Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

ABSTRACT

In paediatric primary Sjögren’s syndrome (SS), the initial symptoms manifest systemically, such as fever, general fatigue, and lymphadenopathy, rather than sicca symptoms. Most children with primary SS have autoantibodies, such as antinuclear, anti-Ro/SS-A, and/or anti-La/SS-B antibodies; however, some patients are seronegative. Similar to paediatric patients with primary SS, those with Takayasu arteritis (TAK) initially only present constitutional symptoms, making it difficult to suspect, unless characteristic features are present. To our knowledge, there have been no reports of the coexistence of both diseases in children. We present a rare case of seronegative SS complicated by TAK in a 9-year-old girl who presented with a persistent low-grade fever, general fatigue, cervical lymphadenopathy, and multiple caries. Although blood examination revealed all autoantibodies to be negative, a lip biopsy revealed lymphocytic sialadenitis, and a sialoscintigraphy indicated hypofunctional salivary glands, leading to the diagnosis of seronegative SS. The patient was treated with low-dose glucocorticoid and immunosuppressant administration to inhibit persistent inflammation and the progression of salivary gland dysfunction; although the symptoms resolved, inflammatory markers remained elevated. When the patient was 14 years old, cervical bruits were incidentally found, and TAK was suspected based on cervical ultrasonography and magnetic resonance angiography findings. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography results demonstrated increased fluorodeoxyglucose accumulation from the ascending to descending aorta. Therefore, she was diagnosed with SS complicated by TAK, which is rare. Aortitis should be suspected when the cause of persistent inflammation cannot be ascertained in patients with SS.

DOI： 10.1093/mrcr/rxac062

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Language：English   Publishing type：Research paper (scientific journal)  

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited retinal disorders involving the progressive dysfunction of photoreceptors and the retinal pigment epithelium, for which there is currently no treatment. The rd6 mouse is a natural model of autosomal recessive retinal degeneration. Given the known contributions of oxidative stress caused by reactive oxygen species (ROS) and selective inhibition of potent ROS peroxynitrite and OH·by H2 gas we have previously demonstrated, we hypothesized that ingestion of H2 water may delay the progression of photoreceptor death in rd6 mice. H2 mice showed significantly higher retinal thickness as compared to controls on optical coherence tomography. Histopathological and morphometric analyses revealed higher thickness of the outer nuclear layer for H2 mice than controls, as well as higher counts of opsin red/green-positive cells. RNA sequencing (RNA-seq) analysis of differentially expressed genes in the H2 group versus control group revealed 1996 genes with significantly different expressions. Gene and pathway ontology analysis showed substantial upregulation of genes responsible for phototransduction in H2 mice. Our results show that drinking water high in H2 (1.2-1.6 ppm) had neuroprotective effects and inhibited photoreceptor death in mice, and suggest the potential of H2 for the treatment of RP.

DOI： 10.1038/s41598-022-17903-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

ABSTRACT

Childhood-onset systemic lupus erythematosus (cSLE) has been recognised as a more acute and severe autoimmune disease than adult-onset SLE. With the development of medications for the disease and supportive therapy, the mortality rate associated with cSLE has drastically improved; the 10-year survival rate among patients with cSLE between 1995 and 2006 in Japan was 98.3%. However, the 10-year survival rate without any permanent functional impairment remained low at 66.1%. Therefore, the current treatment goal for cSLE is to ensure that they can perform normal daily activities throughout their lives by preventing the occurrence and/or progression of organ damage.

For this purpose, appropriate treatments and evaluations are required according to the severity and risk of organ damage; however, there are no established guidelines for cSLE. Therefore, the Pediatric Rheumatology Association of Japan and the Pediatric Rheumatology Subcommittee in the Japan College of Rheumatology developed a comprehensive guidance for clinical practice based on cSLE-related data collected from Japanese national surveys and relevant articles from both domestic and international sources. However, due to the lack of indications for defined and objective evidence quality levels, this guidance should be used on the basis of the judgement of the attending physicians for individual patients.

DOI： 10.1093/mr/roab002

PubMed

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Other Link： https://academic.oup.com/mr/article-pdf/32/2/239/42644831/roab002.pdf

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

ABSTRACT

Background

Although Lowe syndrome and Dent disease-2 are caused by Oculocerebrorenal syndrome of Lowe (OCRL) mutations, their clinical severities differ substantially and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1–7 lead to Dent disease-2, whereas those in exons 8–24 lead to Lowe syndrome. Herein we identified the mechanism underlying the action of novel OCRL protein isoforms.

Methods

Messenger RNA samples extracted from cultured urine-derived cells from a healthy control and a Dent disease-2 patient were examined to detect the 5′ end of the OCRL isoform. For protein expression and functional analysis, vectors containing the full-length OCRL transcripts, the isoform transcripts and transcripts with truncating mutations detected in Lowe syndrome and Dent disease-2 patients were transfected into HeLa cells.

Results

We successfully cloned the novel isoform transcripts from OCRL exons 6–24, including the translation-initiation codons present in exon 8. In vitro protein-expression analysis detected proteins of two different sizes (105 and 80 kDa) translated from full-length OCRL, whereas only one protein (80 kDa) was found from the isoform and Dent disease-2 variants. No protein expression was observed for the Lowe syndrome variants. The isoform enzyme activity was equivalent to that of full-length OCRL; the Dent disease-2 variants retained >50% enzyme activity, whereas the Lowe syndrome variants retained <20% activity.

Conclusions

We elucidated the molecular mechanism underlying the two different phenotypes in OCRL-related diseases; the functional OCRL isoform translated starting at exon 8 was associated with this mechanism.

DOI： 10.1093/ndt/gfab274

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Other Link： https://academic.oup.com/ndt/article-pdf/37/2/262/42771908/gfab274.pdf

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However, the differences in clinical features and pathogenesis of these are not fully understood. Therefore, we performed systematic literature reviews for IKAROS and CTLA4 deficiencies. The reviews suggested that patients with IKAROS deficiency develop AD earlier than hypogammaglobulinemia. However, no study assessed the detailed changes in clinical manifestations over time; this was likely due to the cross-sectional nature of the studies. Therefore, we conducted a retrospective longitudinal study on IKAROS and CTLA4 deficiencies in our cohort to evaluate the clinical course over time. In patients with IKAROS deficiency, AD and hypogammaglobulinemia often develop in that order, and AD often resolves before the onset of hypogammaglobulinemia; these observations were not found in patients with CTLA4 deficiency. Understanding this difference in the clinical course helps in the clinical management of both. Furthermore, our results suggest B- and T-cell-mediated ADs in patients with IKAROS and CTLA4 deficiencies, respectively.

