The calcium-binding photoprotein clytin II: Expression of the preferred human codon-optimized clytin II gene in Chinese hamster ovary-K1 cells and its use in the G-protein-coupled receptor assays.

Clytin II (CLII) is a Ca2+-binding photoprotein and has been identified as an isotype of clytin I (CLI). CLII consists of apoCLII (an apoprotein) and 2-peroxide of coelenterazine (an adduct of molecular oxygen to coelenterazine), which is identical to the widely used Ca2+-binding photoprotein, aequorin (AQ). However, CLII triggered by Ca2+ exhibits a 4.5-fold higher maximum luminescence intensity (Imax) compared to both AQ and CLI, and it is approximately 5 times less sensitive to Ca2+ than AQ. To confirm the suitability of the preferred human codon-optimized CLII (pCLII) gene for cell-based G-protein-coupled receptor (GPCR) assays, a transformant stably expressing apoprotein of pCLII using the pCLII gene in the mitochondria of CHO-K1 cells was established and in situ regenerated pCLII in the cells were applied to the high-throughput screening system. An ATP-stimulated GPCR assay for endogenous P2Y purinergic receptors was confirmed using the established stable transformant.

Verification of the increase in concomitant dysplasia and cancer with the size of sessile serrated lesions.

Background and study aims This study aimed to evaluate the relationship between sessile serrated lesion (SSL) size and the comorbidity rate of SSL with dysplasia (SSLD) and cancer in SSL (SSL-cancer). Patients and methods This retrospective, single-center analysis identified SSL cases that underwent endoscopic resection between January 2015 and December 2022. The prevalence of SSL, SSLD, and SSL-cancer and their annual trends were assessed. The tumor diameter was stratified as 0 to 5 mm, 6 to 9 mm, 10 to 19 mm, and ≥ 20 mm in size. Furthermore, the frequency of SSL-D/SSL-cancer was determined in each group. Results The prevalence of SSL was 2.9% (1328/45799). This prevalence was 1.8% (112/6192) in 2015 and 4.2% (230/5500) in 2022, indicating an increasing trend over time. A total of 1825 lesions were assessed: 1751 (96.0%), 55 (3.0%), 14 (0.8%), and 5 (0.3%) of lesions were SSL, SSL with low-grade dysplasia, SSL with high-grade dysplasia and SSL-cancer, respectively. Stratifying the SSLs by size: 0 to 5 mm, 5 to 9 mm, 10 to 19 mm, and ≥ 20 mm, SSLD and SSL-cancer rates were 2.3% (10/429), 2.4% (16/674), 5.3% (31/584), and 11.8% (16/136), respectively. SSLD and SSL-cancer were observed in 2.4% (26/1103) of small SSLs < 10 mm. Conclusions In cases of SSL, the rate of SSLD and SSL-cancer increased as the lesion diameter increased. A certain rate of SSLD and SSL-cancer was observed even in small SSLs less than 5mm.

Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation.

BACKGROUND: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. METHODS: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. RESULTS: Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. CONCLUSIONS: AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

Decreased intracellular chloride enhances cell migration and invasion via activation of the ERK1/2 signaling pathway in DU145 human prostate carcinoma cells.

Our previous study revealed that changes of the intracellular Cl- concentration ([Cl-]i) affected cell proliferation in cancer cells. However, the role of Cl- on cell migration and invasion in cancer cells remains unanalyzed. Therefore, the aim of the present study is to investigate whether changes of [Cl-]i affects cell migration and invasion of cancer cells. In human prostate cancer DU145 cells, cell migration and invasion were enhanced by culturing in the low Cl- medium (replacement of Cl- by NO3-). We also found that DU145 cells in the low Cl- condition caused significant transient ERK1/2 activation followed by an increase of MMP-1 mRNA levels. Inhibition of ERK1/2 activation in the low Cl- condition reduced enhancement of MMP-1 mRNA levels and decreased cell migration and invasion. These observations indicate that [Cl-]i plays important roles in metastatic function by regulating the ERK1/2 signaling pathway in human prostate cancer cells, and intracellular Cl- would be one of the key targets for anti-cancer therapy.

