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This article discusses the use of texture and color enhancement imaging (TXI) in the detection of small gastric adenocarcinomas of fundic-gland type (GA-FGs). The study focuses on a man in his 60s who underwent endoscopic resection for multiple superficial GA-FGs. During a follow-up gastroscopy, new suspicious lesions were detected using TXI that were not visible on previous endoscopies. The study concludes that TXI can improve the detection of subtle gastric lesions like GA-FGs, which may be missed using conventional imaging techniques. [Extracted from the article]

Objectives: The aim of this study was to evaluate the applicability of genotyping of the ABCG2 gene using MALDI‐TOF MS and to estimate the allele frequency in the Japanese population. Background: Jr (a−) phenotype has a prevalence of approximately 0·05% among Japanese blood donors; DNA‐based genotyping was conducted to investigate the molecular basis of the Jr (a−) phenotype along with serological typing. To detect all SNPs of the ABCG2 gene, a high‐throughput SNP genotyping platform is needed. Methods: Overall, 1004 Jr (a−) blood samples were collected from blood donors in Japan and pre‐genotyped. To detect the SNPs of the ABCG2 gene using MALDI‐TOF MS, polymerase chain reaction and unextend primer were designed. In total, 205 Jr (a−) samples were genotyped using MALDI‐TOF MS analysis. Results: The SNPs of 1004 Jr (a−) samples were identified using the HRM analysis and DNA sequencing, and 799 of 1004 (80%) Jr (a−) samples had the homozygous for c.376 T. The designed primers for MALDI‐TOF MS perfectly detected the SNPs of the ABCG2 gene. A total of 205 Jr (a−) samples were genotyped using MALDI‐TOF MS. Calling failures occurred in only two samples with the mutations c.736CT to c.376C and c.421C to c.421CA. The concordance rate between the pre‐genotyped and MALDI‐TOF MS‐based genotyping results was very high (99·02%) for all ABCG2 alleles. Conclusions: Jr (a‐) Japanese donors had almost the homozygous for c.376 T. However, detections of more than 20 SNPs of the ABCG2 gene for the JR blood group genotyping are needed. MALDI‐TOF MS‐based genotyping was highly concordant with the pre‐genotyped results for all ABCG2 alleles. [ABSTRACT FROM AUTHOR]

The article discusses an international forum from the journal "Vox Sanguinis" about donor notification and counselling techniques for transfusion-transmissible infections markers. Topics include notifying donors on positive screening test on the blood that has been donated, the role of counselling and donor notification in both blood safety and donor care, and the important elements for a notification message.

The Working Party has met twice since the last report: in Seoul, South Korea 2014, and in London, UK 2015, both in association with the International Society of Blood Transfusion ( ISBT) Congress. As in previous meetings, matters pertaining to blood group antigen nomenclature were discussed. Eleven new blood group antigens were added to seven blood group systems. This brings the current total of blood group antigens recognized by the ISBT to 346, of which 308 are clustered within 36 blood groups systems. The remaining 38 antigens are currently unassigned to a known blood group system. [ABSTRACT FROM AUTHOR]

Background and Objectives Molecular analyses of Rhnull individuals have revealed that abnormalities occur only at the RH or RHAG gene. Rhnull phenotype arises from two distinct genetic mechanisms, the amorph and the regulator type. Here, we genetically analysed a Japanese Rhnull family and identified a novel RHAG mutation. Materials and Methods RBC samples from two family members were phenotyped using the standard serological techniques and BLOODchip Reference for the predicted phenotype. Scanning electron micrographs of red blood cells ( RBCs) were generated. All 10 RHAG exons were subjected to DNA sequencing. Results RBCs in 2 Rhnull samples did not contain Rh or Rh AG antigens. The screening tests for irregular RBC antibodies identified anti-Rh29 in 2 samples and anti-C+e in the older sister of the proband. A molecular base analysis revealed a novel c.790C>T (p.Arg263X) mutation in exon 5 of RHAG gene. Conclusion The samples with the novel c.790C>T (p.Arg263X) mutation in exon 5 of the RHAG gene were identified as regulator type. [ABSTRACT FROM AUTHOR]