DOI： 10.3389/fimmu.2021.784901

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s13730-021-00617-7

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Other Link： https://link.springer.com/article/10.1007/s13730-021-00617-7/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Although Lowe syndrome and Dent disease-2 are both caused by OCRL mutations, their clinical severities differ substantially, and their molecular mechanisms remain unclear. Truncating mutations in OCRL exons 1 through 7 lead to Dent disease-2, whereas those in exons 8 through 24 lead to Lowe syndrome. Herein, we identified the mechanism underlying the action of novel OCRL protein isoforms.


</sec>
<sec>
<title>Methods</title>
mRNA samples extracted from cultured urine-derived cells from a healthy control and the Dent disease-2 patient were examined to detect the 5′ end of the OCRL isoform. For protein expression and functional analysis, vectors containing (1) the full-length OCRL transcripts, (2) the isoform transcripts, and (3) transcripts with truncating mutations detected in Lowe syndrome and Dent disease-2 patients were transfected into HeLa cells.


</sec>
<sec>
<title>Results</title>
We successfully cloned the novel isoform transcripts from OCRL exons 6–24, including the translation-initiation codons present in exon 8. In vitro protein-expression analysis detected proteins of two different sizes (105 and 80 kDa) translated from full-length OCRL, whereas only one protein (80 kDa) was found from the isoform and Dent disease-2 variants. No protein expression was observed for the Lowe syndrome variants. The isoform enzyme activity was equivalent to that of full-length OCRL; the Dent disease-2 variants retained &amp;gt; 50% enzyme activity, whereas the Lowe syndrome variants retained &amp;lt; 20% activity.


</sec>
<sec>
<title>Conclusions</title>
We elucidated the molecular mechanism underlying the two different phenotypes in OCRL-related diseases; the functional OCRL isoform translated starting at exon 8 was associated with this mechanism.


</sec>

DOI： 10.1093/ndt/gfab274

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Language：English   Publishing type：Research paper (scientific journal)  

IgA vasculitis (IgAV) is the most frequent form of vasculitis in childhood which classically presents with purpura of the lower extremities, joint pain or swelling and abdominal pain. Though it is a self-limiting disease, and its prognosis is generally good, glomerulonephritis is one of the most important complications. IgAV is classified as a small vessel vasculitis, and though glomerulonephritis develops in IgAV, necrotizing arteritis is rarely seen. Here, we present a case of a 13-year-old girl with IgAV, glomerulonephritis, and necrotizing arteritis in the small renal arteries. There have been only a few reports of adult cases of IgAV with necrotizing arteritis in the kidneys, but there have been no pediatric cases. Some previous reports showed a high mortality rate and implied the possibility of overlap with other vasculitides. In the current report, a rare case of IgAV is described which exhibited necrotizing arteritis rather than overlap with another vasculitis, with a relatively typical clinical course for IgAV and laboratory tests.

DOI： 10.1007/s13730-021-00617-7

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Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.jnms.2021_88-305

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Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.jnms.2021_88-305

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.1080/14397595.2020.1761075

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The aim of this study was to measure the serum levels of brain-derived neurotrophic factor (BDNF) in primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients in Japan. METHODS: This was a prospective, observational study that examined serum BDNF levels in 78 patients who underwent cataract surgery or trabeculectomy (27 glaucoma patients and 51 non-glaucoma cataract patients as controls). The patients' age was 68.8 ± 11.1 years (mean ± standard deviation; range 35-86 years). The number of patients with POAG and NTG was 16 and 11, respectively. The diagnosis of POAG was done by intraocular pressure measurement, gonioscopy, optic nerve head change, and the presence of a visual field defect. RESULTS: The serum BDNF concentration was significantly lower in the glaucoma group, including both POAG and NTG, than in the control group (7.2 ± 3.6 ng/mL vs. 12.2 ± 9.3 ng/mL, p=0.004). The serum BDNF concentration was lower in the early phase than in the moderate phases of glaucoma. There was no correlation between the serum BDNF concentration and age. When the NTG and POAG patient groups were compared, the serum BDNF concentration was lower in NTG patients than in POAG patients. No significant correlations were found between glaucoma parameters, including optical coherence tomography and visual field defects, and the serum BDNF concentration. CONCLUSION: This is the first study to have investigated serum BDNF concentrations in glaucoma patients in Japan. Further investigations are needed to evaluate the role of BDNF as a potential biomarker of glaucoma.

DOI： 10.1272/jnms.JNMS.2020_87-605

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

BACKGROUND: In 2015, infliximab was approved for the treatment of patients with intravenous immunoglobulin-refractory Kawasaki disease (KD) in Japan. However, limited real-world data exist on the usefulness of infliximab for acute KD patients. We conducted a postmarketing surveillance study in patients with acute KD refractory to conventional therapies to evaluate the safety (including any live vaccine-related infections) and the effectiveness of infliximab. METHODS: This was a multicenter, prospective, open-label, single-cohort, observational study in patients with acute KD refractory to conventional therapy who were prescribed a single 5 mg/kg dose of infliximab. Safety and effectiveness of infliximab were evaluated at 1 month, and live vaccine-related infections were further observed until 6 months from KD onset. Effectiveness assessments included fever resolution rate, the incidence of coronary artery lesions and change in coronary diameter Z scores. RESULTS: A total of 291 patients were enrolled, and all patients completed the study. Adverse drug reactions and serious adverse drug reactions were reported in 12.4% and 3.1% of patients, respectively. Live vaccine-related infections were not observed. In the 208 patients with effectiveness assessments, the fever resolution rate within 48 hours after infliximab infusion was 77.4% (95% confidence interval: 71.1-82.9). Median time until fever resolution was 16.6 hours. After infliximab administration, the incidence (at baseline: 10.9%; at the final observation point: 12.0%; maximum value: 14.6%) and severity of coronary artery lesions did not change notably. CONCLUSIONS: In this study, Infliximab for patients with acute KD refractory to conventional therapies was well tolerated and effective.

