“Phosphoproteins and phosphopeptides were expressed by E.


“Phosphoproteins and phosphopeptides were expressed by E. coli to give yields of 30-200 mg of purified protein per litre with an average degree of phosphorylation at multiple sites of 61-83%. The method employed two compatible cohabiting plasmids having low and high copy number,

expressing a protein kinase and, more abundantly, the substrate (poly)peptide, selleck chemicals respectively. It was used to phosphorylate recombinant beta-casein or osteopontin at multiple casein kinase-2 sites. Two constructs were designed to produce shorter peptides containing one or more clusters of phosphorylation sites resembling the phosphate centres of caseins. In the first, a 53-residue 6-His tagged phosphopeptide was expressed at a 5-fold higher molar yield. The second had multiple tandem repeats of

a tryptic phosphopeptide sequence to give a similar increase in efficiency. Each recombinant phosphopeptide was purified (30100 mg) and small-angle X-ray scattering measurements showed that they, like certain casein and osteopontin phosphopeptides, sequester amorphous calcium phosphate to form calcium phosphate nanoclusters. In principle, the method can provide novel phosphopeptides for the control of biocalcification or be adapted for use with other kinases and cognate proteins or peptides to study the effect of specific phosphorylations on protein structure. Moreover, the insertion of a phosphate centre sequence, possibly with a linker peptide, may allow thermodynamically stable, biocompatible nanoparticles to be BMS202 molecular weight made from virtually any sequence. (C) 2009 Elsevier Inc. All rights reserved.”
“Purpose: Guidelines recommend serum total testosterone measurement as the initial test to evaluate male hypogonadism, reserving free testosterone assessment for men with suspected sex hormone-binding globulin abnormalities or total testosterone near the lower limit of normal. We determined the performance of total testosterone measurement as a test to identify men with normal vs low free testosterone.

Materials and Methods: We examined the electronic

medical records of all 3,672 men evaluated for hypogonadism by a serum testosterone panel, including total testosterone, AZD8055 nmr sex hormone-binding globulin, albumin and calculated free testosterone, from January 1, 1997 through December 31, 2007 in a network that serves veterans in Washington.

Results: The sensitivity and specificity of low total testosterone (less than 280 ng/dl) to rule out and predict low calculated free testosterone was 91.0% and 73.7%, respectively. At thresholds of less than 350 and less than 400 ng/dl the sensitivity of total testosterone for low calculated free testosterone increased to 96.8% and 98.2%, and at thresholds of less than 150 and less than 200 ng/dl specificity increased to 98.9% and 92.6%, respectively.

Conclusions: Total testosterone between 280 and 350 ng/dl is not sensitive enough to reliably exclude hypogonadism.

Thirty-nine (61%) ipsilateral arteries showed intraplaque hemorrh

Thirty-nine (61%) ipsilateral arteries showed intraplaque hemorrhage. During follow-up, five ipsilateral strokes and a total of 14 ipsilateral ischemic events were observed. Thirteen of these ischemic events, of which five were strokes, occurred in those with ipsilateral carotid intraplaque hemorrhage (hazard ratio = 9.8, 95% confidence interval 1.3-75.1, P=.03).

Conclusions: MR IPH is a good predictor of ipsilateral stroke and TIA in patients with symptomatic mild to moderate (30%-69%) carotid

stenosis. This technique could help in the check details selection of patients for carotid endarterectomy.”
“OBJECTIVE: A penetrating injury to the brainstem is usually a fatal injury. The number of cases in which the brainstem is traversed

during the injury and the patient survives is exceedingly small.

CLINICAL PRESENTATION: We report a case of an automobile collision in which blunt injury to the face of a 22-year-old man resulted in a fragment of the clivus being impacted posteriorly traversing through the pons in a left-sided through-and-through manner. The striking radiographic images demonstrate a potentially devastating brainstem injury. Surprisingly, the patient was able to follow commands and move his left side on arrival at the LY2874455 hospital.

INTERVENTION: The patient required a temporary tracheostomy and underwent surgical repair of his facial fractures. His hospital course was complicated by meningitis, and he required a long stay on the rehabilitation service. The patient made a remarkable recovery and became able to converse and walk with assistance. He has been able to live independently.

