), and advice to cease smoking immediately. A trained

biomedical technician collected a 10-ml venous blood sample from each participant. Blood samples were collected in trace metal-free tubes (BD Vacutainer; BD Vacutainer, Franklin Lakes, NJ, USA) that contained ethylenediamine tetraacetic acid (EDTA) anti-coagulants. Two millilitres of blood were then pipetted into an Eppendorf tube previously cleaned in a class 100 clean room and frozen immediately at −70°C before analysis. Quantitative

determinations of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17 and Doxacurium chloride IL-23 were performed on plasma samples using the sandwich enzyme-linked immunosorbent assay (ELISA) [DuoSet® ELISA Development Systems; R&D Systems, Minneapolis, MN, USA]. The cytokine concentrations in plasma were determined by a double-ligand using an ELISA plate scanner (Molecular Devices SpectraMax 250, El Cajon, CA, USA). The cytokine concentration was expressed in pg/ml by the kit’s standard curve. The non-parametric Mann–Whitney U-test, Kruskal–Wallis and Wilcoxon’s tests were used for cytokine data analysis. The null hypothesis was rejected when the possibility of chance occurrence of observed differences did not exceed 5% (P < 0·05). Figure 1 shows the values of proinflammatory cytokine activities (IL-1β, TNF-α and IL-6) in the plasma of control individuals (non-smoker, ex-smoker and active smokers) (n = 10 for each group) and patients with TAO (active smokers and former smokers) (n = 10 for each group) expressed in pg/ml.

The difference was statistically significant (P = 0·005). Among the six extremely virulent strains from the sylvatic cycle, two were sampled from the tsetse flies and four from the buffaloes. The median survival time of mice infected

see more with strains isolated in the sylvatic transmission cycle was 7·9 (C.I. 6·9–9·0) compared to 11·1 (C.I. 9·9–12·4) for those from the domestic transmission cycle (P < 0·001). The comparison of the virulence of the 62 T. congolense strains belonging to the Savannah subgroup confirms the observation made by Masumu et al. (9) that virulence greatly differs from strain to strain. As experiments performed by Bengaly et al. (7,8) have BMS-777607 manufacturer shown concordance between virulence tests in mice and results of the same tests in cattle, our findings can be extrapolated to a field situation. Moreover, based on the limited number of strains from four geographical areas, the outcome of the analysis shows that virulent strains are not distributed evenly over the transmission cycles but that the proportion of highly virulent strains is significantly

higher in the sylvatic transmission cycle. This may indicate that the evolution of trypanotolerance in wildlife has acted as an important selective pressure on trypanosomes by selecting for higher parasite SB-3CT replication rates to maximize the production of

transmission forms and, at the same time, increasing the virulence of the strains in a susceptible host (16). The persistence of a relatively small proportion of strains with low virulence in the sylvatic cycle could be explained by variations in the susceptibility to trypanosomal infections in game animals with some species being more susceptible than others (17). The predominance of virulent trypanosome strains in wildlife may be the reason why livestock trypanosomiasis epidemics with high morbidity and high mortality are usually encountered when livestock is introduced in wildlife areas or when livestock is kept at a game/livestock interface and is thus exposed to tsetse flies transmitting highly virulent strains picked from wild animals. For example, the restocking of cattle into tsetse-infested areas of northern, central and southern Mozambique after the civil war resulted in serious problems with livestock trypanosomiasis (18). Similarly, the introduction of livestock in the tsetse-infested zones of the Rift Valley in Ethiopia has resulted in important trypanosomiasis outbreaks with high mortality in the livestock population (19). Finally, the bovine trypanosomiasis epidemics in South Africa are all closely linked to the game/livestock interface of the Hluhluwe-iMmfolozi Game Park (20,21).