DOI： 10.1097/inf.0000000000002503

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

BACKGROUND: Regular assessment of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) is essential for detecting glucocorticoid-induced osteoporosis in juvenile-onset autoimmune diseases. Z-score is used in children for standardization of osteoporosis assessment. Z-score in children can be evaluated with only one of the three models in Japan. The purpose of this study was to investigate how many domestic medical facilities for pediatric rheumatic diseases could not evaluate osteoporosis using Z-score exist. METHODS: Electronic questionnaires were distributed between 2017 and 2019 to hospitals belonging to the Pediatric Rheumatology Association of Japan and to university hospitals and public children' s hospitals that provide medical care for pediatric rheumatic diseases. The questionnaire included the location of DXA measurement, manufacturer (Hologic, GE healthcare, Hitachi), and measurement site, and the answers were collected using Google Forms. Statcel 4 was used for analysis. RESULTS: Overall,120 facilities responded to the survey, of which 117 had DXA. In the remaining three facilities, DXA was not installed in two and was out of order in one. Bone loss in childhood was evaluated using a Z-score calculated from age-based reference values. It was revealed that 30% of hospitals without HOLOGIC DXA could not evaluate osteoporosis by Z-score in Japanese childhood. The characteristics of the hospitals enrolled in this study did not bias the selection of Hologic DXA. CONCLUSIONS: Neighboring institutions should consider sharing access to Hologic DXA equipment to ensure the use of uniform reference values. GE BMD reference values for Japanese children should be established.

DOI： 10.1272/jnms.jnms.2021_88-407

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.jnms.2021_88-502

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Thin basement membrane nephropathy (TBMN) is diagnosed by diffuse thinning of the glomerular basement membrane (GBM) without any clinical and pathologic findings of Alport syndrome and the other renal diseases. TBMN is characterized clinically by benign familial hematuria but rarely develops into end-stage renal disease. METHODS: In 27 cases of biopsy-proven TBMN, we evaluated the pathologic characteristics of TBMN, and examined the correlation between these pathologic characterizations and renal dysfunction. RESULTS: All patients had hematuria, and 21 patients (77.8%) had proteinuria. In six patients (28.6%) who were more than 50 years of age, the estimated glomerular filtration rate (eGFR) decreased from G3a to G4 in the chronic kidney disease stage. Pathologically, an irregular decrease in intensity of type IV collagen α5(IV) chain was seen in GBM, and irregular thinning with diffuse rough etched images was observed on the GBM surface with several sizes of holes by low-vacuum scanning electron microscopy. The glomerular morphology of TBMN was characterized by an increased number of small glomerular capillaries with an increased extracellular matrix (ECM). These characteristic morphologic alterations were evident from a young age in patients with TBMN, but were not correlated directly with the decrease of eGFR, the degree of hematuria, and proteinuria. The decrease of eGFR in patients with TBMN who were more than 50 years of age might be primarily mediated by arteriolosclerosis-associated glomerulosclerosis and interstitial fibrosis. CONCLUSION: Characteristic pathological glomerular findings and GBM alterations occurred from a young age but were not associated directly with renal impairment in biopsy-proven TBMN.

DOI： 10.1007/s10157-018-01687-1

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Publishing type：Research paper (scientific journal)  

© 2019 The Author(s) Purpose: Hydrogen (H2) has been reported to scavenge free radicals, particularly the hydroxyl radical (·OH). Ultrasound oscillation in an aqueous solution produces ·OH. Our recent study demonstrated that H2 dissolved in an irrigation solution prevented corneal endothelial damage during phacoemulsification in an animal model. We examined the effects of H2 during clinical phacoemulsification. Design: A single-center, prospective, randomized, double-masked clinical trial. Methods: Thirty-two patients who had cataracts of similar nucleus hardness in both eyes (age: 75.4±7.68 years; 17 males, 15 females) were recruited. Phacoemulsification was performed using a solution of dissolved H2 in one eye, and a conventional solution in the contralateral eye. Endothelial cell density (ECD) at the center of the cornea was measured using noncontact specular microscopy preoperatively and at 1 day, 1 week, and 3 weeks postoperatively. Results: Reduction rates of ECD (mean ± standard deviation) were 16.0%±15.7% at 1 day, 15.4%±16.1% at 1 week, and 18.4%±14.9% at 3 weeks in the control group, compared to 6.5%±8.7% at 1 day (P =.003), 9.3%±11.0% at 1 week (P =.039), and 8.5%±10.5% at 3 weeks (P =.004) in the H2 groups. These rates were significantly smaller in the H2 group at all time points. Conclusions: H2 dissolved in irrigation solution reduced corneal endothelial damage during phacoemulsification. This suggests that a considerable part of the corneal endothelial damage during phacoemulsification is caused by oxidative stress, and that H2 is useful in clinical phacoemulsification.

DOI： 10.1016/j.ajo.2019.04.014

Scopus

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Publishing type：Research paper (scientific journal)   Publisher：American Society of Nephrology (ASN)  

DOI： 10.1681/asn.2018030228

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations and a 22q partial tetrasomy were identified in one family each. All patients identified with causative genes suffered from hearing loss. Second branchial arch anomalies, including a cervical fistula or cyst, preauricular pits, and renal anomalies, were frequently identified (>60%) in patients with EYA1 aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1 aberrations. Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients.

DOI： 10.1038/s10038-018-0429-8

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CiNii Research

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Other Link： http://www.nature.com/articles/s10038-018-0429-8.pdf

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/mgg3.277

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

In phacoemulsification, ultrasound induces hydroxyl radical (center dot OH) formation, damaging corneal endothelium. Whether H-2 can prevent such oxidative damage in phacoemulsification was examined by in vitro and in vivo studies. H-2 was dissolved in a commercial irrigating solution. The effects of H-2 against center dot OH generation were first confirmed in vitro by electron-spin resonance (ESR) and hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal magnitude, and fluorescence intensity by oxidized HPF was significantly less in the H-2-dissolved solution. The effects of H-2 in phacoemulsification were evaluated in rabbits, comparing H-2-dissolved and control solutions. Five hours after the procedure, the whole cornea was excised and subjected to image analysis for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)-1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and immunohistochemistry. Corneal edema was significantly less and the increases in anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed in the H-2 group. In addition, corneal endothelial cell expressions of two oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H-2 group. In conclusion, H-2 dissolved in the ocular irrigating solution protected corneal endothelial cells from phacoemulsification-induced oxidative stress and damage.

