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1.
J Infect Chemother ; 28(7): 859-865, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35307263

ABSTRACT

INTRODUCTION: Seasonal human coronavirus (HCoV)-229E, -NL63, -OC43, and -HKU1 are seasonal coronaviruses that cause colds in humans. However, the clinical characteristics of pediatric inpatients infected with HCoVs are unclear. This study aimed to compare and clarify the epidemiological and clinical features of HCoVs and respiratory syncytial virus (RSV), which commonly causes severe respiratory infections in children. METHODS: Nasopharyngeal swabs were collected from all pediatric inpatients with respiratory symptoms at two secondary medical institutions in Fukushima, Japan. Eighteen respiratory viruses, including RSV and four HCoVs, were detected via reverse transcription-polymerase chain reaction. RESULTS: Of the 1757 specimens tested, viruses were detected in 1272 specimens (72.4%), with 789 single (44.9%) and 483 multiple virus detections (27.5%). RSV was detected in 639 patients (36.4%) with no difference in clinical characteristics between RSV-A and RSV-B. HCoV was detected in 84 patients (4.7%): OC43, NL63, HKU1, and 229E in 25 (1.4%), 26 (1.5%), 23 (1.3%), and 16 patients (0.9%), respectively. Patients with HCoV monoinfection (n = 35) had a significantly shorter period from onset to hospitalization (median [interquartile range] days, 2 [1-4.5] vs. 4 [2-5]), significantly shorter hospitalization stays (4 [3-5] vs. 5 [4-6]), and more cases of upper respiratory infections (37.1% vs. 3.9%) and croup (17.1% vs. 0.3%) but less cases of lower respiratory infection (54.3% vs. 94.8%) than patients with RSV monoinfection (n = 362). CONCLUSION: Seasonal HCoV-infected patients account for approximately 5% of children hospitalized for respiratory tract infections and have fewer lower respiratory infections and shorter hospital stays than RSV-infected patients.


Subject(s)
COVID-19 , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , COVID-19/epidemiology , Child , Child, Hospitalized , Humans , Infant , Pandemics , Respiratory Tract Infections/epidemiology , Seasons
2.
Anal Bioanal Chem ; 413(19): 4727-4738, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34080034

ABSTRACT

N-Glycosylation of therapeutic antibodies is a critical quality attribute (CQA), and the micro-heterogeneity affects the biological and physicochemical properties of antibodies. Therefore, the profiling of N-glycans on antibodies is essential for controlling the manufacturing process and ensuring the efficacy and safety of the therapeutic antibodies. To monitor N-glycosylation in recombinant proteins, a high-throughput (HTP) methodology for glycan analysis is required to handle bulk samples in various stages of the manufacturing process. In this study, we focused on the HTP methodology for N-glycan analysis using a commercial microchip electrophoresis-based DNA analyzer and demonstrated the feasibility of the workflow consisting of sample preparation and electrophoretic separation. Even if there is a demand to analyze up to 96 samples, the present workflow can be completed in a day without expensive instruments and reagent kits for sample preparation, and it will be a promising methodology for cost-effective and facile HTP N-glycosylation analysis while optimizing the manufacturing process and development for therapeutic antibodies.


Subject(s)
Antibodies, Monoclonal/chemistry , High-Throughput Screening Assays/methods , Oligonucleotide Array Sequence Analysis , Polysaccharides/chemistry , Animals , CHO Cells , Cell Line, Tumor , Cricetinae , Cricetulus , Fluorescent Dyes , Mice , Reproducibility of Results , Sensitivity and Specificity
3.
Tohoku J Exp Med ; 253(2): 125-134, 2021 02.
Article in English | MEDLINE | ID: mdl-33612573

