Correlation between circulating fibrocytes, and activity and progression of interstitial lung diseases

Background and objective: Interstitial lung diseases (ILD) are characterized by progressive interstitial pulmonary fibrosis and a decline in lung function. Fibrocytes are bone marrow‐derived mesenchymal progenitor cells that may play a role in the pathogenesis of pulmonary fibrosis. Circulating fibrocyte numbers have been correlated with the prognosis of patients with idiopathic pulmonary fibrosis. The aim of the present study was to evaluate the relationship between circulating fibrocytes, and parameters of disease activity and progression in several groups of patients with ILD. Methods: The study population comprised 41 patients with ILD and seven healthy control subjects. Circulating CD45⁺ collagen‐I⁺ fibrocytes were evaluated by flow cytometry. Results: The number of circulating fibrocytes was significantly increased in all patients with ILD and particularly in patients with idiopathic interstitial pneumonitis and interstitial pneumonitis associated with collagen vascular disease as compared with healthy control subjects. The numbers of circulating fibrocytes were significantly correlated with pulmonary function test parameters and with serum levels of sialylated carbohydrate antigen, a marker of disease activity. Temporal changes in circulating fibrocyte numbers were evaluated in two patients, and the results suggested that these changes correlated with the activity of ILD. Conclusions: The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.     

Synthesis of New RE3+ Doped Li1+xTa1?xTixO3 (RE: Eu,Sm, Er,Tm, and Dy) Phosphors with Various Emission Colors

New phosphors with various emission colors for RE³⁺ doped Li_1+xTa_1−xTi_xO₃ (LTT) (RE: Eu, Sm, Er, Tm, and Dy) were synthesized by electric furnace at 1423 K for 15 h. The microstructure of the host material and the photoluminescence (PL) property were determined and compared to those of RE³⁺ doped Li_1+xNb_1−xTi_xO₃ (LNT)_. In the LTT phosphor, the highest PL intensity was achieved for the mixture composition Li_1.11Ta_0.89Ti_0.11O₃ with a LiTaO₃ structure, although it has an M-phase superstructure. In the LTT host material, the effective activators were Eu³⁺ and Sm³⁺ ions, in contrast to the LNT host material. Here, we discuss the relationship between PL property and the host material’s structure.     

Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients

Background

Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients.

Methods

A total of 201 PegIFN-na?ve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180?μg) or PegIFNα-2b (60–150?μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene (rs8099917).

Results

PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P?=?0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19–15.50, and odds ratio 7.31; 95% CI 3.45–4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P?=?0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60?kg, women, and patients aged >60?years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively).

Conclusions

PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype.     

Transcatheter renal artery embolization improves lung function in patients with autosomal dominant polycystic kidney disease on hemodialysis

Background

Since 1996, transcatheter renal artery embolization (renal TAE) has been performed to reduce the volume of the kidneys in patients with autosomal dominant polycystic kidney disease (ADPKD) and complications of nephromegaly at our hospital. Respiratory dysfunction is often a serious problem in these patients before TAE.

Patients and methods

Between January 2006 and October 2008, renal TAE was performed and lung function testing [percent vital capacity (%VC) and percent forced expiratory volume in 1?s (%FEV_1.0)] was done by spirometry in 28 patients on maintenance hemodialysis who had respiratory symptoms.

Results

Renal volume was 6,330.5?±?3,126.5?cm³ (range 1,771–12,761?cm³) before TAE, and decreased significantly to 2,892.2?±?1,841.7?cm³ (range 622–6,961?cm³) by 12?months after TAE (p?=?0.0001). The percent decrease of renal volume at 12?months after TAE versus baseline was 45.6?±?14.6% (range 6.6–67.3%). %VC showed a significant increase from 95.9?±?14.8% (range 63–127%) before renal TAE to 100.1?±?11.7% (range 78–120%) at 12?months after TAE (p?<?0.01). %FEV_1.0 was also significantly increased from 87.9?±?15.0% (range 55–110%) before renal TAE to 92.5?±?14.4% (range 58.0–115.0%) at 12?months after TAE (p?<?0.01). The changes of VC (ΔVC%) and FEV_1.0 (ΔFEV_1.0%) both showed a significant positive correlation with the reduction of renal volume (Δ renal volume) (p?=?0.001 and p?=?0.004, respectively).