DOI： 10.1038/srep31190

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Other Link： http://www.nature.com/articles/srep31190.pdf

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOLECULAR VISION  

Purpose: We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF).
Methods: The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer.
Results: Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were preserved after transient IOP elevation in eyes treated with tm-scAAV2-BDNF but not in the other I/R groups. Significantly reduced glial fibrillary acidic protein (GFAP) immunostaining after I/R injury in the rats that received tm-scAAV2-BDNF indicated reduced retinal stress, and electroretinogram (ERG) analysis confirmed preservation of retinal function in the tm-scAAV2-BDNF group.
Conclusions: These results demonstrate the feasibility and effectiveness of neuroprotective gene therapy using tm-scAAV2-BDNF to protect the inner retina from transiently high intraocular pressure. An in vivo gene therapeutic approach to the clinical management of retinal diseases in conditions such as glaucoma, retinal artery occlusion, hypertensive retinopathy, and diabetic retinopathy thus appears feasible.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Purpose: Because dry eye greatly reduces quality of life, this study aimed to examine rebamipide instillation in patients with dry eye and assess the improvement of signs and symptoms as evaluated with the Ocular Surface Disease Index, which is the most popular index and is highly reliable.
Methods: From June 2013 through January 2014, we examined 50 eyes of 25 patients with dry eye (6 men and 19 woman) at our institution. Dry eye was diagnosed on the basis of the presence of symptoms, tear dynamics, and ocular surface abnormalities according to the Japanese criteria for dry eye. Before being enrolled, all patients underwent ocular surface health assessment, including history interviews, and completed the Ocular Surface Disease Index questionnaire. Patients received 2% rebamipide ophthalmic solution 4 times daily for 4 weeks. Signs and symptoms were analyzed before and 4 weeks after rebamipide administration. Tear dynamics, tear break-up time, and ocular surface abnormalities were measured and compared between before and 4 weeks after rebamipide administration.
Results: Of the 25 patients, 9 had definite dry eye and 16 had probable dry eye. Tear break-up time and the fluorescein staining score significantly improved after 4 weeks. However, no significant change was observed for the Schirmer test I and the lissamine green staining score.
Conclusions: The administration of 2% rebamipide 4 times daily for 4 weeks improves the signs and symptoms of dry eye and improves patients' quality of life.

DOI： 10.1272/jnms.82.229

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: End-stage renal disease (ESRD) in children is considered a rare, but serious condition. Epidemiological and demographic information on pediatric ESRD patients around the world is important to better understand this disease and to improve patient care. The Japanese Society for Pediatric Nephrology (JSPN) reported epidemiological and demographic data in 1998. Since then, however, there has been no nationwide survey on Japanese children with ESRD. METHODS: The JSPN conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011. RESULTS: The average incidence of ESRD was 4.0 per million age-related population. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2 % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis. Initial treatment modalities in patients who commenced renal replacement therapy (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT mortality rate was 18.2 deaths per 1000 person-years of observation. CONCLUSION: The incidence of ESRD is lower in Japanese children than in children of other high-income countries. Since 1998, notably, there has been a marked increase in pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.

DOI： 10.1007/s10157-014-1077-8

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Language：English   Publisher：Ovid Technologies (Wolters Kluwer Health)  

PURPOSE OF REVIEW: Cytokines are immunomodulatory proteins important in cell signaling. Complex interactions of innate and adaptive immune cells, as well as structural cells and their cytokines, play crucial roles in regulating allergic airway inflammation. Here, we summarize current knowledge about the potential roles of known and newly identified helper T cells and epithelial cell-derived cytokines [interleukin (IL)-9, IL-17, IL-22, IL-25, and IL-33] in allergic rhinitis and asthma. RECENT FINDINGS: Although T-helper (Th)2 cells were considered to be the main orchestrators of allergic airway inflammation, recent studies have revealed the potential interaction of other helper T cells and their cytokines in this process. Th17 cells may have a role in allergic rhinitis and asthma, and chronic rhinosinusitis with nasal polyps. An IL-9-producing subset called Th9 cells, Th22 cells which primarily secrete IL-22, IL-13, tumor necrosis factor-α, Th25 cells via producing IL-25 and epithelial cell-derived thymic stromal lymphopoietin, IL-33, IL-31, and IL-25 are believed to be important for the initiation of allergic reactions and inducing airway inflammation. SUMMARY: A new paradigm of an interplay of cytokines is important in allergic rhinitis and asthma in orchestrating the allergic inflammatory response. Potential therapeutic applications emerging from the roles of these cytokines are promising, but need further research.

DOI： 10.1097/ACI.0000000000000129

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

OBJECTIVE: To evaluate the long-term outcome of patients with juvenile idiopathic arthritis (JIA) using data from a large cohort database, Institute of Rheumatology, Rheumatoid Arthritis, managed by the Tokyo Women's Medical University. METHODS: Of 182 patients identified from the database from 2000 to 2013, 114 were verified as having JIA. The transition of medical care and the contributions of biological DMARDs were evaluated. RESULTS: The mean age of the patients (93 females, 81.6%) at the latest examination was 36.6 ± 13.3 years. The mean age at disease onset and mean disease duration were 11.6 ± 3.4 and 25.0 ± 13.3 years, respectively. Of the 114 patients, 106 (93.0%) had poly- or oligoarthritis. Only one-fourth transferred from general pediatricians or pediatric rheumatologists. More patients with recent disease onset were treated with biological DMARDs (16.7% in the 1970s, vs. 80.0% in the 2000s). Disease activity assessed with DAS28 was significantly lower when disease onset was more recent (3.9 ± 1.3 for onset in the 1960s vs. 2.2 ± 1.1 for onset in the 2000s, p = 0.04). The percentage of patients requiring orthopedic surgery has decreased (53.8% before the 1970s vs. 10.0% in the 2000s). CONCLUSION: Patients with more recent disease onset showed an improved outcome. Establishing and sharing a transition program among pediatric and non-pediatric rheumatologists is desirable.

DOI： 10.3109/14397595.2014.929558

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Language：Japanese   Publisher：The Japanese Society for Dialysis Therapy  

DOI： 10.4009/jsdt.47.167

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Other Link： http://search.jamas.or.jp/link/ui/2014159627

Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Membranous nephropathy (MN) is caused by subepithelial deposition of immune complexes in the glomerular basement membrane, with secondary MN arising in association with infection. In secondary MN caused by hepatitis B virus (HBV), seroconversion has been known to occur after the onset of MN, particularly in children. In patients with high serum concentrations of HBV DNA, treatment with interferon-ab or a nucleoside analog has been reported to induce seroconversion and suppress HBV-DNA levels. We treated a 7-year-old boy who presented with proteinuria and liver dysfunction. He had a history of HBV infection since shortly after birth, as his mother was HBV-positive, and he was neither vaccinated nor treated with immunoglobulin at birth. Chronic hepatitis related to HBV was diagnosed following percutaneous needle biopsy of the liver. Percutaneous renal biopsy revealed REV-related glomerulonephritis with diffuse global subepithelial and focal segmental mesangial and subendothelial deposits. Therefore, HBV-associated MN was diagnosed. Treatment with the nucleoside analog lamivudine was started to reduce serum HBV-DNA levels, but lamivudine was discontinued and treatment with entecavir was started at a dosage of 0.5 mg/day after 6 weeks because of possible adverse effects. Tests for HB envelope antibody were positive in week 16 of treatment, and proteinuria had resolved by week 22. Elevated levels of aspartate aminotransferase and alanine aminotransferase were seen with both treatments but were probably attributable to the developing immune response to HBV. In the present case, HBV levels needed to be reduced to: 1) lower elevated serum HBV-DNA titers, which put the patient at high risk of hepatocellular carcinoma; and 2) remove the immune complexes causing MN. Use of nucleoside analogs to suppress the HBV load may facilitate early remission of MN, and entecavir therapy did not cause any serious adverse reactions in this case. Given the advent of lamivudine-resistant HBV, entecavir appears promising for patients with elevated serum levels of HBV DNA.