Background and Objectives At Japanese Red Cross ( JRC) Blood Centers, all donated blood is screened for hepatitis C virus ( HCV) by serological and nucleic acid amplification testing. Donor plasma that tested reactive for anti- HCV by serological test is disqualified even if the donor tests negative for HCV RNA. These test results reflect both true-positive results because of past HCV infection and false-positive results because the cross-reactivity of plasma IgG, which current testing methods are unable to distinguish. To characterize these antibody test results, we examined the neutralizing activity of these plasma samples. Material and Methods Donor plasma samples that tested reactive for anti- HCV by serological test but negative for HCV RNA ( n = 43) were analysed for determining their neutralizing activities measured by the inhibition of the cellular entry of pseudoparticles harbouring HCV envelope glycoproteins ( HCVpp). Results Strong and broad neutralizing activities against HCVpp entry similar to the samples that tested reactive for anti- HCV serological test and positive for HCV RNA (considered to be derived from individuals with chronic HCV infection) were observed in three of 43 plasma samples from donors who tested anti- HCV reactive but HCV RNA negative. Conclusion By examining the neutralizing activities of plasma samples, we identified individuals with a past HCV infection from those in whom we were unable to confirm HCV infection according to the current testing algorithms of JRC, which do not perform anti- HCV confirmatory tests. [ABSTRACT FROM AUTHOR]

Background and Objectives We developed a hollow-fibre column system specifically adapted to prepare washed platelet concentrates ( WPCs). This study was performed to evaluate the efficacy of the hollow-fibre column system for preparing WPCs. Materials and Methods First, the percentages of platelet ( PLT) recovery and remaining plasma proteins were calculated by determining the PLT count, volume and plasma protein levels in both the prewash and postwash. Secondly, washed PLTs and unwashed control PLTs were stored for 5 days, and the changes during this 5-day storage of in vitro PLT characteristics were determined. Results The hollow-fibre column system effectively removed >98% of plasma in platelet concentrates ( PCs), and the PLT recovery was 97% on an average. The CD62P-expression level on washed PLTs immediately after washing was approximately twofold higher than that on prewashed PLTs as well as on PLTs washed via manual methods or cell washing devices. Until day 5 during storage, PLT aggregability, hypotonic shock response and swirling scores of washed PLTs were not significantly different from those of the control PCs. Conclusion Our novel hollow-fibre column system proved valuable in preparing washed PLTs with <2% of residual plasma proteins and high recovery of PLTs. [ABSTRACT FROM AUTHOR]

The International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology convened during the International congress in Cancun, July 2012. This report details the newly identified antigens in existing blood group systems and presents three new blood group systems. [ABSTRACT FROM AUTHOR]

SUMMARY Background Blood-group genotyping arrays have been widely used in Caucasian and African American populations, but have not been thoroughly tested in Japanese subjects. Aim To evaluate, using the BLOODchip® Reference genotyping system, the concordance of previously typed samples with expected phenotypes and the coverage of the Japanese variants. Methods Blood samples from 100 Japanese donors were obtained. DNA was extracted with QIAsymphony (Qiagen, Hilden, Germany). Samples were typed by serological methods and processed with the BLOODchip®. When a non-concordant result was identified, further sequencing by polymerase chain reaction-single specific primer ( PCR-SSP) was performed. Results Concordance between systems was 98% (736/751), and 98.8% (742/751) if only non-software-related non-concordances were considered. In the ABO group, 6 'No Call' ( NC, inability of the BLOODchip® to assign a result) were ascribed to a variant of blood subtype A1 ( A102; 467C>T), a common subtype in Asian populations, whereas three NC presented additional polymorphisms not contained in the BLOODchip® ( A102/ A205, A102/ O06 and A204/ O02). In the RhD group, one discrepancy was correctly genotyped as RHD* 1227A (Del phenotype) by the BLOODchip® (phenotyped as partial D, RHD* DIVb). Another was phenotyped as D+ by the BLOODchip® (phenotyped weak D by serology) and confirmed as RHD*D- CE(2)-D heterozygous by sequencing. The 3 RhD NC can be solved by further software update. For RhCE, one discrepancy was correctly genotyped for both systems; however, only the BLOODchip® was able to detect RHCE* CX allele. Conclusions By programming the A102 ABO variant into the system software with the new allele combinations, the BLOODchip® Reference is a suitable genotyping tool to be applied to Asian samples. [ABSTRACT FROM AUTHOR]

Background The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Study Design and Methods Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. Results Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41 841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). Conclusion This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 492-500 (2012) Abstract Aims Skin autofluorescence, a non-invasive measure of the accumulation for advanced glycation end products, has been reported to be a useful marker for diabetic vascular risks in the Caucasian population. The aim of this study was to evaluate associations between skin autofluorescence and vascular complications in non-Caucasian patients with Type 2 diabetes. Methods Subjects in this cross-sectional study comprised 130 Japanese patients with Type 2 diabetes. Skin advanced glycation end products were assessed by skin autofluorescence using an autofluorescence reader. Association between skin autofluorescence and severity of vascular complications was evaluated. Results Of the 130 patients, 60 (46.2%) had microvascular complications such as diabetic retinopathy, neuropathy and nephropathy, 10 (7.7%) had macrovascular complications and 63 (48.5%) had micro- and/or macrovascular complications. Skin autofluorescence increased with severity of vascular complications. Independent determinants of skin autofluorescence were age (β = 0.24, P < 0.01), mean HbA1c in previous year (β = 0.17, P = 0.03), microvascular complications (β = 0.44, P < 0.01) and macrovascular complications (β = 0.27, P < 0.01). Multiple logistic regression analysis revealed that diabetes duration (odds ratio 1.15, P < 0.01), systolic blood pressure (odds ratio 1.04, P = 0.01), skin autofluorescence (odds ratio 3.62, P = 0.01) and serum albumin (odds ratio 0.84, P < 0.01) were independent factors for the presence of vascular complications in these patients. Conclusions Skin autofluorescence had independent effects on vascular complications in Japanese patients with Type 2 diabetes. This indicates that skin advanced glycation end products are a surrogate marker for vascular risk and a non-invasive autofluorescence reader may be a useful tool to detect high-risk cases in non-Caucasian patients with diabetes. [ABSTRACT FROM AUTHOR]

The article offers information on the meeting of the Working Party of the International Society of Blood Transfusion (ISBT) during the 2010 ISBT Congress in Berlin, Germany. It states that the group was renamed the Working Party on Red Cell Immunogenetics and Blood Group Terminology during the event. It also says that doctor Geoff Daniels gave terms of reference to advise the ISBT on red cell immunogenetics, and to maintain and monitor terminologies for blood group antigens.

Rare blood types are generally defined as those that occur at a frequency of 1 : 1000 or less. However, some rare blood types have much different frequencies in global regions or specific ethnic groups. This review explores rare blood types in the following categories: rare blood types that lack high-frequency antigens and where to find them, rare blood types that express low-frequency antigens, rare blood types with higher or lower frequencies in the Asia Pacific region and rare blood types that are difficult to find in the Asia Pacific region but are provided by the JRC. In addition, the study of rare blood types has revealed clinical correlations with disease states and resistance to infections. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented commenting on the examination of allergic transfusion reactions by the basophil activation test.

The article presents the changes and updates made by the International Society of Blood Transfusion committee to the classification in Blood Terminology 2004 during its meeting in Macau Special Administrative Region, China. It states that a new blood group system was established and new antigens were added to Rh, Kell, and Dombrock systems. It also mentions that there are already a total number of 308 antigens recognized at present times.

The article reports on the updated classification of blood group systems by the International Society of Blood Transfusion (ISBT) Committee. The new antigens were added to MNS, Kell, Scianna, Cromer, Indian, Knops and JMH systems. The changes recommended to the terminology for blood group genes by the committe are also discussed.