Conclusion

Since TAE not only led to a significant decrease of renal volume in ADPKD patients with nephromegaly, but also improved lung function (both %VC and %FEV_1.0), pulmonary dysfunction should be recognized as one of the extrarenal complications of ADPKD.     

RNAi suppression of rice endogenous storage proteins enhances the production of rice-based Botulinum neutrotoxin type A vaccine

Mucosal vaccines based on rice (MucoRice) offer a highly practical and cost-effective strategy for vaccinating large populations against mucosal infections. However, the limitation of low expression and yield of vaccine antigens with high molecular weight remains to be overcome. Here, we introduced RNAi technology to advance the MucoRice system by co-introducing antisense sequences specific for genes encoding endogenous rice storage proteins to minimize storage protein production and allow more space for the accumulation of vaccine antigen in rice seed. When we used RNAi suppression of a combination of major rice endogenous storage proteins, 13 kDa prolamin and glutelin A in a T-DNA vector, we could highly express a vaccine comprising the 45 kDa C-terminal half of the heavy chain of botulinum type A neurotoxin (BoHc), at an average of 100 μg per seed (MucoRice-BoHc). The MucoRice-Hc was water soluble, and was expressed in the cytoplasm but not in protein body I or II of rice seeds. Thus, our adaptation of the RNAi system improved the yield of a vaccine antigen with a high molecular weight. When the mucosal immunogenicity of the purified MucoRice-BoHc was examined, the vaccine induced protective immunity against a challenge with botulinum type A neurotoxin in mice. These findings demonstrate the efficiency and utility of the advanced MucoRice system as an innovative vaccine production system for generating highly immunogenic mucosal vaccines of high-molecular-weight antigens.     

Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats

Atrogin-1 and MuRF1, muscle-specific ubiquitin ligases, and autophagy play a role in protein degradation in muscles. We hypothesized that branched-chain amino acids (BCAAs) may decrease atrogin-1, MuRF1, and autophagy, and may have a protective effect on disuse muscle atrophy. To test this hypothesis, we selected hindlimb suspension (HS)–induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to investigate the effects of decreased muscle activity. Sprague-Dawley male rats were assigned to 4 groups: control, HS (14 days), oral BCAA administration (600 mg/[kg day], 22.9% l-isoleucine, 45.8% l-leucine, and 27.6% l-valine), and HS and BCAA administration. After 14 days of the treatment, muscle weights and protein concentrations, cross-sectional area (CSA) of the muscle fibers, atrogin-1 and MuRF1 proteins, and microtubule-associated protein 1 light chain 3 II/I (ratio of LC3 II/I) were measured. Hindlimb suspension significantly reduced soleus muscle weight and CSA of the muscle fibers. Branched-chain amino acid administration partly but significantly reversed the HS-induced decrease in CSA. Hindlimb suspension increased atrogin-1 and MuRF1 proteins, which play a pivotal role in various muscle atrophies. Branched-chain amino acid attenuated the increase in atrogin-1 and MuRF1 in soleus muscles. Hindlimb suspension significantly increased the ratio of LC3 II/I, an indicator of autophagy, whereas BCAA did not attenuate the increase in the ratio of LC3 II/I. These results indicate the possibility that BCAA inhibits HS-induced muscle atrophy, at least in part, via the inhibition of the ubiquitin-proteasome pathway. Oral BCAA administration appears to have the potential to prevent disuse muscle atrophy.     

Carcinosarcoma,an atypical subset of gallbladder malignancies

Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor. The patient was a woman in her 70s. Abdominal sonography revealed that the gallbladder lumen was half-filled by a large mass (maximum diameter, 68 mm) showing heterogeneous echogenicity slightly higher than that of bile. However, despite the large size of the mass, gallbladder shape was well-preserved. Considering the findings on computed tomography, cholecystectomy was performed under a diagnosis of gallbladder malignancy. Pathological examination revealed two types of malignant histology: a sarcomatous element of malignant spindle cells and a carcinomatous element of adenocarcinoma tissue. Foci of malignant cartilage and bone areas were also found sporadically. Accompanied by immunohistochemical examination, the mass was diagnosed as carcinosarcoma. The present case showed somewhat different imaging findings from those of ordinary gallbladder carcinoma. Carcinosarcoma should be considered when a well-preserved shape of the gallbladder is recognized along with protrusion of a large heterogeneously echogenic mass into and filling the gallbladder lumen.     

The radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation

Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders.