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Nutritional status potentially influences immune responses; however, how nutritional signals regulate cellular dynamics and functionality remains obscure. Herein, we report that temporary fasting drastically reduces the number of lymphocytes by â¼50% in Peyer's patches (PPs), the inductive site of the gut immune response. Subsequent refeeding seemingly restored the number of lymphocytes, but whose cellular composition was conspicuously altered. A large portion of germinal center and IgA+ B cells were lost via apoptosis during fasting. Meanwhile, naive B cells migrated from PPs to the bone marrow during fasting and then back to PPs during refeeding when stromal cells sensed nutritional signals and upregulated CXCL13 expression to recruit naive B cells. Furthermore, temporal fasting before oral immunization with ovalbumin abolished the induction of antigen-specific IgA, failed to induce oral tolerance, and eventually exacerbated food antigen-induced diarrhea. Thus, nutritional signals are critical in maintaining gut immune homeostasis.
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Linfocitos B/fisiología , Inmunidad Mucosa , Animales , Antígenos/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Médula Ósea/inmunología , Médula Ósea/metabolismo , Quimiocina CXCL13/genética , Quimiocina CXCL13/metabolismo , Ayuno , Regulación de la Expresión Génica , Glucólisis , Inmunoglobulina A/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Estado Nutricional , Ovalbúmina/inmunología , Ganglios Linfáticos Agregados/inmunología , Ganglios Linfáticos Agregados/metabolismo , Ganglios Linfáticos Agregados/patología , Receptores CXCR5/genética , Receptores CXCR5/metabolismo , Transducción de Señal , Células del Estroma/citología , Células del Estroma/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Intestinal regulatory T cells (Treg cells) are necessary for the suppression of excessive immune responses to commensal bacteria. However, the molecular machinery that controls the homeostasis of intestinal Treg cells has remained largely unknown. Here we report that colonization of germ-free mice with gut microbiota upregulated expression of the DNA-methylation adaptor Uhrf1 in Treg cells. Mice with T cell-specific deficiency in Uhrf1 (Uhrf1(fl/fl)Cd4-Cre mice) showed defective proliferation and functional maturation of colonic Treg cells. Uhrf1 deficiency resulted in derepression of the gene (Cdkn1a) that encodes the cyclin-dependent kinase inhibitor p21 due to hypomethylation of its promoter region, which resulted in cell-cycle arrest of Treg cells. As a consequence, Uhrf1(fl/fl)Cd4-Cre mice spontaneously developed severe colitis. Thus, Uhrf1-dependent epigenetic silencing of Cdkn1a was required for the maintenance of gut immunological homeostasis. This mechanism enforces symbiotic host-microbe interactions without an inflammatory response.
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Colitis/inmunología , Colon/inmunología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Epigénesis Genética , Proteínas Nucleares/inmunología , Linfocitos T Reguladores/inmunología , Traslado Adoptivo , Animales , Proteínas Potenciadoras de Unión a CCAAT , Puntos de Control del Ciclo Celular , Proliferación Celular , Células Cultivadas , Clostridium/inmunología , Colitis/genética , Colon/microbiología , Metilación de ADN , Perfilación de la Expresión Génica , Interleucina-2 , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microbiota/inmunología , Proteínas Nucleares/biosíntesis , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Interferencia de ARN , ARN Interferente Pequeño , Simbiosis/inmunología , Ubiquitina-Proteína Ligasas , Regulación hacia ArribaRESUMEN
L-Arabinose (L-Ara) is a plant-specific sugar found in cell wall polysaccharides, proteoglycans, glycoproteins, and small glycoconjugates, which play physiologically important roles in cell proliferation and other essential cellular processes. L-Ara is synthesized as UDP-L-arabinose (UDP-L-Ara) from UDP-xylose (UDP-Xyl) by UDP-Xyl 4-epimerases (UXEs), a type of de novo synthesis of L-Ara unique to plants. In Arabidopsis, the Golgi-localized UXE AtMUR4 is the main contributor to UDP-L-Ara synthesis. However, cytosolic bifunctional UDP-glucose 4-epimerases (UGEs) with UXE activity, AtUGE1, and AtUGE3 also catalyze this reaction. For the present study, we first examined the physiological importance of bifunctional UGEs in Arabidopsis. The uge1 and uge3 mutants enhanced the dwarf phenotype of mur4 and further reduced the L-Ara content in cell walls, suggesting that bifunctional UGEs contribute to UDP-L-Ara synthesis. Through the introduction of point mutations exchanging corresponding amino acid residues between AtUGE1 with high UXE activity and AtUGE2 with low UXE activity, two mutations that increase relative UXE activity of AtUGE2 were identified. The crystal structures of AtUGE2 in complex forms with NAD+ and NAD+/UDP revealed that the UDP-binding domain of AtUGE2 has a more closed conformation and smaller sugar-binding site than bacterial and mammalian UGEs, suggesting that plant UGEs have the appropriate size and shape for binding UDP-Xyl and UDP-L-Ara to exhibit UXE activity. The presented results suggest that the capacity for cytosolic synthesis of UDP-L-Ara was acquired by the small sugar-binding site and several mutations of UGEs, enabling diversified utilization of L-Ara in seed plants.
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Proteínas de Arabidopsis , Arabidopsis , Pared Celular , Citosol , UDPglucosa 4-Epimerasa , Azúcares de Uridina Difosfato , Arabidopsis/genética , Arabidopsis/enzimología , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Citosol/metabolismo , Citosol/enzimología , Azúcares de Uridina Difosfato/metabolismo , Pared Celular/metabolismo , UDPglucosa 4-Epimerasa/genética , UDPglucosa 4-Epimerasa/metabolismo , Mutación , Uridina Difosfato Xilosa/metabolismo , Uridina Difosfato Xilosa/genéticaRESUMEN
The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on the gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota. Purified diet-fed mice exhibited shorter villi and crypt lengths and slower epithelial turnover, particularly in the ileum. In addition, antimicrobial products, including REG3γ, were substantially decreased in purified diet-fed mice. Purified diet feeding also suppressed α1,2-fucosylation on the epithelial surface. Furthermore, the purified diet induced metabolic rewiring to fatty acid oxidation and ketogenesis. 16S ribosomal RNA gene sequencing of the ileal contents and mucus layer revealed distinct gut microbiota compositions between the purified and crude diet-fed mice. Purified diet feeding reduced the abundance of segmented filamentous bacteria (SFB), which potently upregulate REG3γ and fucosyltransferase 2 (Fut2) by stimulating group 3 innate lymphoid cells (ILC3s) to produce IL-22. These observations illustrate that the intake of a crude diet secures epithelial barrier function by facilitating SFB colonization, whereas a purified diet insufficiently establishes the epithelial barrier, at least partly owing to the loss of SFB. Our data suggest that the influence of purified diets on the epithelial barrier integrity should be considered in experiments using purified diets.
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Microbioma Gastrointestinal , Ratones , Animales , Inmunidad Innata , Linfocitos , Dieta , Bacterias , Proliferación CelularRESUMEN
Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.
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Necrosis de la Cabeza Femoral , Lupus Eritematoso Sistémico , Esteroides , Carboxipeptidasas/genética , Proteínas Portadoras/genética , Cabeza Femoral , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/complicaciones , Necrosis de la Cabeza Femoral/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Cadenas Pesadas de Miosina/genética , Polimorfismo de Nucleótido Simple , Esteroides/efectos adversosRESUMEN
Intestinal microfold cells (M cells) are an enigmatic lineage of intestinal epithelial cells that initiate mucosal immune responses through the uptake and transcytosis of luminal antigens. The mechanisms of M-cell differentiation are poorly understood, as the rarity of these cells has hampered analysis. Exogenous administration of the cytokine RANKL can synchronously activate M-cell differentiation in mice. Here we show the Ets transcription factor Spi-B was induced early during M-cell differentiation. Absence of Spi-B silenced the expression of various M-cell markers and prevented the differentiation of M cells in mice. The activation of T cells via an oral route was substantially impaired in the intestine of Spi-B-deficient (Spib(-/-)) mice. Our study demonstrates that commitment to the intestinal M-cell lineage requires Spi-B as a candidate master regulator.
