, Carver, MA), in order to determine vascular patency. Animals were euthanized with an intraperitoneal injection of Sleepaway (pentobarbital sodium) at a dose of 200 mg/kg. A 2 mm sample of the transplant was removed, decalcified, and formalin fixed. Three resin-embedded 5 µm sections were cut and placed on a 1.35-µm-thick polyethylene naphthalate (PEN) membrane metal-framed slide (Arcturus Bioscience, Inc., Mountain View, CA) (Fig. 1B). The membrane slide was then placed in the Veritas Laser Capture Microdissection System (ArcturusXT).[11] From one section,

a half circumferential cortical sample was selected and laser cut (Fig. 1C). From the two remaining sections, active bone forming areas, identified by fluorescent labels, were selected at 200× magnification and laser cut. Separately, areas located from the inner (endosteal) border of the transplant and areas from the outer cortex (periosteal) BMS-907351 cost were selected. This provided three different samples: overall cortical (C) bone, inner (I) active bone remodeling areas, and outer (O) active bone remodeling areas. The bone samples were captured on a specialized cap (CapSure Macro LCM caps, Arcturus Bioscience, Inc., Mountain View, CA). To prevent any soft Afatinib supplier tissue to be included after capturing, the bone samples were inspected at 40× magnification for any adherent

extraosseous tissue as well as capillary tissue, which Adenosine were removed with the Ablation Laser. DNA was extracted from the sample with stable Proteinase K (PicoPure DNA Extraction Kit, Arcturus Bioscience, Inc.,

Mountain View, CA) and 24 hours of incubation at 65°C (Fig. 1D). Spin columns (Performa Spin columns – Catalog # 13266, Edge Bio Systems, Gaithersburg, MD) were used to further purify the extracted product, which averaged 21.1 ng/µl DNA. This procedure involved preparing the Performa Gel Filtration Cartridge by centrifuging at 750 × g for 2 minutes and then transferring the cartridge to a 1.5 ml microcentrifuge tube. Afterward, the sample was added dropwise to the center of the packed column and centrifuged again for 2 minutes at 750 × g. The eluate was retained and frozen in a −20º C freezer for further evaluation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed using a Bio-Rad MyiQ Real-Time Instrument (description) and Bio-Rad Sybr Green Super mix (Bio-Rad Laboratories catalog # 170-8880, Hercules, CA.). RT-PCR was carried out using primer sets for the SRY gene (Sex Determining Region on the Y chromosome) as the gene of interest and Cyclophilin, a commonly used housekeeper gene. The SRY gene is used in sex-mismatched transplantation models to detect recipient- or donor-specific cells. Sequences used were Rattus norvegicus Sry (NM 012772.1) and Cyclophilin (M19533.1). Primer sets were designed using Beacon Designer software (Premier Biosoft International, Palo Alto CA.).

L. and Y.M. and a postdoctoral grant from ‘Stichting tegen Kanker’ to J.A.V.G. The authors declare no conflict of interest. Figure  S1 Claudin-1, claudin-2 and claudin-11 proteins are undetectable in IL-4 or TGF-β stimulated BALB/c thio-PEM. BALB/c thio-PEM were left untreated Rapamycin concentration (N) or were treated for 24 h with IL-4 or TGF-β, after which cell lysates were prepared for Western blot. Cell lysates were also prepared from total mouse brain, liver, kidney and spleen tissue. Table  S1 Basal gene expression levels (DCT ± SEM) in unstimulated naive macrophages. “
“Aicardi–Goutières

syndrome (AGS) is a genetically determined disorder, affecting most particularly the brain and the skin, characterized by the inappropriate induction of a type I interferon-mediated immune response. In most, but not all, cases the condition is severe, with a high associated morbidity and mortality. A number of important recent advances have helped to elucidate the biology of the AGS-related proteins, thus providing considerable insight into disease pathology. In this study, we outline the clinical phenotype of AGS, paying particular attention to factors relevant to therapeutic intervention. We then discuss the pathogenesis of AGS from a molecular

and cell biology perspective. Finally, we suggest possible treatment strategies in light of these emerging Selleck MK2206 insights. Other Articles published in this series Mouse models for Aicardi–Goutières syndrome provide clues to the molecular pathogenesis of systemic autoimmunity.

