High-angular resolution diffusion imaging generation using 3d u-net.

PURPOSE: To investigate the effects on tractography of artificial intelligence-based prediction of motion-probing gradients (MPGs) in diffusion-weighted imaging (DWI). METHODS: The 251 participants in this study were patients with brain tumors or epileptic seizures who underwent MRI to depict tractography. DWI was performed with 64 MPG directions and b = 0 s/mm2 images. The dataset was divided into a training set of 191 (mean age 45.7 [± 19.1] years), a validation set of 30 (mean age 41.6 [± 19.1] years), and a test set of 30 (mean age 49.6 [± 18.3] years) patients. Supervised training of a convolutional neural network was performed using b = 0 images and the first 32 axes of MPG images as the input data and the second 32 axes as the reference data. The trained model was applied to the test data, and tractography was performed using (a) input data only; (b) input plus prediction data; and (c) b = 0 images and the 64 MPG data (as a reference). RESULTS: In Q-ball imaging tractography, the average dice similarity coefficient (DSC) of the input plus prediction data was 0.715 (± 0.064), which was significantly higher than that of the input data alone (0.697 [± 0.070]) (p < 0.05). In generalized q-sampling imaging tractography, the average DSC of the input plus prediction data was 0.769 (± 0.091), which was also significantly higher than that of the input data alone (0.738 [± 0.118]) (p < 0.01). CONCLUSION: Diffusion tractography is improved by adding predicted MPG images generated by an artificial intelligence model.

Diagnostic reference value of antibody levels measured using enzyme immunoassay for subacute sclerosing panencephalitis.

High measles-specific antibody titers in the cerebrospinal fluid (CSF) have important diagnostic significance for subacute sclerosing panencephalitis (SSPE), a progressive neurological disorder caused by measles virus variants. However, the diagnostic reference value of antibody levels and the usefulness of the CSF/serum ratio measured using enzyme immunoassays (EIAs) for SSPE diagnosis remain unclear. To facilitate SSPE diagnosis using EIAs, measles immunoglobulin G (IgG) titers in the CSF and serum of patients with and without SSPE were measured and their CSF/serum antibody ratios evaluated. Serum and CSF antibody levels were compared among three patients with SSPE (59 paired samples), 37 non-SSPE patients, and 2618 patients of unknown backgrounds. Of the 59 paired samples from three patients with SSPE, 56 paired samples (94.9%) showed CSF measles IgG levels ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, whereas non-SSPE cases showed CSF measles IgG levels <0.1 IU/mL and a CSF/serum ratio <0.03. Of the 2618 CSF samples with unknown backgrounds, 951 showed measurable IgG levels with EIA, with a CSF/serum ratio peak of 0.005-0.02, with a 90th percentile of 0.05. Assuming the SSPE criteria as CSF measles IgG ≥0.5 IU/mL and a CSF/serum ratio ≥0.05, only 20 samples (0.8%) with unknown backgrounds were categorized as having SSPE. Conversely, assuming the non-SSPE criteria as CSF measles IgG <0.1 IU/mL and a CSF/serum ratio <0.03, 2403 samples (92%) with unknown backgrounds were categorized as not having SSPE. In conclusion, high CSF/serum ratios (≥0.05) and high measles CSF IgG levels (≥0.5 IU/mL) may be useful for diagnosing SSPE.

Hemodynamic changes during the obliteration process for cerebral arteriovenous malformations after radiosurgery.