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Diferenciación Celular , Células Epiteliales/citología , Mucosa Intestinal/citología , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Proto-Oncogénicas c-ets/metabolismo , Animales , Linaje de la Célula , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Humanos , Inmunidad Mucosa/genética , Mucosa Intestinal/embriología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ligando RANK/farmacología , Linfocitos T/inmunologíaRESUMEN
Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-ß-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.
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BACKGROUND: To identify specific human neutrophil antigen (HNA) antibodies, assays using neutrophils such as monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA) are recommended. However, these assays are limited by labor-intensive neutrophil preparation and varying antigen expression levels. METHODS: We evaluated a newly developed immunocomplex capture fluorescence assay (ICFA) for identifying HNA-1 antibodies and compared it to MAIGA and LABScreen Multi (LABM), which utilizes recombinant HNA-coated Luminex beads. For ICFA, HNA-1a or HNA-1b transfected cells replaced neutrophils. Cells incubated with serum were lysed, and immune complexes were captured using five CD16 monoclonal antibody-conjugated Luminex beads. Nine antisera with known specificity and 26 samples suspected of containing HNA antibodies were analyzed by ICFA and MAIGA using neutrophils or transfected cells (ICFA-N or ICFA-T, and MAIGA-N or MAIGA-T, respectively). RESULTS: ICFA-T and MAIGA-N accurately determined the specificity of all antibodies in the nine antiserum samples. The ICFA-T detection limit was 2048-fold for anti-HNA-1a and 256-fold for anti-HNA-1b; the limits of MAIGA-T, MAIGA-N, and LABM were 32-, 4 ~ 64-, and 128-fold for anti-HNA-1a and 64-, 16 ~ 64-, and 32-fold for anti-HNA-1b, respectively. Twelve and 7 of the remaining 26 samples tested negative and positive, respectively, in both ICFA-T and MAIGA-N. Antibody specificity against HNA-1a or HNA-1b determined using ICFA-T agreed with that determined using MAIGA-N and LABM. Another seven samples tested positive in ICFA-T but negative in MAIGA-N. CONCLUSION: The novel ICFA is highly sensitive and exhibits specificity similar to MAIGA and LABM for detecting HNA-1 antibodies.
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Inmunoensayo , Isoantígenos , Neutrófilos , Humanos , Anticuerpos Monoclonales/inmunología , Isoantígenos/química , Isoantígenos/inmunología , Neutrófilos/inmunología , Transfección , Colorantes Fluorescentes/química , Inmunoensayo/métodosRESUMEN
Photo-induced glycosylations of trichloroacetimidate donors and alcohols using an edible polyphenol, curcumin, were examined under visible photo-irradiation (470 nm). It was found, for the first time, that these glycosylations proceed smoothly under mild reaction conditions to give the corresponding glycosides in high yields. In addition, the present glycosylation method was applicable to a wide range of trichloroacetimidate donors and alcohol acceptors and showed high chemoselectivity over glycosyl phosphite, phosphate, (N-phenyl)trifluoroacetimidate, fluoride, glycal and thioglycoside.
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BACKGROUND: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed. CASE PRESENTATION: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome. CONCLUSIONS: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy.
