These possibilities

remain to be investigated. One model system that shows promise in revealing the role of the Cpx response in bacterium–host interactions involves the organism Xenorhabdus nematophila. X. nematophila associates mutualistically with the entomopathogenic nematode Steinernema carpocapsae; the bacterium Buparlisib nmr and the nematode cooperatively kill a variety of insect hosts (Chaston & Goodrich-Blair, 2010). Interestingly, inactivation of the Cpx response reduces the ability of X. nematophila to both colonize its nematode host and successfully infect an insect host (Herbert et al., 2007). Subsequent studies determined that the nematode colonization defect of the cpxR mutant likely results from diminished expression of the envelope-localized colonization factors NilA, NilB and NilC (Herbert Tran et al., 2009), while the virulence buy Ribociclib defect could be the result of insufficient expression of the

virulence-related transcriptional regulator LrhA (Herbert Tran & Goodrich-Blair, 2009). It therefore appears that the Cpx response has important functions in multiple stages of the X. nematophila life cycle. Further studies in this pathogen and others will undoubtedly improve our understanding of the role of the

Cpx response in bacterium–host interactions. It is now clear that the Cpx envelope stress response represents more than simply a means to detect and repair misfolded periplasmic proteins. A variety of signals can enter the Cpx signalling pathway at multiple points, with NlpE sensing adhesion, CpxA possibly sensing misfolded envelope proteins, and CpxR sensing growth and metabolism. A variety of target genes are regulated by phosphorylated CpxR, including those encoding envelope Buspirone HCl protein complexes, IM proteins, peptidoglycan metabolic enzymes and other regulators. Finally, the Cpx response regulates virulence processes in numerous pathogens (Table 1). Most of these inducing cues and regulatory targets still pertain to the cell envelope, validating the original characterization of CpxAR as an envelope stress response; however, the Cpx response also promotes envelope function in diverse ways not previously recognized (summarized in Fig. 1). In spite of these advances, many questions remain.

The affinity of LPS to its pattern recognition receptors, such as the TLRs and CD14, enables discrimination between commensal and pathogenic species. The P. gingivalis LPS is a stimulator of proinflammatory

responses and bone resorption, as demonstrated in experimental animal models (Chiang et al., 1999; Nishida et al., 2001). In vitro, it stimulates proinflammatory cytokine production of, for example, IL-1α, IL-1β, IL-6, IL-8, IL-18 and tumour necrosis factor (TNF)-α in monocytes (Zhou et al., 2005; Bostanci et al., 2007a, b; Hamedi et al., 2009). Yet, P. gingvalis LPS exhibits controversial features with regard to the induction of an inflammatory response. Apart from being a weaker cytokine stimulator compared with the LPS of other Gram-negative (i.e. enteropathogenic) species (Liu et al., 2008), it can also antagonize the cytokine-stimulating capacity of other putative pathogens (Bostanci et al., 2007a, b).

Structurally, P. gingivalis LPS Alpelisib cell line exhibits unique features compared with the LPS of other species. These include differences in the structure of the O-antigen between P. gingivalis strains that can confer antigenic differences (Paramonov et al., 2001, 2009), as well as in the acylation patterns and receptor-activating capacities of the lipid A component. While the lipid A of most Gram-negative species is a strong activator of TLR4 responses, P. gingivalis lipid A is predominantly a TLR2 activator and may even act as antagonist to TLR4 (Darveau et al., 2004), dampening the immune responses (Hajishengallis, 2009). When considering further the heterogeneous acylation patterns of P. gingivalis Dabrafenib concentration lipid A, two forms are predominant: the tetra-acylated and penta-acylated forms. These two structures induce opposing host responses. The penta-acylated lipid A activates TLR4, whereas tetra-acylated lipid A acts as

a TLR4 antagonist (Darveau et al., 2004; Nemoto et al., 2006). These changes of P. gingivalis lipid A acylation are dependent on microenvironmental Tacrolimus (FK506) conditions. In particular, when hemin availability is high (a condition that reflects inflammation), penta-acylated lipid A is converted into tetra-acylated lipid A (Al-Qutub et al., 2006). Hence, by modifying its lipid A structure according to the microenvironment, P. gingivalis may modulate the binding affinity of its LPS to its cognate TLR receptors, subsequently selecting how to affect downstream host immune signalling. Interestingly, a second type of LPS has also been identified in P. gingivalis, containing a distinct anionic polysaccharide linked to lipid A, known as A-LPS (Paramonov et al., 2005). A-LPS is required for cell integrity and serum resistance (Shoji et al., 2002; Paramonov et al., 2005; Slaney et al., 2006) and is structurally associated with the Arg-X gingipain (Curtis et al., 1999; Paramonov et al., 2005). It is also a weaker inducer of cytokine responses by human monocytes, as compared with the conventional LPS (Rangarajan et al., 2008).

