trachomatis infection and in the development of disease. Therefore, while our data indicate that C. trachomatis infection may generally induce susceptibility to NK cell activity,

we hypothesize that an individual’s NK2GD and MICA allelic composition may modify the degree of protection conferred by NK cells. Thus, in some individuals, selleck compound a specific NKG2D and MICA allelic composition may facilitate C. trachomatis’ escape from the NK cell-mediated immune response more efficiently than other alleles. Such possibilities may explain why C. trachomatis infection remains an endocervical infection is some women but establishes acute ascending infection in others. They may also provide insight into why infection may be spontaneously cleared in several weeks or months in some individuals but remain for highly extended periods of time in others (Morre et al., 2002; Molano et al., 2005; Brunham & Rekart, 2008). This work was supported by NIH grants U19AI061972 and AI095859 and by the Louisiana Vaccine Center and the South Louisiana Institute for Infectious Disease Research

SB203580 ic50 sponsored by the Louisiana Board of Regents. We thank Connie Porretta for technical assistance with flow cytometric experiments and Dr. Tim Foster for insightful comments with respect to data presentation. Phosphatidylinositol diacylglycerol-lyase “
“Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USAFax: +1-617-525-5566 Intracellular pathogen-specific antibodies (Abs) can contribute to host protection by a number of different mechanisms. Ab opsonization of pathogens residing outside a host cell can prevent infection of

target cells either via neutralization of the critical surface epitopes required for host cell entry, complement-mediated degradation, or via subsequent intracellular degradation. In the case of intracellular localization, Abs can bind to infected cells and thus mark them for destruction by Fc receptor (FcR)-bearing effector cells. This review focuses on the protective role of Abs against intracellular bacteria and parasites involving FcR interactions that modulate the intracellular trafficking of the pathogen, the ability of FcRs to interfere with the establishment of an intracellular replicative niche and the involvement of FcRs to modulate pathogen-specific T-cell responses. Antibodies (Abs) have been implied in protection against all types of pathogenic organisms, i.e. viruses, bacteria, fungi, and multicellular parasites. In order to fulfill their action against this multitude of pathogens, Abs mediate their protective effects through a wide panel of direct and indirect effector mechanisms.

There is a growing body of literature on the symptom management of patients with ESKD. Patients need clear information about the potential effects dialysis and non-dialysis pathways on symptom burden and how this can change GDC-0199 ic50 with time. Standardization of tools used to collate information about symptoms can assist in the provision of information to patients. We recommend the Patient Outcome Scale symptom module (Renal Version) tool (accessible via the kcl.ac.uk website) for assessing symptom burden. Patients with end-stage kidney disease (ESKD)

whether or not on renal replacement therapy (RRT) have considerable prevalence of symptoms. Indeed this group is among the most heavily burdened of any disease group.[1-3] A large, systematic review of prevalence studies of symptoms,[4] experienced by dialysis patients showed a significant burden of symptoms.

A subsequent study by the same group found a similar prevalence of symptoms in patients being managed conservatively.[5] A summary of the results of those studies appears below in Table 1. In addition to individual symptoms, it is important to note that patients may experience multiple symptoms simultaneously. These may be from multiple sources, some from the renal failure (e.g. pruritus and restless legs), from comorbidities (e.g. diabetic peripheral neuropathy, Ganetespib diabetes-related gastroparesis, angina) or be related to dialysis therapies (intradialytic hypotension, cramping, sleep disturbance from automated peritoneal dialysis alarms). Also, the interaction

of individual symptoms may exacerbate other problems. For example, the simultaneous presence of nocturnal Niclosamide uraemic pruritus, restless legs syndrome and pain secondary to arthritis, may result in significantly disturbed sleeping, in turn leading to daytime somnolence and enhanced fatigue. Symptoms experienced by patients with ESKD are consistently underassessed and inadequately managed. In addition to the experience of the individual symptom itself, some symptoms (e.g. uraemic pruritus) have been shown to be associated with reduced quality of life and a shortened life expectancy.[6] Symptom burden is likely to alter and increase over time for patients choosing either a dialysis or non-dialysis pathway and therefore needs to be regularly reassessed. In the experience of the St George’s Hospital Renal Unit, New South Wales, in approximately one-fifth patients, symptoms are not improved by initiation of dialysis. In the Renal Supportive Care clinic at this unit, two-thirds of the patients who attend are on dialysis and one-third are following the Renal Supportive Care pathway, showing also the symptom burden of those dialysing. Anecdotally, some patients may have very few symptoms, regardless of management choice and stage of disease.