ABSTRACT

Childhood idiopathic nephrotic syndrome (NS) is defined by proteinuria and hypoproteinemia. The incidence of childhood idiopathic NS varies with age, race, residential areas, and social conditions. In Japan, its incidence was estimated to be 6.49 cases/100,000 children. Our study aimed to investigate the incidence, characteristics, and rate of relapse of idiopathic NS in Fukushima between 2006 and 2016. Overall, 158 children aged from 6 months to 15 years old (65.8% male) developed idiopathic NS (median age at onset, 5.3 years). The peak age at onset was three years. The average annual incidence of childhood idiopathic NS was 5.16 (range, 3.47-9.26) cases/100,000 children. The highest incidence was in 2011, which was the year of the Great East Japan Earthquake and nuclear power plant accident, and reportedly caused psychological distress in the children at the time. Conversely, the five-year birth cohort showed minor difference from 2008 to 2012. The rate of incidence in males aged < 5 years was thrice greater than in females of the same age and almost the same for males and females aged 11-15 years. Of 507 total relapses in 115 NS children, common triggers of relapses were steroid discontinuation or reduction and infection. The average annual incidence of childhood NS based on the Fukushima population was lower than previously reported in Japan, and the annual incidence has changed over an 11-year period. These changes may be affected by social or environmental factors, including mental stress associated with lifestyle changes after the disaster.


Subject(s)
Nephrotic Syndrome/epidemiology , Adolescent , Age Distribution , Child , Child, Preschool , Cohort Studies , Female , Humans , Incidence , Infant , Infant, Newborn , Japan/epidemiology , Male , Nephrotic Syndrome/drug therapy , Recurrence , Steroids/therapeutic use
4.
Analyst ; 145(23): 7759-7764, 2020 Nov 23.
Article in English | MEDLINE | ID: mdl-33006340

ABSTRACT

A new indirect chemosensor for the detection of cyanide in blood is developed. 2-(5-Bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol, a yellow dye, forms a blue-coloured complex with palladium ions. The yellow colour of this complex is regained upon reaction with cyanide ions. The complex shows high selectivity for the detection of cyanide over 16 other anions. The system was applied to two different methods for the detection of cyanide in human whole blood. As a quantitative absorbance method, blood samples were mixed with acid, and the resulting vaporised hydrogen cyanide was absorbed in an alkaline solution containing the complex in a Conway cell. The resulting absorbance response of the solution at 450 nm is linear over the range 4-40 µM (R2 = 1.000), and the limit of detection is 0.6 µM. Furthermore, the complex-soaked paper is applicable as a test strip for cyanide detection. When a test strip is used with 0.5 mL of blood, the limit of detection is 15 µM. The detection limits of these two methods are below the toxic blood cyanide concentration (19 µM). Therefore, both methods allow the quantification and screening of cyanide in blood samples. Furthermore, the test strip is low cost and enables on-site analysis.


Subject(s)
Cyanides , Phenol , Anions , Humans , Phenols
5.
Anal Chem ; 90(14): 8387-8395, 2018 07 17.
Article in English | MEDLINE | ID: mdl-29886736

ABSTRACT

Changes in the structures and quantities of sulfated glycans play important roles in inflammatory and neurological diseases and cancer. Therefore, sulfated glycans are expected to become diagnostic markers for a variety of diseases such as Alzheimer's disease and cancer. On the other hand, structural abnormalities in the phosphorylated glycans on lysosomal enzymes cause a number of lysosomal diseases, while novel phosphorylated glycans have been found in other proteins. As with sulfated glycans, structural and quantitative changes in these phosphorylated glycans and their associations with disease are also of interest. In this article, we introduce a new method for the simultaneous analysis of sulfated and phosphorylated glycans. We first employ a serotonin-immobilized column to enrich these glycans. Glycans obtained in this manner were sequentially subjected to other analytical techniques without desalting. We employed hydrophilic interaction chromatography to distinguish the sulfate and phosphate groups of the glycans and were able to analyze sulfated and phosphorylated N-glycans expressed on thyroglobulin, ovalbumin, and myozyme. We showed that our method not only analyzes sulfated and phosphorylated glycans, but also glycans containing the GlcNAc-HPO3 residue. We comparatively analyzed sulfated glycans, phosphorylated glycans, and GlcNAc-HPO3-residue-containing glycans expressed on MKN7 cells (well-differentiated gastric cancer cells) and MKN45 cells (poorly differentiated gastric cancer cells). To the best of our knowledge, this is the first report of a method for the simultaneous and quantitative analysis of sulfated and phosphorylated glycans.

