Efficacy of Upper Gastrointestinal Endoscopic Examination to Identify Patients with Obstructive Sleep Apnea Syndrome: A Retrospective Cross-Sectional Study.

BACKGROUND/AIMS: Despite the high prevalence of obstructive sleep apnea syndrome (OSAS), most individuals are unaware of its diagnosis. We assessed whether an upper gastrointestinal (GI) endoscopy can accurately predict the incidence of OSAS. METHODS: After endoscopic evaluation of laryngo-pharyngeal collapse, a total of 154 subjects with laryngo-pharyngeal collapse and 52 control subjects underwent polysomnography. Based on the modified Fujita Classification, upper airway obstruction was classified into 3 different types: oropharyngeal, supraglottic and combined type, and associations between upper airway obstruction and OSAS were evaluated. RESULTS: Of 154 subjects with laryngo-pharyngeal collapse, 108 (70.1%) were diagnosed as OSAS, while only 4 (7.7%) control subjects were diagnosed as OSAS (p < 0.001). The sensitivity and specificity of endoscopic diagnosis were 96.4 and 51.1%, respectively. Oropharyngeal involvement was frequently found in 90.2% of the subjects (139/154). The severity of upper airway obstruction was significantly correlated with the apnea-hypopnea index score (r = 0.55, p < 0.001). A multivariate logistic regression analysis revealed that a male sex (OR 5.20; 95% CI 2.65-10.2, p < 0.001), body mass index ≥25 kg/m2 (OR 4.98; 95% CI 2.23-11.2, p = 0.02) and severe obstruction (OR 7.79; 95% CI 3.34-18.2, p < 0.001) were significant independent predictors of severe OSAS. CONCLUSION: A conventional upper GI endoscopic examination might be useful as a diagnostic modality for OSAS.

Lyn signaling to upregulate GANP is critical for the survival of high-affinity B cells in germinal centers of lymphoid organs.

Signals through BCR and costimulatory molecules play essential roles in selecting high-affinity B cells with Ig V-region mutations in the germinal centers (GCs) of peripheral lymphoid organs. Lyn-deficient (lyn(-/-)) mice show impaired BCR signal triggering for cell proliferation and GC formation, causing hyper-IgM, and display autoimmunity after aging. In this study, we demonstrate that Lyn-mediated signaling to upregulate GANP is essential for the survival of mature GC-like (mGC) B cells with high-affinity type BCR mutations upon Ag immunization. Transgenic ganp expression into lyn(-/-) mice did not recover the Lyn-deficient phenotype with regard to B cell differentiation, serum Igs, and impaired GC formation in spleens after immunization with nitrophenyl-chicken γ-globulin, but it markedly rescued cell survival of mGC B cells by suppressing DNA damage, thereby increasing the frequency of the Trp(33)-to-Leu mutation in the IgV(H)-186.2 region and affinity maturation of nitrophenyl-binding B cells. GANP may play a critical role in Lyn-mediated signaling for the selection of high-affinity B cells in peripheral lymphoid organs.

Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP.

Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint progression and cause resistance to various anti-cancer treatments. DNA damage occurs at actively transcribed genes during G1-phase in yeast cells that have a deficient mRNA export capacity. Here, we show that germinal center-associated nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA export, is indispensable for ensuring the stability of human genomic DNA and that GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells. Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease in the number of cells in S-phase, caused late apoptosis and necrosis in p53-insufficient cancer cells through both caspase-dependent and -independent mechanisms. siGanp effectively induced DNA damage leading to cell death in p53-insufficient cancer cells in vitro and protect the growth of cancer cells transplanted into immunocompromized mice, suggesting that siGanp has potential as a selective treatment for p53-insufficient cancer cells.

Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression.

The mitotic checkpoint is essential for maintaining genomic stability in differentiating B cells undergoing genetic alterations of the Ig gene. In this study, using real-time RT-PCR and in situ RNA hybridization, we demonstrated that MAD2 mRNA export is selectively regulated by Pcid2/Thp1. Pcid2 small interfering RNA induced a cell-cycle abnormality with increased apoptosis and polyploidy, as previously observed in MAD2-knockdown cells. Pcid2 small interfering RNA reduced MAD2 expression, but not the expression of other cell-cycle checkpoint proteins, such as MAD1 and BUBR1, or the cell-cycle-associated proteins, cyclin A, cyclin B1, and cyclin-dependent kinase 1. In mouse B lineage cells, Pcid2 transcripts appeared in a stage-dependent manner at high levels in bone marrow pre-B and immature B cells, and in spleen transitional 1 and follicular B cells, but at lower levels in pro-B, transitional 2, and marginal zone B cells, suggesting a stage-dependent requirement for MAD2 regulation. Cd19-cre-derived targeting of the Pcid2 gene induced a mature B cell deficiency in mice. These findings indicate that Pcid2 is essential for B cell survival through the regulation of MAD2 expression during B cell differentiation.