Subsequent publications59,60 from the US demonstrate that, in some centres, 20–30% of donors have a BMI > 30 kg/m2 and data from the Organ Procurement and Transplantation Network/United DZNeP supplier Network for Organ Sharing (OPTN/UNOS) registry suggest that from 7/2004 to 12/2005, 13% of US donors had a BMI > 30 kg/m2. There are data to suggest that acceptance of obese donors is also increasing in Australia.61 Preliminary data from the ANZ live donor registry presented in 2007 at the ANZSN ASM, suggest that 16% of donors from 2004–2006 had a

BMI of between 30 and 35 kg/m2 and 2.3% had a BMI > 35 kg/m2. Assessment of living donors involves both the assessment of early risk associated with perioperative morbidity and mortality and long-term risk, predominantly associated with the risk of future kidney disease. Retrospective analysis of a US healthcare registry62 using discharge data for 3074 patients from 28 centres identified comorbidities and complications using ICD-9-CM coding data. Obesity was associated with an increased risk of overall complication rate (OR 1.92, 95% CI 1.06–3.46), however, numbers were too small to assess the impact of obesity on the incidence of major complications, and the study was not able to discriminate between

open and laparoscopic nephrectomy. Similar results have been reported from a number of single centre studies, demonstrating an increase in minor complications in obese donors for both open and laparoscopic nephrectomy Galeterone (see Table 3).59,63,64 Selleckchem Apoptosis Compound Library Complications are predominantly wound related and include wound infection, seroma and hernias. The rates of wound infection approach 10% in the obese compared with 2% in normal weight donors. Operative time is longer in obese patients

– with increases ranging from 10 to 41 min, but no increase in length of hospital stay is reported.59,63,65,66 Nor is there any reported increase in delayed graft function in the recipient. Numbers are small and results relating to conversion from laparoscopic to open procedure are mixed, with some studies reporting no difference59,67 and others66 reporting increased conversion in obese men. They also commented that the perinephric distribution of fat in obese men increased the technical difficulty. There is a consistent pattern of greater blood loss and increased transfusion requirements in obese patients, which is not significant in each of the single centre studies due to small numbers.63,66–69 In addition, laparoscopic donor nephrectomy has been a relatively new technique and there may have been an increased complication rate in the more technically challenging obese patients as part of the learning curve. Rhabdomyolysis is a rare complication of donor nephrectomy. Sporadic case reports of rhabdomyolysis in donors are characterized by the following risk factors – long operative time, laparoscopic procedure and high BMI.

Cochrane Reviews are undertaken by teams of volunteer authors, who have access to free training resources, reference texts and software for preparing and maintaining their review. Here we selleck kinase inhibitor aim to describe the steps involved to undertake a new or

update an existing Cochrane Review. “
“The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy

individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus Tamoxifen cell line on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy. Hepatitis B virus (HBV) infection is a substantial global health problem. It is estimated that more than two billion people worldwide have serological evidence of current or historical infection.1 HBV is highly infectious compared with other blood-borne viruses: An untreated percutaneous exposure to an infected source carries a risk of seroconversion of up to 30%. By contrast,

the risks for hepatitis C virus and human immunodeficiency virus (HIV) are 1.8% and 0.31%, respectively.2 Acute infection occasionally results in fulminant hepatitis, but more importantly can progress to a chronic state, where decompensation, cirrhosis and hepatocellular carcinoma are all potential complications. Compared with the general population, dialysis patients are at increased risk of acquiring HBV. Reasons very include increased exposure to blood products, shared haemodialysis (HD) equipment, breaching of skin and immunodeficiency. Haemodialysis, which requires access to the bloodstream, also affords an opportunity for transmission of HBV between patients, and between patients and staff. Viral hepatitis complicating HD has been recognized from the earliest days of this therapy. While the introduction of vaccination programmes and stringent infection control measures have succeeded in limiting the spread of hepatitis infection within dialysis facilities, outbreaks continue to occur periodically and prevalence rates remain unacceptably high. As such, HBV infection remains an important issue in renal replacement therapy. Hepatitis B is a blood-borne virus. Modes of infection include perinatal, and through percutaneous or mucosal exposure to infected blood or body fluids.3 There are considered to be more than 350 million people worldwide with chronic hepatitis B infection.