Clinical and Experimental Immunology 2014, 175: 9–16. Aicardi–Goutières syndrome: a model disease for systemic autoimmunity Clinical and Experimental Immunology 2014, 175: 17–24. We have previously published a description of the genotype–phenotype correlation in 121 patients with Aicardi–Goutières syndrome (AGS) [1]. Based on that work, and an ongoing exercise to assimilate clinical and laboratory data from >250 cases (http://www.nimbl.eu/ni/Home), the natural history of AGS is becoming clearer. In a significant minority of patients with AGS, problems are recognized CYTH4 at birth, i.e. the disease process begins in utero. Over time, severe neurological dysfunction manifests as progressive microcephaly, spasticity, psychomotor retardation and, in approximately 35% of cases, death in early childhood. Typical clinico-radiological features include intracranial calcification, white matter changes and raised numbers of white cells in the cerebrospinal fluid (CSF). To a remarkable degree this form of the disease, seen most consistently in association with mutations in TREX1, RNASEH2A and RNASEH2C, mimics the sequelae of congenital, transplacentally acquired infection (hence the tag: ‘pseudo-TORCH’ syndrome – Toxoplasmosis, Rubella, Cytomegalovirus and Herpes) [2]. More frequently, a later-onset presentation of AGS is seen, occurring in some cases after several months of normal development [3, 4].

OVA257–264 (SIINFEKL), tyrosine-related protein-2 tyrosinase-related protein (TRP)-2180–188 (SVDYDFFDWL), OVA323–339 (ISQAVHAAHAEINEAGR) and lymphocytic choriomeningitis virus–glycoprotein (LCMV GP)61–80 (GLKGPDIYKGVYQFKSVEFD) were obtained from A&A Laboratories (San Diego, CA, USA). DC were isolated from

spleens of naive mice or mice treated for 9 days with 10 µg human recombinant (hr)FLT3L as described previously [34]. hrFLT3L was a kind gift ABT-199 in vitro from Amgen (Thousand Oaks, CA, USA). DC were analysed for the expression of CD4, CD8α, CD11b, CD11c, CD40, CD54, CD80, CD86, Kb, Db and I-A/E by flow cytometric analysis (antibodies/isotype controls; eBioscience/Biolegend, San Diego, CA, USA; DCs were subsorted by flow cytometry based on their expression of CD11c, CD11b, CD8α or PDCA-1 by flow cytometry to purity of >95% and viability >95% (7-AAD staining). OT-1 and OT-2

T cells were isolated using CD8 or CD4 microbeads buy Y-27632 (Miltenyi Biotec, Auburn, CA, USA) and labelled with 5,6-carboxy-succinimidyl-fluorescein-ester (CFSE) (Molecular Probes, Eugene, OR, USA) as described previously [38]. Purity of sorted cells was >98% and viability was >97% as determined by CD4/CD8/Vα2/Vβ5 expression and 7-AAD staining. Purified DCs (1 × 105) were cultured with irradiated splenocytes in a 1:3 ratio in 96-well U-bottomed plates. After 3, 6 and 16 h supernatant was analysed for type I IFN by reporter assay [39] and IL-10, tumour necrosis factor (TNF)-α and TGF-β by quantitative polymerase chain reaction (PCR) using SybrGreen and the following primers: ml32 forward 5-GAAACTGGCGGAAACCCA-3, ml32 reverse 5-GGATCTGGCCCTTGAACCTT-3, TNF-α forward 5-GTACTGGCATGTGTATGTCA-3, Inositol monophosphatase 1 TNF-α reverse 5-TGGTTGAGGGAATCATT-3, IL-10 forward 5-GGTTGCCAAGCCTTATCGGA-3, IL-10 reverse 5-ACCTGCTCCACTGCCTTGCT-3, TGF-β forward 5-GACCGCAACAACGCCATCTA-3, TGF-β reverse 5-GGCGTATCAGTGGGGGTCAG-3. The fold increase of specific RNA (mRNA after apoptotic cells exposure/mRNA before apoptotic cells) was

determined after normalization to L32 for each sample. Purified DCs (1 × 105) were cultured with irradiated purified ActmOVA-Kbm1 T cells in a 1:3 ratio in 96-well U-bottomed plates. After 24 h, 1 × 105 CFSE-labelled OT-1 or OT-2 T cells were added to the wells. This experimental set-up allows us to study exclusively cross-priming by the DC subsets because the mutated peptide binding groove of Kbm1 cannot bind the OVA257–264 peptide [40] and the lack of MHC class II on the T cells prevents direct activation of the OT-2 T cells [41]. As positive control, DCs were pulsed with OVA peptides for 10 min and washed thoroughly. OT-1 and OT-2 T cell proliferation and survival were determined after 70 h by analysis of CFSE dilution together with staining for Vα2, CD4/CD8 and 7-AAD.

