Branched and linear lipopeptide vaccines have different effects on primary CD4+ and CD8+ T-cell activation but induce similar tumor-protective memory CD8+ T-cell responses

We compared murine T-cell responses to synthetic lipopeptide vaccines in which the TLR2 ligand Pam(2)Cys was attached to co-linear CD4+ and CD8+ T-cell epitopes of ovalbumin (OVA) in a linear or branched configuration. Mice received OVA-specific transgenic CD8+ and CD4+ T-cells followed by one injection of vaccine. Although the branched lipopeptide was more potent in activating OVA-specific CD4+ and CD8+ T-cells in the primary response, both vaccines induced cytolytic T lymphocytes (CTL) that expressed perforin, granzyme A-C, and IFN-gamma mRNAs and conferred long-term protection of most mice against challenge with OVA-expressing tumor cells. OVA epitope display was reduced in tumors that developed in some mice, suggesting CD8+ T-cell dependent selection.     

Functions of corazonin and histamine in light entrainment of the circadian pacemaker in the Madeira cockroach,Rhyparobia maderae

The circadian pacemaker of the Madeira cockroach, Rhyparobia (Leucophaea) maderae, is located in the accessory medulla (AME). Ipsi‐ and contralateral histaminergic compound eyes are required for photic entrainment. Light pulses delay locomotor activity rhythm during the early night and advance it during the late night. Thus, different neuronal pathways might relay either light‐dependent delays or advances to the clock. Injections of neuroactive substances combined with running‐wheel assays suggested that GABA, pigment‐dispersing factor, myoinhibitory peptides (MIPs), and orcokinins (ORCs) were part of both entrainment pathways, whereas allatotropin (AT) only delayed locomotor rhythms at the early night. To characterize photic entrainment further, histamine and corazonin were injected. Histamine injections resulted in light‐like phase delays and advances, indicating that the neurotransmitter of the compound eyes participates in both entrainment pathways. Because injections of corazonin only advanced during the late subjective night, it was hypothesized that corazonin is only part of the advance pathway. Multiple‐label immunocytochemistry in combination with neurobiotin backfills demonstrated that a single cell expressed corazonin in the optic lobes that belonged to the group of medial AME interneurons. It colocalized GABA and MIP but not AT or ORC immunoreactivity. Corazonin‐immunoreactive (‐ir) terminals overlapped with projections of putatively light‐sensitive interneurons from the ipsi‐ and contralateral compound eye. Thus, we hypothesize that the corazonin‐ir medial neuron integrates ipsi‐ and contralateral light information as part of the phase‐advancing light entrainment pathway to the circadian clock. J. Comp. Neurol. 525:1250–1272, 2017. © 2016 Wiley Periodicals, Inc.     

Evaluation of asymptomatic venous disease by Doppler ultrasonography in Behçet’s disease patients

Aim of the work

Evaluation of asymptomatic venous disease in patients with Behçet’s disease (BD) using venous Doppler ultrasonography (US) and its relation to different disease manifestations and activity.

Severe erythema nodosum due to Behçet's disease responsive to erythromycin

A patient with severe erythema nodosum due to Beh?et's disease is reported on here. Erythema nodosum lesions did not respond to classical treatments; however, they cleared after erythromycin treatment, which was prescribed for the treatment of coincidental erythrasma. Erythromycin treatment appears to be an effective treatment option in erythema nodosum. The hypothetical anti-inflammatory effects of erythromycin, besides its antibiotic properties, are reviewed and discussed to explain such a clinical improvement.     

Bullous erythema ab igne

Erythema ab igne is a localized, cutaneous condition, consisting of reticulate hyperpigmentation, dusky erythema, epidermal atrophy, and telangiectasia, all the result of repeated exposures to heat. We describe a patient with a bullous form of erythema ab igne: bullae and crusts within a localized area of reticular, brown, macular pigmentation on the lateral side of the left leg, an area that had repeated close exposure to an electrical heater over the previous 3 months. We believe that bullous erythema ab igne, something rarely reported in the literature, should be considered a well-defined variant of erythema ab igne; it may be more common than the literature suggests.     

Intracranial hemorrhage as initial presentation of biliary atresia: two cases report

Biliary atresia in infants occasionally presents as intracranial, nasal or gastrointestinal bleeding, instead of the classical triad of jaundice, acholia and choluria. We present two female infants aged four and two months, who were hospitalized with convulsive episode, cephalohematoma and drowsiness. Computed tomography findings were subdural hemorrhage in one patient and intraventricular and parenchymal bleeding in the other one. At admission they have history, clinical and laboratory signs of cholestasis of unknown etiology. The patient with subdural hemorrhage required surgical drainage. The other girl with intraventricular and parenchymal bleeding received vitamin K and no surgery. Biliary atresia was diagnosed and treated in both girls. At six months both had an adequate neurological outcome and required liver transplantation at one year old. Biliary atresia should be considered in all infants with sudden acute bleeding and cholestasis.     