[31] Interestingly, we found that IL-33, but not IL-1β and HMGB1, is the earliest inflammatory cytokine induced in inflamed

colonic epithelium in colitis (Fig. 1 and data not Ibrutinib cost shown). Hence, colon-derived IL-33 may be a critical initiator of pathogenesis of DSS colitis. (ii) ST2−/− mice have impaired colitis (Fig. 2). (iii) IL-33 is capable of specifically inducing the key pathogenic cytokines (IL-4, IL-5, IL-13, IL-6, IL-17, IFN-γ, TNF-α and VEGF) and chemokines but reducing immunosuppressive (IL-10) cytokines in DSS-induced colitis via ST2 (Fig. 3). Although it is recognized that type II cytokines, IL-4, IL-5 and IL-13 play a pathogenic role in the development of UC,[5, 7, 28] until now, it was unknown how these typical Th2 cytokines were induced in the innate context of colitis and whether these cytokines contributed to the IL-33-mediated selleck screening library effect. Our mechanistic

studies suggest that IL-33 can induce these type II cytokines and directly via IL-4 and IL-4R in colitis. It is well documented that IL-33 can induce all these type II cytokines by an array of innate cells, including eosinophils, basophils, mast cells, but not nuocytes which only produce IL-5 and IL-13, not IL-4[12-17] and data not shown). In contrast, T cells, which are the key cells expressing type II cytokines in allergy and asthma, are not the main IL-4 producers in this innate immune UC model, because naive T cells do not express ST2 in the absence of T-cell receptor activation and are thus unresponsive to IL-33.[14, 15] Our results also show for the first time that IL-4 is required for IL-33-mediated exacerbation of colitis, and for subsequent VEGF and CXCL9 production (Figs. 3 and 4). VEGF is a major pro-angiogenic cytokine and plays

an important role in the pathogenesis of colitis by enhancing colonic permeability and facilitating migration of inflammatory cells.[29] CXCL9 and CXCL10 are the key chemokines for the recruitment of monocytes and macrophages, and these are intimately associated with the pathogenesis of colitis.[30, 32] Together, these results provide a possible mechanism underlying the BCKDHB IL-33 / IL-4 pathogenic pathway in colitis. Interleukin-12 and IL-17 are the key cytokines for type I and 17 responses and are also thought to play pathogenic roles in UC, Crohn’s disease and the chronic stage of DSS-induced colitis.[2, 8, 10] We noted in this study that IL-33 can also induce serum IL-12 and IL-17, at the later stages of the disease, 20 days after DSS administration (Fig. 3). This suggests that in addition to its role in the early stages of disease, IL-33 may also contribute to the switching of the early type II to late type I and IL-17 responses in the chronic stages of UC and Crohn’s disease.

A number of molecular tools have been used to study outbreaks of A. baumannii infections in hospitals. Graser et al. used RAPD to investigate an outbreak of A. baumannii (28). However, because there have been limited studies on unrelated isolates our study, involving as it does different types of cases and sources, assumes significance and explains the genetic heterogeneity seen in the RAPD analysis (Fig. 3). Although biofilm forming HIF-1�� pathway ability is associated with bacterial virulence

there are limited studies on biofilm formation by Acinetobacter spp. (1, 29). In our study, more A. baumannii (79.2%) produced biofilm than other Acinetobacter spp (42.9%). Since biofilm formation helps the organism to adhere to surfaces including host cells (12), the higher prevalence of A. baumannii in clinical cases may be related to its biofilm forming ability. LY2606368 Our study also assumes significance in the context of involvement of Acinetobacter species, including