22–24 We compared the SD-induced apoptotic percentage of β-arrestin 2+/+ with β-arrestin 2−/− MEFs. As shown in Fig. 5(a), β-arrestin 2−/− MEFs showed TUNEL-positive cells at higher rate for a period of 24 hr, whereas β-arrestin 2+/+

MEFs seemed relatively resistant to SD-induced apoptosis, which is consistent with the previous observation in N-formyl-peptide-receptor-induced apoptotic events.22 Apoptosis of HEK293/TLR4 was also Cabozantinib mw assessed in the absence or presence of β-arrestin 2. Results also showed that β-arrestin 2 caused reduced apoptosis upon stimulation of SD (Fig. 5b), in agreement with the observation from MEFs. Nevertheless, β-arrestin 2 failed to inhibit apoptosis with statistical significance when co-transfected with GSK-3β active mutant S9A, or pre-treatment with the PI3K inhibitor LY294002, both of which are known to produce active GSK-3β, directly or indirectly,8,11 indicating that highly active GSK-3β is able to mask the anti-apoptotic effect of β-arrestin 2. Therefore, MK-2206 concentration we conclude that GSK-3β inactivation is required for the inhibition of SD-induced apoptosis by β-arrestin 2. Although TLRs are well-defined receptors in the innate immune response against invading pathogens, an additional role of cell surface TLR4 is to sense danger signals from tissue damage, necrotic cells or stressful survival conditions where the infection is not necessary.3 The TLR4 appears to

be functionally activated when exposed to such danger signals.1,3 Activation of apoptosis through TLR4 signalling is an alternative regulatory mechanism for deciding cell fate.29,32,33 The current study was designed to identify the potential mechanism accounting for the increased susceptibility to cell damage resulting from trophic withdrawal in the presence of TLR4. Apoptotic signalling induced by TLR4 shares a number of components from its immune signalling pathway, MyD88, IRF3 for instance.34–36 The GSK-3β previously has been identified as a vital regulator ID-8 in pro-inflammatory and anti-inflammatory cytokine production through transcription factor cAMP response element binding

protein and c-Jun, following LPS treatment.7,8 Also, it has been well characterized as having roles in inhibition of cell proliferation and induction of cell death.9,10,37 The mechanism of how TLR4 induction of apoptosis occurs via GSK-3β is to be addressed in our study. The GSK-3β is activated in serum deprivation culture because starvation inhibits the upstream PI3K/Akt pathway.10–12 Intriguingly, TLR4 causes dramatic GSK-3β activation relative to the same condition without TLR4. It raises the possibility that the regulation of GSK-3β activity may account for the excessive apoptotic event induced by TLR4. This study demonstrates that excessive apoptosis is attenuated by GSK-3β inhibition. Notably, a reduced apoptotic signal can be achieved by the GSK-3β inhibitor SB216763 or the inactive mutant GSK-3β (K85A).

Results gathered in this study suggest that a status of “immunoprivileged self” in tumors barricades specific Teff cells. This suggestion portends that it might be very difficult, if possible, to circumvent autoimmunity toxicity in a systemic immunotherapy against cancer, unless a substantial antigenic difference is identified between the tumor target and healthy tissue. Therefore, targeting immunoregulatory elements at the tumor site would be desirable. Indeed, local delivery of engineered dendritic cells secreting anti-CTLA4 antibodies promoted immunity against melanoma in

mice without eliciting autoimmunity [44]. A nexus of immunosuppressive elements evolved at the tumor site likely suppress self-antigen-specific T lymphocytes as well as bona fide tumor-specific

T cells. A subtle reduction of CTLA4 in Teff cells by RNAi silencing could substantially overcome the tumor barrier, suggesting Regorafenib in vitro a practical approach to enhance the efficacies of antigen-specific T cells for cancer therapies. Transgenic and knockout mouse models constructed for auto-immunity studies HDAC inhibitor were transitioned to study autoimmune mechanisms in antitumor immunity. A detailed description of the use of these models in the current study is provided in a supplementary table (Supporting information Table 1). BDC2.5/NOD, Foxp3-deficient C57BL/6 (B6) and NOD, NOD.Foxp3DTR, Rag-deficient-BDC2.5/NOD, and CTLA4 shRNA (CTLA4KD7) and PL4 transgenic mice were described previously [24, 29, 34, 35, 45, 46]. CTLA4KD7 and PL4 mice were backcrossed onto B6 background for more than ten generations, and then crossed with BALB-neuT [36], FIR (Foxp3-IRIS-RFP “knockin”) mice [47], or OT1 transgenic line [33]. All animals were maintained in a specific pathogen-free barrier facility and the studies are approved by the Institutional Animal Care and Use Committee at the University of Miami. The NIT-1 insulinoma, EL4 lymphoma, and E.G7-OVA lymphoma cell Etoposide in vitro lines were obtained from ATCC (Manassas, VA, USA) and implanted subcutaneously