Background Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is characterized by a progressive loss of higher cognitive functions. The brain of an individual with AD exhibits extracellular senile plaques (SPs) of aggregated amyloid-beta peptide (Aβ) and intracellular neurofibrillary tangles (NFTs). Given the critical role of neuronal transport of both proteins and organelles, it is not surprising that perturbation of microtubule-based transport may play a major role in the pathogenesis of AD. Materials and methods We used the cDNA subtraction methodology and in vitro neural cell culture analyses to study the meaning of the brain site-specific gene expression pattern in cerebral tissue obtained from AD patients and also from control subjects at autopsy. Results We observed that cytoskeleton-associated proteins were down-regulated in AD subjects. We also noted an altered expression of the microtubule-associated protein 1B (MAP1B), the heat-shock protein (HSP)-90 (a key chaperone molecule), the tripartite motif-containing proteins (TRIM)-32/37 (an anti apoptotic enzyme with ubiquitin-protein ligase activity) and the Reticulon-3 (a modulator of the amyloid-precursor-protein (APP) cleavage) in AD brains. Additional molecular- and cell-biological studies revealed that small interfering RNA (siRNA)-mediated down-regulation of MAP1B expression leads to neuronal cell death in vitro. Conclusion Altered expression of MAP1B, HSP90, TRIM32/37 and Reticulon-3 provides new clues by which the ubiquitin-proteasome-, the protein-chaperon- and the APP-processing systems are disturbed in AD, thus, leading to neuritic amyloid plaques and neurofibrillary tangles. [ABSTRACT FROM AUTHOR]

Although flow cytometric (FCM) analysis is one of the most widely used approaches to screen the presence of leucocyte antibodies, it has several drawbacks. First, neutrophils and, especially, monocytes exhibit high background reactivity. Second, to determine antibody specificity, it is often necessary to examine not only neutrophils and monocytes but also other lineage cells including T cells, B cells and platelets. Therefore, we attempted to establish an FCM analysis system in which four lineages of leucocytes and platelets are simultaneously tested with low background. FCM analysis was performed using ethylene diamine tetraacetic acid-anticoagulated whole blood as cell sample without any cell preparation. Discrimination of five cell lineages was carried out based on the differences in forward vs. side scatter distribution and in the expression of CD4, CD20 and CD14. When anti-HNA (human neutrophil antigen) 1b antiserum was applied to HNA 1b-positive blood samples, only neutrophils were unambiguously positive. When anti-Naka (anti-CD36) antiserum was applied, only platelets and monocytes were positive. The background reactivity of neutrophils and monocytes was low enough. When anti-human leucocyte antigen (HLA) class II antiserum was tested, only B-lymphocytes and monocytes were positive. When anti-HLA class I antiserum was tested, all the five-lineage cells were positive. [ABSTRACT FROM AUTHOR]

Presents a chart that depicts the blood group terminology. System name; System symbol; Gene name; Chromosomal location.

Focuses on a report given by the International Society of Blood Transfusion Committee on terminology for red cell surface antigen. Addition of three antigens to the existing Rh factor system; Identification of an antigen of very high incidence called GUTI; Creation of I system for the gene encoding N-acetylglucosaminyltransferase.

Background and Objectives Mutations detected in 161 weak D samples from Caucasians have been classified into 16 types. Because flow cytometry using monoclonal anti-D antibodies (mAbs) has shown that weak D red cells display type-specific antigen density, these mutations in transmembranous regions have been assigned weak D phenotypes. The present study attempts to confirm or refute this assignment. Materials and Methods We amplified DNA from four Japanese weak D samples using the polymerase chain reaction (PCR), and directly sequenced the amplified DNA. Using site-directed mutagenesis, we constructed three vectors expressing mutant RHD s – G212C, V270G (weak D type 1) and G358A (type 2) – in K562 cells. The expression of RhD antigens was examined by flow cytometry using mAbs. Results A new mutation resulting in a conversion at amino acid residue 212 (Gly to Cys) was detected in a Japanese weak D sample. K562 cells transduced with mutant RhD cDNA reacted weakly in a type-specific manner with mAbs. Conclusions The mutations – G212C (new weak D type), V270G (weak D type 1) and G358A (type 2) – in transmembranous regions had obvious effects on the D epitopes recognized by mAbs. The results of this study provide direct evidence that these mutations can account for weak D phenotypes. [ABSTRACT FROM AUTHOR]