A. baumannii, in nosocomial infections, their multidrug resistance and ability to form biofilms that could be a virulence marker and help in their survival. Though the problem is recognized globally, these factors have not been addressed sufficiently. This comprehensive study provides information on the prevalence of carbapenemase resistance, presence of blaOXA-51 gene, and biofilm forming ability of A. baumannii and, through the use of RAPD, provides an insight into their clonal relationships and genetic

heterogeneity. The authors are grateful to Dr. Srikala Baliga and Dr. C. V. Raghuveer for reading the manuscript and their valuable discussions. “
“Previous studies demonstrated that the CXCL12 peptide analogue CTCE-0214 (CTCE) has beneficial effects in experimental sepsis induced by cecal ligation and puncture (CLP). We examined the hypothesis that CTCE recruits neutrophils (PMN) to the site of infection, enhances PMN function and improves survival of mice in CLP-induced sepsis with antibiotic Cyclin-dependent kinase 3 treatment. Septic mice (n=15) were administered imipenem (25mg/kg) and CTCE (10 mg/kg) subcutaneously vs. vehicle control at designated intervals post-CLP. CTCE treatment increased PMN recruitment in CLP-induced sepsis as evidenced by increased PMN in blood by 2.4±0.6 fold at 18h, 2.9±0.6 fold at 24h, respectively and in peritoneal fluid by 2.0±0.2 fold at 24h vs. vehicle control. CTCE treatment reduced bacterial invasion in blood (CFU decreased 77±11%), peritoneal fluid (CFU decreased 78±9%) and lung (CFU decreased 79±8% vs. CLP vehicle). The improved PMN recruitment and bacterial clearance correlated with reduced mortality with CTCE treatment (20% vs. 67% vehicle controls). In vitro studies support the notion that CTCE augments PMN function by enhancing phagocytic activity (1.25±0.

Notably, the SFK member Hck was recently demonstrated to be indispensable for macrophage buy X-396 podosome formation [[7, 8]]. Within the cross-talk between different tyrosine kinases in signal transduction to the cytoskeleton, activation of Abl by SFKs has emerged as a key step in both hematopoietic and nonhematopoietic cells [[9-11]]. Our own recent study implicated the SFK members Fgr and Hck, and Abl in macrophage migration [[12]]. Here, we show

for the first time that Abl is one of the components of human and murine macrophage podosomes and regulates podosome formation, organization, and function. Plating of mouse bone marrow-derived macrophages (BMDMs) on fibronectin results in the organization of podosome

clusters, known as rosettes, whose formation requires the SFK member selleckchem Hck [[8]]. As shown by Cougoule et al. [[7, 8]] these rosettes can be identified as actin- and vinculin-based circular structures (Fig. 1A, green arrows) also enriched in phospho-cortactin (Supporting Information Fig. 1), a substrate of the cytoplasmic tyrosine kinases of the Src and Abl families [[13, 14]]. The strict dependence of rosette assembly on SFKs was confirmed by the marked defect in rosette formation in BMDMs from mice with the double (hck–/–fgr–/–) or the single (fgr–/–) deficiency of myeloid leukocyte-specific SFKs (Supporting Information Fig. 2). Activation of Abl by SFKs has emerged as a key step within the cross-talk between different tyrosine kinases in signal transduction to the cytoskeleton in both hematopoietic and nonhematopoietic cells [[9-11]]. Additionally, we recently demonstrated that macrophage migration is regulated by both the SFK members Fgr and Hck and Abl [[12]]. Because Abl interacts with Fgr or Hck bound to integrins [[12]], one of the components of podosomes [[2]], we asked whether Abl is present in BMDM rosettes. Notably, staining

of BMDMs with a specific Ab showed that Abl Cediranib (AZD2171) distributed in the nucleus, in punctate structures in the ventral face of the membrane or underneath the plasma membrane (Fig. 1A, white arrow heads) and in podosome rosettes. In all nonnuclear localization Abl clearly colocalized with actin (Fig. 1A, merge). To strengthen the finding that Abl is a podosome component, we extended studies to human monocyte-derived macrophages (Fig. 1B). Human macrophages plated on fibronectin or glass (not shown) did not shown the typical rosettes observed in mouse cells, but more classical individual podosomes containing actin and vinculin (Fig. 1B), and phospho-cortactin (Supporting Information Fig. 1). Notably, Abl colocalized with actin also in human macrophage podosomes.