Bilateral Eyelid Edema in a Pediatric Patient With COVID-19: A Case Report and Literature Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted through the eyes, nose, or mouth. Ophthalmic complications, such as conjunctivitis and dacryoadenitis, have been reported in patients with coronavirus disease 19 (COVID-19). We report the case of an early adolescent girl who presented with bilateral urticarial rashes, eyelid edema, fever, and cough. She was diagnosed with acute dacryoadenitis with SARS-CoV-2 infection confirmed by a nasopharyngeal polymerase chain reaction and clinical investigations. The patient was treated with dexamethasone (3 mg daily) for three days, which resulted in the resolution of fever and urticarial rash, and improvement of eyelid edema. While bilateral upper eyelid edema and acute dacryoadenitis commonly occur in pediatric patients due to Epstein-Barr virus (EBV) infection and Kawasaki disease, they are rarely associated with other diseases. However, ocular symptoms have been reported in 11.4% of patients with COVID-19. In addition, eyelid edema and acute dacryoadenitis have also been reported after COVID-19 messenger RNA (mRNA) vaccination. The underlying mechanisms of these complications are not yet completely understood. Our case highlights the possibility of bilateral eyelid edema in children with COVID-19, which can occur in addition to other viral infections such as EBV.

Repeated steroid injection and polyglycolic acid shielding for prevention of refractory esophageal stricture.

BACKGROUND: Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. METHODS: This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019. RESULTS: The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029). CONCLUSION: Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

Novel double staining of the stratum corneum with fluorescent ε-poly-l-lysine and anionic dextran.

OBJECTIVE: ε-Poly-l-lysine (PLL) is a cationic polymer consisting of 25-35 l-lysine residues. Our previous study revealed that fluorescently labelled PLL can stain the stratum corneum (SC) via ionic interactions between PLL and SC constituents. In this study, to further clarify the mechanisms underlying the interaction between PLL and the SC, the staining properties of fluorescent PLL were compared with that of fluorescently labelled anionic dextran (aDex), which has approximately the same molecular weight as PLL. METHODS: SC samples were collected by non-invasive tape stripping and stained with fluorescent PLL and/or fluorescent aDex. Fluorescence images were acquired using a fluorescence microscope and then analysed. RESULTS: The SC could be stained with either fluorescent PLL or aDex, both of which were inhibited by the addition of high concentrations of salt solutions. In particular, aDex staining was inhibited at a lower salt concentration than PLL staining. Moreover, PLL staining was inhibited under acidic conditions, while aDex staining was inhibited under neutral to alkaline conditions. Double staining of SC with both fluorescent polymers produced heterogeneous staining patterns: corneocytes stained with both polymers, corneocytes stained with PLL or aDex in a mutually exclusive manner, and unstained corneocytes. Staining of SC samples from the face was more extensive than staining of SC samples from the inside of the upper arm with both polymers. In addition, pretreatment of the SC with ethanol resulted in enhanced staining with both polymers. These results suggest that double staining of SC with both polymers can provide information on the damaged SC. CONCLUSION: Staining of SC with fluorescent PLL depends on its properties of a cationic and hydrophobic polymer with appropriate molecular size, which can distinguish the damaged SC. Double staining of SC with fluorescent PLL and aDex is a novel approach to obtain information for the analysis of skin conditions.

OBJECTIF: La ε-poly-L-lysine (PLL) est un polymère cationique constitué de résidus de 25 à 35 L-lysines. Notre précédente étude a révélé que la PLL marquée par fluorescence peut colorer le stratum corneum (SC) par des interactions ioniques entre la PLL et les constituants du SC. Dans cette étude, afin de clarifier davantage les mécanismes sous-jacents à l'interaction entre la PLL et le SC, les propriétés de coloration de la PLL fluorescent ont été comparées à celles du dextran anionique (aDex) marqué par fluorescence, qui a à peu près le même poids moléculaire que la PLL. MÉTHODES: Les échantillons SC ont été prélevés par «tape stripping¼ non invasif et colorés avec de la PLL fluorescente et/ou de l'aDex fluorescent. Les images de fluorescence ont été acquises au microscope à fluorescence puis analysées. RÉSULTATS: Le SC pouvait être coloré avec de la PLL ou de l'aDex fluorescents, tous deux inhibés par l'ajout de fortes concentrations de solutions salines. En particulier, la coloration par aDex était inhibée à une concentration en sel inférieure à la coloration par PLL. En outre, la coloration de la PLL a été inhibée dans des conditions acides, tandis que la coloration de l'aDex a été inhibée dans des conditions neutres à alcalines. La double coloration de SC avec les deux polymères fluorescents a produit des modes de coloration hétérogènes: cornéocytes colorés avec les deux polymères, cornéocytes colorés avec de la PLL ou de l'aDex d'une manière mutuellement exclusive, et cornéocytes non colorés. La coloration des échantillons de SC sur le visage était plus étendue que la coloration des échantillons de SC sur la face intérieure du haut du bras avec les deux polymères. En outre, le prétraitement du SC avec de l'éthanol a entraîné une coloration améliorée avec les deux polymères. Ces résultats indiquent qu'une double coloration du CS avec les deux polymères peut fournir des informations sur le CS endommagé. CONCLUSION: La coloration du CS avec de la PLL fluorescente dépend de ses propriétés de polymère cationique et hydrophobe de taille moléculaire appropriée, ce qui permet de distinguer le CS endommagé. La double coloration de SC avec de la PLL et de l'aDex fluorescents est une nouvelle approche pour obtenir des informations pour l'analyse des affections cutanées.