OBJECTIVE: The process of cerebral arteriovenous malformation (AVM) obliteration following radiosurgery is poorly understood. Authors of this retrospective study aimed to assess the changes in AVM hemodynamics after stereotactic radiosurgery (SRS) by using 3D flow magnetic resonance imaging (MRI) to elucidate the process of AVM obliteration. METHODS: Twenty-four patients with AVMs treated with SRS between July 2015 and December 2017 were included in this study and classified into two groups depending on the duration of AVM obliteration: group A, obliteration within 3 years (n = 15); and group B, obliteration taking more than 3 years or no obliteration (n = 9). Blood flow (ml/min) in the largest feeding artery was measured before and after SRS by using time-averaged 3D flow MRI. The decreasing rate of blood flow in the feeding artery after SRS was calculated as the percent change from baseline blood flow. A Wilcoxon rank-sum test was used to compare the decreasing blood flow rate between the two groups at 4 and 12 months after SRS. RESULTS: For the entire cohort, the mean decrease in blood flow in the feeding artery from baseline was 29% at 4 months and 71% at 12 months after SRS. In general, blood flow after SRS decreased faster in group A and slower in group B. The decreasing rates in blood flow at 4 and 12 months after SRS were significantly different between the two groups (p = 0.02 and < 0.001, respectively). CONCLUSIONS: Tracking changes in AVM hemodynamics after SRS may be useful for assessing the progress of AVM obliteration and the therapeutic effects of SRS, possibly contributing to the prediction of subsequent obliteration outcome.

Early intervention for psychosomatic symptoms of adolescents in school checkup.

BACKGROUND: The purpose of this study was to evaluate the efficacy of early medical intervention for psychosocial problems detected in adolescents in a school health checkup, with the broader goal of prevention of these problems in adolescents. METHODS: The Questionnaire for Triage and Assessment with 30 items score and scores for five subscales (physical symptoms, depression symptoms, anxiety symptoms, self-efficacy, and family function), and an investigation of lifestyle were determined in a school health checkup for 5th grade elementary to 3rd grade junior high school students. Forty-three children were found to be at high risk for psychosomatic disorder, of whom 18 then received a medical intervention (early intervention group) and 25 did not (non-intervention group). Fifty-seven children (outpatient group) treated for psychosomatic disorder for ≤3 months were also included in the study. The Questionnaire for Triage and Assessment with 30 items (QTA30) was completed by all participants every 3 months for 1 year and scores were compared among the groups. RESULTS: In the early intervention group, total Questionnaire for Triage and Assessment with 30 items scores; physical, depression, and anxiety symptoms; and unstable relationships with friends and teachers at school all significantly improved after 1 year compared to the first survey. None of these items improved in the non-intervention group, while the outpatient group had gradual improvement in all scores. Family function scores in the early intervention group improved over time, whereas those in the non-intervention group worsened. CONCLUSIONS: Early detection of children at high risk for psychosomatic disorder at a school health checkup and early medical intervention were useful for prevention of psychosomatic disorder in adolescents.

Late bedtime reflects QTA30 anxiety symptoms in adolescents in a school checkup.

BACKGROUND: In adolescence, physical symptoms may develop due to psychosocial problems but such problems are not fully evaluated in school medical checkups. The aim of this study was to compare lifestyle factors with psychosomatic symptoms in adolescents using the subscales of the Questionnaire for Triage and Assessment with 30 items (QTA30) in school health checkups. METHODS: The QTA30 was used in checkups for 3,414 students from the fifth grade of primary school to the third grade of junior high school in south Wakayama prefecture. The QTA is a self-completed questionnaire with five subscales of physical symptoms, depression symptoms, self-efficacy, anxiety symptoms, and family function. Each subscale is divided into three groups of clinical, borderline, and healthy, based on the subscale score. Subscale scores were compared with lifestyle items of gender, grade, habits, life events, and school attendance. RESULTS: The clinical rate for all subscales was significantly higher for a higher grade (P < 0.001). Anxiety symptoms were correlated with physical symptoms (r = 0.560). Anxiety and physical symptoms were significantly higher for students who went to bed at a later time with no absences in the last month and who had problems with friends and teachers (both P < 0.001). Family function correlated with self-efficacy (r = 0.418) but not with other subscales. Study time was most related to self-efficacy (P < 0.001). CONCLUSIONS: The QTA30 subscale scores facilitated detection of psychosomatic stress and latent risks of psychosomatic disease at an early stage. Thus, the use of the QTA30 in a school medical checkup may permit early intervention for psychosomatic stress in adolescents.