The brain (1360 g after fixation) and spinal cord had a normal external appearance. In sections, the cerebrum, cerebellum, midbrain and medulla oblongata showed no abnormality. In the sections of the left pontine base, a punctate hemorrhage up to a diameter of 1 mm was noted. Neither ventricular dilatation, discoloration of the cerebellar dentate nuclei, nor atrophy of the mesencephalic tegmentum or superior cerebellar peduncles was found. Microscopically, the loss of Betz Roscovitine cost cells in the motor cortex was moderate; and that of cells in the hypoglossal nuclei, cervical and lumbar anterior horns (AHs), and Clarke’s nuclei were obvious. Onufrowicz nuclei were well preserved. Bilateral tract degeneration was moderate in the spinocerebellar

tracts, and mild in the pyramidal tract, but nonexistent in the posterior column (Fig. 1A). In HE-stained sections, hyaline CIs, which were large, irregularly shaped, pale and intracytoplasmic inclusions, were observed in some of the remaining Betz cells (Fig. 1B), motor neurons in the hypoglossal nuclei, and AH cells in the cervical and lumbar spinal cord (Fig. 1D). In the cervical and lumbar AHs, some spheroids were observed. LBHIs, which had an eosinophilic core surrounded by a pale halo, were rarely observed in the hypoglossal nuclei or cervical or lumbar AHs (Fig. 1H). No Bunina bodies were seen. Incidental venous angioma and mild ferruginations were observed in the left pontine base. Immunohistochemical examination of the CIs showed them to be strongly positive for p-NFP (Fig. 1C,E), partially positive for ubiquitin (Fig. 1F), Orotidine 5′-phosphate decarboxylase partially positive for SOD1 (Fig. 1G), negative for TDP-43, p-TDP-43 and Selleckchem Y27632 FUS. The eosinophilic core of LBHIs

was positive for ubiquitin (Fig. 1J) and SOD1 (Fig. 1K) and negative for p-NFP (Fig. 1I). Because the LBHIs were very few, we could not confirm the reactivity of the round inclusions with antibodies against TDP43, p-TDP-43 and FUS. Neither skein-like inclusions nor round hyaline inclusions were identified by p-TDP-43, and no basophilic inclusions were identified by FUS protein. Indeed, it is not always determinable to exclude TDP-43 or FUS pathologies. A number of p-tau protein-positive globose NFTs and threads were observed in the periaqueductal gray matter, oculomotor nuclei, and trochlear nuclei (Fig. 1L,M) and these structures were also positive for both 3-repeat tau and 4-repeat tau (Fig. 1N,O). The tangles were also positive by both Bielschowsky’s silver staining and Gallyas-Braak staining (Fig. 1P). Although this case was initially clinically diagnosed as having sporadic ALS, the neuropathological findings showed features of FALS with a SOD1 mutation. DNA analysis of frozen-brain tissue revealed the presence of the I113T SOD1 mutation (Fig. 2). I113T is one of the most common mutations of the SOD1 gene.[1] Phenotypic expression of this mutation is variable in clinical manifestations, including age of onset and disease prognosis.

Strains used for this study have been verified by rDNA internal transcribed spacer (ITS) and partial β-tubulin (BT2) sequencing and compared with ex-type isolates in the reference collection of the CBS-KNAW Fungal Biodiversity Centre, Utrecht, the Netherlands. We analysed 32 strains of Pseudallescheria, Petriellopsis and Scedosporium (Table 1). Methods of DNA extraction, alignment and phylogenetic analysis were those of Badali et al. [18] Species attribution was verified by sequencing ITS rDNA and partial β-tubulin (BT2) according to Gilgado et al. [10] and by comparing them with ex-type isolates from the reference collection of CBS (Utrecht, the

Netherlands). Pseudallescheria angusta and P. ellipsoidea INK 128 in vitro are listed as part of P. boydii. Three different microtitre plates were used with the Taxa Profile Micronaut system (Merlin Diagnostika GmbH): Taxa Profiles A, C and E. On each microtitre plate, two strains were analysed synchronously for 191 reactions in the case of Taxa Profiles A and C (one growth control) and 188 reactions for Taxa Profile E (three negative controls and one growth control). Taxa Profile A contains amines, amides, amino acids, other organic acids, and includes heterocyclic aromatic compounds. Taxa Profile C contains mono-, di-, tri- and polysaccharides, and sugar derivatives.

