Hematopoietic Stem Cell Transplantation and Vasculopathy Associated With STAT3-Dominant-Negative Hyper-IgE Syndrome.

Dominant negative mutations in the transcription-factor STAT3 underlie the rare primary immunodeficiency Job's syndrome. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has shown promise in correction of the underlying immunological defect, with one report suggesting HSCT can prevent development of wider connective tissue complications. Here, we report the case of a 26 year old male who developed an acute ST-elevation myocardial infarction due to coronary artery ectasia and thrombosis, occurring despite pediatric allogeneic HSCT for STAT3-HIES and a predicted 10-year conventional cardiovascular risk of 0.1%. Vasculopathy associated with STAT3-HIES may persist or arise following HSCT and can precipitate life-threatening complications. This has implications for counseling and vascular surveillance, and highlights the need for further studies to determine the risk, pathogenesis, and optimal management of the vasculopathy associated with STAT3-HIES.

Stress Dissipation in Cucurbit[8]uril Ternary Complex Small Molecule Adhesives.

The ability to control supramolecular and macroscopic self-assembly and disassembly holds great potential for responsive, reversible adhesives that can efficiently broker stresses accumulated between two surfaces. Here, cucurbit[8]uril is used to directly adhere two functionalized mica substrates creating surface-surface interactions that are held together through photoreversible CB[8] heteroternary complexes. Comparison of single-molecule, bulk, and macroscopic adhesion behavior give insight into cooperativity and stress dissipation in dynamic adhesive systems.

Comparison of the Performance of Skin Prick, ImmunoCAP, and ISAC Tests in the Diagnosis of Patients with Allergy.

BACKGROUND: Allergy is diagnosed from typical symptoms, and tests are performed to incriminate the suspected precipitant. Skin prick tests (SPTs) are commonly performed, inexpensive, and give immediate results. Laboratory tests (ImmunoCAP) for serum allergen-specific IgE antibodies are usually performed more selectively. The immuno-solid phase allergen chip (ISAC) enables testing for specific IgE against multiple allergen components in a multiplex assay. METHODS: We retrospectively analysed clinic letters, case notes, and laboratory results of 118 patients attending the National Adult Allergy Service at the University Hospital of Wales who presented diagnostic difficulty, to evaluate which testing strategy (SPT, ImmunoCAP, or ISAC) was the most appropriate to use to confirm the diagnosis in these complex patients, evaluated in a "real-life" clinical service setting. RESULTS: In patients with nut allergy, the detection rates of SPTs (56%) and ISAC (65%) were lower than those of ImmunoCAP (71%). ISAC had a higher detection rate (88%) than ImmunoCAP (69%) or SPT (33%) in the diagnosis of oral allergy syndrome. ImmunoCAP test results identified all 9 patients with anaphylaxis due to wheat allergy (100%), whereas ISAC was positive in only 6 of these 9 (67%). CONCLUSIONS: In this difficult diagnostic group, the ImmunoCAP test should be the preferred single test for possible allergy to nuts, wheat, other specific foods, and anaphylaxis of any cause. In these conditions, SPT and ISAC tests give comparable results. The most useful single test for oral allergy syndrome is ISAC, and SPT should be the preferred test for latex allergy.

Single-Molecule Force Spectroscopy Quantification of Adhesive Forces in Cucurbit[8]Uril Host-Guest Ternary Complexes.

Cucurbit[8]uril (CB[8]) heteroternary complexes display certain characteristics making them well-suited for molecular level adhesives. In particular, careful choice of host-guest binding pairs enables specific, fully reversible adhesion. Understanding the effect of the environment is also critical when developing new molecular level adhesives. Here we explore the binding forces involved in the methyl viologen·CB[8]·naphthol heteroternary complex using single-molecule force spectroscopy (SMFS) under a variety of conditions. From SMFS, the interaction of a single ternary complex was found to be in the region of 140 pN. Additionally, a number of surface interactions could be readily differentiated using the SMFS technique allowing for a deeper understanding of the dynamic heteroternary CB[8] system on the single-molecule scale.

Synthesis of Conducting Polymer-Metal Nanoparticle Hybrids Exploiting RAFT Polymerization.