Clinical impact of a strategy involving endoscopic submucosal dissection for early gastric cancer: determining the optimal pathway.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a technique developed to enable the endoscopic resection (ER) of large and ulcerative neoplastic lesions that were previously unresectable using conventional endoscopic mucosal resection (EMR). We investigated the clinical outcomes of ER of early gastric cancer (EGC) before and after the introduction of ESD, with particular attention to surgery and its potential consequences. METHODS: We reviewed 2,785 consecutive surgical patients with EGC and 2,469 consecutive lesions treated by ER with curative intent between 1990 and 2005. The study was divided into an EMR period (1990-1999) and an ESD period (2000-2005). We analyzed the clinical outcomes of endoscopic and surgical resections and defined 'potentially avoidable surgery' as cases of surgery performed for lesions curable by ER. RESULTS: The rate of potentially avoidable surgery was 3.8% (52/1,369) in the EMR period and 0.2% (3/1,416) in the ESD period (P < 0.001). For ER patients, the rate of overall non-curative ER was 36.9% (154/417) in the EMR group and 17.0% (348/2,052) in the ESD group (P < 0.001). The rate of non-curative ER for lesions defined as having 'positive or difficult to estimate horizontal margins only' decreased significantly, from 26.1% (109/417) in the EMR group to 1.4% (29/2,052) in the ESD group (P < 0.001). Conversely, the rate of non-curative ER for lesions defined as having 'possible lymph node metastasis' significantly increased in the ESD group (15.5%; 319/2,052) compared to that in the EMR group (10.8%; 45/417) (P < 0.01). CONCLUSIONS: The application of a pathway involving ESD resulted in a significant decrease in the rate of potentially avoidable surgery, highlighting the advantages associated with performing ESD.

Esophageal Endoscopic Submucosal Dissection Assisted by an Overtube with a Traction Forceps: An Animal Study.

Esophageal endoscopic submucosal dissection (ESD) is technically difficult. To make it safer, we developed a novel method using overtube with a traction forceps (OTF) for countertraction during submucosal dissection. We conducted an ex vivo animal study and compared the clinical outcomes between OTF-ESD and conventional method (C-ESD). A total of 32 esophageal ESD procedures were performed by four beginner and expert endoscopists. After circumferential mucosal incision for the target lesion, structured as the isolated pig esophagus 3 cm long, either C-ESD or OTF-ESD was randomly selected for submucosal dissection. All the ESD procedures were completed as en bloc resections, while perforation only occurred in a beginner's C-ESD procedure. The dissection time for OTF-ESD was significantly shorter than that for C-ESD for both the beginner and expert endoscopists (22.8 ± 8.3 min versus 7.8 ± 4.5 min, P < 0.001, and 11.3 ± 4.4 min versus 5.9 ± 2.5 min, P = 0.01, resp.). The frequency and volume of the submucosal injections were significantly smaller for OTF-ESD than for C-ESD (1.3 ± 0.6 times versus 2.9 ± 1.5 times, P < 0.001, and 5.3 ± 2.8 mL versus 15.6 ± 7.3 mL, P < 0.001, resp.). Histologically, muscular injury was more common among the C-ESD procedures (80% versus 13%, P = 0.009). Our results indicated that the OTF-ESD technique is useful for the safe and easy completion of esophageal ESD.

Efficacy of a glycyrrhizin suppository for the treatment of chronic hepatitis C: a pilot study.

Intravenous administration of glycyrrhizin has potential efficacy on decreasing serum aminotransferase levels in patients with chronic hepatitis. However, patients receiving this treatment are recommended to attend hospital regularly for several years. To improve the quality of life for these patients, we developed a glycyrrhizin suppository. In this pilot study, we examined the most effective and safe material contents of the suppository and revealed clinical efficacy for patients with biopsy-proven chronic hepatitis C comparing intravenous administration of glycyrrhizin. As content combinations of the suppository, a mixture of 300 mg of glycyrrhizinic ammonium salt and 60 &mgr;g of sodium capric acid, with pH neutralization, was confirmed to be most effective and safe condition, based on analysis of serum glycyrrhizin levels and the grade of rectal irritations in tested patients. The efficacy on decreasing serum alanine aminotransferase levels for 12-week administration of the suppository in 13 patients with chronic hepatitis C was similar to that in another 13 patients intravenously administered glycyrrhizin. Moreover, no serious side effects were observed. In conclusion, the usage of the newly developed suppository of glycyrrhizin can improve the quality of life for chronic hepatitis C patients, especially those who do not respond with viral clearance to interferon therapy. Using this suppository, larger and longer-term studies are needed.

Generation of high affinity monoclonal antibodies for the prevention of HIV infection.

The most critical issue for the application of high affinity monoclonal antibodies is their creation. Here, we summarize the cellular and molecular mechanisms by which high affinity antibodies are generated, and then review the attempts of many investigators to create high affinity monoclonal antibodies against various target molecules. High affinity monoclonal antibodies are generated by one or a combination of the following three major methods. (1) The improvement of antibody affinity by introducing mutations in the immunoglobulin V-region genes by in vitro mutagenesis. (2) Screening many clones from a random combinatory repertoire of IgV-region genes using a phage library established in yeast or bacteria. (3) Attempting to introduce many somatic hypermutation of IgV-region genes. We summarize the advantages and applications of each of these methods including recent patents to facilitate informed individual choice. We also extend our review to the current creation of antibodies for HIV research.