6.
Analyst ; 143(18): 4429-4435, 2018 Sep 21.
Article in English | MEDLINE | ID: mdl-30151536

ABSTRACT

A simple and efficient method was developed for the fabrication of a cationic sample preconcentrator on a channel of a commercial poly(methyl methacrylate) (PMMA) microchip. This approach is based on a simple photochemical copolymerization for the fabrication of a permselective preconcentrator. The intersection of the PMMA microchip was filled with a gel solution comprising acrylamide, N,N-methylene-bis-acrylamide, (3-acrylamidopropyl) trimethylammonium, and riboflavin that functioned as a photocatalytic initiator. In situ polymerization near the cross of the sample outlet channel was performed by pinpoint irradiation with a 488 nm SHG laser beam, which is also used as the light source for fluorimetric detection. The electrokinetic property and electric repulsion between sample components and cationic groups on the polyacrylamide gel layer enables trapping and preconcentration of cations at the boundary of the anodic side of the gel layer. Reproducibility is about 20% RSD due to the variation of the position of the hand-made electrode in sample reservoir, but the preconcentration factors exceeded over 104-fold. The utility of the cationic preconcentrator gel was demonstrated by analyzing rhodamine derivatives, oligosaccharides labeled with rhodamine 110 and cytochrome C labeled with fluorescein isothiocyanate.

7.
Nutr J ; 17(1): 98, 2018 10 30.
Article in English | MEDLINE | ID: mdl-30376838

ABSTRACT

BACKGROUND: We recently reported that successive ingestion of matured hop extract (MHE), produced by oxidation of hops, results in a reduction of body fat in healthy overweight participants. A combined effect of MHE and physical activity on body fat has not been investigated. Thus, we re-analyzed data from the previous study to explore the relationship between the effect of MHE and walking as an index of physical activity. METHODS: This analysis uses existing data from a randomized, double-blind, placebo-controlled parallel group study in which MHE (active) or placebo was given for 12 w to 200 healthy overweight Japanese, from May to December 2014. Correlation between the change in abdominal fat areas at 12 w and the number of steps taken per day was tested by Spearman's correlation coefficient test. The subjects were stratified using the average number of steps per day of Japanese into walking less and walking more subgroups (WL and WM, respectively) as follows: placebo (WL, n = 43; WM, n = 44) and active (WL, n = 49; WM, n = 42). Reductions in total, visceral, and subcutaneous fat area (TFA, VFA and SFA, respectively) were evaluated. The interaction effect between ingestion (active/placebo) and walking (WL/WM) was analyzed using two-way analysis of variance (ANOVA). RESULTS: There was a significant negative correlation between the change in VFA and daily steps taken in the active group (r = - 0.208, P = 0.048). No significant correlation in TFA or SFA. Although the interaction effect in TFA was not significant, the main effect of ingestion was significant (P = 0.045). In contrast, the interaction effect in VFA was suggested to be synergistic (P = 0.055). CONCLUSION: The results suggested that MHE ingestion combined with light intensity exercise would induce a greater reduction in VFA which would be beneficial for obese or overweight individuals in reducing obesity and obesity-related diseases. TRIAL REGISTRATION: UMIN-CTR UMIN000014185 registered 6 June 2014.


Subject(s)
Adipose Tissue/drug effects , Exercise , Humulus , Overweight/diet therapy , Plant Extracts/administration & dosage , Adult , Aged , Body Mass Index , Double-Blind Method , Female , Humans , Japan , Male , Middle Aged , Obesity/diet therapy , Walking , Weight Loss/drug effects , Young Adult
8.
Electrophoresis ; 38(9-10): 1344-1352, 2017 05.
Article in English | MEDLINE | ID: mdl-28261824