The direct covalent attachment of conducting polymers (CP) to nanoparticles (NP) to form CP-NP nanohybrids is of great interest for optoelectronic device applications. Hybrids formed by covalently anchoring CP to NP, rather than traditional blending or bilayer approaches, is highly desirable. CP-NP nanohybrids have increased interfacial surface area between the two components, facilitating rapid exciton diffusion at the p-n heterojunction. These materials take advantage of the facile solution processability, lightweight characteristics, flexibility, and mechanical strength associated with CPs, and the broad spectral absorption, photostability, and high charge carrier mobility of NPs. We demonstrate the ability to polymerize a hole transporting (HT) polymer utilizing reversible-addition-fragmentation chain transfer (RAFT) polymerization and its subsequent rapid aminolysis to yield a thiol-terminated HT polymer. Subsequent facile attachment to gold (Au) and silver (Ag) NPs and cadmium selenide (CdSe) quantum dots (QDs), to form a number of CP-NP systems is demonstrated and characterized. CP-NP nanohybrids show broad spectral absorptions ranging from UV through visible to the near IR, and their facile synthesis and purification could allow for large scale industrial applications.

Correlation between CD8+ T cells specific for prostate-specific antigen and level of disease in patients with prostate cancer.

Modest work has been performed to improve the sensitivity of residual disease detection or investigate the contribution that the immune system makes in controlling metastatic tumor growth, in particular, the frequency and biological actions of peptide-specific CD8+ T lymphocytes in limiting metastatic disease and/or maintaining remission. Fifty-three peripheral blood samples from 32 prostate cancer (PC) patients were investigated for the presence of circulating prostate-specific antigen (PSA)-expressing cells (CPECs) using a highly sensitive and specific assay combining immunomagnetic epithelial cell enrichment with nested RT-PCR of PSA mRNA. Using HLA-A2 tetramer complexes, frequency of CD8+ T cells specific for PSA-derived peptides was determined. Additionally, serum concentrations of PSA and testosterone were measured. CPECs were detected in 26% of peripheral blood samples from PC patients. CD8+ T cells specific for PSA-derived peptides were detected at low frequency in HLA-A2-positive PC patients. The correlation between these PSA-specific CD8+ T cells and residual prostate tumor cells and clinical measures was investigated. Our data suggest that frequency of PSA-specific CD8+ T cells is correlated to CPECs, but not to serum PSA level.

Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer.

Induction of CTL responses specific for prostate-specific antigen (PSA)-derived peptides in healthy individuals and patients with prostate cancer (PC) was investigated. Eight PSA-derived peptides that have the potential to bind HLA-A2 molecules were examined. Peripheral blood lymphocytes isolated from HLA-A2-positive volunteers were expanded using autologous mature, PSA-derived peptide-pulsed dendritic cells. The expansion of IFN-gamma-secreting CD8+ T cells specific for three of the eight PSA-derived peptides (PSA-2(108-117), PSA-4(141-150) and PSA-6(146-154)) was detected in healthy individuals, but not in patients with PC. Using HLA-A2/peptide tetramers, the PSA-specific CD8+ T cells were detectable at low frequency both in healthy individuals and patients with PC. Using flow cytometric cytotoxicity assays, the expanded effectors from healthy individuals were able to kill the PSA-expressing epithelial cell line LNCaP and the peptide-pulsed T2 cells in a MHC class I-restricted manner without involving NK activity. However, such killing by effectors expanded from prostatectomized patients involved a complete or a significant NK activity. Specific recognition of PSA-derived peptides in healthy individuals may occur by an adaptive CTL immune response, while such recognition in PC patients may additionally or alternatively be mediated by an innate NK immune response. In conclusion, our work indicates that the PSA-specific CD8+ T cells exist in both healthy individuals and PC patients, but they have impaired function in patients as they failed to release IFN-gamma and to kill targets without involving NK activity.

Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells.

There is growing interest in the in vitro generation of dendritic cells (DC) from peripheral blood monocytes, but the effect of the method chosen to isolate CD14+ monocytes for subsequent DC generation is poorly documented. The method used to isolate monocytes may have an impact on the subsequent function of DC by affecting their ability to express costimulatory molecules (CD80/86), maturation marker (CD83) and/or to produce important immunomodulatory cytokines. In this study, we show that the positive selection of monocytes by anti-CD14-coated microbeads inhibits the lipopolysaccharide (LPS)-induced production of interleukin (IL)-12, IL-10 and tumour necrosis factor-alpha (TNF-alpha) from human DC. However, when DC were grown from monocytes isolated by plastic adherence, LPS induced the production of much higher levels of these cytokines. DC derived from adherence-isolated monocytes induced the development of potent cytotoxic T lymphocytes of the Tc1 subset specific for influenza matrix protein, as confirmed by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT), cytotoxicity assay, major histocompatibility complex (MHC)-peptide tetrameric complexes and T helper 1/T helper 2 (Th1/Th2) cytokine production assays.