The Utility of Serum IgG4 Concentrations as a Biomarker

IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease

Mechanisms of Lower Bile Duct Stricture in Autoimmune Pancreatitis

Objectives We attempted to clarify the mechanism underlying lower bile duct stricture in autoimmune pancreatitis. Methods Imaging and histologic finding of the bile duct were assessed for 73 patients with autoimmune pancreatitis to clarify whether IgG4-related biliary inflammation or pancreatic head swelling is associated with lower bile duct stricture. Results Lower bile duct stricture was found in 59 (81%) patients. Pancreatic head swelling was significantly more frequent among patients with lower bile duct stricture than those patients without lower bile duct stricture (53 [90%] vs 4 [29%]; P < 0.01). Intraductal ultrasonography findings revealed lower bile duct wall thickening in 21 (95%) of the 22 patients with lower bile duct stricture, and the lower bile duct wall of the patients with pancreatic head swelling was significantly thicker than those patients without pancreatic head swelling (P = 0.028). Among the 38 patients with lower bile duct biopsies, 14 (37%) exhibited abundant IgG4-bearing plasma cell infiltration. Among the patients with lower bile duct stricture, an IgG4-related inflammation seemed to exert a dominant effect under limited conditions, including concomitant middle bile duct stricture and neither pancreatic swelling nor pancreatic duct stricture in the head region. Conclusions Both pancreatic head swelling and IgG4-related biliary inflammation affect lower bile duct stricture, which may be included in IgG4-related sclerosing cholangitis. Pancreatic head swelling affects IgG4-related biliary wall thickening.ArticlePANCREAS. 43(2):255-260 (2014)journal articl

Comparison of carbon dioxide and air insufflation use by non-expert endoscopists during endoscopic retrograde cholangiopancreatography

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is subject to several complications that include a lengthy procedure time, technical difficulty, and active bowel movement induced by air insufflation. In ERCP carried out by non-expert endoscopists who are prone to excessive luminal insufflation, insufflation with carbon dioxide (CO2) may provide better and safer outcomes. We aimed to assess the efficacy and safety of CO2 insufflation during ERCP by non-expert endoscopists. Methods: This study included 208 consecutive patients who received ERCP, excluding those in poor general health or with obstructive lung disease. The first operator for each patient was a non-expert endoscopist having done 50 or fewer ERCP procedures. Primary outcomes were the changes in cardiopulmonary state during ERCP. Secondary outcomes were ERCP complications. We designed a single-center, randomized, prospective, double-blind, controlled trial with CO2 and air insufflation during ERCP. Results: CO2 insufflation did not affect overall procedure progression or results. A positive correlation was observed between procedure time and change in maximal systolic blood pressure from baseline among patients in the air insufflation group, but not in the CO2 insufflation group (correlation coefficient 0.408 vs 0.114, change in the maximal systolic blood pressure from baseline +4.2 vs+1.2mmHg/10min). This was consistent with our findings in patients treated by the first operator alone. The occurrence rate of post-ERCP pancreatitis tended to be lower in the CO2 group than the air group (4/102 [3.9%]vs 0/106 [0%], P=0.056). Conclusions: CO2 insufflation during ERCP by non-expert endoscopists is recommended from the standpoints of efficacy and safety.ArticleDIGESTIVE ENDOSCOPY. 25(2):189-196 (2013)journal articl

Risk factors for pancreatic stone formation in autoimmune pancreatitis over a long-term course

Autoimmune pancreatitis (AIP) has the potential to progress to a chronic state that forms pancreatic stones. The aim of this study was to clarify the risk factors underlying pancreatic stone formation in AIP. Sixty-nine patients with AIP who had been followed for at least 3 years were enrolled for evaluation of clinical and laboratory factors as well as computed tomography and endoscopic retrograde cholangiopancreatography findings. During the course of this study, increased or de novo stone formation was seen in 28 patients, who were defined as the stone-forming group. No stones were observed in 32 patients, who were defined as the non-stone-forming group. Nine patients who had stones at diagnosis but showed no change during the course of this study were excluded from our cohort. Univariate analysis revealed no significant differences in clinical or laboratory factors associated with AIP-specific inflammation between the two groups. However, pancreatic head swelling (P = 0.006) and narrowing of both Wirsung's and Santorini's ducts in the pancreatic head region (P = 0.010) were significantly more frequent in the stone-forming group. Furthermore, multivariate analysis identified Wirsung and Santorini duct narrowing at diagnosis as a significant independent risk factor for pancreatic stone formation (OR 4.4, P = 0.019). A primary risk factor for pancreatic stone formation in AIP was narrowing of both Wirsung's and Santorini's ducts, which most presumably led to pancreatic juice stasis and stone development.ArticleJOURNAL OF GASTROENTEROLOGY. 47(5):553-560 (2012)journal articl

The Effect of a Portable Electrical Muscle Stimulation Device at Home on Muscle Strength and Activation Patterns in Locomotive Syndrome Patients: A Randomized Control Trial