DOI： 10.1272/jnms.80.387

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Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Background: Intravenous cyclophosphamide (IVCY) pulse therapy has been used for lupus nephritis since the latter half of the 1980s; it has been shown to be effective for lupus nephritis and vasculitis and has become a standard therapy for the diffuse proliferative type of lupus nephritis in adults. IVCY therapy has also come to be used in children. This paper reports the long-term outcomes of IVCY therapy in children.
Methods: Six female patients (age range, 13 to 18 years) with systemic lupus erythematosus (SLE) were enrolled in this retrospective study. Three patients had lupus nephritis (World Health Organization class lib, IVa, IVc), 2 had central nervous system (CNS) lupus, and 1 had neither lupus nephritis nor CNS lupus. The mean pretreatment SLE disease activity index (SLEDAI) score was 18.8 +/- 4.6. Cyclophosphamide (initial dose, 500 mg/m(2)) was administered intravenously each month for 6 months and then given every 3 months for maintenance. Prednisolone was given in dosages ranging from 5 to 60 mg/day, adjusted according to laboratory data and clinical symptoms. Levels of C3, C4, CH50, and creatinine; the SLEDAI score; and the SLE responder index were monitored and evaluated. The SLE responder index was considered to have improved if the SLEDAI score had decreased by 4 points or more after 52 weeks.
Results: Prednisolone doses were reduced in all patients. Because methylprednisolone pulse therapy was administered before IVCY therapy, some patients had low titers of immunoglobin G antibodies against double-stranded DNA at the start of IVCY therapy. All patients had low serum creatinine levels. Proteinuria resolved in 1 of the 3 patients with lupus nephritis. The SLEDAI scores improved after 52 weeks in 5 of 6 patients (mean, 5.2 +/- 2.6). No patients had severe bone marrow suppression or hemorrhagic cystitis during IVCY pulse therapy.
Conclusions: IVCY pulse therapy for SLE in children achieved good long-term outcomes with no serious adverse effects, such as digestive symptoms, bone marrow suppression, infection, and hemorrhagic cystitis. IVCY pulse therapy for children with SLE has recently been approved by the Ministry of Health, Labour and Welfare. Accordingly, this paper might become a guideline for this treatment.

DOI： 10.1272/jnms.80.396

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

DOI： 10.11386/jst.48.225

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Language：English   Publisher：Medical Association of Nippon Medical School  

Introduction: A case of mucosa-associated lymphoid tissue (MALT) lymphoma, the most frequent of the various conjunctival lymphoproliferative disorders, in which the initial biopsy was inconclusive but the second biopsy provided a definitive diagnosis, is reported. Case Report: A 26-year-old woman with a 3-month history of bilateral conjunctival swelling was referred by a local physician for suspected MALT lymphoma. A salmon-pink elastic swelling was found to involve both eyes and to extend from the lower palpebral conjunctiva to the bulbar conjunctiva. Tonsillar swelling was also found, and ophthalmologic (left eye) and otolaryngologic biopsies were therefore performed simultaneously under general anesthesia. The otolaryngologic diagnosis was chronic tonsillitis. Light microscope examination of the conjunctival tissue showed proliferation of lymphocytes and small aggregates of small to medium-sized atypical lymphocytes. On immunohistochemical studies, atypical lymphocytes were positive for CD20 and CD79a, but differentiation to plasmacytes was not prominent, and neither Dutcher bodies nor evidence of immunoglobulin light chain restriction was found. The results were not incompatible with MALT lymphoma but were not definitive. A second biopsy of the right eye was therefore performed 3 months later. Staining with hematoxylin and eosin showed proliferation of small lymphocytes and monocytoid B cells and differentiation to plasmacytes. The hyperplastic cells were positive for CD19, CD79a, and CD20, and their cytoplasm were positive for Bcl-2 and slightly positive for Bcl-6. Cells positive for CD38 were noted where differentiation to plasmacytes and immunoglobulin light chain κ restriction was evident on immunohistochemical studies and in situ hybridization. The Ki-67-positivity rate was approximately 5%. The results of paraffin-embedded tissue section fluorescence in situ hybridization were negative for MALT-1 (18q21). A diagnosis of MALT lymphoma was made, and treatment with rituximab was started. Discussion: Few findings lead directly to a definitive diagnosis of MALT lymphoma, and its differential diagnosis from benign lymphoproliferative disorders is difficult. In the present case definitive diagnosis was possible only after a second biopsy. This case suggests repeated biopsy may be necessary when a single biopsy is not definitive.

DOI： 10.1272/jnms.80.475

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Language：Japanese   Publisher：The Japanese Society for Dialysis Therapy  

DOI： 10.4009/jsdt.45.1067

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Other Link： https://jlc.jst.go.jp/DN/JALC/10012337452?from=CiNii

Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Primary Sjogren's syndrome (SS) is a rare autoimmune disease, especially in children. Juvenile primary SS with interstitial nephritis is rare in Japan. We report on a 12-year-old girl in whom salivary gland swelling had recurred from the age of 5 years, SS was diagnosed at the age of 10 years, and interstitial nephritis developed at the age of 12 years. The patient presented with a chief complaint of swelling of both parotid glands. The patient had a history of recurrent parotitis from 5 years of age, with episodes recurring 5 to 6 times a year and resolving within 3 days each time. However, at the age of 11 years, the patient had continuous mild swelling of the parotid glands. Examination on admission showed bilateral nontender parotid gland swelling; mild swelling of the lower extremities. xerostomia, and xerophthalmia but no exanthem. Laboratory findings were as follows: serum protein, 10.1 g/dL; immunoglobulin (Ig) G, 3,828 mg/dL; antinuclear antibodies, 1,280-fold; anti-Ro/SS-A antibody, 512-fold; anti-Ro/SS-B antibody, 4-fold; creatinine, 0.45 mg/dL; blood beta 2-microglobulin, 2.2 mg/L (slightly elevated); and cystatin C, 0.86 mg/L. Urinalysis showed proteinuria and a beta 2-microglobulin concentration of 11,265 mg/L. Thus, this patient had low molecular weight proteinuria. Schirmer's test showed decreased tear secretion (5 mm), and fluorescein staining showed marked bilateral superficial punctate keratitis. A lip biopsy showed infiltration by small round cells (mild to moderate), interstitial fibrosis, loss of salivary gland parenchyma, and atrophy, with no obvious epimyoepithelial islands, leading to a diagnosis of SS. Light microscopic examination of the renal biopsy specimens showed expansion of mononuclear cell infiltration in the renal interstitium. inflammatory cell infiltration of interstitial areas with edema and mild fibrosis, and tubulitis and mononuclear cell infiltration that included many lymphocytes and plasma cells. There were no pathological findings of glomerulonephritis. Small arteries showed no obvious abnormalities. Immunofluorescent staining showed slight, nonspecific deposition of IgM, but no deposition of IgG, complement 1q, 3, or 4. On the basis of the renal biopsy showing nonspecific chronic interstitial nephritis, renal tubular atrophy, and interstitial enlargement, tubulointerstitial nephritis associated with SS was diagnosed. (I Nippon Med Sch 2012; 79: 286-290)

DOI： 10.1272/jnms.79.286

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

Screening for anemia has been performed in schools in Japan for over 30 years. The long-term effect of the nuclear power plant disaster on the prevalence of anemia in school age children is unknown. This research was performed to evaluate the prevalence of anemia in school age children and to determine grade-level and gender-related reference hemoglobin (Hb) levels prior to the nuclear disaster. Data for this research were obtained from results of screening for anemia obtained by venous blood sampling in schools in 2002. Mean Hb levels were calculated for each grade level (elementary school grades 1-6 and junior high school years 1-3) and according to gender, and the prevalence of anemia was determined. In our research, Tokyo Health Service Association guidelines were used to determine reference Hb levels for anemia. We demonstrated that Hb levels in boys increased with age during childhood and adolescence (from 13.1 +/- 0.7 g/dL in 7 year olds to 14.9 +/- 1.1 g/dL in 15 year olds); in girls, Hb levels peaked at menarche (13.7 +/- 0.8 g/dL in 12 year olds), decreasing slightly thereafter (13.4 +/- 1.1 g/dL in 15 year olds). The prevalence of anemia was 0.26% in elementary school boys, 0.27% in elementary school girls, and 1.21% in junior high school boys. The prevalence of anemia in second- and third-year junior high school girls was lower than that in first-year junior high school girls. Among all junior high school girls, 5.73% had mild anemia. Iron-deficiency anemia is the commonest type of anemia in high school girls, secondary to the relative lack of iron due to menstruation, the growth spurt and exercise. Appropriate dietary therapy and treatment of anemia, together with education about the dietary prevention of anemia, are important to reduce the prevalence of anemia in high school students. When complete blood counts are performed in regions thought to be affected by the Fukushima nuclear power plant disaster, our report can serve as a reference during evaluation of Hb levels. (J Nippon Med Sch 2012; 79: 232-235)

DOI： 10.1272/jnms.79.232

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non-specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children. METHODS: Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques. RESULTS: Anti-nuclear antibody titers were higher and the prevalence of anti-Sa antibody was far more frequent in CFS patients than in FM patients. CONCLUSION: CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions.

DOI： 10.1111/j.1442-200x.2011.03514.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

Autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints, consistently positive antinuclear antibodies (ANA), and lack of alternate medical explanations. A newly recognized antibody, named anti-Sa, was detected in approximately 40% of the patients by Western blot (WB) using HeLa extract. Some patients with AIFS later develop chronic fatigue syndrome (CFS), and most of them are positive for anti-Sa. On the other hand, Muro et al. reported anti-DFS70 in patients with CFS. Anti-Sa and anti-DFS70 were turned out to be same specificities by exchanging studies of blind sera. The target antigen of anti-DFS70 was identified as lens epithelium derived growth factor/transcription co-activator p75 (LEDGF/p75). The objectives of this study are to confirm whether the target antigen of anti-Sa is also LEDGF/p75, and to develop ELISA system by using recombinant protein. Recombinant protein of LEDGF/p75 was purchased from Protein One (Bethesda, MD, USA). We developed an ELISA system to detect anti-LEDGF/p75 by coating this recombinant protein. 226 sera of AIFS patients (including 36 CFS patients) were applied to this ELISA assay and Western immunoblot, and it was revealed that anti-Sa-positive sera defined by WB and sera positive for anti-LEDGF/p75 on ELISA were identical. Moreover, reactivities of anti-Sa on WB were inhibited by pre-incubating with recombinant LEDGF/p75, and eluted antibodies from the nitrocellulose membrane could react on the ELISA. These results confirm that the Sa antigen is LEDGF/p75. The ELISA assay using recombinant LEDGF/p75 could be a promising tool for measuring anti-Sa and consequently for diagnosing CFS.

DOI： 10.1080/08916930902736663

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Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000228897

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.3109/s10165-007-0003-2

CiNii Books

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：English   Publisher：AMER ASSOC IMMUNOLOGISTS  

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Although Sjögren's syndrome (SS) is quite rare among children, subclinical conditions without any sicca symptoms have been reported. This condition is characterized by nonspecific rheumatic symptoms and histopathological findings in salivary glands which are equivalent to SS. Many children with subclinical SS are positive for anti-Ro/SSA. On the other hand, autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints and positive antinuclear antibodies, with or without fulfilling the criteria for chronic fatigue syndrome. Although a novel autoantibody against a 62kD nuclear protein (anti-Sa) is detected in about 40% of AIFS patients, few marker antibodies for autoimmune diseases, such as anti-DNA, anti-Sm, anti-U1-ribonucleoprotein (RNP), or anticardiolipin, are found in AIFS patients. In this study, however, anti-Ro/SSA was detected in sera from 8 out of 122 AIFS patients. Seven of the 8 anti-Ro/SSA-positive patients were female. All 8 patients had fatigue and low-grade fever, but none complained of xerosis. Western immunoblot analysis revealed that 7 sera reacted with Ro52, and that none was positive for anti-La/SSB or anti-Sa. Two of the 8 patients had histories of recurrent parotitis. Lip biopsies showed mild chronic inflammation compatible with subclinical SS in these 2 patients, although the other 6 patients had no abnormal histopathology. Thus, at least some anti-Ro/SSA-positive patients could be diagnosed as having SS.