The affinity of LPS to its pattern recognition receptors, such as the TLRs and CD14, enables discrimination between commensal and pathogenic species. The P. gingivalis LPS is a stimulator of proinflammatory

responses and bone resorption, as demonstrated in experimental animal models (Chiang et al., 1999; Nishida et al., 2001). In vitro, it stimulates proinflammatory cytokine production of, for example, IL-1α, IL-1β, IL-6, IL-8, IL-18 and tumour necrosis factor (TNF)-α in monocytes (Zhou et al., 2005; Bostanci et al., 2007a, b; Hamedi et al., 2009). Yet, P. gingvalis LPS exhibits controversial features with regard to the induction of an inflammatory response. Apart from being a weaker cytokine stimulator compared with the LPS of other Gram-negative (i.e. enteropathogenic) species (Liu et al., 2008), it can also antagonize the cytokine-stimulating capacity of other putative pathogens (Bostanci et al., 2007a, b).

Structurally, P. gingivalis LPS Bortezomib clinical trial exhibits unique features compared with the LPS of other species. These include differences in the structure of the O-antigen between P. gingivalis strains that can confer antigenic differences (Paramonov et al., 2001, 2009), as well as in the acylation patterns and receptor-activating capacities of the lipid A component. While the lipid A of most Gram-negative species is a strong activator of TLR4 responses, P. gingivalis lipid A is predominantly a TLR2 activator and may even act as antagonist to TLR4 (Darveau et al., 2004), dampening the immune responses (Hajishengallis, 2009). When considering further the heterogeneous acylation patterns of P. gingivalis Veliparib mouse lipid A, two forms are predominant: the tetra-acylated and penta-acylated forms. These two structures induce opposing host responses. The penta-acylated lipid A activates TLR4, whereas tetra-acylated lipid A acts as

a TLR4 antagonist (Darveau et al., 2004; Nemoto et al., 2006). These changes of P. gingivalis lipid A acylation are dependent on microenvironmental Ergoloid conditions. In particular, when hemin availability is high (a condition that reflects inflammation), penta-acylated lipid A is converted into tetra-acylated lipid A (Al-Qutub et al., 2006). Hence, by modifying its lipid A structure according to the microenvironment, P. gingivalis may modulate the binding affinity of its LPS to its cognate TLR receptors, subsequently selecting how to affect downstream host immune signalling. Interestingly, a second type of LPS has also been identified in P. gingivalis, containing a distinct anionic polysaccharide linked to lipid A, known as A-LPS (Paramonov et al., 2005). A-LPS is required for cell integrity and serum resistance (Shoji et al., 2002; Paramonov et al., 2005; Slaney et al., 2006) and is structurally associated with the Arg-X gingipain (Curtis et al., 1999; Paramonov et al., 2005). It is also a weaker inducer of cytokine responses by human monocytes, as compared with the conventional LPS (Rangarajan et al., 2008).

, 1997; Trotter & Celebrini, 1999; Rosenbluth & Allman, 2002; Durand et al., 2010) and in the posterior parietal cortex (Andersen et al., 1985; Andersen, 1995; Xu et al., 2012) are modulated by gaze direction via gain control mechanisms (termed the

gain fields). However, modulation of neuronal responses by gaze-dependent VE-821 gain fields cannot explain our results, because the spatiotopic learning effect completely transfers to untrained gaze directions as long as the trained stimulus relation remained unchanged (Zhang & Li, 2010). It has been proposed that the gain control mechanisms can be used to transform a retinotopic Talazoparib concentration map into a spatiotopic one (Zipser & Andersen, 1988; Salinas & Thier, 2000; Pouget et al., 2002), whereby neuronal representation of a stimulus becomes independent of its retinal location. Neurons with such spatiotopic properties have been found in the parietal cortex (Galletti et al., 1993; Duhamel et al., 1997). Some imaging and psychophysical studies even suggest the presence of spatiotopic maps in visual cortical areas processing motion (Melcher & Morrone, 2003; d’Avossa et al., 2007; Crespi et al., 2011; Turi & Burr, 2012) and form (Melcher, 2005) information. However, several lines of evidence actually

argue for an absence, in the visual cortex, of any explicit spatiotopic representation that is independent of stimulus location on the retina (Gardner et al., 2008; Wenderoth & Wiese, 2008; Knapen et al., 2009, 2011; Morris et al., 2010; Ong & Bisley,