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Lesión Renal Aguda , Antineoplásicos Inmunológicos , Nefritis Intersticial , Síndrome Nefrótico , Masculino , Humanos , Anciano , Nivolumab/efectos adversos , Ipilimumab/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Lesión Renal Aguda/complicaciones , Nefritis Intersticial/inducido químicamente , Nefritis Intersticial/complicacionesRESUMEN
OBJECTIVE: In an effort to avoid postoperative sick sinus syndrome( SSS), we omit the ablation line to the superior vena cava( SVC) in the Cox-mazeâ ¢ lesion set. We report the long-term outcomes, including the freedom from SSS. METHODS: We studied 102 patients who underwent bi-atrial maze procedure for persistent atrial fibrillation (Af) from 2009 through 2023. Bipolar radio frequency ablation or cryoablation was used except for right-side atriotomy and right atriotomy. Cryoablation was used for atrioventricular annulus. The patient age was 68±9.4. Duration of Af was 3.4±6.5 years (unknown 9 cases). The amplitude of f-wave in V1 was 0.182±0.095 mV and it was<0.1 mV in 19 (18.6%). Diameter of the left atrium was 50±8.9 mm, and left atrial volume index was 89±37 ml/m2. Ninety-one (89.2%) patients underwent concomitant mitral valve surgery. RESULTS: Survival rate was 99% at 1 year and 96% at 5 years. Freedom from Af was 92% at 1 year and 88% at 5 years. Freedom from permanent pacemaker implantation (PPI) was 87% at 1 year and 83% at 5 years. CONCLUSIONS: Defibrillation rate and the incidence of PPI was comparable to those in previous reports after standard Cox-mazeâ ¢. SSS after maze for persistent Af seem due to patient.
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Fibrilación Atrial , Ablación por Catéter , Humanos , Vena Cava Superior/cirugía , Procedimiento de Laberinto , Resultado del Tratamiento , Fibrilación Atrial/cirugía , Atrios Cardíacos/cirugía , Ablación por Catéter/métodosRESUMEN
Rapidly destructive coxopathy (RDC), a rare disease of unknown etiology, is characterized by the rapid destruction of the hip joint. In the current study, the potential involvement of inflammasome signaling in the progression of RDC was investigated. Histopathologic changes and the gene expression of inflammasome activation markers in hip synovial tissues collected from patients with RDC were evaluated and compared with those of osteoarthritis and osteonecrosis of the femoral head patients. The synovial tissues of patients with RDC exhibited remarkable increases in the number of infiltrated macrophages and osteoclasts, and the expression of inflammasome activation markers was also increased compared with those of osteoarthritis and osteonecrosis of the femoral head patients. To further understand the histopathologic changes in the joint, a co-culture model of macrophages and synoviocytes that mimicked the joint environment was developed. Remarkably, the gene expression levels of NLRP3, GSDMD, IL1B, TNFA, ADMTS4, ADMTS5, MMP3, MMP9, and RANKL were significantly elevated in the synoviocytes that were co-cultured with activated THP-1 macrophages, suggesting the association between synovitis and inflammasome activation. Consistent with these findings, osteoclast precursor cells that were co-cultured with stimulated synoviocytes exhibited an increased number of tartrate-resistant acid phosphatase-positive cells, compared with cells that were co-cultured with non-stimulated synoviocytes. These findings suggest that the activation of inflammasome signaling in the synovium results in an increase in local inflammation and osteoclastogenesis, thus leading to the rapid bone destruction in RDC.