On panels A and C, each well contains 1.6 g L−1 of the respective chemical compound. Results were read Copanlisib mw visually and photometrically at 620 nm (single scan). Taxa Profile E contains 95 aminopeptidase and protease reactions, 76 glycosidases, phosphatidases and esterases (each for testing at the different pH values of 8.2, 7.5, 5.5 and 4.0), desaminases and decarboxylases (arginine-dihydrolase, glutamate-, lysine-, ornithine-decarboxylases and relevant control reactions), and 17 classical reactions (such as urease, indol, nitrate and nitride). A full

list of the reactions is provided in Supporting Information. Strains were cultured on potato dextrose agar (PDA; Oxoid, Wesel, Germany), Sabouraud’s 4% glucose agar, water agar, Müller Hinton’s agar and Columbia sheep blood agar. The incubation period was up to 7 days at 35 ± 1 °C to 4��8C obtain optimal conidiation. The plates were covered with 5–6 ml sterilised 0.9% NaCl solution. Conidia were scraped off carefully and transferred into a sterile glass tube using a sterile pipette. The suspensions were vortexed and centrifuged for 5 min at 21 °C at 3000 rpm; sediments were washed three times in 5 ml sterile 0.9% NaCl solution. Suspensions were adjusted with a UV 160 spectrophotometer for Taxa Profiles A and C panels to 0.150–0.170 at 530 nm (1–5 × 104 colony forming units ml−1),19 and to 0.20–0.28 at 560 nm for Taxa Profile E.

Use of this cryptic splice site led mostly to an insertion of 132 bp that introduced 44 amino acids and a premature stop codon between exons 56 and 57 (p.Gly2898GlyfsX36). In

addition, the presence of another putative AG dinucleotide splice acceptor site upstream to the cryptic GPCR Compound Library concentration donor splice site, led to an additional alternative frameshift insertion of 32 nucleotides, also leading to a premature stop codon (p.Gly2898AspfsX54) (Figure 7a). However, no truncated proteins were detected on Western blot analysis, suggesting either instability of the cryptic transcripts as a result of a nonsense-mediated mRNA decay process or an early degradation of the truncated proteins as a result of an unfolded protein response. The residual physiological splicing allowed the production of a low amount of wild-type RyR1

(22 ± 12%) in the muscle of the patient (Figure 6). Patient 7 was p.[Pro3202Leu] + p.[Arg4179His] compound heterozygous. The maternal p.Pro3202Leu (c.9605C>T, exon 65) variant was recurrent in this study (patient 4). The paternal p.Arg4179His (c.12536G>A, exon 90) variant affected a highly conserved arginyl residue that mapped to a cytoplasmic domain of the protein close to the p.Glu4181Lys variant identified in patient 2. We have identified a cohort of seven patients with congenital myopathy and a peculiar morphological pattern in muscle biopsies associated with recessive mutations Y-27632 chemical structure in the gene encoding the skeletal muscle ryanodine receptor (RYR1). All the patients showed early onset of the disease, ophthalmoparesis of variable severity and presence of early disabling contractures, Aspartate especially in the masticators. Rigid spine syndrome was also present in two patients. Otherwise clinical presentation was similar to most congenital myopathies, showing hypotonia of variable severity, delay in the acquisition of developmental motor milestones, axial and proximal limb weakness and restrictive respiratory syndrome. Cardiac and cognitive functions were invariably spared. Our data enlarges the histological phenotype associated with RYR1 mutations. Indeed,

the areas of sarcomeric/myofibrillar disorganization are distinguishable from typical cores. On oxidative stains, these areas are large, diffuse and poorly delimited. Ultrastructurally, they are broader than cores in transverse sections, as they frequently cover extensive cross-sectional areas of the fibre, often reaching the sarcolemma. They are also shorter than cores, as in longitudinal sections they extend along a relatively small number of sarcomeres. In contrast with cores the presence of mitochondria within the lesions accounts for the excessive oxidative staining in some fibres. On the other hand, ‘purple dusty areas’ corresponding to foci of Z line rearrangements are not usually seen in muscle biopsies of patients with classical core myopathies.