ABSTRACT

mAbs are currently mainstream in biopharmaceuticals, and their market has been growing due to their high target specificity. Characterization of heterogeneities in mAbs is performed to secure their quality and safety by physicochemical analyses. However, they require time-consuming task, which often strain the resources of drug development in pharmaceuticals. Rapid and direct method to determine the heterogeneities should be a powerful tool for pharmaceutical analysis. Considering the advantages of electrophoresis and MS, this study addresses the combination of SDS-PAGE and intact mass analysis, which provides direct, rapid, and orthogonal determination of heterogeneities in mAb therapeutics. mAb therapeutics that migrated in SDS-PAGE were recovered from gel by treatment with SDC-containing buffer. Usage of SDC-containing buffer as extraction solvent and ethanol-based staining solution enhanced the recovery of intact IgG from SDS-PAGE gels. Recovery of mAbs reached more than 86% with 0.2% SD. The heterogeneities, especially N-glycan variants in the recovered mAb therapeutics, were clearly determined by intact mass analysis. We believe that the study is important in pharmaceuticals‧ perspective since orthogonal combination of gel electrophoresis and intact mass analysis should be pivotal role for rapid and precise characterization of mAbs.


Subject(s)
Antibodies, Monoclonal/chemistry , Chromatography, High Pressure Liquid/methods , Electrophoresis, Polyacrylamide Gel/methods , Polysaccharides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Antibodies, Monoclonal/analysis , Polysaccharides/analysis
9.
J Eukaryot Microbiol ; 64(4): 440-446, 2017 07.
Article in English | MEDLINE | ID: mdl-27813319

ABSTRACT

Some organisms have retained plastids even after they have lost the ability to photosynthesize. Several studies of nonphotosynthetic plastids in apicomplexan parasites have shown that the isopentenyl pyrophosphate biosynthesis pathway in the organelle is essential for their survival. A phytohormone, abscisic acid, one of several compounds biosynthesized from isopentenyl pyrophosphate, regulates the parasite cell cycle. Thus, it is possible that the phytohormone is universally crucial, even in nonphotosynthetic plastids. Here, we examined this possibility using the oyster parasite Perkinsus marinus, which is a plastid-harboring cousin of apicomplexan parasites and has independently lost photosynthetic ability. Fluridone, an inhibitor of abscisic acid biosynthesis, blocked parasite growth and induced cell clustering. Nevertheless, abscisic acid and its intermediate carotenoids did not affect parasite growth or rescue the parasite from inhibition. Moreover, abscisic acid was not detected from the parasite using liquid chromatography mass spectrometry. Our findings show that abscisic acid does not play any significant roles in P. marinus.


Subject(s)
Abscisic Acid/metabolism , Apicomplexa/growth & development , Apicoplasts/metabolism , Ostreidae/parasitology , Animals , Apicomplexa/drug effects , Apicomplexa/metabolism , Biosynthetic Pathways/drug effects , Chromatography, Liquid , Mass Spectrometry , Phylogeny , Pyridones/pharmacology
10.
Analyst ; 142(18): 3416-3423, 2017 Sep 08.
Article in English | MEDLINE | ID: mdl-28825746

ABSTRACT

A method was developed for the specific entrapment and separation of phosphorylated compounds using a Phos-tag polyacrylamide gel fabricated at the channel crossing point of a microfluidic electrophoresis chip. The channel intersection of the poly(methyl methacrylate)-made microchip was filled with a solution comprising acrylamide, N,N-methylene-bis-acrylamide, Phos-tag acrylamide, and 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], which functioned as a photocatalytic initiator. In situ polymerization at the channel crossing point was performed by irradiation with a UV LED laser beam. The fabricated Phos-tag gel (100 × 100 × 30 µm) contains ca. 20 fmol of the Phos-tag group and therefore could entrap phosphorylated compounds at the femtomolar level. The electrophoretically trapped phosphorylated compounds were released from the gel by switching the voltage to deliver high concentrations of phosphate and EDTA in a background electrolyte. The broad sample band eluted from the gel was effectively reconcentrated at the boundary of a pH junction generated by sodium ions delivered from the outlet reservoir. The reconcentrated sample components were then separated and fluorometrically detected at the end of the separation channel. Under the optimized conditions, the phosphorylated compounds were concentrated by a factor of 100-fold, and the peak resolution was comparable to that obtained by pinched injection. This method was successfully utilized to preconcentrate and analyze phosphorylated peptides in a complex peptide mixture.