at 5 × 106/mouse for insulinoma and 5 × 105 for lymphoma. For the NIT-1 model, tumor burden was quantified by measuring blood glucose levels and tumor mass. The tumor and pancreas samples were fixed in formalin solution. Paraffin-embedded sections were stained with hematoxylin and eosin (H-E) and examined by microscopy. Scoring for pancreas pathology was determined as follows: 0, intact islet with no lymphocytes in the islet area; 1, lymphocytes within the vicinity of the islet, but no infiltration; 2, peripheral insulitic lesion; 3, near or complete destruction of the islet. Flow cytometry analyses were conducted with a standard procedure [29]. The cells were stained with fluorescent-antibody conjugates to determine cells phenotype.

Finally, knowledge-driven gene expression-based predictors can be translated into assays that are simpler and more robust than measurement of transcript abundance for many genes. Gene expression predictors have historically been limited by a lack of reproducibility between experiments [10, 25]. This is thought to be related to the high variance of individual gene measurements commonly seen in datasets of relatively few replicates. This variance results in discordance between lists of predictive genes even in high quality experiments. Using a larger set of genes rather than a small

number of genes may CH5424802 supplier provide some degree of robustness lacking in single gene level predictors. Indeed several platforms have now been developed [26, 27] that allow focused sets of genes to be profiled at high throughput and low cost. Moreover, because gene set based predictors find more can identify not just predictive genes but predictive biological processes, this approach could overcome the limits of predicting clinical responses by measuring gene expression. For instance, our analysis shows that signatures associated with cellular proliferation are predictive of a protective antibody response. It would be relatively easy to translate

this to a flow-cytometry based assay of cellular proliferation in PBMCs using Ki67 staining, for example, that could rapidly be applied to many samples. In contrast, developing and validating a multigene predictive signature of unknown biological significance may prove to be more significantly more complex. Future studies will be required to determine how successfully biological processes discovered by gene set based approaches can

be deployed as simpler, more robust diagnostic tools. Gene set based predictors predicated on biological knowledge may therefore provide a sensitive, relevant, and robust analysis of the human immune response. We analyzed two existing datasets of gene expression profiles of PBMC SPTBN5 from vaccinated subjects: raw Affymetrix array data for subjects vaccinated with YF-17D from Gene Expression Omnibus with the accession number GSE13486 [4], and raw Affymetrix array data from subjects vaccinated with influenza TIV with accession number GSE29619 [16]. The Genepattern module “CollapseDataset” was used to extract the expression values of genes from the raw data file and to map Affymetrix probes to gene symbols [28]. Then we applied quantile normalization and a log2 transformation. The final transformed data were used for the single sample GSEA projection (see below). For analysis of data from the influenza vaccinated subjects, gene expression fold change was calculated as the ratio of expression levels from PBMC profiles day 7 (postvaccine)/day 0 (prevaccine).

The results are expressed as the difference in the percentage of apoptotic K562 cells at a particular effector to target cell ratio minus the percentage of apoptotic K562 cells cultured in the medium alone. Statistical analysis.  Statistical Ponatinib mouse analyses were performed using Statistica 8.0 data analysis software (StatSoft, Inc., Tulsa,

OK, USA). The difference between groups was calculated by the Kruskal–Wallis non-parametric test, and a P value of <0.05 was considered statistically significant. The Mann–Whitney U test was used to determine the difference among groups with the level of significance adjusted to the number of mutual comparisons. Flow cytometry analysis of GNLY expression within gated peripheral blood lymphocytes shows that 4.7% of lymphocytes in healthy person express GNLY with a MFI of 7 (Fig. 1A). The histogram indicates fluctuation in the percentage and MFI of GNLY with respect to isotype-matched controls in patients with NSTEMI (Fig. 1B) on days 1, 7, 14, 21 and 28 after the acute coronary event that matched the summary data shown in the charts (Fig. 1C). The percentage of GNLY-positive lymphocytes was significantly higher (median, 28.67) on day 7 after the acute coronary event

compared with healthy examinees (median, 2.6) or with find more values on day 14 (median 0.28). On day 1, GNLY was slightly increased compared to healthy examinees, but it was significantly higher when compared to that of patients with NSTEMI on day 14 (Fig. 1C). MFI of GNLY in lymphocytes decreased significantly from day 7 to day 28 compared to healthy examinees or to day 1 (Fig. 1C). Using immunocytochemistry,