Accelerated acquisition of carotid MR angiography using 3D gradient-echo imaging with two-point Dixon.

This pilot study tests the feasibility of rapid carotid MR angiography using the liver acquisition with volume acceleration-flex technique (LAVA MRA). Seven healthy volunteers and 21 consecutive patients suspected of carotid stenosis underwent LAVA and conventional time-of-flight (cTOF) MRAs. Artery-to-fat and artery-to-muscle signal intensity ratios were manually measured. LAVA MRA exhibited a significantly larger artery-to-fat signal intensity ratio compared with cTOF MRA in all slices (P < 0.001) and exhibited a larger (P < 0.001) or equivalent (P = 1.0) artery-to-muscle signal intensity ratio in the extracranial carotid arteries. The image quality of the cervical carotid bifurcation and the signal change on each MRA were visually assessed and compared among the MRAs. There was no significant difference between the two MRAs in visual assessment. LAVA MRA can provide visualization similar to cTOF MRA in the evaluation of the cervical carotid bifurcation while reducing scan time by one-fifth.

Utility of the QTA30 in a school medical checkup for adolescent students.

BACKGROUND: In adolescence, physical symptoms may develop due to psychosocial problems, but such problems are not fully evaluated in school medical checkups. The aim of the study was to compare the characteristics of students with high and low scores on the Questionnaire for Triage and Assessment with 30 items (QTA30) in a school health checkup. METHODS: The QTA30 (a self-completed questionnaire) was used in checkups for 3,414 students from the 5th grade of primary schools to the 3rd grade of junior high schools in south Wakayama Prefecture. The students were divided into groups with high (QTA30 ≥ 37) and low (QTA30 < 37) risk for psychosomatic disorder. Eleven items, including gender, grade, lifestyle habits, and life events, were compared between these groups, and in subgroups with and without recent absence from school. RESULTS: The QTA30 response rate was 87.9%. The high-risk group had significantly more 3rd grade students (P< 0.001), females (P< 0.001), problems with teachers or friends (P< 0.001), and experience of bullying (P< 0.001), in addition to game playing for ≥2 h (P< 0.001), late bedtime (P< 0.001), and many absences (P< 0.001). Students in the high-risk group with no absences for 1 month regardless of age still had a late bedtime and problems with friends, and 76.4% of the high-risk students had not visited a medical institution. CONCLUSIONS: Use of the QTA30 facilitated detection of psychosomatic stress in school medical checkups, with latent risks of truancy detectable at an early phase. The QTA30 may thus be useful in early intervention for psychosomatic stress of adolescents.

A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM).

Hereditary folate malabsorption (HFM) is an autosomal recessive disease caused by mutations in SLC46A1 encoding the proton-coupled folate transporter (PCFT). HFM patients present with various clinical features including megaloblastic anemia, thrombocytopenia, combined immunodeficiency and neurodevelopmental disorders. In this study, we report the same deep intronic mutation of c.1166-285 T > G shared by four unrelated Japanese patients with HFM. This mutation was shown to generate a cryptic splice donor site for a 168-bp insertion of intron 3 sequences, leading to premature termination in the middle of this insertion. This mutation could be a founder mutation in the Japanese population, but also could be a hot-spot and could be present in undiagnosed HFM patients worldwide because of the difficulty to detect this mutation.

Atomistic chemical computation of Olefin polymerization reaction catalyzed by (pyridylamido)hafnium(IV) complex: Application of Red Moon simulation.