CONCLUSION: The striking radiographic images of this rare case illustrate an unusual pathology with

an even more unusual outcome.”
“Objectives: Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for treating carotid artery stenosis. We conducted see more a systematic review and meta-analysis of the clinical trials to date comparing these two procedures to determine their relative safety and efficacy.

Methods: Searches of the Cochrane Controlled Trials Register, MEDLINE, and EMBASE identified two cohort studies and eight randomized, controlled trials (RCTs) comparing CEA and CAS. Meta-analysis was performed for the primary outcome of 30-day stroke or death, using an intention-to-treat analysis. Between-trial heterogeneity was assessed using the X(2) test, and fixed-effects models were used to pool estimates in the absence of heterogeneity. Meta-regression was conducted to investigate potential effect differences by patient, intervention, and trial characteristics. To evaluate the effect of study design and inclusion criteria, sensitivity and subgroup analyses were performed.

Results: Ten trials encompassing 3580 patients were analyzed.

Treatment with omacetaxine decreased the number of leukemia stem

Treatment with omacetaxine decreased the number of leukemia stem cells and prolonged the survival of mice with BCR-ABL-induced CML or B-ALL. Leukemia (2009) 23, 1446-1454; doi:10.1038/leu.2009.52; published online 26 March 2009″
“It has been suggested that different brain areas are involved in the modulation and expression of fear and anxiety. GW4869 mw In the present study we investigated these potential differences by using the fear-potentiated-startle (FPS) and light-enhanced-startle (LES) paradigms to differentiate between fear and anxiety, respectively.

Male Wistar rats were tested in the FPS and LES paradigm and perfused I h after the test session. Fos immunoreactivity (IR) was quantified in 21 brain areas and compared between FPS, LES and four LXH254 in vitro control conditions. Both FPS and LES procedures significantly enhanced the acoustic startle response. A principal component analysis of Fos-IR-data showed that 70% of the changes in Fos-IR could be explained by three independent components: an arousal-component, identifying brain areas known to be activated under conditions of vigilance, arousal and stress, a LES- and an FPS-component. The LES component comprised the septohippocampal system and functionally interrelated areas including nucleus accumbens, anterior cingulate cortex, lateral habenula and supramammillary

areas, but not the dorsolateral part of the bed nucleus of the stria terminalis. The central amygdaloid nucleus and the dorsolateral part of the bed nucleus of the stria terminalis loaded exclusively on the FPS component. Analysis of the separate brain areas revealed significantly higher Fos-IR in LES relative to FPS in the anterior cingulate cortex, nucleus accumbens shell, lateral septum, lateral habenula and area postrema. We conclude that the neural circuitry activated during FPS and LES shows clear differences. In anxiety as induced by LES, activation of the septohippocampal system and related areas seems to play a major role. In fear as induced by FPS, the central amygdaloid

nucleus and the dorsolateral part of the bed nucleus of the stria terminalis loaded on the same component, but Fos-IR observed in these brain regions did not differentiate between anxiety and fear. Furthermore, principal-component this website analysis appears a useful tool in detecting and describing correlated changes in patterns of neuronal activity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“We reported that complement (C) becomes activated and cleaved in bone marrow during preconditioning for hematopoietic transplantation and the third C component (C3) cleavage fragments, C3a and (desArg)C3a, increase responsiveness of hematopoietic stem/progenitor cells (HSPCs) to stromal-derived factor-1 (SDF-1). We also showed that this homing-promoting effect is not C3a receptor (C3aR) dependent.


“Purpose: In this feasibility study we assessed the 12-mon


“Purpose: In this feasibility study we assessed the 12-month safety and potential efficacy of autologous muscle derived cells find more (Cook MyoSite Incorporated, Pittsburgh, Pennsylvania) as therapy for stress urinary incontinence.

