Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p < 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p < 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD

Remaining structures at the N- and C-terminal regions of alpha-synuclein accurately elucidated by amide-proton exchange NMR with fitting

AbstractAlpha-synuclein is analyzed in physiological conditions by CLEANEX-PM methodology, in which the amide-proton exchange can be monitored at millisecond scale. The relationship between kex and [OH]− is confirmed as a linear correlation with slope 1, indicating EX2 regime. There are significant residual structures at the N- and C-terminal regions. The structure at the C-terminal region is more stable than that of the N-terminal region. The middle part including NAC region is not completely protected. The data acquired at various pH and mixing time conditions followed by linear fitting give accurate information about residual structures

PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders

Background Most patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) show diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX-LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL-type MTX-LPD. In this study, we examined whether programmed cell death-ligand 1 (PD-L1) expression levels were associated with the prognosis of MTX-LPD after MTX discontinuation. Methods A total of 72 Japanese patients diagnosed with MTX-LPD were clinicopathologically analyzed, and immunohistochemical staining of PD-L1 was performed in 20 DLBCL-type and 24 CHL-type MTX-LPD cases to compare with the clinical course. Results PD-L1 was expressed in 5.0% (1/20) of patients with DLBCL-type MTX-LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL-type MTX-LPD in more than 51% of tumor cells. Most CHL-type MTX-LPD patients with high PD-L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD-L1 high- and low-expression CHL-type MTX-LPD. Conclusion PD-L1 expression was significantly higher in patients with CHL-type than DLBCL-type MTX-LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL-type MTX-LPD patients to achieve complete remission. No association was observed between PD-L1 expression levels and clinical findings at diagnosis, suggesting that PD-L1 expression in tumor cells influences the pathogenesis of CHL-type MTX-LPD after MTX discontinuation

On-chip, High-sensitivity Temperature Sensors Based on Dye-doped Solid-state Polymer Microring Lasers

We developed a chip-scale temperature sensor with a high sensitivity of 228.6 pm/°C based on a rhodamine 6G (R6G)-doped SU-8 whispering-gallery mode microring laser. The optical mode was largely distributed in a polymer core layer with a 30 μm height that provided detection sensitivity, and the chemically robust fused-silica microring resonator host platform guaranteed its versatility for investigating different functional polymer materials with different refractive indices. As a proof of concept, a dye-doped hyperbranched polymer (TZ-001) microring laser-based temperature sensor was simultaneously developed on the same host wafer and characterized using a free-space optics measurement setup. Compared to TZ-001, the SU-8 polymer microring laser had a lower lasing threshold and a better photostability. The R6G-doped SU-8 polymer microring laser demonstrated greater adaptability as a high-performance temperature-sensing element. In addition to the sensitivity, the temperature resolutions for the laser-based sensors were also estimated to be 0.13 °C and 0.35 °C, respectively. The rapid and simple implementation of micrometer-sized temperature sensors that operate in the range of 31 – 43 °C enables their potential application in thermometry

Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers

<p>Abstract</p> <p>Background</p> <p>The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels.</p> <p>Methods</p> <p>We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS).</p> <p>Results</p> <p>In subjects with BMI below 25 kg/m², both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m², smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS.</p> <p>Conclusions</p> <p>Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than non-smokers.</p

Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Drug resistance is a major problem in cancer chemotherapy. Acquisition of chemo-resistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patient's quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems.</p> <p>Result</p> <p>To investigate the mechanisms of drug resistance, a set of cell lines with different levels of sensitivity and possessing different mechanisms of resistance to 5-fluorouracil (5-FU) was established from a colorectal cancer cell line. The expression of thymidylate synthase, orotic acid phosphoribosyltransferase and dihydropyrimidine dehydrogenase, which are well known to be related to drug resistance, differed among these cell lines, indicating that these cell lines acquired different resistance mechanisms. However, swainsonine, an inhibitor of N-glycan biosynthesis, reduced 5-FU-tolerance in all resistant cells, whereas the sensitivity of the parental cells was unchanged. Further analysis of the N-glycan profiles of all cell lines showed partial inhibition of biosynthesis and no cytotoxicity at the swainsonine dosage tested.</p> <p>Conclusion</p> <p>These observations suggest that N-linked oligosaccharides affect 5-FU resistance more widely than do drug-resistance related enzymes in colorectal cancer cells, and that the N-glycan could be a universal target for chemotherapy. Further, swainsonine may enhance the performance of chemotherapy by reducing tolerance.</p

Development and validation of a new scoring system for prognostic prediction of community-acquired pneumonia in older adults

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1, 158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607–0.732) and 0.809 (95% confidence interval, 0.751–0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP

Central airway and peripheral lung structures in airway disease dominant COPD

The concept that the small airway is a primary pathological site for all COPD phenotypes has been challenged by recent findings that the disease starts from the central airways in COPD subgroups and that a smaller central airway tree increases COPD risk. This study aimed to examine whether the computed tomography (CT)-based airway disease-dominant (AD) subtype, defined using the central airway dimension, was less associated with small airway dysfunction (SAD) on CT, compared to the emphysema-dominant (ED) subtype. COPD patients were categorised into mild, AD, ED and mixed groups based on wall area per cent (WA%) of the segmental airways and low attenuation volume per cent in the Kyoto–Himeji (n=189) and Hokkaido COPD cohorts (n=93). The volume per cent of SAD regions (SAD%) was obtained by nonrigidly registering inspiratory and expiratory CT. The AD group had a lower SAD% than the ED group and similar SAD% to the mild group. The AD group had a smaller lumen size of airways proximal to the segmental airways and more frequent asthma history before age 40 years than the ED group. In multivariable analyses, while the AD and ED groups were similarly associated with greater airflow limitation, the ED, but not the AD, group was associated with greater SAD%, whereas the AD, but not the ED, group was associated with a smaller central airway size. The CT-based AD COPD subtype might be associated with a smaller central airway tree and asthma history, but not with peripheral lung pathologies including small airway disease, unlike the ED subtype