Effect of interferon treatment on serum 2',5'-oligoadenylate synthetase levels in hepatitis C-infected patients

Interferon (IFN) is widely used for patients with hepatitis C. Less than half of treated patients respond to IFN therapy, however, and increased resistance to IFN is particularly observed in genotype 1b patients. Recently, genotype 1b patients with the wild type sequence in the NS5A gene were shown to be resistant to therapy, suggesting that the NS5A protein may be involved to IFN resistance. Thus, we investigated the serum 2',5'-oligoadenylate synthetase (2',5'-OAS) levels before and during IFN treatment. In addition, other biochemical markers and NS5A mutations were also examined in 30 HCV genotype 1b-positive patients. Before IFN treatment, 2',5'-OAS activity in sera was significantly lower in wild type patients than in mutant type patients. All patients were subsequently enrolled in IFN therapy, and 2',5'-OAS activity was elevated both in wild and mutant type patients, irrespective of the number of mutations in NS5A. Logistic regression analysis revealed that clearance of serum HCV RNA was independently related to the pretreatment viral load and NS5A mutations, but not to serum 2',5'-OAS activity. We concluded that the NS5A protein, that is associated with the outcome of IFN therapy, affects the kinetics of IFN-induced molecules, such as 2', 5'-OAS. 2',5'-OAS activity does not, however, seem to be related to long-term virological response to IFN therapy.     

Involvement of interleukin-1-like factor(s) in type II collagen-induced arthritis in mice

To explore the role of interleukins in development of arthritis, we induced collagen-induced arthritis in mice and examined interleukin activities in the inflamed joints. Arthritis developed in 90% of mice 4-5 weeks after primary immunization with type II collagen. Joint extracts from mice with collagen-induced arthritis contained high levels of interleukin 1 (IL-1)-like activity but not interleukin 2 (IL-2) or interleukin 4 (IL-4) activity. IL-1-like activities in the lesions were correlated with development of arthritis assessed by joint swelling and erythema. These results suggest that IL-1-like factor(s) may participate in the etiopathogenesis of collagen-induced arthritis in mice.     

Xanthic variant of non-ossifying fibroma (so-called xanthofibroma) of the mandible. An ultrastructural study

An unusual case of a 37-year-old female with xanthomatous bone tumor of the right molar area of the mandible was presented. The tumor was asymptomatic and found to be a well-demarcated intraosseous radiolucent lesion on radiographic examination. Histologically the tumor consisted of two cell types, fibroblastic and xanthomatous cells. There was no osteoid, bone or cartilage formation. However, numerous psammomatous calcified bodies were seen in the fibrous area. Ultrastructural study showed fibroblastic cells in different stages of proliferation as the basis of the tumor which transform itself into xanthomatous cells. From the clinicopathologic findings, our case was thought to be a xanthic variant of non-ossifying fibroma (so-called xanthofibroma) of the mandible.     

Structure of the functional interleukin-2 receptor: Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line

The structural basis of the high affinity interleukin-2 receptorwhich was previously reconstituted in a cultured murine T cellline, EL4 by expressing either wild-type Tac antigen complementaryDNA (cDNA) or a chimeric cDNA was characterized. The chimericcDNA encodes a membrane portion whose extracellular portionconsists of that of Tac antigen whereas transmembrane and cytoplasmicportions consists of those the human insulin beta chain. TheTac antigen/anti-Tac antibody complex was treated by chemicalcrosslinking reagents, purified by goat anti-mouse immunoglobulin(lg), and was analysed by SDS–PAGE. We here demonstrated the presence in mouse EL4 transfectantsof a novel membrane protein which is closely associated withthe products of transfected cDNAs in the absence of interleukln-2.The protein is 75 kDa in size and is detected in cells whichexpress high affinity interieukln-2 receptor but not in cellswhich only express low affinity interleukin-2 receptor. Thetransmembrane region and the cytoplasmic region of Tac antigenis not necessary for the formation of the complex consistingof Tac antigen and 75 kDa molecule, indicating that a murine75 kDa molecule associates with Tac antigen extra-cellularly.     

Porphyromonas gingivalis Fimbriae Use β2 Integrin (CD11/CD18) on Mouse Peritoneal Macrophages as a Cellular Receptor, and the CD18 β Chain Plays a Functional Role in Fimbrial Signaling

In this study, we demonstrate that Porphyromonas gingivalis fimbriae use molecules of β₂ integrin (CD11/CD18) on mouse peritoneal macrophages as cellular receptors and also show that the β chain (CD18) may play a functional role in signalling for the fimbria-induced expression of interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) genes in the cells. Using a binding assay with ¹²⁵I-labeled fimbriae, we observed that fimbrial binding to the macrophages was inhibited by treatment with CD11a, CD11b, CD11c, or CD18 antibody but not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of β₂ integrin (CD11/CD18) on the macrophages. Furthermore, Northern blot analyses showed that the fimbria-induced expression of IL-1β and TNF-α genes in the cells was inhibited strongly by CD18 antibody treatment and slightly by CD11a, CD11b, or CD11c antibody treatment. Interestingly, intracellular adhesion molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial binding to the cells in a dose-dependent manner. In addition, ICAM-1 clearly inhibited the fimbria-induced expression of IL-1β and TNF-α genes in the cells. However, such inhibitory action was not observed with laminin treatment. These results suggest the importance of β₂ integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism in periodontal disease.     

Ingestion of High β-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects

The prebiotic effect of high β-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.     

The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study

Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The ¹³C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant’s Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.     

Characteristics affecting cervical sagittal alignment in patients with chronic low back pain

BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