Materials and Methods: A total of 38 women in whom stress urinary incontinence had not improved with conservative therapy for 12 or more months underwent intrasphincter injection of low doses (1, 2, 4, 8 or 16 x 10(6)) or high doses (32, 64 or 128 x 10(6)) of autologous muscle derived cells, which were derived from biopsies of their quadriceps femoris. All patients could elect a second treatment

of the same dose after 3-month followup. Assessments were made at 1, 3, 6 and 12 months RAD001 nmr after the last treatment. The primary end point was the incidence and severity of adverse events. In addition, changes in stress urinary incontinence severity were evaluated by pad test, diary of incontinence episodes and

quality of life surveys.

Results: Of the 38 patients 33 completed the study. Treatment related complications were limited to minor events such as pain/bruising at the biopsy and injection sites. Of patients who received 2 treatments of autologous muscle derived cells who were eligible for analysis, a higher percentage of those in the high dose vs the low dose group experienced a 50% or greater reduction in pad weight (88.9%, 8 of 9 vs 61.5%, 8 of 13), had a 50% or greater reduction in diary reported stress leaks (77.8%, 7 of 9 vs 53.3%, 8 of 15) and had 0 to 1 leaks during 3 days (88.9%, 8 of 9 vs 33.3%, 5 of 15) at final followup.

Conclusions: Injection of autologous muscle derived cells in a wide range of doses appears safe with no major treatment see more related adverse events reported. In addition, treatment with autologous muscle derived cells shows promise for relieving stress urinary incontinence symptoms and improving quality of life.”
“In this study, we examined the association between insight and decision-making capacity in schizophrenia

using the Iowa Gambling Task (IGT). No association was found between insight and IGT scores. Our results suggest that impaired decision-making ability in schizophrenia patients cannot be solely predicted by lack of insight. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Purpose: Urinary incontinence is a frequent complication of radical prostatectomy with a detrimental impact on quality of life. We identified predictors and trends in the use of procedures for post-prostatectomy incontinence.

Materials and Methods: Using SEER (Surveillance, Epidemiology and End Results) cancer registry data linked with Medicare claims, we identified men 66 years old or older who were treated with radical prostatectomy in 2000 to 2007. The primary outcome was performance of an incontinence procedure. Demographic and clinical predictors of incontinence surgery were evaluated by multi-variable regression analysis.

These findings provide preliminary support for a relationship bet

These findings provide preliminary support for a relationship between the perceptual characteristics

of auditory stimuli and modulation of cortical oxygenation as measured via an emerging neuromonitoring technique.”
“Bisphenol GW786034 supplier A (BPA) is an industrial chemical with estrogenic activity. In our study, 40 rats were given BPA at 4, 40, and 400 mg/kg per day. Controls were treated with corn oil of same volume until the offspring were 30 d olds. At the end of the experiment, the expression of estrogen receptor ( ER)-alpha and the mRNA levels of inerleukin (IL)-2, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in spleens were investigated by Western blotting and real-time reverse-transcription polymerase

chain reaction (RT-PCR). The histopathological change of organs was observed. The results showed that bisphenol A reduced the expression of ER-alpha in males of the high-dose group in the F(0) generation and in middle-and high-dose groups of the F(1) GSK1838705A in vitro generation (p<.05), but increased it in females in the high- dose group of the F0 generation and in middle- and high- dose groups of the F1 generation (p<.05). The levels of IL-2, IL-12, IFN-gamma, and TNF-alpha in spleens were downregulated in all groups in contrast to controls (p<.05). We also found some histological changes in spleens, livers, and kidneys.

These findings demonstrated that bisphenol A has estrogen-like activity and might affect some immune organs and parameters.”
“Event-related potential (ERP) studies revealed an early posterior negativity (EPN) for emotionally arousing pictures. Two studies explored ARN-509 chemical structure how this effect relates to perceptual stimulus characteristics and stimulus identification. Adding various amounts of visual noise varied stimulus perceptibility of high and low arousing picture contents, which were presented as rapid and continuous stream. Measuring dense sensor event-related potentials, study I determined that noise level was linearly related to the PI peak. Subsequently, enlarged EPNs to emotionally arousing contents were observed, however, only for pictures containing low amounts of noise, which also enabled stimulus identification as shown by study II. These data support the notion that the EPN may serve as a measure of affective stimulus evaluation at an early transitory processing period.”
“Blubber was analyzed for a wide range of contaminants from five subadult and eight adult male ringed seals sampled in 2004, namely, for polychlorinated biphenyls ( PCBs), hexachlorobenzene (HCB), toxaphenes, chlordanes, dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenylethers (PBDEs).

02), stenosis determined based on small branch pulmonary artery d

02), stenosis determined based on small branch pulmonary artery diameter was correlated to a prolonged interval to pulmonary valve replacement (P = .009). Initial diagnosis, prior palliative shunt operation, and degree of pulmonary regurgitation had no effect on the interval between pulmonary valve disruption and subsequent pulmonary valve replacement. As determined

by using multivariate analysis, only male sex and small pulmonary artery diameter remained significant BAY 73-4506 ic50 factors.

Conclusions: Male sex appears to shorten the interval between pulmonary valve disruption and pulmonary valve replacement, whereas small branch pulmonary artery diameter appears to lengthen the interval. Knowing which factors are detrimental and which are protective might help identify patients who are prone to a more rapid progression of right heart failure from free pulmonary insufficiency, possibly steering them toward selleck compound more frequent follow-up or more aggressive heart failure medical regimens.”
“Bacopa monnieri, Linn. (Brahmi, BM), traditionally used to improve mental health in Indian ayurvedic system of medicine is known to possess various neuropharmacolgical properties. In the recent past, Drosophila has been widely used as a model to study various neurodegenerative

diseases. Environmental toxins like rotenone, a specific inhibitor of complex I is employed to increase oxidative stress mediated neuropathology and sporadic Parkinson’s disease. In this study, we examined the neuroprotective properties of BM against rotenone induced oxidative damage and neurotoxicity. Flies (Oregon K strain, adult males) exposed to a standardized BM powder for 7 days in the diet exhibited significant diminution in the levels of endogenous oxidative markers viz., malondialdehyde. hydroperoxide and protein carbonyl content. Further, BM offered complete protection against rotenone Prostatic acid phosphatase (500 mu M) induced oxidative stress and markedly inhibited dopamine depletion (head region,

33%; body region, 44%) in flies. Flies exposed to rotenone + BM exhibited a lower incidence of mortality (40-66% protection) and per-formed better in a negative geotaxis assay (45-65%) both suggesting the neuroprotective potential of BM. Interestingly, BM also conferred significant resistance (43-54% protection) in a paraquat oxidative stress bioassay. The neuroprotective effects of BM were highly comparable to those of a commercially available Brahmi preparation. Although the precise mechanism/s underlying the neuroprotective efficacy of BM are not clear, it is hypothesized that it is wholly or in part related to its ability to mitigate rotenone induced oxidative stress. Further, our approach confirms the utility of the Drosophila model in screening putative neuroprotective phytomedicines prior to their use in mammalian models. (C) 2009 Elsevier Inc.

Adverse reactions to adalimumab are limited mainly to injection s

Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. We, however, report a case of Stevens-Johnson

syndrome that required hospitalization and cessation of adalimumab in a patient with rheumatoid arthritis (RA). In this case report, a 53-year-old woman with RA developed severe mucositis, peripheral rash and desquamation and fever concomitant with the fifth Torin 2 dose of 40 mg adalimumab. Infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Severe skin reactions induced by TNF-alpha antagonists can be very serious, and prescribers need to be aware of the potential for the mucocutaneous adverse effects from the use of these agents, particularly due to the significant morbidity and mortality that are associated with SJS.”
“Familial mediterranean fever (FMF) is an autosomal recessive disorder caused by mutations in the FMF gene (MEFV). The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. Since there are several etiological factors, FMF is the most common periodic fever syndrome. However, it is still unknown what triggers or ends these periodical attacks. As Flavopiridol ic50 a pleiotropic hormone,

vitamin D has immunomodulation effects. The aim of this study was to evaluate the vitamin D levels in FMF patients. The study group was comprised of 26 patients

diagnosed with FMF (men/women: Idoxuridine 12/14), and 34 healthy control (men/women: 17/17). Vitamin D levels in FMF patients and healthy controls were 11.05 +/- A 7.11, 17.15 +/- A 6.49, respectively. FMF patients had significantly decreased vitamin D levels compared with healthy controls (P < 0.001). In conclusion, it is thought that vitamin D deficiency in FMF patients may trigger the attacks. Further studies with larger patient populations need to hold to investigate the vitamin D deficiency in patients with FMF and that may assist to clarify the mechanism behind the colchicines resistant cases.”
In this case report, we present a juvenile rheumatoid arthritis patient whose liver enzymes raised while he was under treatment and afterwards HBV reactivation was determined as the cause. When reactivation was detected, we started controlled antiviral therapy. We achieved successful clinical and laboratory results after adding biological agents to the treatment. Careful evaluation of the patients who have indication for immunosuppressive agents and regular follow-up in case of infection may be protective from severe morbidity and/or mortality.”
“The efficacy of adalimumab, a fully human anti-tumor necrosis factor-alpha recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn’s disease.

We conducted a new meta-analysis (including BART) on safety and e

We conducted a new meta-analysis (including BART) on safety and efficacy of aprotinin in cardiac SRT1720 supplier surgery.

Methods: We conducted a mixed treatment comparisons network meta-analysis estimating the effects of aprotinin and alternative agents

in reducing blood loss during surgery. We implemented a combination of direct and indirect evidence in mixed treatment comparisons and estimated relative effects for different agents on all-cause mortality and return to the operating room for bleeding and conducted a supportive analysis of the effects of different agents with only directly randomized trials.

Results: Mixed treatment analysis of 88 trials randomizing 15,528 patients to 1 of 3 antifibrinolytic agents demonstrated no difference in mortality between placebo and antifibrinolytic agents. Analysis of aprotinin versus tranexamic acid and epsilon-aminocaproic acid in 17 and 6 trials, respectively

and tranexamic acid versus epsilon-aminocaproic acid in 5 trials demonstrated no difference in mortality between treatment allocations. All agents were superior to placebo in reducing reexploration for bleeding, with aprotinin numerically superior: aprotinin odds ratio, 2.6 (95% selleck inhibitor confidence interval, 1.9-3.7); tranexamic acid odds ratio, 1.79 (1.2-2.9), and epsilon-aminocaproic acid odds ratio, 2.4 (1.3-6.6).

Conclusions: This mixed treatment comparisons meta-analysis demonstrates no increased mortality risk with aprotinin versus other antifibrinolytic agents. All agents were superior to placebo in reducing reexploration for bleeding after adult cardiac surgery. (J Thorac Cardiovasc Surg 2013;145:234-40)”
“Background. Studies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics

and influence neurocognitive performance in BN.

Method. Attention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17 beta-estradiol plasma levels were assessed. Cloninger’s Temperament and Character Inventory – Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered.

Results. No impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and ‘Self-directedness’ were associated with better performance on conditional learning whereas 17 beta-estradiol had a negative influence on this domain; ‘Reward dependence’ was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively.

Conclusions.

The safety profile was favorable, with the most commonly reported

The safety profile was favorable, with the most commonly reported adverse effect being dysgeusia (38%). Early detection and higher plasma concentrations of OA are a product of rapid buy AG-014699 metabolism of 1-octanol.OA pharmacokinetics mirrored the timing of clinical improvement. These findings provide preliminary evidence for a new class of compound that may be effective in the treatment of ET.”
“Target cell overexpression of the integrase binding domain (IBD) of LEDGF/p75 (LEDGF) inhibits HIV-1 replication. The mechanism and protein structure requirements for this dominant interference

are unclear. More generally, how and when HIV-1 uncoating occurs postentry is poorly defined, and it is unknown whether integrase within the evolving viral core becomes accessible to cellular proteins prior to nuclear entry. We used LEDGF dominant interference to address the latter question while characterizing determinants of IBD antiviral activity. Fusions of green fluorescent protein (GFP) with multiple C-terminal segments

of LEDGF inhibited HIV-1 replication substantially, but minimal chimeras of either polarity (GFP-IBD or IBD-GFP) were most effective. Combining GFP-IBD expression with LEDGF depletion was profoundly antiviral. CD4(+) T cell lines were rendered virtually uninfectable, with single-cycle HIV-1 infectivity reduced 4 logs and high-input (multiplicity of infection click here = 5.0) replication completely blocked. We restricted GFP-IBD to specific intracellular locations and found that antiviral activity was preserved when the protein was confined to the cytoplasm or directed to the nuclear envelope. The life cycle block

