Single nucleotide variations in genes associated with innate immunity are enriched in Japanese adult cases of face and neck type atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is heterogenous in terms of phenotype as well as genetic and environmental factors, while its associated genetic factors and pathophysiology are not fully understood. OBJECTIVE: We identify novel genetic factors enriched in a subgroup of AD patients with characteristic clinical features. METHODS: We clinically subgrouped 18 AD patients who exhibited distinctive characteristic of persistent skin eruption areas on the face and neck from 92 Japanese adult AD patients and identified disease-associated genetic factors enriched within the subgroup. Targeted resequencing and subsequent genetic association analyses were used to identify novel enriched genetic variations in the subgroup compared with the other AD patients. RESULTS: Targeted resequencing of 648 skin associated genes revealed an enrichment of 12 single nucleotide variations (SNVs) in patients with face and neck AD (n = 18) compared with the general Japanese population in the database. Subsequent allele frequency comparison between the face and neck AD and non - face and neck AD subgroups revealed enrichment of five SNVs. Multivariate analysis using genotype data revealed that three SNVs in theTLR1, TIRAP, and PSAPL1 genes, two of the three genes are involved in the Toll-like receptor pathway, were significantly enriched in patients with face and neck AD. CONCLUSION: These findings revealed that the SNVs in genes associated with the innate immune pathway are enriched in a subgroup of AD. The combinational approach of clinical subgrouping and genotyping is valuable for detecting novel disease-associated genetic factors.

Hypocomplementemic cutaneous small vessel vasculitis in a patient with IgG4-related disease.

A 62-year-old man was diagnosed with IgG4-related disease based on multiple sites of lymphadenopathy, lymph node biopsy, and elevated serum levels of IgG4. Hypocomplementemia was also observed. During admission, he was referred to our department complaining of multiple areas of purpura on the lower legs. Histological examination revealed leukocytoclastic vasculitis with fibrinoid necrosis, neutrophil infiltration, and nuclear dust in the upper dermis. To date, only a few cases of cutaneous vasculitis have been reported in IgG4-related disease, all of which showed hypocomplementemia. The role of IgG4 in the etiology of leukocytoclastic vasculitis in IgG4-related disease remains unknown and further studies are necessary.

Diagnostic value of ultrasonography in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome: A case report.

RATIONALE: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare condition that affects the skin, bones, and joints. Diagnosis of SAPHO syndrome is established based on clinical manifestations and imaging features on radiography or magnetic resonance imaging. PATIENT CONCERNS: We report a 44-year-old male with a 20-year history of pustulosis who presented with pain in the lower extremities. Plain radiography demonstrated hyperostosis with subperiosteal erosions in the right tibia. Magnetic resonance imaging and computed tomography showed inflammatory accumulation, whereas musculoskeletal ultrasonography clearly depicted a periosteal reaction, osteitis, and enthesitis with abnormal blood flow in the surface of the right tibia. DIAGNOSES: A diagnosis of SAPHO syndrome was made. INTERVENTIONS: The patient was treated with combination therapy comprising prednisolone, methotrexate, and infliximab, which resulted in clinical improvement. OUTCOMES: The elevated levels of C-reactive protein and matrix metalloproteinase-3 normalized, and the abnormal ultrasonographic findings disappeared. LESSONS: The present case report demonstrates that multiple imaging modalities are important for the definitive diagnosis of SAPHO syndrome. Ultrasonography might be a useful tool for evaluating local musculoskeletal inflammation in patients with SAPHO syndrome.

The utility of FDG-PET/CT imaging in the evaluation of multicentric reticulohistiocytosis: A case report.

INTRODUCTION: Multicentric reticulohistiocytosis (MRH) is a rare histiocytic disorder that involves the skin, joints, and visceral organs. CASE PRESENTATION: We report a 67-year-old woman with MRH who presented with a 2-years history of polyarthralgia and skin nodules. Her symptoms were an inflammatory polyarthropathy with punched-out lesions of the distal interphalangeal (DIP) joints of both hands. Doppler ultrasonography of the hands showed large bone erosions with power Doppler signals in the DIP joints. F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated increased FDG uptake in cutaneous papules surrounding the affected joints, suggesting an inflammatory process. There was no evidence of malignancy. Biopsy samples of skin nodules exhibited dermal infiltration with CD68-positive histiocytes and multinucleated giant cells. The patient was diagnosed with MRH and treated with combination therapy comprising a steroid (prednisolone), tacrolimus, methotrexate, and infliximab, which resulted in clinical improvement. Following infliximab treatment, there was a significant decrease in a bone resorption marker (tartrate-resistant acid phosphatase 5b: TRACP-5b), suggesting that tumor necrosis factor-α targeting therapy may inhibit osteoclast formation and resorption activity in patients with MRH. CONCLUSION: MRH is a progressive destructive arthritic condition, and early diagnostic and therapeutic strategies are necessary to improve the outcome. FDG-PET/CT and joint ultrasonography might be noninvasive imaging modalities that could help diagnose MRH.

