Radiofrequency ablation of very-early-stage hepatocellular carcinoma inconspicuous on fusion imaging with B-mode US: value of fusion imaging with contrast-enhanced US

Background/Aims

To determine the value of fusion imaging with contrast-enhanced ultrasonography (CEUS) and computed tomography (CT)/magnetic resonance (MR) images for percutaneous radiofrequency ablation (RFA) of very-early-stage hepatocellular carcinomas (HCCs) that are inconspicuous on fusion imaging with B-mode ultrasound (US) and CT/MR images.

Methods

This retrospective study was approved by our institutional review board and the requirement for informed consent was waived. Fusion imaging with CEUS using Sonazoid contrast agent and CT/MR imaging was performed on HCCs (<2 cm) that were inconspicuous on fusion imaging with B-mode US. We evaluated the number of cases that became conspicuous on fusion imaging with CEUS. Percutaneous RFA was performed under the guidance of fusion imaging with CEUS. Technical success and major complication rates were assessed.

Results

In total, 30 patients with 30 HCCs (mean, 1.2 cm; range, 0.6-1.7 cm) were included, among which 25 (83.3%) became conspicuous on fusion imaging with CEUS at the time of the planning US and/or RFA procedure. Of those 25 HCCs, RFA was considered feasible for 23 (92.0%), which were thus treated. The technical success and major complication rates were 91.3% (21/23) and 4.3% (1/23), respectively.

Conclusions

Fusion imaging with CEUS and CT/MR imaging is highly effective for percutaneous RFA of very-early-stage HCCs inconspicuous on fusion imaging with B-mode US and CT/MR imaging.     

Arginase activity in alternatively activated macrophages protects PI3Kp110δ deficient mice from dextran sodium sulfate induced intestinal inflammation

Alternatively activated or M2 macrophages have been reported to protect mice from intestinal inflammation, but the mechanism of protection has not been elucidated. In this study, we demonstrate that mice deficient in the p110δ catalytic subunit activity of class I phosphatidylinositol 3‐kinase (PI3Kp110δ) have increased clinical disease activity and histological damage during dextran sodium sulfate (DSS) induced colitis. Increased disease severity in PI3Kp110δ‐deficient mice is dependent on professional phagocytes and correlates with reduced numbers of arginase I⁺ M2 macrophages in the colon and increased production of inflammatory nitric oxide. We further demonstrate that PI3Kp110δ‐deficient macrophages are defective in their ability to induce arginase I when skewed to an M2 phenotype with IL‐4. Importantly, adoptive transfer of IL‐4‐treated macrophages derived from WT mice, but not those from PI3Kp110δ‐deficient mice, protects mice during DSS‐induced colitis. Moreover, M2 macrophages mediated protection is lost when mice are cotreated with inhibitors that block arginase activity or during adoptive transfer of arginase I deficient M2 macrophages. Taken together, our data demonstrate that arginase I activity is required for M2 macrophages mediated protection during DSS‐induced colitis in PI3Kp110δ‐deficient mice.     

Changes in Allergen Sensitization Over The Last 30 Years in Korea Respiratory Allergic Patients: A Single-Center

Purpose

Determining the culprit allergen is important for the diagnosis and management of allergic diseases. The skin prick test (SPT) has been widely used to identify culprit allergens. Skin reactivity to allergens has changed due to changes in lifestyle and outdoor environments. Therefore, the aim of the present paper was to examine changes in allergen sensitization in Korea.

Methods

We enrolled 1,135 patients with respiratory allergic diseases who were diagnosed at Severance Hospital from January 2010 to December 2011. SPTs were performed with inhalant allergens, and were compared to our previous studies of the SPTs in the 1980s and the 1990s.

Results

In the 2010s, the SPT positive rate of allergic rhinitis or allergic conjunctivitis was higher than asthma without allergic rhinitis or allergic conjunctivitis. The SPT positive rate was decreased by increments of age (P value <0.01). Skin reactivity to tree pollens was significantly increased to 36.4% in the 2010s from 19.0% in the 1990s and 8.8% in the 1980s. Among tree pollens, skin reactivity to oak (4.7%->14.4%), birch (7.1%->13.6%), alder (6.3%->13.4%) and pine (2.9%->14.3%) was significantly increased in the 2010s compared with the 1990s, respectively. Current skin reactivity to grass pollens (13.9%) and weed pollens (27.0%) has significantly decreased since the 1990s (20.3%, 40.9%, respectively). Skin reactivity to house dust mites showed no difference between the 1990s (55.2%) and the 2010s (55.6%). Skin reactivity to dog (27.3%->20.7%) and cockroach (25.3%->12.3%) have significantly decreased in the 2010s in comparison with the 1990s.

Conclusions

In light of the above results, we revealed the changes in skin reactivity to inhalant allergens that have occurred in Korean allergic patients over the past three decades. Since outdoor environmental factors such as the amount of pollen, global warming and plant distribution causes the changes in skin reactivity, further study and continuous close observation will be needed.     

Development of a Questionnaire for the Assessment of Quality of Life in Korean Children With Allergic Rhinitis

Purpose

Korean children have their own unique lifestyle based on their living environment and culture. This study aimed to develop a questionnaire to evaluate the quality of life in Korean children with allergic rhinitis.

Methods

After a preliminary survey, an initial questionnaire was developed. Questions were modified to be easily understood by young children aged 6 to 7 years. The modified questionnaire was tested on children aged 6 to 12 years old. Item scores, defined as the proportion of children whose answer score was 1 point or higher was multiplied by the average answer score of each question, were used to identify questions that have practical application to the quality of life in Korean children with allergic rhinitis. Differences in answer scores between children with allergic rhinitis and those who were healthy were assessed by a Wilcoxon rank-sum test. The relationship between nasal index scores and quality of life scores was determined by a Spearman rank order test.

Results

An initial questionnaire was composed of 21 items. We identified 19 questions with item scores above 0.5 in children with allergic rhinitis, many of which were related to nasal symptoms and 10 questions that were different between the allergic rhinitis group and the control group. The final questionnaire included the 10 questions that had both high item scores and a significant difference in the answer scores between the two groups.

Conclusions

The developed questionnaire is essential and practical for assessing discomfort related to the symptoms felt by Korean children with allergic rhinitis.     

Immunogenicity and antigenicity of Plasmodium vivax merozoite surface protein 10

Among the proteins involved in the invasion by merozoite, the glycosylphosphatidylinositol-anchored proteins (GPI-APs) are suggested as potential vaccine candidates because of their localization to apical organelles and the surface; these candidates are predicted to play essential roles during invasion. As a GPI-AP, Plasmodium vivax merozoite surface protein 10 (PvMSP-10) induces high antibody titers. However, such high antibody titers have shown no protective efficacy for animals challenged with P. vivax parasites in a previous study. To adequately evaluate the immunogenicity and further characterize PvMSP-10 in order to understand its vaccine potential, we assessed its immunogenicity by immunizing BALB/c mice with cell-free expressed recombinant PvMSP-10 protein. The antigenicity of MSP-10 was analyzed, and we found 42 % sensitivity and 95 % specificity using serum samples from P. vivax-infected Korean patients. The IgG1 and IgG3 were the predominant immunoreactive antibodies against PvMSP-10 in vivax patient sera, and IgG1 and IgG3 and Th1-type cytokines were predominantly secreted in PvMSP-10-immunized mice. We conclude that the immunogenicity and antigenicity of MSP-10 may serve as a potential vaccine against vivax malaria.     

Divergent and dynamic activity of endogenous retroviruses in burn patients and their inflammatory potential

Genes constitute ~ 3% of the human genome, whereas human endogenous retroviruses (HERVs) represent ~ 8%. We examined post-burn HERV expression in patients' blood cells, and the inflammatory potentials of the burn-associated HERVs were evaluated. Buffy coat cells, collected at various time points from 11 patients, were screened for the expression of eight HERV families, and we identified their divergent expression profiles depending on patient, HERV, and time point. The population of expressed HERV sequences was patient-specific, suggesting HERVs' inherent genomic polymorphisms and/or differential expression potentials depending on characteristics of patients and courses of injury response. Some HERVs were shared among the patients, while the others were divergent. Interestingly, one burn-associated HERV gag gene from a patient's genome induced IL-6, IL-1β, Ptgs-2, and iNOS. These findings demonstrate that injury stressors initiate divergent HERV responses depending on patient, HERV, and disease course and implicate HERVs as genetic elements contributing to polymorphic injury pathophysiology.     

Collagen-based fibrous scaffold for spatial organization of encapsulated and seeded human mesenchymal stem cells

Living tissues consist of groups of cells organized in a controlled manner to perform a specific function. Spatial distribution of cells within a three-dimensional matrix is critical for the success of any tissue-engineering construct. Fibers endowed with cell-encapsulation capability would facilitate the achievement of this objective. Here we report the synthesis of a cell-encapsulated fibrous scaffold by interfacial polyelectrolyte complexation (IPC) of methylated collagen and a synthetic terpolymer. The collagen component was well distributed in the fiber, which had a mean ultimate tensile strength of 244.6 ± 43.0 MPa. Cultured in proliferating medium, human mesenchymal stem cells (hMSCs) encapsulated in the fibers showed higher proliferation rate than those seeded on the scaffold. Gene expression analysis revealed the maintenance of multipotency for both encapsulated and seeded samples up to 7 days as evidenced by Sox 9, CBFA-1, AFP, PPARγ2, nestin, GFAP, collagen I, osteopontin and osteonectin genes. Beyond that, seeded hMSCs started to express neuronal-specific genes such as aggrecan and MAP2. The study demonstrates the appeal of IPC for scaffold design in general and the promise of collagen-based hybrid fibers for tissue engineering in particular. It lays the foundation for building fibrous scaffold that permits 3D spatial cellular organization and multi-cellular tissue development.     

VH gene usage and CDR3 analysis of B cell receptor in the peripheral blood of patients with PBC

We have analyzed the IgM, IgG and IgA BCR repertoire in PBC patients by means of quantitative RT-PCR and CDR3-spectratyping with immunoscope technology. PBMC from 35 PBC patients and 18 normal controls were analyzed. Quantitative B cell repertoire analysis of IgM from healthy donors showed the preferential usage of VH3a, VH3b and VH4 families. Very similar VH family usage was observed in IgM B cells from PBC patients. CDR3 spectratyping of IgM BCR rearrangements showed a Gaussian distribution for dominant VH families in control donors, and similar diversity was found for the VH3b family in PBC patients. In contrast, VH3a and VH4 families showed oligoclonal expansions in some patients. Quantitative B cell repertoire analysis of IgG and IgA did not reveal any difference in VH chain distribution in PBC patients as compared to the control donors. Immunoscope profiles of CDR3 length distribution showed several peak expansions in B cells from control donors, particularly for the VH3a and VH4 families. CDR3 length distribution profiles of IgG and IgA from PBC patients were oligoclonal too, with expansions throughout the various VH chains. However, no common expansions within the CDR3 region were found intraindividually between IgG, IgA and IgM, and between patients. In conclusion, immunoscope technology does provide, for the first time, a sensitive and rapid method for detailed immunoglobulin gene usage analysis in peripheral B cells from PBC patients. This study failed to demonstrate preferential B cell rearrangements in the blood of patients with PBC, but this technology may be more successful if applied to the analysis of compartmental B cells (i.e. liver infiltrating B cells).