We have realized the microscopic simulation of olefin polymerization, that is, the simulation of the catalytic polymerization (CP) reaction system composed of (pyridylamido)hafnium(IV) complex as the catalyst. For this purpose, we adopted Red Moon (RM) method, a novel molecular simulation method to simulate the complex reaction system. First, according to the previous research, with the help of the QM calculation, we proposed a model system and elementary processes and explained the theoretical treatment of the simulation by the RM method (the RM simulation). In addition, we also proposed a macroscopic simulation based on chemical kinetics simulation. Then, we performed two simulations and compared them in terms of the effective time evolution of the three macroscopic physical quantities, the number-average molecular weight Mn , the mass-average molecular weight Mw , and the molar-mass dispersity DM . The comparison showed that the two simulations are in quantitative or partially qualitative agreement with each other. Therefore, it is concluded that the RM simulation could not only simulate the CP reaction process microscopically, but also it is connected essentially to reproduce the time evolution of the macroscopic physical quantities on the basis of its microscopic simulation data. © 2018 Wiley Periodicals, Inc.

Radiation dose reduction with frame rate conversion in X-ray fluoroscopic imaging systems with flat panel detector: basic study and clinical retrospective analysis.

OBJECTIVES: To (a) evaluate the interpolation frames of frame rate conversion (FRC) compared with fluoroscopic frames of conventional method, and (b) compare radiation dose and fluoroscopy time between various clinical examinations without and with FRC retrospectively. METHODS: This study consisted of a basic study and a clinical retrospective analysis. The radiation dosimetry, visual assessment and measurements of contrast to noise ratio were examined. Similarity between interpolation frames and fluoroscopic frames was evaluated using normalised cross-correlation values. In the clinical retrospective analysis approved by the institutional review board, we extracted 270 examinations performed without FRC (conventional group, 12.5 pulses/s) and with FRC (FRC group, 6.25 pulses/s) from 23 May to 31 December 2016. The fluoroscopy parameters and demographics of the two groups of the clinical examinations were compared. Statistical analyses were performed with Wilcoxon signed-rank test, Brunner-Munzel test and χ2 test. RESULTS: In the basic study, the only significant difference was that the radiation dose of FRC was approximately half that of the conventional method in the same fluoroscopy time (p = .031). The interpolation frames of FRC were similar to the fluoroscopic frames of the conventional method. In the clinical retrospective analysis, the only significant difference was that FRC reduced the fluoroscopy dose by 48% and the total dose by 31% compared with the conventional method (p < .001). There was no significant difference in the others. CONCLUSION: FRC significantly reduced the radiation dose without extending the fluoroscopy time and maintaining the image quality compared to the conventional method. KEY POINTS: • Although X-ray fluoroscopic techniques are widely used for various clinical purposes, X-ray fluoroscopic examinations have radiation risks. • Frame rate conversion is an image processing technique for radiation dose reduction. • Clinical retrospective analysis showed that FRC reduces radiation doses of patients.

Diffusional kurtosis imaging and white matter microstructure modeling in a clinical study of major depressive disorder.

Major depressive disorder (MDD) is a globally prevalent psychiatric disorder that results from disruption of multiple neural circuits involved in emotional regulation. Although previous studies using diffusion tensor imaging (DTI) found smaller values of fractional anisotropy (FA) in the white matter, predominantly in the frontal lobe, of patients with MDD, studies using diffusion kurtosis imaging (DKI) are scarce. Here, we used DKI whole-brain analysis with tract-based spatial statistics (TBSS) to investigate the brain microstructural abnormalities in MDD. Twenty-six patients with MDD and 42 age- and sex-matched control subjects were enrolled. To investigate the microstructural pathology underlying the observations in DKI, a compartment model analysis was conducted focusing on the corpus callosum. In TBSS, the patients with MDD showed significantly smaller values of FA in the genu and frontal portion of the body of the corpus callosum. The patients also had smaller values of mean kurtosis (MK) and radial kurtosis (RK), but MK and RK abnormalities were distributed more widely compared with FA, predominantly in the frontal lobe but also in the parietal, occipital, and temporal lobes. Within the callosum, the regions with smaller MK and RK were located more posteriorly than the region with smaller FA. Model analysis suggested significantly smaller values of intra-neurite signal fraction in the body of the callosum and greater fiber dispersion in the genu, which were compatible with the existing literature of white matter pathology in MDD. Our results show that DKI is capable of demonstrating microstructural alterations in the brains of patients with MDD that cannot be fully depicted by conventional DTI. Though the issues of model validation and parameter estimation still remain, it is suggested that diffusion MRI combined with a biophysical model is a promising approach for investigation of the pathophysiology of MDD.