Staining of stratum corneum with fluorescent ε-poly-L-lysine and its application to evaluation of skin conditions.

BACKGROUND: ε-Poly-L-lysine (PLL) is a cationic polymer consisting of 25 to 35 L-lysine residues that adheres to the surface of skin as well as hair. However, the properties of PLL regarding its adhesion to the skin remain to be elucidated. In this study, we examined the staining of stratum corneum (SC) with fluorescence-labeled PLL and explored its relationship with skin condition. MATERIALS AND METHODS: Alexa Fluor 488-labeled PLL (AF-PLL) was reacted with tape-stripped stratum corneum (SC), and the staining properties were monitored by fluorescence microscopy. Clinical study was performed by measuring the water content of the cheek SC and transepidermal water loss (TEWL), and the tape-stripped SC was subjected to staining with AF-PLL. RESULTS: AF-PLL staining of the SC was inhibited at acidic pH or by the addition of high concentration of salt solution, suggesting the involvement of ionic interaction between PLL and the SC, at least in part. The AF-PLL staining was inhibited by unlabeled PLL or various alkyl amines, but not by L-lysine monomer. AF-PLL staining was observed inside the corneocytes as well as surrounding cornified envelope. Clinical study revealed that AF-PLL staining intensity of the SC was negatively correlated with its water content and positively correlated with its TEWL. CONCLUSION: PLL can efficiently adhere to SC and AF-PLL staining of SC can be applied to evaluate skin conditions.

Reverse mutants of the catalytic 19 kDa mutant protein (nanoKAZ/nanoLuc) from Oplophorus luciferase with coelenterazine as preferred substrate.

Native Oplophorus luciferase (OpLase) and its catalytic 19 kDa protein (wild KAZ) show highest luminescence activity with coelenterazine (CTZ) among CTZ analogs. Mutated wild KAZ with 16 amino acid substitutions (nanoKAZ/nanoLuc) utilizes bis-coelenterazine (bis-CTZ) as the preferred substrate and exhibits over 10-fold higher maximum intensity than CTZ. To understand the substrate selectivity of nanoKAZ between CTZ and bis-CTZ, we prepared the reverse mutants of nanoKAZ by amino acid replacements with the original amino acid residue of wild KAZ. The reverse mutant with L18Q and V27L substitutions (QL-nanoKAZ) exhibited 2.6-fold higher maximum intensity with CTZ than that of nanoKAZ with bis-CTZ. The catalytic properties of QL-nanoKAZ including substrate specificity, luminescence spectrum, luminescence kinetics, luminescence products of CTZ, and luminescence inhibition by deaza-CTZ analogs were characterized and were compared with other CTZ-utilizing luciferases such as Gaussia and Renilla luciferases. Thus, QL-nanoKAZ with CTZ could be used as a potential reporter protein for various luminescence assay systems. Furthermore, the crystal structure of QL-nanoKAZ was determined at 1.70 Å resolution. The reverse mutation at the L18Q and V27L positions of α2-helix in nanoKAZ led to changes in the local structures of the α4-helix and the ß6- and ß7-sheets, and might enhance its binding affinity and oxidation efficiency with CTZ to emit light.

Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future.

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.

Autoimmune gastritis induces aberrant DNA methylation reflecting its carcinogenic potential.

BACKGROUND: Autoimmune gastritis (AIG) is a chronic inflammatory condition in gastric mucosa and is associated with increased cancer risk, though not as high as that by Helicobacter pylori (H. pylori)-associated gastritis (HPG). Although aberrant DNA methylation is induced by HPG and the level correlates with the risk of gastric cancer, DNA methylation induction by AIG is unknown. METHODS: Gastric mucosa samples from the corpus were collected from 12 people with AIG without H. pylori infection, 10 people with HPG, and eight healthy volunteers. Genome-wide DNA methylation analysis was conducted using Infinium Methylation EPIC array. Gene expression was analyzed by quantitative RT-PCR. RESULTS: The AIG samples had extensive aberrant DNA methylation but presented unique methylation profiles against the HPG samples after correction of leucocyte fractions. Comparison between the AIG and HPG samples showed that AIG induced methylation, but less than HPG, in overall CpG sites and also in promoter CpG islands. Promoter CpG islands of tumor-suppressor genes in the pathway of cell cycle, cell adhesion, p53, and WNT were highly methylated in the AIG samples, but more so in the HPG samples. The expression levels of IL1B and IL8, secreted by macrophage, were significantly lower in the AIG samples than in the HPG samples, suggesting that a difference in inflammatory response affected the degree and patterns of aberrant DNA methylation. CONCLUSIONS: AIG induced aberrant DNA methylation in gastric mucosa. However, the degree of DNA methylation was less than that by HPG, which reflected carcinogenic risk.

The natural history of sporadic non-ampullary duodenal epithelial tumors: Can we wait and see?

Objectives: The natural history of sporadic non-ampullary duodenal epithelial tumors (SNADETs) is poorly documented. The aim of this study was to evaluate the history of SNADETs in patients where immediate resection could not be performed. Methods: This is a single-center retrospective study of 86 consecutive cases of SNADETs who did not undergo immediate resection and were followed-up with upper gastrointestinal endoscopy for more than 6 months. Results: During a follow-up period of 36.8 (6.0-613.0) months, macroscopic progression was admitted in eight (9.3%). Of these, the final histology in four was adenocarcinoma, and three cases demonstrated submucosal invasion. Rates of macroscopic progression at 150 months after detection were 11.1%, 16.7%, and 30.0% for SNADETs <5 mm, <10 mm, and ≥10 mm, respectively. Conclusion: The overall risk of SNADETs progressing to invasive cancer is low. However, changes in macroscopic size or shape of SNADETs signify a high risk of progression to invasive cancer.

Two cases of bacterial meningitis due to meropenem-resistant Streptococcus pneumoniae: A threat of serotype 35B, ST 558 lineage.

Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.

Isolation of three new meroterpenoids and seven known compounds from Albatrellus yasudae and their Aß-aggregation inhibitory activity.

Alzheimer's disease is a serious neurologic disorder that cannot be cured completely. In this study, we targeted compounds that inhibit amyloid-beta (Aß) aggregation, based on the amyloid cascade hypothesis. Ten compounds (1-10) were isolated from CHCl3 extracts of the mushroom Albatrellus yasudae using Aß-aggregation inhibitory activity-guided separation. The structures of these compounds were elucidated from 1D and 2D NMR and MS spectral data. Compounds 1-3 were novel, whereas 4-10 were identified as the known compounds grifolin, grifolic acid, neogrifolin, confluentin, 2-hydroxyneogrifolin, daurichromenic acid, and a cerebroside derivative. Compounds 1-10 were tested for Aß-aggregation inhibitory activity. Compounds 1, 3, 5, 6, 8, and 9 have potential as Aß-aggregation inhibitory activity.

Efficacy and safety of eradication therapy for elderly patients with helicobacter pylori infection.