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Enfermedades Óseas Metabólicas , Osteoartritis , Osteonecrosis , Sinovitis , Biomarcadores/metabolismo , Enfermedades Óseas Metabólicas/metabolismo , Humanos , Inflamasomas/metabolismo , Osteoartritis/patología , Osteoclastos/metabolismo , Membrana Sinovial/metabolismo , Sinovitis/patologíaRESUMEN
BACKGROUND: The Kidd blood group gene SLC14A1 (JK) accounts for approximately 20 Kb from initiation codon to stop codon in the genome. In genomic DNA analysis using Sanger sequencing or short-read-based next generation sequencing, it is difficult to determine the cis or trans positions of single nucleotide variations (SNVs), which are occasionally more than 1 Kb away from each other. We aimed to determine the complete nucleotide sequence of a 20-Kb genomic DNA amplicon to characterize the JK allelic variants associated with Kidd antigen silencing in a blood donor. STUDY DESIGN AND METHODS: The Jk(a-b-) phenotype was identified in this donor by standard serological typing. A DNA sample obtained from whole blood was amplified by long-range PCR to obtain a 20-Kb fragment of the SLC14A1 gene, including the initiation and stop codons. The fragment was then analyzed by Sanger sequencing and single-molecule sequencing. Transfection and expression studies were performed in CHO cells using the expression vector construct of JK alleles. RESULTS: Sanger sequencing and single-molecule sequencing revealed that the donor was heterozygous with JK*01 having c.276G>A (rs763262711, p.Trp92Ter) and JK*02 having c.499A>G (rs2298719, p.Met167Val), c.588A>G (rs2298718, p.Pro196Pro), and c.743C>A (p.Ala248Asp). The two JK alleles identified have not been previously described. Transfection and expression studies indicated that the CHO cells transfected with JK*02 having c.743C>A did not express the Jkb and Jk3 antigens. CONCLUSIONS: We identified new JK silencing alleles and their critical SNVs by single-molecule sequencing and the findings were confirmed by transfection and expression studies.
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ADN , Sistema del Grupo Sanguíneo de Kidd , Animales , Cricetinae , Sistema del Grupo Sanguíneo de Kidd/genética , Alelos , Cricetulus , HeterocigotoRESUMEN
BACKGROUND AND OBJECTIVES: In Japan, the prevalence of haptoglobin deficiency is approximately 1 in 4000. Haptoglobin-deficient individuals may produce anti-haptoglobin from allo-immunization, leading to serious transfusion reactions. Therefore, implementation of a consistent supply of haptoglobin-deficient fresh frozen plasma is crucial. We developed a novel reagent to facilitate large-scale identification of haptoglobin-deficient individuals as potential donors of plasma products. MATERIALS AND METHODS: We established mouse monoclonal anti-haptoglobin-producing cell lines (three clones) using the hybridoma method by immunizing mice with the haptoglobin protein. Purified antibodies were conjugated with carboxylate-modified polystyrene latex beads and used for haptoglobin measurements by the latex agglutination method using an automatic analyser (LABOSPECT008). Samples with low protein concentrations were re-examined by enzyme-linked immunosorbent assay to confirm the results. Additionally, the haptoglobin gene was amplified by polymerase chain reaction to confirm the haptoglobin deletion allele (Hpdel ). RESULTS: From February to October 2022, 7476 blood donor samples were screened. Two haptoglobin-deficient and 21 low-haptoglobin-expressing individuals were identified. Two haptoglobin-deficient donors were found homozygous for Hpdel , and 19 (90%) of the 21 low-haptoglobin-expressing individuals were heterozygous for Hpdel , which includes the first reported case of heterozygous Hpdel /HpJohnson . CONCLUSION: We developed a new reagent for the detection of haptoglobin deficiency, which is automatable and inexpensive and appears useful for large-scale screening of blood donors.
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Donantes de Sangre , Haptoglobinas , Animales , Humanos , Ratones , Ensayo de Inmunoadsorción Enzimática , Haptoglobinas/química , Haptoglobinas/genética , Heterocigoto , Reacción en Cadena de la Polimerasa/métodos , Anticuerpos Monoclonales/químicaRESUMEN
BACKGROUND AND OBJECTIVES: Human neutrophil antigens (HNAs) are categorized into five systems: HNA-1 to HNA-5. Given the importance of neutrophils in immunity, we sought to create awareness of the role of HNA diagnostic services in managing immune neutropenia and transfusion-related acute lung injury. To provide health communities all around the world with access to these services, we conducted a survey to create a directory of these HNA diagnostic services. MATERIALS AND METHODS: An Excel table-based survey was created to capture information on the laboratory's location and was emailed to 55 individuals with known or possible HNA investigation activity. The collected data were then summarized and analysed. RESULTS: Of contacted laboratories, the surveys were returned from 23 (38.2%) laboratories; 17 have already established HNA diagnostic (of them 12 were regular participants of the International Granulocyte Immunobiology Workshop [ISBT-IGIW]), 4 laboratories were in the process of establishing their HNA investigation and the remaining 2 responder laboratories, did not conduct HNA investigations. In established laboratories, investigation for autoimmune neutropenia (infancies and adults) was the most frequently requested, and antibodies against HNA-1a and HNA-1b were the most commonly detected. CONCLUSION: The directory of survey respondents provides a resource for health professionals wanting to access HNA diagnostic services. The present study offers a comprehensive picture of HNA diagnostics (typing and serology), identifying weak points and areas for improvement for the first time. Identifying more laboratories involved in HNA diagnostics with limited access to international societies in the field will globally improve HNA diagnostics.