GNLY protein was visualized PIK3C2G as red-labelled granules beneath the cell membrane of lymphocytes in healthy examines and patients with NSTEMI. The highest expression of GNLY was on day 7, and the lowest expression of GNLY was on day 14 (Fig. 1D). Labelling with irrelevant isotype-matched mouse immunoglobulin G1 (IgG1) was negative (upper left microphotographs in Fig. 1D). In the dot plots of PBL from healthy examinees shown in Fig. 2A, CD3+ CD56− T cells are located within the solid line rectangle and CD3+ CD56+ NKT cells are presented within the dashed line rectangle with respect to isotype-matched control. In patients with NSTEMI, the frequency of GNLY-positive NKT cells (Fig. 2B) and T cells (Fig. 2D) was increased on day 7 compared to the percentage observed in healthy examinees and in patients with NSTEMI on day 14 after an acute coronary event. On day 1, the percentage of GNLY+NKT cells was higher than in healthy examinees (Fig. 2B). The MFI of GNLY essentially did not change in NKT (Fig. 2C) and T cells (Fig. 2E) during the investigation period. The dot plots in Fig. 3A show a sample flow cytometry with the gates set up for the analysis of GNLY expression in total NK cells and their subsets.

In recent years, mucosal vaccines have received more attention. Because

oral immunization antigens are easily destroyed by digestive GSK2126458 juices during their passage through the gastrointestinal tract, we chose intranasal immunization as the means of mucosal immunization in this study. Zhang Yan et al used EHEC O157:H7 outer membrane protein to immunize mice via the nasal cavity and detected high-titer IgA in feces and intestinal lavage; they also confirmed that nasal immunization can protect mice from EHEC O157:H7 infection to some extent (22). This study showed that the KT-12 peptide of IntC300 of EHEC O157:H7 has high antigenicity and can induce a protective immune response, suggesting that this peptide might be a potential vaccine candidate against EHEC O157:H7. The rate of protection of mice by intranasal immunization was not very high in this study, which may be because a single peptide was not enough to stimulate the production of protective antibodies. In EHEC O157:H7 infection, toxic substances produced by the bacteria are very complex, therefore

the immune protective effect induced by a single protective antigen is limited. In accordance with the MAP principle, future experiments will connect multiple short peptides to a main chain of poly-l-lysine, in order to form both B- and T-cell epitopes in a limited space, and thus to produce a polyvalent synthetic peptide vaccine capable of inducing both humoral and cell-mediated immunity. Where necessary,

we can consider increasing ABT-263 datasheet a number of other important protective antigens such as Stx1B, Stx2B, and Hly and integrating several kinds of protective antigen epitopes Loperamide into multiple antigen peptides to enhance the protective effectiveness of the peptide vaccine. We thank former members of the laboratory for their contributions to materials and technical assistance, Professor Sheng-He Huang of the Division of Infectious Diseases, Children’s Hospital Los Angeles, University of Southern California, USA, for his support and guidance throughout the study and Jun Luo for some of the bacterial strains used in this study. This study was supported by a grant from Guangdong Province 211 project (No. GW2010XX). “
“IL-33, a proposed alarmin, stimulates innate immune cells and Th2 cells to produce IL-13 and is rapidly upregulated upon antigen exposure in murine helminth infection. The human IL-33 response to helminth antigen was analysed in Malians infected with Schistosoma haematobium by disrupting parasite integrity via chemotherapy. Plasma IL-33 was measured pretreatment, and 24 h and 9 weeks post-treatment. At 24 h post-treatment, IL-33 levels were low. Nine week post-treatment IL-33 levels were elevated and were associated with an increase in intracellular IL-13 in eosinophils.