Subject(s)
Acrylic Resins/chemistry , Electrophoresis, Microchip , Electrophoresis, Polyacrylamide Gel , Peptides/analysis , Phosphorylation , Pyridines
11.
Mod Rheumatol ; 27(6): 1098-1100, 2017 Nov.
Article in English | MEDLINE | ID: mdl-25867226

ABSTRACT

Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a systemic autoinflammatory disease caused by increased production of interleukin (IL)-1ß. We present a case of CINCA syndrome followed up to skeletal maturity. Joint contracture and valgus deformity of the knee had developed before diagnosis. Surgical interventions by soft tissue release and hemiepiphysiodesis improved the contracture and the deformity, and IL-1 receptor antagonist dramatically controlled systemic inflammation, and the patient lives without any disabilities.


Subject(s)
Contracture/diagnosis , Cryopyrin-Associated Periodic Syndromes/diagnosis , Antirheumatic Agents/therapeutic use , Contracture/drug therapy , Contracture/surgery , Cryopyrin-Associated Periodic Syndromes/drug therapy , Cryopyrin-Associated Periodic Syndromes/surgery , Humans , Infant , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Knee Joint/pathology , Knee Joint/surgery , Male
12.
Antimicrob Agents Chemother ; 59(11): 6960-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26324278

ABSTRACT

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe(2+)) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug.


Subject(s)
Aminolevulinic Acid/therapeutic use , Malaria/drug therapy , Aminolevulinic Acid/administration & dosage , Animals , Body Weight/drug effects , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Parasitemia/drug therapy , Plasmodium falciparum/drug effects , Plasmodium falciparum/pathogenicity , Polymerase Chain Reaction
13.
Antimicrob Agents Chemother ; 59(3): 1643-9, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25547357

ABSTRACT

We estimated the efficacy of the current single administration of peramivir on the basis of peramivir pharmacokinetics in the upper respiratory tract (URT) and determined the predictive peramivir concentration-time curve to assess its efficacy against viruses with decreased susceptibility to neuraminidase inhibitors. Serum, nasal swab, or aspiration samples were collected from 28 patients treated with 10 mg/kg body weight peramivir. The sequential influenza viral RNA load and susceptibility after peramivir administration were measured using a quantitative real-time reverse transcription-PCR and neuraminidase inhibition assay. The peramivir concentrations in the serum and URT after a single administration at 10 mg/kg were measured, and the predictive blood and URT peramivir concentration-time curves were determined to assess various administration regimens against resistant variants. The peramivir concentration decreased to <0.1% of the maximum concentration of drug in serum (Cmax) at 24 h after administration. Rapid elimination of peramivir from the URT by 48 h after administration may contribute to an increase in the influenza A viral load after day 3 but not to a decrease in the influenza B viral load, despite the absence of a decrease in the susceptibility to peramivir. A longer maintenance of a high level of peramivir in the URT is expected by divided administration rather than once-daily administration. When no clinical improvement is observed in patients with normal susceptibility influenza A and B, peramivir readministration should be considered. In severe cases caused by resistant variants, better inhibitory effectiveness and less frequent adverse events are expected by divided administration rather than once-daily administration with an increased dosage.


Subject(s)
Cyclopentanes/administration & dosage , Cyclopentanes/pharmacokinetics , Drug Resistance, Viral/drug effects , Guanidines/administration & dosage , Guanidines/pharmacokinetics , Influenza A virus/drug effects , Influenza B virus/drug effects , Influenza, Human/drug therapy , Viral Load/drug effects , Acids, Carbocyclic , Adolescent , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacokinetics , Child , Child, Preschool , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacokinetics , Female , Humans , Infant , Influenza A virus/metabolism , Influenza B virus/metabolism , Kinetics , Male , Neuraminidase/antagonists & inhibitors , Viral Proteins/metabolism
14.
Anal Bioanal Chem ; 407(20): 6201-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26044740

ABSTRACT

A novel method was developed for D/L-isomeric separation of aldopentoses and aldohexoses as their (S)-(+)-4-(N,N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole derivatives using phenylboronate buffer containing sodium dodecyl sulfate as a background electrolyte. The combination of derivatization with a chiral labeling reagent and micellar electrokinetic chromatography with phenylboronate made possible the efficient separation of D/L isomers as well as epimeric isomers of aldopentoses and aldohexoses. Laser-induced fluorescence detection permitted the micromolar-level determination of monosaccharide derivatives. The limit of detection was 105 amol (300 nM), and the repeatabilities of the migration times and peak area responses were 0.8 % and 7.9 % (relative standard deviation; n = 6), respectively. The method was applied to the determination of D/L- galactose in red seaweed.