c.) infected with L. amazonensis or L. braziliensis stationary promastigotes (2 × 106 in PBS) in the right hind foot. At indicated time of infection, we collected popliteal draining LN cells and splenocytes from individual selleck inhibitor mice. To ensure sufficient cells for staining and subsequent analyses, we conveniently pooled draining LN cells within the group into two sample sets, such as three draining LNs into one set and the other two draining LNs into the other set. Cells were then stimulated with a PMA/ionomycin/Golgi Plug (BD Biosciences) for 6 h. Cells were first stained for surface markers, including CD3, CD4 and individual TCR Vβ. Then,

the intracellular IFN-γ production was stained following cytofixation/permeabilization with a Cytofix/Cytoperm Kit (BD Biosciences). The percentages of CD4+ TCR Vβ+ cells gated on CD3+ cells and TCR Vβ+ IFN-γ+ cells gated on CD4+ cells were analysed on the FACScan (BD Biosciences), and results were analysed using FlowJo software (TreeStar, Ashland, OR, USA). To obtain the absolute cell number of CD4+Vβ+ cells, we first got an averaged cell number per draining LN from each sample set. We then calculated the absolute cell number of CD3+ CD4+ TCR Vβ+ cells by multiplying the averaged absolute cell number per LN by their corresponding percentages of positively stained cells (CD3, CD4 and the individual

TCR Vβ in CD4 cells). For TCR Vβ analysis of lesion-derived cells, foot lesional tissues were collected and pooled as mentioned earlier and digested in the complete Iscove’s modified Dulbecco’s medium containing 10% FBS, 1 mm sodium pyruvate, 50 μm AZD9291 in vitro 2-ME, 50 μg/mL gentamicin and 100 U/mL penicillin, as well as collagenase/dispase (100 μg/mL) and DNase I (100 U/mL; Roche), for 2 h at 37°C. After passage through the cell strainer (40 μm; BD Biosciences), the single-cell suspension was on the top of 40% and 70% Percoll solution (Sigma). After centrifugation for 25 min at room temperature,

the purified GNA12 cells from a 40/70% layer of Percoll were collected and stained with CD3, CD4 and TCR Vβ Abs. The percentages of TCR Vβ+ cells gated on CD3+ CD4+ cells were analysed by FACS. B6 mice were infected with 2 × 106La or Lb promastigotes for 4 weeks. Draining LN cells were restimulated with the corresponding La or Lb antigens for 3 day, and CD4+ T cells were purified via positive selection. Naïve CD4+ T cells were used as controls. TCR Vβ repertoire clonality for purified CD4+ T cells was analysed by RT-PCR and gel-based assays using specially designed SuperTCRExpress™ kits by scientists in BioMed Immunotech Incorporation (Tampa, FL, USA). Leishmania braziliensis stationary promastigotes (2 × 106) were injected subcutaneously (s.c.) in the right hind foot. After the healing of lesions at 8 or 24 weeks, some of the mice were injected with stationary promastigotes of La (2 × 106) in the left hind foot. Naïve mice were similarly infected and used as controls.

Altogether these data suggest that RyR1 depletion in skeletal muscle is one of the pathophysiological mechanisms of the disease as already reported in recessive forms of RYR1-related congenital myopathy [19,28,38–40]. In conclusion, we have identified a specific clinical MG 132 and histological phenotype

associated with recessive RYR1 mutations. Our data clearly show that in this group of patients, the histological phenotype shares features traditionally described in different forms of congenital myopathies, namely centronuclear and core myopathies. They strongly support the idea that the presence of disorganized myofibrillar areas with irregular borders in muscle biopsies from patients with clinical manifestations of congenital myopathy are likely to be due to RYR1 mutations, even in the presence of numerous fibres with internalized nuclei. Hence, this peculiar morphological pattern should be consistently associated with the subgroup of ‘congenital myopathies with cores’. This will improve molecular diagnosis and consequently, genetic counselling and the prognosis given to patients. We are grateful to Professor S. Lyonnet for giving us DNA samples of patient 1. We thank Dr Anna Buj-Bello; Dr R. Peat and Dr Y. Corredoira for proof-reading of the manuscript

and helpful advice and L. Manéré, G. Brochier, E. Lacène, M. Beuvin, M.T. Viou, P. Thérier and S. Drouhin for their excellent technical help. “
“R. Bolea, P. Hortells, I. Martín-Burriel, MEK inhibitor A. Vargas, B. Ryffel, M. Monzón and J. J. Badiola (2010) Neuropathology and Applied Neurobiology36, 300–311 Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a find more murine model of scrapie Aims: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains.

The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. Methods: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (−Cu), loaded manganese (+Mn), depleted copper/loaded manganese (−Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. Results: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the −Cu, −Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death.