Red Moon methodology compatible with quantum mechanics/molecular mechanics framework: Application to solid electrolyte interphase film formation in lithium-ion battery system.

The Red Moon (RM) method [a hybrid Monte Carlo (MC)/molecular dynamics reaction method] is capable of realizing the practical atomistic simulation for complex chemical reaction systems beyond the range of application of the traditional molecular simulation techniques. In the RM method, the chemical reaction is treated stochastically based on the MC method. In the present study, to extend the applicability of the RM methodology, a new energy estimation method for the MC procedure has been proposed by using the quantum mechanics (QM)/molecular mechanics (MM) method. To validate its calculation reliability, we have examined it in a typical dimerization reaction in electrolytes of lithium-ion batteries (LIBs) and found that both solute internal energy and short-range solute-solvent interaction energy are significantly improved in comparison to the conventional energy estimation method using the MM method. As a practical application, we have dealt with the solid electrolyte interphase film formation in LIB, focusing on the bifurcation of dimerization reactions between the reduction products, and were able to reproduce the tendency similar to that in the experimental observations. It is concluded that the present RM methodology compatible with the QM/MM framework is expected to make a significant contribution to a variety of materials design and function development involved in various complex chemical reactions.

Comparison of long-term follow-up outcomes between multiple-drugs combination therapy and tonsillectomy pulse therapy for pediatric IgA nephropathy.

BACKGROUND: To clarify the long-term efficacy of multiple-drugs combination therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory findings as well as the prognosis for IgAN patients treated with each treatment at long-term follow-up. METHODS: We collected data on 61 children who had been diagnosed with severe IgAN. The children were retrospectively divided into two groups. Group 1 consisted of 44 severe IgAN children treated with PWDM, and Group 2 consisted of 17 severe IgAN children treated with TPT. The clinical features, pathological findings, and prognosis were analyzed for both groups. RESULTS: The mean urinary protein excretion, serum creatinine, IgA levels, MESTCG scores, and percentage of glomeruli showing crescents in both groups at the second renal biopsy were lower than those at the first renal biopsy. At the time of the second biopsy, the IgA level in Group 2 was lower than that in Group 1; however, there were no significant differences in the mean urinary protein excretion, frequency of hematuria, serum albumin, creatinine, or e-GFR between the two groups. At the most recent follow-up, there were no significant differences in prognosis between the groups. CONCLUSIONS: Our study suggested that PWDM and TPT are effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN.

A transformation theory of stochastic evolution in Red Moon methodology to time evolution of chemical reaction process in the full atomistic system.

Atomistic information of a whole chemical reaction system, e.g., instantaneous microscopic molecular structures and orientations, offers important and deeper insight into clearly understanding unknown chemical phenomena. In accordance with the progress of a number of simultaneous chemical reactions, the Red Moon method (a hybrid Monte Carlo/molecular dynamics reaction method) is capable of simulating atomistically the chemical reaction process from an initial state to the final one of complex chemical reaction systems. In the present study, we have proposed a transformation theory to interpret the chemical reaction process of the Red Moon methodology as the time evolution process in harmony with the chemical kinetics. For the demonstration of the theory, we have chosen the gas reaction system in which the reversible second-order reaction H2 + I2 ⇌ 2HI occurs. First, the chemical reaction process was simulated from the initial configurational arrangement containing a number of H2 and I2 molecules, each at 300 K, 500 K, and 700 K. To reproduce the chemical equilibrium for the system, the collision frequencies for the reactions were taken into consideration in the theoretical treatment. As a result, the calculated equilibrium concentrations [H2]eq and equilibrium constants Keq at all the temperatures were in good agreement with their corresponding experimental values. Further, we applied the theoretical treatment for the time transformation to the system and have shown that the calculated half-life τ's of [H2] reproduce very well the analytical ones at all the temperatures. It is, therefore, concluded that the application of the present theoretical treatment with the Red Moon method makes it possible to analyze reasonably the time evolution of complex chemical reaction systems to chemical equilibrium at the atomistic level.