Subject(s)
Boronic Acids/chemistry , Hexoses/isolation & purification , Oxadiazoles/isolation & purification , Pentoses/isolation & purification , Sulfonamides/isolation & purification , Chromatography, Micellar Electrokinetic Capillary/methods , Galactose/analysis , Galactose/isolation & purification , Hexoses/analysis , Oxadiazoles/analysis , Pentoses/analysis , Seaweed/chemistry , Stereoisomerism , Sulfonamides/analysis
15.
Anal Bioanal Chem ; 407(5): 1499-503, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25433688

ABSTRACT

A selective separation method using a poly(methylmethacrylate) microchip was developed for 7-amino-4-methylcoumarin-labeled saccharides in a crude reaction mixture. In an alkaline borate buffer, saccharide derivatives formed strong anionic borate complexes. These complexes moved from the cathode to the anode in an electric field and were detected near the anode. Excess labeling reagents and other foreign substances remained at the inlet reservoir. A confocal fluorimetric detection system enabled the determination of monosaccharide derivatives with good linearity between at least 5 and 100 nM, corresponding to 50 fmol to 1 pmol per injection. The lower limit of detection (signal-to-noise = 5) was 2 nM. The sensitivity and linear quantitation range were comparable to reported values using fluorometric detection, capillary electrophoresis, or liquid chromatography. Application of the method showed excellent resolution in the analysis of O-linked glycans chemically released from glycoproteins.


Subject(s)
Electrophoresis, Microchip/methods , Oligosaccharides/chemistry , Oligosaccharides/isolation & purification , Coumarins/chemistry , Electrophoresis, Microchip/instrumentation , Glycoproteins/chemistry , Sensitivity and Specificity
17.
Pediatr Int ; 57(4): 650-5, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25615939

ABSTRACT

BACKGROUND: We examined the epidemiology, clinical manifestations, and prognosis of pediatric systemic lupus erythematosus (SLE) in Fukushima Prefecture, Japan over a 35 year period. METHODS: We collected the medical records of 37 patients diagnosed with SLE between 1977 and 2013. These children were divided into two groups. group 1 consisted of 19 patients who were diagnosed between 1977 and 1995, and group 2 consisted of 18 patients diagnosed between 1996 and 2013. The epidemiology, clinical features, and prognosis were retrospectively compared between the two groups. RESULTS: The mean number of patients per 100,000 children per year for group 1 and group 2 was 0.33 ± 0.25 and 0.35 ± 0.30, respectively. The duration from onset of symptoms to treatment in group 2 was shorter than that in group 1, but the clinical and laboratory findings at onset did not differ between the two groups. All patients were treated with prednisolone, and 17 patients in group 1 and 18 in group 2 were treated with methylprednisolone pulse therapy. The frequency of cyclophosphamide treatment decreased whereas the frequency of cyclosporine, tacrolimus and mizoribine pulse therapy increased in group 2. SLE disease activity index (SLEDAI) score at the latest follow up in group 2 was lower in group 1. The survival rate was 84% in group 1 and 100% in group 2. CONCLUSION: The frequency and severity of SLE in group 1 were similar to those in group 2, and the prognosis of SLE in group 2 was better than that in group 1.


Subject(s)
Forecasting , Lupus Erythematosus, Systemic/epidemiology , Age of Onset , Biopsy , Child , Female , Follow-Up Studies , Humans , Incidence , Japan/epidemiology , Lupus Erythematosus, Systemic/diagnosis , Male , Retrospective Studies , Severity of Illness Index , Survival Rate/trends
18.
Pediatr Int ; 56(1): 77-82, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23937579