Rare blood is generally defined as one that occurs at a frequency of 1:100~1000 individuals or less, and it is sometimes difficult to provide such blood types to patients because of their rarities. The Japanese Red Cross ( JRC) Society lists 46 rare blood phenotypes that are divided into two categories. The rare blood types listed in Category I occur much less frequently than those listed in Category II. We screen for rare blood cells using monoclonal antibodies (MoAbs). Since 1987, our blood centre has established 93 MoAbs (32 human and 61 murine) and has provided them to the other blood centres. Many of IgG MoAbs are available on the machine by saline or bromelin method by cross-linking with anti-human or anti-mouse IgG. Thus, more than 10 000 donors with rare blood phenotypes (Category I, 748; Category II, 9314) are registered in Japan. We freeze rare blood, particularly Category I types. Since 1977, a total of 576 units of rare blood with phenotypes Di(b−), D−−, Jr(a−), Ko and Lan-, etc. have been supplied to 23 international countries. Thus, the JRC contributes to the International Panel of Donors of Rare Blood Type ( IDP) which is maintained by the International Blood Group Reference Laboratory ( IBGRL) in Bristol, UK. The IDP provides information on the location of rare blood donors when they cannot be found in their respective countries. We also joined the ISBT Working Party on Rare Donors which handles all matters related to rare blood. Our rare blood donor programme is successful because of international co-operation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the medical concept of transfusions of red blood cells from an occult hepatitis B virus carrier, which appeared in the previous issue.

Presents a letter to the editor of the journal 'Vox Sanguinis' describing a novel mutation in the RHD gene in Japanese individuals with weak D, encoding an amino acid change in the 11th transmembraneous domain of the RhD protein.

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, has been available for the treatment of moderate to severe psoriasis and psoriatic arthritis since February 2015 in Japan. Because there was a time gap after the previous approval of biologics for psoriatic disease indication, it was suggested that patients to be treated with secukinumab at its launch might have refractory disease symptoms. In order to assess the safety and effectiveness of secukinumab in those patients, a 52-week, open-label, multicenter, observational cohort study was conducted. In total, 306 and 250 patients were included in the safety and effectiveness analysis sets, respectively. Over half of patients had previously received biologics (56.9%). Adverse events, serious adverse events and adverse reactions were reported in 41.2%, 7.2% and 24.2% of patients, respectively. The most commonly reported adverse reactions were oral candidiasis (2.9%), consistent with those reported in clinical studies. In addition, none of the patient characteristics assessed for the effect on safety of secukinumab increased the occurrence of adverse reactions. Psoriasis Area and Severity Index score (mean ± standard deviation) improved from baseline (14.7 ± 12.3) to week 12 (1.78 ± 3.3), which was maintained up to week 24 (1.59 ± 3.0). The proportion of patients with a Dermatology Life Quality Index score of 0/1 improved from baseline (2.2%) to week 12 (64.7%) and sustained up to week 24 (71.4%). In addition to the skin symptoms, improvement was observed in all psoriatic arthritis disease-related assessments. The current study reaffirmed the safety and effectiveness of secukinumab with broader patients than those in the clinical studies., (© 2020 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