triggered by the cytoplasm-restricted protein manifested after nuclear entry, at the level of integration. We conclude that integrase within the viral core becomes accessible to host cell protein interaction PLEKHO1 in the cytoplasm. LEDGF dominant interference and depletion impair HIV-1 integration at distinct postentry stages. GFP-IBD may trigger premature or improper integrase oligomerization.”
“Interneuron progenitors from the embryonic medial ganglionic eminence (MGE) can migrate, differentiate, and enhance local inhibition after transplantation into the postnatal cortex. Whether grafted MGE cells can reduce ictal activity in adult neocortex is unknown. We transplanted live MGE or killed cells (control) from pan green fluorescent protein expressing mice into adult mouse sensorimotor cortex. One week, 2 and 1/2 weeks, or 6 to 8 weeks after transplant, acute focal ictal epileptiform discharges were induced by injection of 4-aminopyridine (4-AP) 2 mm away from the site of transplantation. The local field potential of the events was recorded with 2 electrodes, 1 located in the 4-AP focus and the other 1 in the transplantation site.

MMP-9 is unlikely to be a clinically useful biomarker of CHD risk

MMP-9 is unlikely to be a clinically useful biomarker of CHD risk, but may still play a role in the pathogenesis of CHD.”
“Cranial visceral afferent nerve transfers information about visceral organs to nucleus tractus solitarii (NTS) by releasing the excitatory neurotransmitter glutamate. Various endogenous modulators affect autonomic reflex responses by changing glutamatergic responses in the NTS. Although the expression of GABA(A) and GABA(B) receptors in glutamatergic terminals is known, their functional contribution on glutamate release is poorly characterized. Here, we used mechanically isolated

NTS neurons to examine the mechanisms by which presynaptic GABA(A) Selleck Capmatinib and GABA(B) receptors modulate glutamatergic excitatory

postsynaptic currents (EPSCs). EPSC were isolated by clamping voltage at equilibrium potential for chloride (-49 mV) without any GABA receptors antagonists. In all neurons, GABA(A) agonist, muscimol (1 and 10 mu M), increased EPSC frequency (284.1+/-57% and 278.4+/-87% of control, respectively), but the GABA(B) agonist, baclofen (10 mu M), decreased EPSC frequency (43+/-8% of control). The GABA(A) antagonist, gabazine (18 mu M), decreased EPSC frequency in 50% of tested neurons, whereas GABA(B) antagonist, CGP (5 mu M), increased the EPSC frequency in 36% of tested neurons. External application of GABA (1 and 30 mu M) facilitating the EPSC frequency. The facilitation of the GABA(A) receptor-mediated release of glutamate was blocked by Na+-K+-Cl- cotransporter type 1 antagonist or Na+ and 4SC-202 chemical structure Ca2+ channel inhibitors indicating GABA(A) presynaptic depolarization. Thus, tonically released GABA activates GABA(A) and GABA(B) receptors to modulate the release of glutamate. These findings provide cellular mechanisms of heterosynaptic GABA-glutamate integration of peripheral visceral afferent signals in the NTS. (C) 2012 IBRO. Published by Elsevier

Ltd. All rights reserved.”
“Plasmid DNA vaccines serve in a wide array of applications ranging from prophylactic vaccines to potential therapeutic tools against infectious diseases and cancer. In this study, we analyzed the mechanisms underlying the activation of natural killer (NK) cells and their potential role in adaptive immunity during DNA-based immunization against Methylitaconate Delta-isomerase hepatitis B virus surface antigen in mice. We observed that the mature Mac-1(+) CD27(-) NK cell subset increased in the liver of mice early after DNA injection, whereas the number of the less mature Mac-1(+) CD27(+) NK cells in the liver and spleen was significantly reduced. This effect was attributed to bacterial sequences present in the plasmid backbone rather than to the encoded antigen and was not observed in immunized MyD88-deficient mice. The activation of NK cells by plasmid-DNA injection was associated with an increase in their effector functions that depended on the expressed antigen.