DOI： 10.1007/s101650200035

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s004390051017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

We have previously reported that approximately 50% of children with chronic nonspecific complaints were positive for antinuclear antibodies (ANA), and that a novel autoantibody to a 62kD protein (anti-Sa) was found in 40% of these ANA-positive patients. Therefore, we proposed a distinct disease entity termed autoimmune fatigue syndrome (AIFS), We hypothesized that if autoimmune mechanisms did play an important role in the pathogenesis of AIFS, it is possible that it is immunogenetically regulated as observed in other autoimmune disorders. In order to examine the immunogenetic background of AIFS patients, HLA-A, -B, -C, and -DR loci were analyzed serologically in 61 AIFS patients. AIFS was found to be positively associated with the class I antigen HLA-B61 and with the class II antigen HLA-DR9, with odds ratios of 2.77 (p = 0.015, P-corr = 0.48) and 2.60 (p = 0.013, P-corr = 0.17), respectively. A negative association was also found between AIFS and HLA-DR2 with odds ratio of 0.25 (p = 0.029, P-corr = 0.041). When comparing anti-Sa positive AIFS patients with healthy controls, the odds ratios associated with HLA-B61, DR9, and DR2 were 3.42 (p = 0.021, P-corr = 0.22), 3.96 (p = 0.0011, P-corr = 0.015), and 0.16 (p = 0.0022, P-corr = 0.031), respectively. Thus, the HLA associations observed in this study suggested that immunogenetic background might play a role in AIFS.

DOI： 10.3109/08916930008994092

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HARWOOD ACAD PUBL GMBH  

Children who are chronically complaining nonspecific symptoms such as headache, fatigue, abdominal pain, and low grade fever are commonly seen in daily pediatric outpatient clinics. Some of them are unable to go to school and are diagnosed as school refusal by physicians or educational staff. On the other hand, there are children who do not fulfill any criteria of collagen diseases and whose anti-nuclear antibodies (ANA) are found to be positive. Some of these children have chronic nonspecific complaints. We prospectively studied the prevalence of ANA in children who visited a pediatric outpatient clinic because of chronic nonspecific complaints. Surprisingly, 74 out of 140 symptomatic children (52.4%) were positive for ANA, while only 5 out of 82 healthy control children (6.1%) were positive (p &lt; 0.0001). 39 of 74 ANA positive patients (52.1%) have low ANA titers less than or equal to 1:80, nevertheless 36 patients (47.9%) have high ANA titers greater than or equal to 1:160. ANA fluorescent patterns were homogeneous and speckled in 75.3%, speckled in 17.6% and others in 6.8%. ANA positive patients tended to have general fatigue and low grade fever, while gastrointestinal problems such as abdominal pain and diarrhea and orthostatic dysregulation symptoms were commonly seen in ANA negative patients. Children who were unable to go to school more than 1 day a week were seen significantly more in ANA positive patients than in negative patients. Autoantibody analysis using Western immunoblot revealed that 26 out of 63 ANA positive sera (41.3%) had antibodies to the 62 kD protein which had not been previously noticed. These data suggest that autoimmune mechanism may play a role in childhood chronic nonspecific symptoms. We therefore propose a new disease entity of the autoimmune fatigue syndrome in children. When chronically complaining children visit a pediatric out-patient clinic, immunological approaches should be considered before they are discriminated as school refusal or having psychogenic disorders.

DOI： 10.3109/08916939708994733

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：HARWOOD ACAD PUBL GMBH  

Recent studies have shown that Ro/SSA autoantigen is heterogeneous. There are two isoform families; the 60 kD forms (Ro60) and the 52 kD forms (Ro52). Recently we have found that autoantibodies to the Ro/SSA proteins are conformation dependent. Anti-Ro60 antibodies are mainly directed to the native protein and conversely anti-Ro52 antibodies are directed only to the denatured protein.
It has been known that UV irradiation to cultured keratinocytes induces cell surface expression of Ro/SSA and this phenomenon has been thought to be related with photosensitivity in patients with anti-Ro/SSA antibodies. We studied the quantitative and qualitative changes of the Ro/SSA protein induced by stress, such as with heal shock and UV irradiation, and found that only Ro52 could be expressed on the cell surface of human peripheral lymphocytes by either heat shock or UV irradiation. Moreover, flow cytometric analysis revealed that HS-treated and UV-treated lymphocytes could be stained with patient sera, and by using a technique which combined immunoprecipitation and Western immunoblotting, it has been confirmed that Ro52 expressed on the cell surface can be recognized by anti-Ro/SSA antibodies in native form while cytoplasmic Ro52 cannot be recognized.
These data suggest that Ro52 can be antigenic in vivo when expressed on the cell surface and may explain the mechanism of direct tissue damage by anti-Ro/SSA antibodies.

DOI： 10.3109/08916939508995297

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Language：Japanese   Publisher：特定非営利活動法人 日本小児外科学会  

DOI： 10.11164/jjsps.30.5_1018_1

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Authorship：Lead author   Language：Japanese   Publisher：(株)診断と治療社  

●関節痛では、関節滑膜、滑液包、軟骨、腱、腱鞘滑膜をエコーで評価して鑑別する。●Bモードとカラードプラにより初期診断と疾患活動性を評価する。●関節エコーは触診よりも感度よく病変を検出でき、X線よりも骨びらんが感度よく検出できる。●若年性特発性関節炎の撮像法と滑膜炎の評価には、成人のガイドラインが使用できる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公社)日本小児保健協会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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Language：Japanese   Publisher：日本小児皮膚科学会  

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Language：Japanese   Publisher：日本小児放射線学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(NPO)日本小児血液・がん学会・(NPO)日本小児がん看護学会・(公財)がんの子供を守る会  

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Language：Japanese   Publisher：日本小児リウマチ学会  

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Language：Japanese   Publisher：(公社)日本皮膚科学会  

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CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2013134678

Language：Japanese   Publisher：(一社)日本腎臓学会  

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症例は15歳女子で、左眼充血、羞明感を主訴に、近医眼科にてブドウ膜炎と診断され、内科的疾患合併の精査加療目的に当科紹介となった。血液・尿検査では高度の腎機能障害を認め、腎生検の結果、尿細管間質性腎炎と診断した。ブドウ膜炎の合併からTINU症候群と考え、ステロイドパルス療法を2クール施行したところ、尿中β2MGは速やかに改善し、約6ヵ月後の腎生検では間質性腎炎の活動性は低下し、間質に線維化や代償性の尿細管肥大がみられた。なお、ブドウ膜炎に対してはステロイド点眼にて改善がみられたが、再発を繰り返していた。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J06126&link_issn=&doc_id=20121227170010&doc_link_id=10.34539%2Fpraj.3.2_85&url=https%3A%2F%2Fdoi.org%2F10.34539%2Fpraj.3.2_85&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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J-GLOBAL