Evaluation of histopathological findings at the injection site following degarelix administration.

PURPOSE: The aims of the present study were to investigate the incidence of injection site reactions (ISRs) following administration of 240 mg degarelix and identify the risk factors for ISRs. METHODS: This study was conducted in 50 consecutive men treated with degarelix for the first time. ISRs after an initial degarelix dose of 240 mg (administered subcutaneously as two 3 ml subcutaneous injection) were evaluated using the five categories of the Common Terminology Criteria for Adverse Events Version 4 of the National Cancer Institute. We also assessed the differences in patient background between patients with and without an ISR. RESULTS: The mean age of patients and prostate-specific antigen (PSA) level just before degarelix administration were 75.6 and 198.4 ng/ml, respectively. Hormonal therapy with degarelix was administered for the first time to 33 patients; 11 of the 50 patients were receiving an oral steroid, 6 for prostate cancer, 1 for hematological disease, and 4 for allergic conditions. ISRs were observed in 25 patients, and all of the ISRs were categorized as grade 1 or 2; however, 2 patients discontinued this procedure due to the ISR. Significant differences in the first experience with subcutaneous therapy (p = 0.007) and rate of combination with a steroid (p = 0.017) were observed between patients with and without ISRs. CONCLUSION: The incidences of ISRs in patients receiving subcutaneous therapy for the first time and in patients also receiving an oral steroid were 64 and 18 %, respectively. Patients should be provided with information concerning the possible occurrence of ISR due to degarelix prior to the administration, particularly patients who are not receiving steroids and patients who have no experience with subcutaneous injections.

Cell-based in vivo dual imaging probes using genetically expressed tags and chemical contrast agents.

We report a method for specifically labelling the surface of cells with two kinds of chemical probes (near-infrared (NIR) fluorescent probes and magnetic resonance (MR) imaging probes) via two genetically expressed tags, and demonstrate the application for in vitro and in vivo dual imaging.

Review of molecular modification techniques for improved detection of biomolecules by mass spectrometry.

After a soft ionizing method was established, MS (mass spectrometry) has become a more common tool in biochemistry because soft ionization made it possible to detect large molecules such as proteins. Many kinds of applications were established to further utilize MS for the identification or quantitation of biomolecules. In this review, we introduce recent applications with special focus on chemical modification techniques and chemical probes developed for the MS determination of biomolecules.

Newly developed chemical probes and nano-devices for cellular analysis.

A cellular analyzing system including a "real-time cellular imaging system" and a "comprehensive analyzing system for cellular responses" was developed. A "real-time cellular imaging system" is a system used to measure real-time imaging of multiple phenomena of a single cell with high special and temporal resolutions for the purpose to understand the pathology and physiology in a single cell and realize to single cell level diagnosis. A "real-time cellular imaging system" includes multi-probe imaging with AFM (atomic force microscopy), optical and SECM (scanning electrochemical microscopy) modes, which provides us with topological information and biochemical reactions at the local area of the interior and exterior of a cell. Scanning electrochemical/optical microscopy was applied to image PC12 cells. On the other hand, cells respond to their specific substances via their ligands. Therefore, the comprehensive analysis of protein-protein interaction is the important issue to determine the functions of cells. For this purpose, a "comprehensive analysis system for cellular responses" was developed. This system is based on SPR (surface plasmon resonance) and MS (mass spectrometry) using a nano-fabricated substrate. The interaction between IL-1 beta and anti-IL-1 beta antibodies was detected.

Basic design and synthesis of sulfonated contrast agents for magnetic resonance imaging based on gadolinium complexes.

Magnetic resonance angiography (MRA) is an imaging method to examine blood vessels based on the magnetic resonance imaging (MRI) technique. For this purpose, blood pool contrast agents have been developed to selectively increase the signal intensity of the intravascular lumen for improvement of the contrast-to-noise ratio in MR images. Here, we describe the design and the syntheses of six novel sulfonated contrast agents (KMR-Sulfo1 - 6), their chemical properties and their in vivo applications. In this study, we investigated the lipophilicity and the hydrophilicity of a gadolinium complex using a convenient two-step synthesis route, with the goal of prolonging the plasma half-life by binding mainly to human serum albumin. We confirmed that KMR-Sulfo5 fulfilled the requirements as a blood pool contrast agent: it showed a sufficient relaxivity r(1) of 5.9 mM(-1) s(-1), a long plasma half-life of 25.7 min and complete elimination from the body within 12 h after the administration.