Long-term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy.

BACKGROUND: The aim of this study was to clarify the long-term efficacy of tonsillectomy plus methylprednisolone pulse therapy (tonsillectomy pulse therapy [TMP]) for pediatric immunoglobulin A nephropathy (IgAN). The clinical and laboratory findings as well as the prognosis for IgAN treated with TMP at long-term follow up were evaluated. METHODS: We collected data on 33 IgAN children treated with TMP. The children were retrospectively divided into two groups. Group 1 consisted of 18 children treated with TMP as the initial therapy, and group 2 consisted of 15 children treated with TMP as rescue therapy for IgAN relapse. The clinical features, and laboratory and pathological findings, including those at first and second renal biopsy as well as at the latest follow up, were analyzed for both groups. RESULTS: Mean urinary protein excretion, incidence of hematuria, and serum creatinine in groups 1 and 2 were all decreased significantly after TMP compared with beforehand. The percentage of glomeruli showing crescents after TMP in groups 1 and 2 was significantly lower than before TMP. At the most recent follow up, 94% of patients in group 1 and 87% in group 2 had normal urine, 6% in group 1 and 13% in group 2 had minor urinary abnormalities, and no patients in either group had active renal disease or renal insufficiency. CONCLUSIONS: TMP is effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN both as an initial and as a rescue treatment.

Differences in clinical findings, pathology, and outcomes between C3 glomerulonephritis and membranoproliferative glomerulonephritis.

BACKGROUND: To clarify the clinical manifestations of pediatric complement component C3 glomerulonephritis (C3GN), we retrospectively evaluated differences in the clinicopathological findings and prognosis between C3GN and immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN). METHODS: Thirty-seven patients diagnosed with "idiopathic MPGN" were enrolled in this retrospective study. The patients were divided into two groups, with Group 1 consisting of 19 patients diagnosed with IC-MPGN and Group 2 consisting of 18 patients diagnosed with C3GN. The clinical findings and the prognosis were investigated for both groups. RESULTS: Thirteen patients in Group 2 were identified by mandatory annual school screening for urinary abnormalities. The incidence of macro-hematuria and the frequency of low serum C4 values were lower in Group 2 patients than in Group 1 patients. At the time of the second renal biopsy, urinary protein excretion, incidence of hematuria, frequency of low serum C3 values, and scores for mesangial proliferation, glomerular sclerosis, and interstitial fibrosis were higher in Group 2 patients than in Group 1 patients. At the most recent follow-up examination, the number of patients categorized as non-responding or with end-stage renal disease was higher in Group 2 patients than in Group 1 patients. CONCLUSIONS: Our results suggest that the treatment response and prognosis of patients with C3GN are worse than those of patients with IC-mediated MPGN. Therefore, in the clinical context regarding treatment options and prognosis, it may be useful to classify idiopathic MPGN as C3GN or IC-MPGN. In addition, long-term follow-up of C3GN is necessary.

Rituximab and low-dose cyclosporine combination therapy for steroid-resistant focal segmental glomerulosclerosis.