The aim of the present study was to quantify the effect of electrical muscle stimulation (EMS) intervention using a portable device on muscle strength and activation patterns in locomotive syndrome. Nineteen women were randomly assigned to the intervention group (n = 10; age = 71–82 years) and control group (n = 9; age = 70–84 years). Participants in the intervention group used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min/5 days/week). To understand the effects of EMS, the following measurements were made at baseline, 8 weeks, and 12 weeks: locomotive syndrome assessment score, knee extensor strength, vastus lateralis muscle activation patterns during a maximal isometric knee extension contraction using multi-channel surface electromyography, and muscle thickness. The locomotive syndrome assessment, muscle strength, muscle thickness, and muscle activity patterns in the intervention group were significantly different to control after 8 weeks (p \u3c 0.05). However, these results were not sustained at 12 weeks. EMS increased locomotor assessment scores, which were accompanied by enhanced muscle strength, increased muscle thickness, and changes in muscle activation patterns in locomotive syndrome patients. These results suggest that EMS is potentially useful for improving muscle neural activation and force output in locomotive syndrome

Laterality of the Activation of the Vastus Lateralis Muscle in Females with Parkinson\u27s Disease during the Medication State Compared with Healthy Controls

This study quantified the laterality of motor unit activation properties in females with Parkinson’s disease during force production (low to high-intensity contraction) using high-density surface electromyography. Sixteen females with Parkinson’s disease (age = ± 7.6 years, disease duration = 4.9 ± 5.1 years) and 14 healthy female subjects (age = 68.6 ± 3.6 years) performed submaximal ramp-up contractions during isometric knee extension. High-density surface electromyography signals were recorded from both vastus lateralis muscles. The level of heterogeneity was calculated in the spatial distribution patterns of the high-density surface electromyography signals to determine the modified entropy, coefficient of variation of the root mean square and correlation coefficient to evaluate motor unit activation properties. Pearson’s correlation coefficients were calculated to examine the relationships between disease severity and the root mean square and electromyography variables. The root mean square value and heterogeneity were significantly higher and lower on the more-affected side in females with Parkinson’s disease than on the contralateral side in females with Parkinson’s disease or either side in control subjects (p \u3c 0.05). Females with Parkinson’s disease that exhibited temporal changes of spatial motor unit activation properties showed significant laterality when compared to healthy control subjects in both the low and high-intensity contractions. Moderate-to-strong correlations were observed between disease severity and root mean square and electromyography variables in females with Parkinson’s disease (r\u3e 0.6, p \u3c 0.001). The laterality of motor unit activation properties was compared between the subjects with Parkinson’s disease and the control subjects. The findings suggest that females with Parkinson’s disease have asymmetrical motor unit activation properties, independent of the magnitude of force production

Fertilization Recovery after Defective Sperm Cell Release in Arabidopsis

SummaryIn animal fertilization, multiple sperms typically arrive at an egg cell to “win the race” for fertilization. However, in flowering plants, only one of many pollen tubes, conveying plant sperm cells, usually arrives at each ovule that harbors an egg cell [1, 2]. Plant fertilization has thus been thought to depend on the fertility of a single pollen tube [1]. Here we report a fertilization recovery phenomenon in flowering plants that actively rescues the failure of fertilization of the first mutant pollen tube by attracting a second, functional pollen tube. Wild-type (WT) ovules of Arabidopsis thaliana frequently (∼80%) accepted two pollen tubes when entered by mutant pollen defective in gamete fertility. In typical flowering plants, two synergid cells on the side of the egg cell attract pollen tubes [3–5], one of which degenerates upon pollen tube discharge [3, 6]. By semi-in vitro live-cell imaging [7, 8] we observed that fertilization was rescued when the second synergid cell accepted a WT pollen tube. Our results suggest that flowering plants precisely control the number of pollen tubes that arrive at each ovule and employ a fertilization recovery mechanism to maximize the likelihood of successful seed set

Abeta Is Internalized via Macropinocytosis

Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells

Fluorescence and chemiluminescence behavior of distyrylbenzene bearing two arms of dipicolylaminomethyl groups: Interactions with zinc ion and ATP

Available online 31 January 2018.The absorption and fluorescence spectral study of the distyrylbenzene bearing two arms of the dipicolylaminomethyl groups, the effective ligands for Zn2+, was studied in the presence of Zn2+ and ATP. Upon complexation of the distyrylbenzene with zinc ions in acetonitrile, enhancement of the fluorescence intensity was observed due to inhibition of intramolecular PET (photo-induced electron transfer) quenching, but no effect was found in aqueous media because the equilibrium laid to the free form of the ligands. In contrast, the addition of ATP disodium salt was effective to enhance the fluorescence intensity of the combination of the distyrylbenzne and Zn2+ in aqueous media. This assembly was applied to the peroxyoxalate chemiluminescence system and a significant increase in the intensity was observed, which provides a potential detection for ATP by chemiluminescence. (C) 2018 Elsevier B.V. All rights reserved.ArticleSPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY. 195:223-229 (2018)journal articl