MPAI (mass probes aided ionization) method for total analysis of biomolecules by mass spectrometry.

We have designed and synthesized various mass probes, which enable us to effectively ionize various molecules to be detected with mass spectrometry. We call the ionization method using mass probes the "MPAI (mass probes aided ionization)" method. We aim at the sensitive detection of various biological molecules, and also the detection of bio-molecules by a single mass spectrometry serially without changing the mechanical settings. Here, we review mass probes for small molecules with various functional groups and mass probes for proteins. Further, we introduce newly developed mass probes for proteins for highly sensitive detection.

Anesthetic management of a patient with a history of Batista procedure for dilated cardiomyopathy undergoing gastric surgery.

We experienced anesthetic management for an operation to remove a hemorrhagic gastric submucosal tumor in a patient who had undergone left ventricular volume reduction (the Batista procedure) for dilated cardiomyopathy (DCM) 2 years previously. Preoperative evaluations indicated the relapse of severe DCM. Intravenous and epidural anesthesia was employed with the aid of an intraaortic balloon pump (IABP). Safe anesthetic management was achieved under the guidance of a Swan-Ganz catheter without inducing overreduction of afterload or excessive preload.

Mass probe-assisted ionization method for total analysis of biomolecules with electrospray ionization-mass spectrometry.

In this paper, we review the mass probes used for the derivation of a variety of biomolecules efficiently detected by the electrospray ionization-mass spectrometry and mass probe-assisted ionization method for total analysis and determination by consecutive detection with a single instrument. We describe mass probes for a variety of molecules including proteins, nucleobases, metallic cations, and other small molecules.

Improved method of the MALDI-TOF analysis of DNA with nanodot sample target plate.

We report a new sample target plate for MALDI-TOF mass spectrometry made of SiO2 with 30 nm Pt dots for which a highly reproducible and improved DNA analysis was achieved.

Vaccination with an immunodominant peptide of bovine type II collagen induces an anti-TCR response, and modulates the onset and severity of collagen-induced arthritis.

T cell responses directed toward TCR-derived peptides have been shown to be an important regulatory mechanism of protection against autoimmunity. Here, we show that a naturally induced TCR-directed immune response can delay the onset of collagen-induced arthritis (CIA), an animal model of autoimmune rheumatoid arthritis in humans. DBA/1 mice were pretreated with an immunodominant peptide, p245-270, from bovine type II collagen (bCII) and were subsequently immunized with whole bCII for the induction of arthritis. The results showed that preactivation of p245-270-reactive cells delayed the onset and reduced the severity of CIA, compared with animals in the control group. Interestingly, the serum antibody response to bCII and the bCII-specific cytokine were not affected under these conditions. This result indicates that the observed protection was neither directly due to a lower antibody response nor due to the immune deviation of the anti-bCII T cell response. Furthermore, immunization with p245-270, but not bCII, induced a strong response to the B5 peptide, an immunodominant region of the TCR V(beta)8.2 (amino acids 76-101) that binds very strongly to I-A(q). These data suggest that at a critical phase in the loss of self-tolerance, an effective anti-TCR response, induced naturally, can regulate the pathogenic autoimmune response and thus may provide protection against autoimmunity.

Design and synthesis of labeling reagents (MS probes) for highly sensitive electrospray ionization mass spectrometry and their application to the detection of carbonyl, alcohol, carboxylic acid and primary amine samples.

Novel labeling reagents, called MS probes, which possess a positively charged quaternary amine moiety and can transform a neutral analyte into a charged compound by simply mixing with the analyte and allowing the mixture to stand from several minutes to 30 min at room temperature or while heating to 50 degrees C, were designed and synthesized for the highly sensitive detection of carbonyl, alcohol, carboxylic acid and primary amine samples by electrospray ionization mass spectrometry (ESI-MS). The positively charged products can be detected with high sensitivity in an ESI-MS system, which is the most popular liquid MS instrument. All of the labeled products showed a remarkably large increase in the molecular-ion peak abundance detection sensitivity of over 500-fold at picomolar concentration levels compared to that of unlabeled analytes in an ESI-MS system. These MS probes, used together with liquid MS detection, are widely applicable as a convenient method for the highly sensitive detection of less than picomolar levels of analytes, and therefore greatly enhance the power of ESI-MS analysis.