BACKGROUND: We investigated the efficacy of rituximab and low-dose cyclosporine combination therapy for focal segmental glomerulosclerosis (FSGS) in children with steroid-resistant nephrotic syndrome (SRNS). METHODS: Five FSGS children with SRNS were treated twice with rituximab and low-dose cyclosporine (CyA) combination therapy (RTX-CyAT). The clinical features and laboratory data were investigated before and after RTX-CyAT, and the outcomes were assessed. RESULTS: Prednisolone (PSL) was discontinued 3 months after RTX-CyAT in all patients. The number of CD19-positive cells decreased to <1% of all white blood cells in all patients at 1 month after RTX-CyAT, and was maintained at this level for 259.6 ± 68.2 days. All patients remained in remission for the duration of the decrease in CD19-positive cells to <1%. Two patients also remained in remission throughout the observation period, with three patients having a single relapse at 333 ± 89 days (range, 231-376 days) after RTX-CyAT. In all patients, the mean steroid and CyA doses after RTX-CyAT were lower than those before RTX-CyAT. CONCLUSIONS: RTX-CyAT is effective in FSGS patients with SRNS and may ameliorate the side-effects of PSL and immunosuppressive drugs.

Serum myeloid-related protein 8/14 in minimal change- and glomerulonephritis-related nephrotic syndrome.

BACKGROUND: Myeloid-related protein 8/14 (MRP8/14) forms stable heterodimers and is the major calcium-binding protein secreted by activated granulocytes and monocytes. We evaluated whether serum MRP8/14 level is a useful indicator for a differential diagnosis of glomerulonephritis (GN)- and minimal change disease (MC)- related nephrotic syndrome (NS). METHODS: Serum MRP8/14 complex was evaluated in 37 NS patients with MC or GN. These patients were divided into two groups. Group 1 consisted of 13 NS patients with MC, and group 2 consisted of 24 NS patients with GN. Group 2 was further divided into four subgroups: IgA nephropathy (IgAN; n = 5), Henoch-Schönlein purpura nephritis (HSPN; n = 6), focal segmental glomerulosclerosis (FSGS; n = 12), and acute GN Poststreptococcal acute glomeruloNephritis (PSAGN; n = 1). RESULTS: The clinical manifestations, laboratory findings, serum MRP8/14 level, and renal accumulation of MRP8 were investigated for each group. No significant inter-group differences were observed for serum total protein, serum albumin, or blood urea nitrogen and urinary protein excretions. Mean serum MRP8/14 in the IgAN, HSPN, FSGS, and PSAGN groups was higher than in group 1. Further, the mean glomerular and interstitial MRP8 staining scores in the IgAN, HSPN, and PSAGN groups were higher than in group 1. CONCLUSIONS: Serum MRP8/14 level may be a useful indicator for differential diagnosis between GN- and MC- related NS.

Activation of focal adhesion kinase via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury.

Impairment of epithelial barrier is observed in various intestinal disorders including inflammatory bowel diseases (IBD). Numerous factors may cause temporary damage of the intestinal epithelium. A complex network of highly divergent factors regulates healing of the epithelium to prevent inflammatory response. However, the exact repair mechanisms involved in maintaining homeostatic intestinal barrier integrity remain to be clarified. In this study, we demonstrate that activation of M1 muscarinic acetylcholine receptor (mAChR) augments the restitution of epithelial barrier function in T84 cell monolayers after ethanol-induced epithelial injury, via ERK-dependent phosphorylation of focal adhesion kinase (FAK). We have shown that ethanol injury decreased the transepithelial electrical resistance (TER) along with the reduction of ERK and FAK phosphorylation. Carbachol (CCh) increased ERK and FAK phosphorylation with enhanced TER recovery, which was completely blocked by either MT-7 (M1 antagonist) or atropine. The CCh-induced enhancement of TER recovery was also blocked by either U0126 (ERK pathway inhibitor) or PF-228 (FAK inhibitor). Treatment of T84 cell monolayers with interferon-γ (IFN-γ) impaired the barrier function with the reduction of FAK phosphorylation. The CCh-induced ERK and FAK phosphorylation were also attenuated by the IFN-γ treatment. Immunological and binding experiments exhibited a significant reduction of M1 mAChR after IFN-γ treatment. The reduction of M1 mAChR in inflammatory area was also observed in surgical specimens from IBD patients, using immunohistochemical analysis. These findings provide important clues regarding mechanisms by which M1 mAChR participates in the maintenance of intestinal barrier function under not only physiological but also pathological conditions.