We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so

far (CD133+ cells, ALDH+, MuStem, ES, iPS). Finally, we provide an update of ongoing clinical trials using cell therapy strategies. “
“Microglial cells have been originally identified as a target for the CXC chemokine, SDF-1, by their expression of CXCR4. More recently, it has been recognized that SDF-1 additionally binds to CXCR7, which depending on the cell type acts as either a nonclassical, a classical or a scavenger chemokine receptor. Here, we asked whether primary microglial cells additionally express CXCR7 and if so how this chemokine receptor PXD101 datasheet functions in this cell type. CXCR4 and CXCR7 expression was analysed in cultured rat microglia and in the brain of animals with permanent occlusion of the middle cerebral artery (MCAO) by either Western blotting, RT-PCR, flow cytometry and/or immunocytochemistry. The function of CXCR4 and CXCR7 was assessed in the presence of selective antagonists. Cultured primary rat microglia expressed CXCR4 and CXCR7 to similar levels. Treatment with SDF-1 resulted in the activation of Erk1/2 and Akt signalling. Erk1/2 and Akt

signalling were required for subsequent SDF-1-dependent promotion of microglial proliferation. In contrast, Erk1/2 signalling was sufficient for SDF-1-induced migration of microglial cells. Both SDF-1-dependent signalling and the resulting effects Talazoparib datasheet on microglial proliferation and Neratinib cell line migration were abrogated following pharmacological inactivation of either CXCR4 or CXCR7. Moreover, treatment of cultured microglia with lipopolysaccharide resulted in the co-ordinated up-regulation of CXCR4 and CXCR7 expression.

Likewise, reactive microglia accumulating in the area adjacent to the lesion core in MCAO rats expressed both CXCR4 and CXCR7. CXCR4 and CXCR7 form a functional receptor unit in microglial cells, which is up-regulated during activation of microglia both in vitro and in vivo. “
“Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3. The clinical manifestations of SCA3 include peripheral neuropathy, which is an important cause of disability in a subset of patients. Although the loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the cause of this neuropathy, the precise mechanism remains to be elucidated. To clarify the clinicopathological characteristics of SCA3-associated peripheral neuropathy, we performed nerve conduction studies and histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 patients.

1, right). Patient data are summarized in Table 1. All skin defects could be covered by the flaps and all

wounds of donor site could be closed without skin grafts. Postoperatively, all flaps survived completely, and no wound complications occurred in any patient. The mean follow-up period was 11.5 months (range, 4 to 22 months). The functional and aesthetic results were satisfactory in all patients. A 44-year-old woman presented with a malignant fibrous histiocytoma of the right scapular region. Wide resection of the tumor resulted in a 13.5 × 12-cm2 skin defect, and the medial edge of the scapula was exposed (Fig. 2A). To reconstruct PF-01367338 chemical structure this defect, a latissimus dorsi musculocutaneous flap with an 18 × 7-cm2 skin island was harvested from the right side. The skin island was designed so that its longitudinal axis was perpendicular to the line of least

skin tension of the recipient site (Fig. 2B). The recipient defect was partially closed primarily at both ends, and the flap was transferred to the remaining defect through a subcutaneous tunnel. The donor site was closed primarily (Fig. 2C). The postoperative course was uneventful. Four months after the operation, the cosmetic outcome was satisfactory with minimal contour deformity, and no functional disturbance was observed (Fig. 2D). Closing large skin defects of the upper back is a challenging problem. The high tension on the wound edges resulting from primary closure might lead to dehiscence or tension necrosis. However, the tautness of the surrounding skin precludes the use of local flaps. Because the scapula or vertebrae selleck chemicals are often exposed, skin grafts directly to the defect are not indicated. Furthermore, if dead space is not adequately obliterated, wound healing can be delayed because of the mobility of the scapula. Transfer of a pedicled latissimus

dorsi musculocutaneous flap is the method of choice for reconstructing the skin of the upper back.[2] Advantages include a large, consistent, CYTH4 and reliable vascular pedicle; a highly flexible skin island design; ease of flap elevation; and minimal donor-site morbidity.[6] The only problem with this flap is that closure of the donor site interferes with closure of the recipient site, which can become enlarged, depending on the orientation of the skin island. Our flap design is novel because closure of the flap donor site changes the shape of the recipient site to one that is easier to close. The longitudinal axis of the skin island is perpendicular to the line of least skin tension of the recipient site, and primary closure of the flap donor site changes the shape of recipient site from circular to elliptical. This change in shape allows partial primary closure of the recipient site and reduces the required width of the skin island. The elliptical skin defect can be closed with the skin island of the flap without undue tension.