Correction to: Characterization of the first fully human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy

Abstract

Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional (3D) structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope. The rapid internalization of scFv78 and scFv78-labeled nanoparticles was triggered after specific TEM1 binding. The scFv78-saporin immunoconjugate also exerted dose-dependent cytotoxicity with high specificity to TEM1-positive cells in vitro. Finally, specific and sensitive tumor localization of scFv78 was confirmed with optical imaging in a mouse tumor model that has highly endogenous mTEM1 expression in the vasculature. Our data indicate that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has unique and favorable features that are advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.

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A Rare Case of Retrogastric Abscess Occurring Six Months after N-Butyl-2-Cyanoacrylate Injection into Gastric Varices

Background. Injection with N-butyl-2-cyanoacrylate is a proven and successful therapeutic modality for treatment of patients with bleeding gastric varices. However, a variety of complications have also been associated with its use. Here, we report a rare case of retrogastric abscess which occurred almost six months after this therapy. This abscess was attributed to the hampered microbial clearance caused by the venous obliterations from N-butyl-2-cyanoacrylate. The abscess was successfully treated with 3 months of antibiotics.

http://ift.tt/2CQar4J

Gastrointestinal Histoplasmosis Presenting as an Acute Abdomen with Jejunal Perforation

Introduction. Gastrointestinal histoplasmosis (GH) is a well-described albeit uncommon disease. It is found almost exclusively in the immunocompromised host, especially those with untreated HIV and low CD4 counts. Presentation with intestinal perforation is seen mostly commonly in the colon. We present a patient with jejunal perforation, and there have been only 3 previous cases reported in the literature. Case. A 39-year-old male with known, untreated HIV presented to the ED with an acute abdomen after experiencing worsening intermittent abdominal pain for 2 months before that was associated with nausea, vomiting, diarrhea, and weight loss. CT of the abdomen and pelvis revealed evidence of gas in the mesentery, small bowel thickening, edema, and free fluid in the abdomen. Emergency exploratory laparotomy was conducted. Intraoperative findings included a perforated jejunum that was studded with nodular lesions as well as mesenteric masses. Histopathologic exam of these mesenteric masses and jejunal lesions were positive for histoplasmosis. Conclusion. Disseminated histoplasmosis is a life-threatening disease that occurs nearly exclusively in immunocompromised hosts. Untreated, mortality is as high as 80%. This rare presentation with jejunal perforation highlights the need for awareness of histoplasmosis involvement throughout the entirety of the GI tract.

http://ift.tt/2m8U7BV

KIR3DL2 expression in patients with adult T-cell lymphoma/leukemia

Abstract

Adult T-cell lymphoma/leukemia (ATLL) is a hematologic malignancy of mature CD4-positive T-cells associated with chronic infection by human T-lymphotropic virus 1 (HTLV-1). Four different subtypes of ATLL have been described: acute, lymphomatous, chronic and smoldering forms. ATLL prognosis remains poor, with overall survival duration depending on the subtype, because there is no curative treatment of ATLL and patients often suffer from opportunistic infections.

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Dietary deoxynivalenol does not affect mineral element accumulation in breast and thigh muscles of broiler chicken

Abstract

Deoxynivalenol (DON), a well-known contaminant of feed, can have negative effects on gut permeability and function in poultry, which then could affect major and trace element content of the broilers' breast and thigh muscles, and ultimately reduce meat quality. To study this hypothesis, DON-contaminated diet was fed to broiler chicks. Two groups of birds were housed in metabolic cages with free access to water and feed, with or without DON (10 mg/kg). After 5 weeks, birds were dissected and samples of the breast and thigh muscles, feed and droppings were analysed for five macro (Ca, K, Mg, Na, and P) and ten micro elements (Al, Cr, Cu, Fe, Mn, Li, Mo, Ni, Pb, Rb, and Zn) by inductively coupled plasma optical emission spectrometry (ICP-OES) or inductively coupled plasma mass spectrometer (ICP-MS) methods. In both groups, increased (p < 0.05) concentrations of Ca Na, Fe, Mn, and Zn were found in thigh muscles compared with the breast, whereas the concentrations of Mg, P, and Rb were higher in the breast muscles. DON had no effect on the elemental contents of the broilers' breast and thigh muscles. In conclusion, DON at a level of 10 mg/kg feed to broiler chicken over of 5 weeks did not alter the macro or micro element composition in muscle meat.

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Tumour necrosis factor-α-inhibitor-induced neutrophilic folliculitis presenting with strong lesional expression of interleukin-36γ

http://ift.tt/2D9exCQ

Depression- and anxiety-like behaviour is related to BDNF/TrkB signalling in a mouse model of psoriasis

Summary

Background

The prevalence of anxiety and depression is significantly higher in individuals with psoriasis than in the general population. Clinical data also show that anti-anxiety and antidepression drugs can reduce skin lesions in patients with psoriasis, but the actual mechanism is still poorly understood.

Aim

To investigate whether brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB) signalling plays a role in the mechanism underlying psoriasis with depression and anxiety behaviours.

Methods

Expression of BDNF and tropomyosin receptor kinase B (TrKB) in the K5.Stat3C mouse, an animal model of psoriasis, were investigated by reverse transcription PCR and Western blotting. Anxiety-like behaviours in the elevated-plus maze test and changes in BDNF/TrkB that have been implicated in depression and anxiety behaviours were measured. Skin lesions induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) were also measured when the mice were administered fluoxetine and K252a, an antagonist of TrkB.

Results

The antidepression and anti-anxiety drug fluoxetine reduced TPA-induced skin lesions and increased expression of BDNF and TrkB in K5.Stat3C mice. More importantly, the effects of fluoxetine were reversed by the TrkB antagonist K252a.

Conclusions

BDNF/TrkB signalling participates in the pathological mechanism of depression and anxiety behaviours in psoriasis. Our findings provide a new therapeutic strategy for the treatment of skin lesions in psoriasis.

http://ift.tt/2CDfrGD