The Kg-antigen was first discovered in an investigation of a mother whose infant had haemolytic disease of the newborn (HDN). The antibody against the Kg-antigen is believed to be responsible for HDN. The Kg-antigen is provisionally registered under the number 700045, according to the Red Cell Immunogenetics and Blood Group Terminology. However, the molecular nature of the Kg-antigen has remained a mystery for over 30 years. In this study, a monoclonal antibody against the Kg-antigen and the recombinant protein were developed that allowed for the immunoprecipitation analysis. Immunoprecipitants from the propositus' red blood cell ghosts were subjected to mass spectrometry analysis, and DNA sequence analysis of the genes was also performed. A candidate for the Kg-antigen was molecularly isolated and confirmed to be a determinant of the Kg-antigen by cell transfection and flow cytometry analyses. The Kg-antigen and the genetic mutation were then screened for in a Japanese population. The molecular nature of the Kg-antigen was shown to be RhAG with a Lys164Gln mutation. Kg phenotyping further clarified that 0.22% of the Japanese population studied was positive for the Kg-antigen. These findings provide important information on the Kg-antigen, which has been clinically presumed to give rise to HDN., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

The molecular basis of interleukin (IL)-17A in driving psoriasis pathogenesis is not fully elucidated yet. To investigate the underlying mechanisms and biomarkers associated with IL-17A and the role in psoriasis pathogenesis, over 30 serum proteins were evaluated in a study assessing the effectiveness and safety of secukinumab, where treatment was directly switched from cyclosporin A to secukinumab. Serum β-defensin 2 (BD-2) levels rapidly and robustly reduced following secukinumab treatment. BD-2 levels were well-correlated with Psoriasis Area and Severity Index (PASI) score; changes in BD-2 levels preceded change in PASI score. Serum BD-2, an easily measurable protein, can possibly be used as a suitable surrogate biomarker to monitor responses to IL-17A-targeted therapies for psoriasis in clinical practice., (© 2020 Novartis Pharma K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Secukinumab, a fully human monoclonal antibody neutralizing interleukin-17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long-term (3-year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI-75) response at week 12 were re-randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52-week core study, and 47 patients entered the extension study with the same double-blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI-90 and -100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two-thirds of 300 mg FI patients, and all EuroQoL 5-Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified., (© 2019 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Little attention has been given to the burden of chronic urticaria (CU) in Japan compared with other skin diseases, such as atopic dermatitis (AD) and psoriasis. The primary objective of the RELEASE study was to evaluate the real-life quality-of-life impairment in CU patients in Japan. Data were collected from 1443 urticaria, 1668 AD and 435 psoriatic patients; 552 urticaria patients who presented urticaria symptoms for over 6 weeks were defined as CU. The mean Dermatology Life Quality Index (DLQI) total score was 4.8, 6.1 and 4.8 in CU, AD and psoriatic patients, respectively. Disease control of urticaria evaluated by the Urticaria Control Test (UCT) and DLQI exhibited a strong correlation with a Spearman's rank correlation coefficient of -0.7158. CU and AD patients had relatively higher scores in all Work Productivity and Activity Impairment - General Health subscales except for absenteeism. At the time of the survey, approximately 64% of CU patients reported UCT scores of <12 and demonstrated higher work productivity loss and activity impairment versus patients with UCT scores of ≥12. Patients with lower UCT scores also displayed a higher percentage of dissatisfaction with their health state and the treatment they received. Approximately 85% of patients with CU had visited dermatology clinics, and less than 20% had visited hospital, indicating existence of a highly burdened population outside specialized centers. These results highlight the unmet medical needs of CU patients, suggesting the need to increase awareness of CU burden among both physicians and patients and to pursue improved real-life patient care., (© 2018 Novartis K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate-to-severe psoriasis. In this multicenter, open-label, phase IV study, 34 patients with moderate-to-severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end-point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end-point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy., (© 2017 Novartis Pharma KK. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Subtelomeric imbalances are a frequent cause of cytogenetic abnormalities in patients with unexplained intellectual disability. Functional disomy of Xq28 involving the methyl-CpG-binding protein 2 gene (MECP2) has been observed mostly in subtelomeric duplications. We identified three patients with functional disomy of Xq28. A female patient showed an unbalanced translocation between 12q24.33 and Xq28. Two male patients showed an unbalanced translocation between Xq27.1- Yq11.22 and a recombinant X-chromosome containing duplicated material from Xq27.1 on Xp telomere, respectively. All three patients exhibited severe developmental delay, hypotonia, seizures, and distinctive facial features, including flat nasal bridge and hypertelorism. Additionally, brain magnetic resonance imaging (MRI) showed characteristic findings in each patient, including frontal dominant brain atrophy and hypoplasia of the corpus callosum, which are common findings in patients with functional disomies of Xq28 and interstitial duplications of Xq28, including MECP2. Brain MRI revealed a cystic lesion in the periventricular white matter in a patient, similar to our previous experience in patients with MECP2 duplication syndrome. Thus, white matter abnormalities may frequently be seen in cases of patients with additional MECP2 copies. © 2013 Wiley Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