The pool of long-lived Treg cells in the thymus was sustained by retention of Treg cells in the thymus and

by recirculation Ivacaftor of peripheral Treg cells back into the thymus. These long-lived thymic Treg cells suppressed T-cell proliferation to an equivalent extent to splenic Treg cells. Together, these data demonstrate that long-lived Treg cells accumulate in the thymus by both retention and recirculation. “
“As research on parasitic helminths is moving into the post-genomic era, an enormous effort is directed towards deciphering gene function and to achieve gene annotation. The sequences that are available in public databases undoubtedly hold information that can be utilized for new interventions and control but the exploitation

of these resources has until recently remained difficult. Only now, with the emergence of methods to genetically manipulate and transform parasitic worms will it be possible to gain a comprehensive understanding of the molecular mechanisms involved in nutrition, metabolism, developmental switches/maturation and interaction with the host immune system. This review focuses on functional genomics approaches in parasitic helminths that are currently used, to highlight potential applications of these technologies in the areas of cell biology, systems Tipifarnib solubility dmso biology and immunobiology

of parasitic helminths. Parasitic worms have an enormous public health impact, and they are responsible for the infection of a vast number of people. It has been estimated that more than 2 billion people Parvulin are infected with helminth parasites of the phyla Nematoda (roundworms) and Platyhelminthes (flatworms). Worm infections account for morbidity equivalent to more than 100 million disability-adjusted life years – rivalling that of malaria or HIV/AIDS (1). For a number of these helminth parasites, entire genome sequences are now available [Brugia malayi (2), Schistosoma mansoni (3), Schistosoma japonicum (4) and recently Trichinella spiralis (5)], and currently, further sequencing endeavours are aimed at determining entire genome sequences for a number of other parasitic helminths. These sequencing efforts are creating an invaluable resource that will advance our understanding of the fundamental biology and evolution of helminth parasites as well as their host–parasite interactions (2,4,5) and should also underpin the discovery of novel drug and vaccine targets (3,6). The ability to introduce an exogenous gene into a target organism provides an unequivocal means by which the function of that gene can be investigated in vivo, particularly when combined with gene silencing studies.

Quantitative sensory testing showed improvement, as did two

EMG/NCTs obtained postoperatively. This showed improvement in conduction velocity at the fibular tunnel and posterior tibial nerve at the tarsal tunnel. This is the first report of nerve decompressions in the lower and upper extremity of HIV patients in the literature outside of the median nerve in the carpal tunnel. © 2011 Wiley-Liss, Inc. Microsurgery, 2012. “
“In women with early-stage breast cancer, breast-conserving therapy (BCT) provides comparable survival to mastectomy. BCT has the advantage of preserving most of the breast, its skin envelope and the nipple–areola complex. However, deformity may result from the excision of significant amounts of breast tissue, as well as radiation therapy. Several studies have compared patients who underwent BCT to different patients RGFP966 cost who underwent https://www.selleckchem.com/products/FK-506-(Tacrolimus).html mastectomy and reconstruction, and found

superior aesthetic outcomes in the latter group. Our goal in this study was to compare the aesthetic outcomes in the same women who underwent BCT followed by mastectomy and reconstruction. Between 2007 and 2012, 42 women with a history of BCT developed cancer recurrence and underwent mastectomy and microsurgical breast reconstruction at our institution. Photographs before and after mastectomy and reconstruction were rated by a panel of nine judges (two independent plastic surgeons, three surgical oncologists, one radiation oncologist, one medical oncologist, and two medical students), using a validated scale Overall, patients received a significantly higher aesthetic score after mastectomy and reconstruction than after BCT. The greatest areas of aesthetic improvement were breast volume, contour, and projection. Patients whose lumpectomy was in the lower inner quadrant, those undergoing bilateral mastectomy and reconstruction and those completing all stages of their reconstruction had the greatest aesthetic improvement When advising patients with early-stage breast cancer, the superior aesthetic outcome of mastectomy and microsurgical reconstruction

next compared to BCT must be weighed against disadvantages such as loss of sensation, length of surgery, and donor-site morbidity. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014. “
“The purpose of this study is to report the outcomes of patients with locally advanced (T3–T4) oral cancers undergoing surgical resection and free tissue reconstruction without the lower lip-split procedure. In this retrospective chart review, we analyzed 86 consecutive patients presenting between July 2000 and December 2009 at our university-based, tertiary care medical center. The oral site distribution was: 73 (86%) oral cavity, 10 (12%) oropharynx, and 3 (2%) combined. The average specimen volume was 240.3 cm3 (range 17.5–3718 cm3). Sixty-seven patients (78%) had widely clear histopathologic margins. Performing mandibulectomy had no advantage over maintaining mandible continuity to achieve clear margins (P = 0.97).