2011; Golomb & Kanwisher, 2012). Our finding that the learning-induced spatiotopic effect depended on the trained retinal location also argues against an explicit spatiotopic map for processing simple stimulus attributes. Instead, the retinotopic dependence of the spatiotopic learning effect and its orientation dependency suggest that the underlying spatiotopic processing is directly based on a retinotopic map; but how is this process accomplished? PD184352 (CI-1040) Considering that the first stimulus in our experiments was followed by a saccade, one might speculate that the spatiotopic learning effect and its retinotopic dependency might involve peri-saccadic updating of the visual representation of the first stimulus on a retinotopic map. Such a transient spatiotopic mechanism, which has been reported in the parietal (Duhamel et al., 1992; Merriam et al., 2003), frontal (Sommer & Wurtz, 2006) and even visual (Nakamura & Colby, 2002; Merriam et al., 2007) cortical areas, enables updating of a visual stimulus from one retinotopic location to another around saccadic eye movements.

The stability and crystallization of the resulting mutant proteins Cry1Ac′1 and Cry1Ac′3 were affected. Both of them lost their toxicity to the Lepidopteran larvae Ephestia kuehniella. Unlike Cry1Ac′1, Cry1Ac′3 became very sensitive to proteases. Accordingly, the three-dimensional structures of the two mutants were studied. The obtained models showed that both of the residues, Y229, located near the bottom of the α7 helix, and F603, located in the core of domain III, are involved in hydrophobic interactions essential for protein stability and toxicity. These results reveal that conserved amino acids blocs of Cry

toxins have conformational and functional roles. The gram-positive bacteria Bacillus thuringiensis produces insecticidal proteins called δ-endotoxins, or Cry proteins. These proteins Natural Product Library manufacturer are expressed during sporulation and are packaged into parasporal crystalline inclusions. After ingestion by susceptible insect larvae, crystals are solubilized by the effect of the alkaline pH of the insect midgut. The resulting protoxins (solubilized δ-endotoxins) are converted to their toxic form by midgut proteases. The activated toxins bind to specific receptors situated on midgut epithelial cells and insert into the membrane (Bravo et al.,

1992), leading to the death of the larvae via pore formation and disruption of midgut cellular functions (Schnepf et al., 1998). Cry1A proteins are composed of two structural regions: the N-terminal region, corresponding to the true

toxin, and the C-terminal region, which is cleaved selleck and removed after protoxin activation (Hofte & Whiteley, 1989). The X-ray crystal structure of Cry1Aa has been determined and has revealed a three-domain composition (Grochulski et al., 1995). Domain I is composed of an α-helix bundle formed by seven helices. Domains II and III are composed mostly of β-sheets (Grochulski et al., 1995; Boonserm et al., 2005, 2006). Domain I is believed to be Morin Hydrate involved in toxin insertion into the membrane (Schnepf et al., 1998), whereas domains II and III are thought to be implicated in receptor binding and toxin specificity (Pigott & Ellar, 2007). Five blocks of conserved amino acids residues have been identified in the family of Cry toxins (Hofte & Whiteley, 1989; Schnepf et al., 1998). Except for conserved block 1, which covers the central helix (helix 5) of domain I, all the other conserved blocks are entirely or partially involved in domain–domain interactions (Guo et al., 2009). The high homology of such regions suggests that they play important roles in the function of the Cry proteins. To elucidate the role of some amino acids in the structure stability of Cry toxins, a large number of mutagenesis studies have been performed. Some studies have demonstrated the role of hydrophobic amino acids in maintaining the stability of δ-endotoxins (Nuñez-Valdez et al., 2001; Padilla et al., 2006). In a previous work (Dammak et al.