Helicobacter pylori (H. pylori) is the most prevalent chronic bacterial infection and is associated with chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Although eradication therapy is widely performed for H. pylori infection, adverse events (AEs) are of particular concern in the elderly. This study investigated the efficacy and safety of H. pylori eradication therapy for elderly patients.Retrospective investigation of 1271 cases (median age: 61 years, 730 male) of H. pylori infection was performed to compare clinical indications and outcomes among the younger group (<65 years old), elderly group (65-74 years old), and super-elderly group (>75 years old).Chronic gastritis (77.0%) and gastric and/or duodenal ulcer (16.4%) were the most frequent indications for eradication therapy in the cohort. The respective eradication and AE rates for the first and second treatment regimens were 92.1% (1044 of 1133 cases) and 9.1% (103 of 1133 cases) and 84.2% (123 of 146 cases) and 8.9% (13 of 146 cases). No significant differences were detected for eradication rate or AE frequency between the super-elderly group and the other groups. Prior to therapy, the super-elderly group had significantly less frequent chronic gastritis than the other groups but more frequent gastric or duodenal ulcer and post-gastric cancer treatment (all P < .001), indicating a reluctance for clinicians to treat very old patients, possibly due to unfounded concerns of complications.Triple therapy for H. pylori eradication is effective and safe, even for elderly patients.

Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial.

BACKGROUND: Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. METHODS: We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. FINDINGS: We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25-0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). INTERPRETATION: Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. FUNDING: Japan Agency for Medical Research and Development (grant CCT-B-2503).

Modification of the HCMV-specific IFN-γ release test (QuantiFERON-CMV) and a novel proposal for its application.

Human cytomegalovirus (HCMV) is universally distributed among humans without any adverse effects; however, it induces severe diseases in immunocompromised patients such as organ transplant recipients and AIDS patients. To manage these immunocompromised patients, an easy clinical examination for the monitoring of disease risk is required. In this study, we modified the interferon-γ (IFN-γ) release test (QuantiFERON®-CMV) using HCMV immediate early-1 (IE-1) or pp65 whole proteins, or UV-inactivated HCMV particles as an antigen. The response of heparinized peripheral blood from healthy volunteers to the pp65 protein showed an obvious dose-dependent sigmoid curve, although no correlation was observed between results of this assay and an ELISPOT assay. The addition of pp65 to the blood samples at a final concentration of 1×103 to 1×105 pg/ml was found to be optimum. Using this assay, we observed a significant enhancement in cellular immunity in volunteers after the daily ingestion of yogurt for 8 weeks, which suggested a novel application of the assay in addition to monitoring HCMV infection risk. IFN-γ secretion from peripheral blood cells on HCMV-antigen stimulation differed significantly between individuals; therefore, the assay could not be normalized. Nevertheless, it was found to be particularly useful for observing fluctuations in cellular immune activity on an individual level.

Prospective study of factors important to achieve observation of the entire colon on colon capsule endoscopy.

BACKGROUND: Colon capsule endoscopy (CCE) is a procedure in which capsule swallowing facilitates observation of the lumen of the entire digestive tract. It does not require an air supply, and is a noninvasive procedure with a markedly low risk of adverse events in comparison with conventional colonoscopy (CS). It reduces patient stress, and may be acceptable to patients. A limitation of this procedure is that the entire colon observation rate (CCE excretion rate, completed CCE rate) is not 100%. In this study, we prospectively investigated clinical factors important to achieve observation of the entire colon on CCE. METHODS: The participants were 70 patients for whom CCE was scheduled, and from whom written informed consent regarding participation in this study was obtained. We selected patient background/examination factors, and analyzed all factors involved in observation of the entire colon and factors for completion of the CCE within 4 h after the start of examination using multivariate analysis. RESULTS: Of the 70 enrolled patients, 64 were analyzed, excluding 6. On multiple logistic analysis, only a water intake of ⩾12.0 ml/min during examination [p = 0.025, odds ratio (OR): 46.753, 95% confidence interval (CI): 1.630-1341.248] was identified as an independent predictive factor involved in observation of the entire colon. With respect to factors involved in the completion of CCE within 4 h, multiple logistic analysis showed that a body mass index (BMI) of ⩾25 (p = 0.039, OR: 13.723, 95% CI: 1.135-165.913), the absence of constipation (p = 0.030, OR: 13.988, 95% CI: 1.287-152.047), and a water intake of ⩾12.0 ml/min during examination (p = 0.004, OR: 12.028, 95% CI: 2.225-65.029) were independent predictive factors. CONCLUSIONS: Completion of a CCE was most closely related to water intake per hour. In addition to water intake, CCE-promoting factors included a high BMI and the absence of constipation.