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Neutropenia , Neutrófilos , Adulto , Humanos , Granulocitos , Anticuerpos , Encuestas y CuestionariosRESUMEN
Plants adapt to freezing stress through cold acclimation, which is induced by nonfreezing low temperatures and accompanied by growth arrest. A later increase in temperature after cold acclimation leads to rapid loss of freezing tolerance and growth resumption, a process called deacclimation. Appropriate regulation of the trade-off between freezing tolerance and growth is necessary for efficient plant development in a changing environment. The cell wall, which mainly consists of polysaccharide polymers, is involved in both freezing tolerance and growth. Still, it is unclear how the balance between freezing tolerance and growth is affected during cold acclimation and deacclimation by the changes in cell wall structure and what role is played by its monosaccharide composition. Therefore, to elucidate the regulatory mechanisms controlling freezing tolerance and growth during cold acclimation and deacclimation, we investigated cell wall changes in detail by sequential fractionation and monosaccharide composition analysis in the model plant Arabidopsis thaliana, for which a plethora of information and mutant lines are available. We found that arabinogalactan proteins and pectic galactan changed in close coordination with changes in freezing tolerance and growth during cold acclimation and deacclimation. On the other hand, arabinan and xyloglucan did not return to nonacclimation levels after deacclimation but stabilized at cold acclimation levels. This indicates that deacclimation does not completely restore cell wall composition to the nonacclimated state but rather changes it to a specific novel composition that is probably a consequence of the loss of freezing tolerance and provides conditions for growth resumption.
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Proteínas de Arabidopsis , Arabidopsis , Congelación , Aclimatación/fisiología , Frío , Arabidopsis/metabolismo , Pared Celular/metabolismo , Monosacáridos/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits. CASE PRESENTATION: The patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/gâ Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/gâ Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney. CONCLUSIONS: We experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.
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Diabetes Mellitus Tipo 2 , Glomerulonefritis Membranosa , Glomerulonefritis , Hipertensión , Enfermedades Renales , Masculino , Humanos , Persona de Mediana Edad , Inmunoglobulina G , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Proteinuria , Anticuerpos MonoclonalesRESUMEN
BACKGROUND: This study compared the re-revision rate and radiographic outcomes of revision total hip arthroplasty (THA) using a Kerboull-type acetabular reinforcement device (KT plate) with bulk structural allograft and metal mesh with impaction bone grafting (IBG). METHODS: Ninety-one hips of 81 patients underwent revision THA for American Academy of Orthopedic Surgeons (AAOS) classification type III defects from 2008 to 2018. Of these, seven hips of five patients and 15 hips of 13 patients were excluded due to insufficient follow-up information (< 24 months) and large bone defects with a vertical defect height ≥ 60 mm, respectively. The current study compared the survival and radiographic parameters of 45 hips of 41 patients using a KT plate (KT group) and 24 hips of 24 patients using a metal mesh with IBG (mesh group). RESULTS: Eleven hips (24.4%) in the KT group and 1 hip (4.2%) in the mesh group exhibited radiological failure. Moreover, 8 hips in the KT group (17.0%) required a re-revision THA, while none of the patients in the mesh group required a re-revision. The survival rate with radiographic failure as the endpoint in the mesh group was significantly higher than that in the KT group (100% vs 86.7% at 1-year and 95.8% vs 80.0% at 5-years, respectively; p = 0.032). On multivariable analysis evaluating factors associated with radiographic failure, there were no significant associations with any radiographic measurement. Of the 11 hips with radiographic failure, 1 (11.1%), 3 (12.5%), and 7 (58.3%) hips were of Kawanabe classification stages 2, 3, and 4, respectively. CONCLUSIONS: The findings of this study suggest that revision THA using KT plates with bulk structure allografts could provide poorer clinical outcomes than revision THA using a metal mesh with IBG. Although revision THA using KT plates with bulk structural allografts could set the true hip center, there is no association between a high hip center and clinical outcomes. The relationship between the position of the KT plate and the host bone might be considered more carefully.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Trasplante Óseo , Mallas Quirúrgicas , Resultado del Tratamiento , Falla de Prótesis , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Reoperación , Metales , Estudios de Seguimiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Based on the Japanese Pediatric Orthopaedic Association's guidelines, secondary screening and imaging including ultrasonography and radiography, are recommended in infants with limited hip abduction (<70°) or in those with multiple risk factors including the following: asymmetrical skin creases, a family history of developmental dysplasia of the hip, female sex, and pelvic position at delivery. However, there is still little information regarding the usefulness of this guideline. The objective of this study was to investigate the association between the risk factors and developmental dysplasia of the hip diagnosed using ultrasound and radiography. METHODS: A total of 356 infants (67 boys and 289 girls) underwent secondary ultrasonographic and radiological screening for developmental dysplasia of the hip in our hospital. Risk factors were documented from their medical records. The recommended item score, which we defined as an integrated value of the recommended item, was calculated for each patient. The limitation of hip abduction alone was a criterion for secondary screening; therefore, we defined the scores as follows: the limitation of hip abduction scored 2 points and other recommended scores were assigned 1 point. If the recommended item score was 2 points or more, we classified the infants as high-risk. RESULTS: A total of 280 of 356 infants were included in the high-risk group, which showed a higher ratio of cases with abnormal imaging findings than the low-risk group. According to the multivariate logistic regression analyses among the recommended items, being female, skin asymmetry, and limb limitation were identified as independent risk factors for imaging abnormality and the need for Pavlik harness treatment. CONCLUSIONS: The recommended items for secondary screening based on the Japanese Pediatric Orthopaedic Association's guidelines could be useful for screening infants in need of treatment.
RESUMEN
INTRODUCTION: There is still little information regarding the advantages of a using a polished tapered stem for Crowe Type IV developmental dysplasia of the hip (DDH). This study aimed to investigate the mid-term clinical and radiological outcomes of primary total hip arthroplasty (THA) with femoral shortening osteotomy using modular and polished tapered stems and to compare the results between the modular and polished tapered stems. MATERIALS AND METHODS: This retrospective review included 32 patients (37 hips) with Crowe type IV DDH who underwent primary THA with femoral shortening osteotomy using a modular stem (cementless group, 14 hips) or a polished tapered stem (cement group, 23 hips) between 1996 and 2018. Clinical data and radiographic assessments were reviewed to analyze the differences between the two groups. RESULTS: The mean duration of patient follow-up of the cementless group (134.4 months) was longer than that of the cement group (75.5 months). There were no differences in clinical results, time of bone union, and survival rate between the two groups. However, the cementless group exhibited a higher ratio of intraoperative fracture and thinning of cortical bone including stress shielding, medullary changes, stem alignment changes, and osteolysis, compared to the cement group. CONCLUSIONS: The findings of this study suggest that THA with femoral shortening osteotomy using both cemented and modular stems can provide satisfactory results. However, considering the occurrence of intraoperative fracture and radiographic analysis in the current study, the cement stem may have an advantage for patients with bone fragility and deterioration in bone quality.