4D, middle panels) than in wild-type neurons (Fig. 4D, upper panels). Addition of HA-Cbln1 to the culture medium restored accumulation of endogenous NRXs associated with GluD2 puncta on cbln1-null Purkinje cell dendrites (Fig. 4D, lower panels). Together, these results indicate that Cbln1/GluD2 serves as a presynaptic CDK and cancer organizer by directly accumulating its presynaptic receptor NRXs(S4+). Cbln1 also serves as a postsynaptic organizer that induces clustering of GluD2 and its

associated proteins at the postsynaptic site. To examine whether NRX functions as a postsynaptic organizer by forming a tripartite complex with Cbln1 and GluD2, we cultured HEK293 cells expressing GluD2 with beads coated with NRX1β. GluD2 clustering was induced around beads coated with NRX1β(S4+) only when HA-Cbln1 was added to the culture medium (Fig. 5A). However, beads coated with NRX1β(S4−) did not cause clustering of GluD2 even in the presence of HA-Cbln1 (Fig. 5A), suggesting that NRX1β(S4+) caused GluD2 clustering in HEK293 cells by forming a complex with Cbln1. The C-terminus of GluD2 interacts directly with several intracellular molecules in neurons; many of these serve as scaffolds for other postsynaptic molecules. Thus, to examine whether NRX also functions MK-2206 as a postsynaptic organizer in neurons,

we cultured cbln1-null Purkinje cells with beads

coated with NRX1β(S4+) from 10 to 13 DIV. Immunocytochemical analyses showed that GluD2 clustering was induced around beads only in the presence of HA-Cbln1 (Fig. 5B). Similarly, shank2, a scaffold protein that binds to the C-terminus of GluD2, clustered around beads coated with NRX1β(S4+) (Fig. 5B). In contrast, beads coated with NRX1β(S4−) did not cause clustering of GluD2 or shank2 even in the presence of HA-Cbln1 (Fig. 5B). Coimmunostaining of presynaptic synapsin I and postsynaptic GluD2 showed that Lepirudin GluD2 puncta induced by beads coated with NRX1β(S4+) in the presence of HA-Cbln1 were not associated with synapsin I-positive presynaptic terminals (Fig. 5C), indicating that NRX1β(S4+)-beads directly induced GluD2 clustering at the contact sites. These results indicated that the tripartite complex consisting of NRX, Cbln1 and GluD2 serves as a bidirectional synaptic organizer. Of the Cbln family members, Cbln1, Cbln2 and Cbln4 mRNAs are expressed in various brain regions outside the cerebellum, including the olfactory bulb, entorhinal cortex and certain thalamic nuclei (Miura et al., 2006). As NRXs(S4+) are also highly expressed in these regions (Ichtchenko et al., 1995), Cbln family members may also be involved in synapse formation by forming complexes with NRXs.

, 2007; Meier et al., 2008; Pereira et al., 2009). In this study, we evaluate the inhibitory activity of PYRH-1 (sodium 3-[4-tert-butyl-3-(9H-xanthen-9-ylacetylamino)phenyl]-1-cyclohexylmethylpropoxycarbonyloxyacetate)

as a potential antimicrobial agent by targeting the bacterial UMP kinase, PyrH, which serves as a kinase in de novo pyrimidine biosynthesis pathway required for the growth of certain bacteria such as S. pneumoniae (Thanassi et al., 2002; Song et al., 2005) and H. influenzae (Akerley et al., 2002). PYRH-1 was discovered in the course of a 1536-well high throughput screening of an in-house large chemical library by the selection of chemicals directly inhibiting PyrH of S. pneumoniae. To test the inhibitory activity of PYRH-1 against PyrH, we used a luminescence-based ATP quantitative reagent. Moreover, molecular interaction analysis between PYRH-1 and S. pneumoniae CT99021 PyrH by surface plasmon resonance (SPR) and susceptibility tests of PYRH-1 against some bacteria were Akt inhibitor performed. This is the first report that PYRH-1 inhibits PyrH. Bacterial strains used in this study are described in Table 1. Escherichia coli DH5α (competent high E. coli DH5α, Toyobo Co., Ltd.) was used for the cloning of PyrH. Escherichia

coli Rosetta-Gami B (DE3) (Novagen) was used as the host for recombinant protein expression. These were grown at 35 °C in Luria–Bertani (LB) broth or LB agar (BD Biosciences) containing 100 μg mL−1 of carbenicillin (Sigma). The culture medium used Baricitinib for each bacterium is as follows: S. pneumoniae, cation-adjusted Mueller–Hinton Broth (CAMHB; BD Biosciences) containing 5% of lysed horse blood (Nippon Bio-Test Laboratories Inc.) or Todd Hewitt Broth (Becton, Dickinson and Co.); S. aureus and E. coli, CAMHB; H. influenzae, Haemophilus test medium [CAMHB containing 5 mg mL−1 of Yeast Extract (BD Biosciences), 15 μg mL−1 of Hemin (Sigma) and 15 μg mL−1 of β-NAD (Sigma)]. This strain was constructed by deleting

the acrA gene and replacing it with a gene that confers resistance to chloramphenicol (cat) Streptococcus pneumoniae TIGR4 and H. influenzae Rd KW20 genomic DNA were extracted with a DNeasy Tissue Kit (Qiagen). Plasmid DNA was extracted with a QIAprep Spin Miniprep Kit (Qiagen). PCR products and plasmids digested by restriction enzyme were purified with a QIAquick PCR Purification Kit (Qiagen). PCR products digested by restriction enzyme were purified with a MinElute Reaction Cleanup Kit (Qiagen). The open reading frame of the pyrH gene was amplified from S. pneumoniae TIGR4 genomic DNA with primers SpPyrH-N-XhoI (5′- CCG CTC GAG GTG AAA ATG GCG AAT CCC AAG T -3′) and SpPyrH-C-BamHI (5′- CGC GGA TCC TTA TTC CTT TTC TTC GAT ATT ATT TGA AAC TGT TG -3′). The open reading frame of pyrH was amplified from H.

neoformans electron transport chain and suggest that the effect of microplusin on the growth of the fungi may be related to the damage of the classical respiratory chain, probably at the copper-containing complex IV. Although we cannot entirely discard the effects of Fe2+ on microplusin, our assumption that microplusin is preferentially a copper chelator is based on the fact that the four respiratory complexes that have iron as prosthetic groups or bound to the heme Staurosporine cost group remained functional, whereas complex IV, the only complex that has copper as a prosthetic group, was affected by microplusin. We also show that microplusin stimulated the alternative respiratory

pathway in C. neoformans, likely Roxadustat cell line to compensate for the damaged classical electron transport chain. The alternative pathway is not coupled to oxidative phosphorylation and ATP synthesis, and hence, energy production in microplusin-treated yeasts is likely to be deficient. However, uncoupled respiration helps the cells to manage reactive oxygen species production under stress conditions. Similar to complex IV, the assembly and functioning of other copper proteins, such as the antioxidant enzyme Cu-Zn superoxide dismutase (SOD1), might also be compromised in microplusin-treated C. neoformans. Microplusin

at concentrations ≥3.12 μM clearly inhibited C. neoformans melanization as well as reduced laccase activity. This further suggests that the copper-chelating ability of microplusin may affect the loading of copper ions to laccase apoenzyme. In addition, we observed that copper supplementation of the medium prevented the inhibition of melanization by microplusin, according to 1 : 1 binding ratio

(Silva et al., 2009). A correct laccase metallation is reportedly crucial for its biological activity, as shown for the laccase produced by the avirulent Δvph1 mutant of C. neoformans. Protein tyrosine phosphatase Defective vesicular acidification disrupts the insertion of copper cofactors into proteins, resulting in the inability of Δvph1 laccase to catalyze phenolic compounds to melanin (Erickson et al., 2001). As expected, addition of 1 mM of the copper chelator BCS to the medium abolished laccase activity not only in the Δvph1 mutant but also in the wild-type strain and copper supplementation, restored laccase activity as well as induced its transcription (Zhu et al., 2003). Therefore, these data support the hypothesis that microplusin sequesters copper and may affect the availability of this metal to copper-dependent enzymes, such as laccase. The microplusin concentrations that inhibited melanization (≥3.12 μM) also increased the autopolymerization of l-dopa. l-dopa autopolymerization is a process that occurs spontaneously by exposure to light (Mason, 1955). Microplusin probably stimulates the spontaneous autopolymerization of the products derived from l-dopa oxidation; however, this possible action did not interfere with its inhibitory effect on melanization of C.

The secretion was more efficient in induction media in the absence of calcium. In animal pathogenic bacteria, Ivacaftor cell line a decrease in calcium concentrations has been proposed as one of the signals that trigger T3SS secretion of T3SS effectors (Lee et al., 2001; Deng et al., 2005). Although no canonical T3SS signal sequence is present in Mlr6316, we demonstrated that its N-terminal region (160 aa) directs secretion in a T3SS-dependent manner. The homologous Mlr6316 protein expressed by M. loti R7A is encoded

by the msi059 gene and is translocated into the host cell through a type IV secretion system (T4SS) (Hubber et al., 2004). It has been suggested that an RxR motif in the C-terminal region forms part of the T4SS signal (Hubber et al., 2004). Mlr6316 and the protein encoded by msi059 (Msi059) share 88% of amino acid identity, and very few differences have been observed between their respective N-terminal regions. Both Msi059 and Mlr6316 also have an RxR

motif in their C-terminal region. It is possible that the two proteins conserve the capacity to be secreted both by T3SS and T4SS. The case of mlr6331 is similar to that of mlr6316 as it does not have the characteristic amino acid pattern present in T3SS substrates. PARP activity However, Yang et al. (2010) applied a computational prediction of type III secreted proteins in Gram-negative bacteria and found that the protein encoded by mlr6331 is a putative T3SS substrate. Competitive experiments were carried out to analyze the participation of M. loti T3SS or putative M. loti T3SS effectors in the symbiotic process. Competitive assays have been used in several works to analyze the changes in the symbiotic phenotype (Lagares et al., 1992; Vinuesa et al., 2002; Hubber et al., 2004). This method

has the advantage that the symbiotic capacities of two bacterial strains are compared on the same plant, and this could improve the sensitivity for the detection of a subtly altered phenotype. The results presented here demonstrate that symbiotic competitiveness on Lo. tenuis cv. Esmeralda was negatively affected by a functional T3SS. To determine which proteins were responsible for this effect Epothilone B (EPO906, Patupilone) and taking into account that a particular T3SS effector is often only partially responsible for the overall effect of the T3SS (Kambara et al., 2009), we went on to analyze the nodulation competitiveness phenotype on Lo. tenuis cv. Esmeralda using single, double, and triple mutants affected in the potentially secreted M. loti T3SS proteins described. Surprisingly, we observed a significantly diminished competitiveness associated with the triple mutant compared to the wt strain. The same phenotype was observed on Lo. japonicus MG-20. The results of the nodulation kinetic test indicate that the triple mutant also induced a lower number of nodules than the wt strain on Lo. tenuis cv. Esmeralda.

Nonetheless, the negative-predictive value is high [35]. Therefore, re-biopsy of residual FDG-avid lesions post-therapy should always be considered. Those with persistent disease should be considered for salvage therapy, and those who have achieved a CR, observed. The decision to offer consolidation radiotherapy should be made at presentation (i.e., to bulk disease or bony lesions) and not to residual FDG-avid lesions in those treated with curative intent, as PET-positive lesions may represent more widespread disease. RT may be offered to those with PET-positive lesion(s) and who are ineligible for salvage learn more chemotherapy. There are scant data regarding long-term follow-up of survivors of lymphoma treatment

in the HIV setting. However, it is well described in the HIV-negative setting that prior anthracyclines (e.g., doxorubicin) are associated with cardiomyopathy and heart failure. Although it is unclear www.selleckchem.com/products/PF-2341066.html if the incidence is higher in the HIV setting, patients with other cardiovascular risk factors (e.g., blood pressure, lipids, family history) may deserve greater surveillance. Chemotherapy for lymphoma is associated with an increased risk of myelodysplasia and acute myeloid leukaemia arising some 2–7 years later, often with cytogenetic abnormalities of chromosomes 5, 7 or 12. Chemotherapy

is also associated with an increased risk of second solid tumours, although previous radiotherapy is the greater risk factor. Other potential issues include endocrine and metabolic complications. Follow-up varies between centres but generally patients with aggressive histologies are seen every 3 months in the first year, 4–6 monthly for the second and third and thereafter 6 monthly until 5 years post treatment.

Patients are then often discharged to Nutlin-3 manufacturer primary care (having received an ‘end-of-treatment summary’) although data regarding long-term side effects in patients with HIV who have received treatment for lymphoma are scant. In light of this some patients continue to be monitored on an annual basis. 1 Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet 1991; 337: 805–809. 2 Biggar RJ, Rosenberg PS, Cote T. Kaposi’s sarcoma and non-Hodgkin’s lymphoma following the diagnosis of AIDS. Multistate AIDS/Cancer Match Study Group. Int J Cancer 1996; 68: 754–758. 3 Cote TR, Biggar RJ, Rosenberg PS et al. Non-Hodgkin’s lymphoma among people with AIDS: incidence, presentation and public health burden. AIDS/Cancer Study Group. Int J Cancer 1997; 73: 645–650. 4 Engels EA, Biggar RJ, Hall HI et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 2008; 123: 187–194. 5 Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 2000; 92: 1823–1830. 6 Stebbing J, Gazzard B, Mandalia S et al.