Nestin-positive, keratin 15 (K15)-negative multipotent hair follicle stem cells are located above the hair follicle bulge. We have termed this location the hair follicle pluripotent stem cell area. We have previously shown that transplantation of nestin-expressing hair follicle stem cells can regenerate peripheral nerve and spinal cord injuries. In the present study, we regenerated the impinged sciatic nerve by transplanting hair follicle pluripotent stem cells. Human hair follicle stem cells were transplanted around the impinged sciatic nerve of ICR nude (nu/nu) mice. The hair follicle stem cells were transplanted between impinged sciatic nerve fragments of the mouse where they differentiated into glial fibrillary acidic protein-positive Schwann cells and promoted the recovery of pre-existing axons. The regenerated sciatic nerve functionally recovered. These multipotent hair follicle stem cells thereby provide a potential accessible, autologous source of stem cells for regeneration therapy of nerves degenerated by compression between bony or other hard surfaces., (© 2011 Japanese Dermatological Association.)

Aims: The risk factors associated with poor prognosis of nonalcoholic fatty liver disease (NAFLD) are not fully understood. Our aim was to assess the role of progressive hepatocellular telomere shortening in the clinical course of NAFLD., Methods: We measured average telomere lengths in liver tissue samples from 44 patients with NAFLD by quantitative fluorescence in situ hybridization using a telomere-specific probe. Patients in which telomeres measured at least 80% of the lengths of age-matched controls were categorized as group A. Those patients with telomeres measuring less than 80% of the control lengths formed group B., Results: Within group B, some samples showed a remarkable shortening of hepatocyte telomeres in younger patients, whereas some group A patients showed almost normal telomere lengths until their seventies. Among clinicopathological factors, body mass index (BMI), homeostasis model assessment insulin resistance (HOMA-IR), histological degree of steatosis and intensity of 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunostaining were all significantly higher in group B than in group A. Ki-67 immunohistochemistry demonstrated that group B liver tissues were significantly less proliferative than those from group A, despite no significant difference in the necroinflammatory activities of group A and B samples. In group B patients, the ratios of Ki-67 positive index to alanine aminotransferase value were significantly lower than group A., Conclusions: Greater insulin resistance can result in more severe hepatic steatosis among group B patients, leading to an overproduction of reactive oxygen species, which may accelerate telomere erosion. Furthermore the regenerative response of hepatocytes with prominent telomere shortening may be impaired, making these cells vulnerable to the effect of a 'second-hit' insult.

Glanzmann's thrombasthenia (GT) is a hereditary bleeding disorder caused by a quantitative or qualitative defect in the integrin alphaIIbbeta3. A new mutation, a T to C substitution at base 258 in the alphaIIb gene, leading to the replacement of Leu55 with Pro, was found by sequence analysis of a patient's alphaIIb cDNA. In transfection experiments using COS7 cells, the cells co-transfected with the mutated alphaIIb cDNA containing C258 and wild-type beta3 cDNA scarcely expressed the alphaIIbbeta3 complex. The Leu55 to Pro substitution in the alphaIIb gene was found to be responsible for this case of Glanzmann's thrombasthenia.