The changes in expression of ICAM-3, Ki-67, PCNA,and CD31 in psoriatic lesions before and after methotrexate treatment

Although the effectiveness of methotrexate (MTX) in the treatment of psoriasis is very well established, the mechanism of action is poorly understood. It was suggested that the therapeutic effect of MTX in psoriasis might be mediated by inhibition of adhesion molecule expression. The aim of our study was to investigate the different effects of MTX treatment on cell proliferation, inflammatory infiltrate, adhesion molecules, and angiogenesis in psoriasis, and to clarify the mechanism by which MTX exerts its therapeutic effects. Clinical response, the morpho–phenotypic changes, epidermal thickness, and mitosis count were analyzed and the expression of CD31 and ICAM-3, proliferative markers such as Ki-67, PCNA, were evaluated by immunohistochemical techniques in lesional psoriatic epidermis, before and after the treatment with MTX in ten patients. In posttreatment biopsies a decrease in the degree of epidermal hyperplasia and a significant reduction in the severity of the inflammatory infiltrate (P<0.05) were observed. In addition, CD31 and ICAM-3 expression was significantly decreased on dermal cellular infiltrate, (respectively; P<0.05, P<0.01). Ki67 and PCNA expression were suppressed concurrently in about 90% of cases (P<0.01). We suggest that MTX may have an inhibitory effect on an initial integral component of the pathways that lead to psoriasis. Immunopharmacologic intervention in adhesion event has the potential to improve psoriasis. Inhibition of revascularization may be another mechanism of action of MTX.     

Increased uptake of the P2X7 receptor radiotracer 18F-JNJ-64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice

Objective

The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested ¹⁸F-JNJ-64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure-damage and epileptogenesis.

Methods

Status epilepticus was induced via an intra-amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of ¹⁸F-JNJ-64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. ¹⁸F-JNJ-64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy.

Results

P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi- and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control.

Significance

Taken together, our data suggest that P2X7R-based PET imaging may help to identify seizure-induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R-based treatments.     

Activity of the Oral Neuraminidase Inhibitor A-322278 against the Oseltamivir-Resistant H274Y (A/H1N1) Influenza Virus Mutant in Mice

The new oral neuraminidase (NA) inhibitor A-322278 was evaluated in mice infected with influenza A/H1N1 wild-type virus or the oseltamivir-resistant (H274Y mutant) virus. A-322278 decreased mortality rates and lung virus titers significantly more than oseltamivir in mice infected with the NA H274Y mutant when therapy was started 4 h before or even 48 h after infection.     

Impact of schistosomiasis on patient and graft outcome after renal transplantation: 10 years' follow-up.

BACKGROUND: Schistosomiasis is a major health problem in some areas of the world. Schistosomal-specific nephropathy is a well-known occurrence and eventually leads to end-stage renal failure. Patients with schistosomal infection were considered to be suitable recipients for renal transplantation. However, the long-term impact of schistosomiasis on kidney transplantation is not yet been reported. METHODS: The long-term impact of schistosomiasis on patient and graft outcomes was studied by comparing two groups of subjects from a total of 243 patients. Group I consisted of cases with schistosomal infections and group II consisted of schistosoma-free controls. Schistosomiasis was documented in group I by identifying schistosoma eggs in urine, stool or rectal mucosal biopsy. Also intra-operative biopsies from bladder mucosa of the graft recipients and from the lower end of the ureter of living donors were obtained to search for schistosoma eggs. RESULTS: Sixty-three cases of schistosomiasis were diagnosed in both recipients and donors, 65 cases in recipients only, and eight cases in donors only. Infected recipients and donors with active lesions were treated at least 1 month before transplantation by combined antischistosomal drugs (praziquantel and oxamniquine). The 243 patients (136 schistosoma-infected cases and 107 controls) were followed regularly for a period of 10 years after transplantation. We found that there was no significant difference in the incidence of acute and chronic rejection between the groups; however, higher cyclosporin doses were needed for the infected group with subsequent higher incidence of both acute and chronic cyclosporin nephrotoxicity. Moreover, the schistosomal group had a significantly higher incidence of urinary tract infection and urological complications with no evidence of schistosomal re-infection. CONCLUSIONS: Despite a higher incidence of schistosoma-related complications after renal transplantation, schistosomal infection is not a major risk factor for transplantation. Therefore, infected patients can be considered as suitable recipients if they have been properly treated before transplantation.