ABSTRACT

BACKGROUND: There have been a number of reports on large outbreaks of hemolytic uremic syndrome (HUS), but there have been no long-term studies of sporadic HUS in Japan. This study therefore investigated the epidemiology and prognosis of HUS in Fukushima Prefecture over a 26 year period. METHODS: The medical records of 26 patients with HUS between 1987 and 2012 were collected. These children were divided into two groups: those with HUS following an episode of gastroenteritis, often with bloody diarrhea (D + HUS; n = 24) and those with HUS not associated with prodromal diarrhea (D-HUS; n = 2). The D + HUS group was further subdivided into group A (11 patients requiring dialysis) and group B (13 patients not requiring dialysis). The epidemiological and clinical data, as well as prognosis, were retrospectively investigated for each group. RESULTS: Approximately 90% of HUS patients belonged to the D + HUS group. In this group, the mean number of patients per year from 1987 to 1999, and from 2000 to 2012 was 0.92 ± 0.95, and 1.08 ± 0.86, respectively. On admission, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine and serum fibrinogen degradation product (FDP) levels in group A were all higher than in group B. Serum albumin level and estimated glomerular filtration rate (eGFR) in group A were lower than in group B. At 6 months after the onset of HUS in the D + HUS group, renal function was normal. CONCLUSIONS: The frequency of HUS was constant from 1987 to 2012 in Fukushima. and serum LDH, ALT, BUN, creatinine, and FDP levels as well as eGFR might be risk factors for dialysis in D + HUS children.


Subject(s)
Disasters , Forecasting , Hemolytic-Uremic Syndrome/epidemiology , Radioactive Hazard Release , Child , Child, Preschool , Female , Follow-Up Studies , Hemolytic-Uremic Syndrome/diagnosis , Hemolytic-Uremic Syndrome/etiology , Humans , Incidence , Japan/epidemiology , Male , Retrospective Studies , Severity of Illness Index
19.
Sci Rep ; 14(1): 11519, 2024 05 21.
Article in English | MEDLINE | ID: mdl-38769131

ABSTRACT

Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the Enterococcus faecalis 2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and p-glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased N-methyl-D-aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII/CREB/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII/CREB/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.


Subject(s)
Anti-Anxiety Agents , Dextran Sulfate , Disease Models, Animal , Enterococcus faecalis , Animals , Mice , Anti-Anxiety Agents/pharmacology , Anti-Anxiety Agents/therapeutic use , Dextran Sulfate/toxicity , Male , Anxiety/drug therapy , Lipopolysaccharides , Corticosterone/blood , Prefrontal Cortex/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/microbiology , Mice, Inbred C57BL
20.
Jpn J Infect Dis ; 77(3): 137-143, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38171847

ABSTRACT

Human metapneumovirus (hMPV) is genetically classified into two major subgroups, A and B, based on attachment glycoprotein (G protein) gene sequences. The A2 subgroup is further separated into three subdivisions, A2a, A2b (A2b1), and A2c (A2b2). Subgroup A2c viruses carrying 180- or 111-nucleotide duplications in the G gene (A2c 180nt-dup or A2c 111nt-dup ) have been reported in Japan and Spain. The coronavirus disease 2019 (COVID-19) pandemic disrupted the epidemiological kinetics of other respiratory viruses, including hMPV. In this study, we analyzed the sequences of hMPV isolates in Tokyo and Fukushima obtained from 2017 to 2022, i.e., before and after the COVID-19 pandemic. Subgroup A hMPV strains were detected from 2017 to 2019, and most cases were A2c 111nt-dup, suggesting ongoing transmission of this clade, consistent with global transmission dynamics. Subgroup B viruses, but not subgroup A viruses, were detected in 2022 after the COVID-19 peak. Phylogenetic analysis showed that the subgroup B viruses were closely related to strains detected in Yokohama from 2013 to 2016, and strains detected in Fukushima in 2019, suggesting the reappearance of local endemic viruses in East Japan.


Subject(s)
COVID-19 , Metapneumovirus , Molecular Epidemiology , Paramyxoviridae Infections , Phylogeny , Metapneumovirus/genetics , Metapneumovirus/classification , Metapneumovirus/isolation & purification , Humans , COVID-19/epidemiology , COVID-19/virology , COVID-19/transmission , Japan/epidemiology , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/virology , SARS-CoV-2/genetics , SARS-CoV-2/classification , Child, Preschool , Child , Infant
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