The specificity of autoantibodies in autoimmune hemolytic anemia (AIHA) has been studied using the serological procedure and immunoprecipitation technique with rare phenotype red cells. We attempted to analyze specificity using recombinant rhesus (Rh) blood group and band3 antigens expressed on erythroleukemic cell lines, KU812E. The autoantibody eluates were isolated by the acid elution procedure from the red cells of 20 AIHA patients. The recombinant Rh antigens, RhD, cE, ce, CE, and chimera antigens CE-D and D-CE, were obtained by retroviral cDNA transduction into KU812E cells, and the cell line expressing the antigens was cloned. Band3 cDNA was also obtained and introduced into KU812E and cloned KU812 expressing RhcE. The reactivities of AIHA eluates with recombinant Rh and band3 antigens were studied by flow cytometry. Fifteen eluates reacted with at least one of the RhcE, ce, or CE antigens, and four eluates reacted with RhD. Seven eluates with strong Rh specificity were studied further using chimera antigen. Five eluates showed reduced or lost reactivity, although two eluates reacted identically with the chimera antigens as wild type. These results indicated that conformational epitopes constituted by RhD or CE specific exofacial peptide loops are important for autoantibodies in most cases. Seven eluates reacted with band3, five exclusively. The coexpression study of RhcE and band3 did not enhance the expression of either antigen nor the reactivity with patient eluates, indicating that association of Rh and band3 was not involved in the appearance of autoantigen., (Copyright 2001 Wiley-Liss, Inc.)

Three cases of chemotherapy-induced acral erythema are reported. All the patients had received cyclophosphamide, vincristine, adriamycin, prednisolone, and granulocyte-colony stimulating factor (G-CSF) for the treatment of leukemia or malignant lymphoma. From 35 to 45 days after the start of chemotherapy, painful erythematous lesions developed on their palms, soles, fingers, and toes, resulting in blister formation and desquamation. The recent higher incidence of chemotherapy-induced acral erythema may be correlated with the popularity of G-CSF, which allows the use of higher doses of chemotherapeutic drugs.

The human immune response to extracellular substances (ES) from Actinobacillus actinomycetemcomitans Y4 were analyzed. Twenty-nine periodontal patients with generalized severe alveolar bone loss and 13 healthy volunteers were examined for serum IgG antibody titers against ES. Among the patients, 17 had higher antibody titers than healthy individuals (high-titer patients) but the remainder (low-titer patients) did not. Two-dimensional electrophoresis (2DE) and Western blots demonstrated that two proteins (40 and 37 kDa) and three smeared substances reacted with IgGs from high-titer patients, but not with IgGs from healthy volunteers. The low-molecular-mass smear at the acid side reacted with over 90% of all patients. This smear reacted with anti-A. actinomycetemcomitans lipopolysaccharide (LPS) monoclonal antibody which recognized LPS from each A. actinomycetemcomitans serotype. The high molecular mass smear at the acid side might be serotype-specific O-antigens of LPS. Another high molecular mass smear which located from the alkaline to the neutral side reacted with anti-serotype-b-specific capsular polysaccharide monoclonal antibody. Moreover, the 40- and 37-kDa proteins reacted with this anti-capsular polysaccharide antibody. This results suggested that 40- and 37-kDa proteins which reacted with 100% or 88% of high-titer patients might be glycoproteins linked with capsular polysaccharide.

The effect of riboflavin on nitrite treated erythrocytes from normal subjects and patients with hereditary methaemoglobinaemia due to the deficiency of NADH-cytochrome b5 reductase was studied in the presence of glucose, 2-deoxy-D-glucose or lactate. When glucose or 2-deoxy-D-glucose was used as a substrate for these erythrocytes, the rate of methaemoglobin reduction in these cells was accelerated more than two-fold in the presence of riboflavin. The acceleration was dependent on the concentration of riboflavin and was suppressed by the addition of atebrin. The stimulative effect of riboflavin was, however, not observed when lactate was used in place of glucose or 2-deoxy-D-glucose. On the basis of these results, the acceleration of methaemoglobin reduction by riboflavin was considered to be due to the activation of NADPH-flavin reductase (Yubisui et al, 1977) in erythrocytes by the reagent. The availability of riboflavin for patients with methaemoglobinaemia due to the deficiency of NADH-cytochrome b5 reductase and for those with toxic methaemoglobinaemia is discussed in relation to methaemoglobin reducing systems in erythrocytes.