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：金原出版(株)  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2011199355

Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本疲労学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese  

CiNii Books

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Language：Japanese   Publisher：(株)東京医学社  

＜ポイント＞JIAは早期からメトトレキサート(MTX)を用いた治療により寛解導入し、生物学的製剤の併用で、関節破壊進行の抑止が可能となった。(著者抄録)

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Language：Japanese   Publisher：(株)日本小児医事出版社  

リウマチ熱は本邦においては激減したといわれていたが、近年の米国における小流行から、本邦においても今後流行の可能性が懸念されている。当科においても、新たなリウマチ熱患者は20年以上認められなかったが、比較的短期間に3例を経験した。3例とも発症前に溶連菌感染の病歴が明らかでなく、抗菌薬の投与がされていなかった。またうち2例では発症初期には認められなかった心炎が経過中に認められるようになった。今後の流行の可能性に備えて、リウマチ熱の診断、治療、予防についての再検討が必要と思われる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：日本疲労学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：金原出版(株)  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2008303788

Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本疲労学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(株)診断と治療社  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：FEDERATION AMER SOC EXP BIOL  

Web of Science

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：English  

Autoimmune fatigue syndrome (AIFS) is defined by chronic nonspecific complaints, a positive antinuclear antibody (ANA) assay, and the absence of another explanation for the complaints. Some severe cases fulfill the criteria for chronic fatigue syndrome (CFS). CFS is a syndrome characterized by disabling severe fatigue and defined by the criteria proposed by the U.S. Centers for Disease Control and Prevention. In this report, a patient with chronic fatigue syndrome and positive ANA assay was described as having developed postpartum thyroiditis 5 years after the onset. Subchemical hypothyroidism is characterized by clinical hypothyroidism not meeting biochemical criteria but showing evidence of thyroid autoimmunity. The relation between AIFS and subchemical hypothyroidism is discussed. © Japan College of Rheumatology and Springer-Verlag Tokyo 2004.

DOI： 10.1007/s10165-004-0332-3

PubMed

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

DOI： 10.15036/arerugi.53.993_3

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本小児腎臓病学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：FEDERATION AMER SOC EXP BIOL  

Web of Science

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

思春期には性ホルモン自体による自己免疫疾患増悪の可能性があるばかりでなく,1)性ホルモン,2)自律神経,3)情動の3つの中枢としての視床下部に大きなストレスが加わる.その結果,神経-内分泌-免疫連関に狂いが生じ,心身のバランスを崩しやすい.更に,多感な年頃の患者には精神的ストレスが多く,他の時期の患者と比べて,疾病治療を最優先できない状況もよく起こる.又,外見を気にする思春期の患者にとって,ステロイド剤は「太る薬」である.したがって,代替治療も考慮し,治療に対するコンプライアンスを高めるため,家族のみならず本人と十分話し合って,全人格的な医療を心掛けなければならない

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：鳥居薬品(株)  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

自己免疫疾患の発症メカニズムはいまだ明らかではないが,ウイルス感染が関与している可能性は大きい.EBV,パルボウイルス,HTLV-I,HIVなど,直接自己免疫疾患を発症させうるウイルスもあるが,自己抗体産生のきっかけとなるような分子レベルでの免疫応答は,どんなウイルスに対しても起こりうる.ウイルス排除機構は,細胞ごと破壊するという意味で一種の自己免疫であり,更に持続感染や自己抗原類似のアミノ酸構造を有するウイルスの感染が起こると,次第に自己の細胞や抗原も標的とされてしまうようになる.とくにウイルスによく似た構造をもつリポ核酸蛋白などは標的とされやすい.自己免疫はウイルスに対する過剰防衛とも考えられる

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：金原出版(株)  

肺炎球菌性髄膜炎に両側対称性の視床梗塞を合併した3歳男児例を経験したので,画像診断を中心に報告した.今回症例の視床病変は,CT,MRI所見から脳梗塞と思われた.視床以外にも梗塞巣が認められたこと,および視床病変はbasilar-top灌流域である視床前方に限局していた3点を重視した.視床梗塞は,感染を契機とした炎症に伴うthrombosisもしくはvasospasm等に起因する血管性病変がbasilar-top起始部から左右に分岐する迄の領域に起こり,上行網様体系を障害,意識障害が長期継続したものと推定した

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：日本医科大学医学会  

自己免疫性疲労症候群(AIFS)患者の中から慢性疲労症候群(CFS)のみならず線維筋痛症(FM)へと進行するものが存在すること,そしてAIFS患者では,FMの診断基準を満たさなくても,平均5.6ヶ所という多くの圧痛点を有することがわかった.小児の患者では肩凝りやその他の疼痛については訴えてこない場合も多く,積極的に圧痛点の検索をすることも重要であるといえる.CFS,FMという疾患概念についても自己免疫という観点から更に検討を進める必要性があると思われた

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Language：Japanese   Publisher：(一社)茨城県医師会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：金原出版(株)  

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Language：Japanese   Publisher：日本小児血液学会  

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Language：Japanese   Publisher：(株)先端医学社  

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Language：Japanese   Publisher：金原出版(株)  

インドへの一時帰国後に発症した三日熱マラリア・熱帯熱マラリア混合感染の7歳男児例を報告した.国際交流の発展に伴いマラリアを初めとする輸入感染症にも留意すべきと考えられた

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Language：Japanese  

CiNii Books

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Language：Japanese   Publisher：(NPO)日本小児外科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT-RAVEN PUBL  

Web of Science

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：日本小児呼吸器学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT-RAVEN PUBL  

Web of Science

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Language：Japanese   Publisher：(株)診断と治療社  

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Language：Japanese   Publisher：日本小児血液学会  

CALLの7歳男児.東京小児白血病研究グループ(TCLSG) 11次案S2プロトコールに従い,初回寛解を持続してきたが,3年目の維持療法中に急激な貧血と血小板減少をきたした.骨髄は,低形成で,ウイルス抗体価,DNA診断にてヒトパルボウイルスB19 (B19)感染による骨髄不全と診断した.B19に対する抗体の産生に伴い,貧血と血小板減少を認めてから1ヵ月後に血液所見の改善をみた.B19感染は白血病治療経過中のような,ある種の免疫抑制状態の患児では骨髄不全を惹起する可能性が示唆される

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