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1.
BMC Surg ; 24(1): 217, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068411

RESUMEN

BACKGROUND: The usefulness of high-resolution impedance manometry (HRIM) in patients who underwent total gastrectomy with Roux-en-Y (R-Y) anastomosis has never been well validated. This study aimed to investigate whether intraesophageal pressure affects quality of life in patients who underwent total gastrectomy with R-Y anastomosis. METHODS: The participants comprised 12 patients who underwent total gastrectomy for gastric cancer between October 2014 and July 2022 and underwent a postsurgical HRIM examination. The association between the HRIM data and Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37) questionnaires was analyzed. RESULTS: Esophageal body motility was normal in almost all patients. The anastomosis shape (circular stapler and overlap method with linear stapler) did not influence intraesophageal pressure. The integrated relaxation pressure and lower esophageal sphincter (LES) residual pressure during swallowing-induced relaxation were involved in "diarrhea subscale" scores (p = 0.0244 and p = 0.0244, respectively). The average maximum intrabolus pressure was not involved in postgastrectomy symptom. The contractile front velocity correlated with the "indigestion subscale," "diarrhea subscale," and "constipation subscale" (p = 0.0408, p = 0.0143, and p = 0.0060, respectively). The distal latency, i.e., the time from upper esophageal sphincter relaxation to contractile deceleration, was also associated with the "abdominal pain subscale" (p = 0.0399). LES pressure and esophageal body motility affected patients' quality of life after total gastrectomy. CONCLUSIONS: HRIM for the evaluation of intraesophageal pressure is useful for the functional assessment of esophagojejunostomy with the R-Y reconstruction after total gastrectomy.


Asunto(s)
Gastrectomía , Manometría , Presión , Calidad de Vida , Neoplasias Gástricas , Humanos , Gastrectomía/métodos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Gástricas/cirugía , Anciano , Anastomosis en-Y de Roux , Esófago/cirugía , Esófago/fisiopatología , Síndromes Posgastrectomía/etiología , Síndromes Posgastrectomía/fisiopatología , Adulto
2.
Parasitol Int ; 102: 102924, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39019105

RESUMEN

While biogeographic patterns of free-living organisms are well documented, the biogeography of parasitic fauna remains largely unclear. Due to morphological similarities, parasites are often difficult to identify without the aid of molecular genetics, further complicating the interpretation of their biogeographic patterns. We investigated trematode parasites infecting the East Asian freshwater snail Semisulcospira libertina to understand their biogeography and to evaluate how molecular approaches influence the interpretation of biogeographic patterns of the trematode fauna. We identified 46 genetically delimited species from 19 morphologically distinguishable trematodes infecting S. libertina and found that their species richness was negatively correlated to latitude. We also found that potential definitive host (fishes) richness and host body size were positively correlated with trematode species richness, suggesting that host attributes are essential factors shaping the biogeographic pattern in trematodes. These trends were observed irrespective of species identification methods, demonstrating that classical morphological identification can also effectively identify the latitudinal gradient pattern in trematodes. We further detected the distance decay of similarity in trematode communities, although this trend was only detectable in the biogeographic dataset based on molecular identification. Our study showed that morphological identification sufficiently reflects the latitudinal richness gradient while molecular identification is essential to estimate accurate local species richness and increase the resolution of the large-scale pattern of population similarities in the trematode communities.


Asunto(s)
Agua Dulce , Caracoles , Trematodos , Animales , Trematodos/genética , Trematodos/clasificación , Trematodos/fisiología , Caracoles/parasitología , Agua Dulce/parasitología , Larva/crecimiento & desarrollo , Filogenia , Filogeografía , Peces/parasitología
3.
J Evol Biol ; 37(9): 1055-1063, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39037492

RESUMEN

Determining species boundaries within rapidly evolving species flocks is essential to understanding their evolutionary history but is often difficult to achieve due to the lack of clear diagnostic features. Ancient Lake Biwa harbours endemic snails in the genus Semisulcospira, a species flock with 19 described species. However, their morphological and genetic similarity cast doubt on the validity of their species status and their histories of explosive speciation. To evaluate their species boundaries, we examine patterns of gene flow among the sympatric or parapatric nominal Semisulcospira species in Lake Biwa. The principal component analysis and Bayesian structure analysis based on the genome-wide genotyping dataset demonstrated no gene flow between five pairs of the Semisulcospira species. However, we found the hybrids between the closely related species pair, Semisulcospira decipiens and S. rugosa. Despite the presence of hybrids, these nominal species still formed their own genetic clusters. There are variations in the chromosome numbers among these species, potentially providing an intrinsic barrier to panmictic gene flow. Our study showed complete or partial reproductive isolation among the sympatric or parapatric Semisulcospira species, demonstrating that the Semisulcospira snails are real species assemblages radiated in Lake Biwa. Our study provides significant implications for establishing species boundaries among rapidly evolving freshwater species in ancient lakes.


Asunto(s)
Flujo Génico , Lagos , Aislamiento Reproductivo , Caracoles , Animales , Caracoles/genética , Especiación Genética , Teorema de Bayes
4.
Ann Med Surg (Lond) ; 86(2): 712-719, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38333281

RESUMEN

Background: Objective functional assessment of esophagogastric anastomosis in patients who underwent proximal gastrectomy with the hinged double flap method for gastric cancer has not been well investigated. This study aimed to perform a functional analysis of reconstruction using high-resolution impedance manometry (HRIM). Materials and methods: The authors enroled 25 patients who underwent proximal gastrectomy for gastric cancer between May 2015 and April 2020 and subsequently underwent HRIM postoperatively. Eligible questionnaires [Postgastrectomy Syndrome Assessment Scale-37 (PGSAS-37)] were retrieved from 16 patients. The association between HRIM data and PGSAS-37 was analyzed. Results: The amplitudes of distal oesophageal peristaltic waves, contractile front velocity, and distal latency assessed by HRIM were almost normal after surgery. Most patient's lower oesophageal sphincter (LES) resting pressure created by the hinged double flap was within normal limits. Conversely, LES residual pressure values during swallowing-induced relaxation were abnormally high in most patients, and the lower the values, the more severe the reflux and diarrhoea symptoms (P=0.038, P=0.041, respectively). In addition, even when the integrated relaxation pressure (IRP) was normal, lower values corresponded to more severe reflux symptoms (P=0.020). The required LES pressure may be higher after proximal gastrectomy because of the relatively higher intragastric pressure due to the reduced volume of the remnant stomach. This also suggests that swallowing-induced relaxation of the LES was considered a trigger for oesophageal reflux in post-proximal gastrectomy patients. Conclusion: LES residual pressure and IRP values in HRIM correlated with reflux symptoms in patients after proximal gastrectomy.

5.
Mol Phylogenet Evol ; 191: 107987, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081401

RESUMEN

Ancient lakes are a hotspot of biodiversity. Freshwater species often experience spectacular species radiation after colonizing lakes from riverine habitats. Therefore, the relationship between the fauna of the ancient lakes and the surrounding riverine system has a special significance in understanding their origin and evolutionary history. The study of ancient lake species often focused on the lake colonization of riverine species. In contrast, far less attention has been placed on the reverse direction: the riverine colonization of the lake species, despite its importance in disentangling their complex evolutionary history. The freshwater snails in the genus Semisulcospira involve endemic groups that radiated in the ancient Lake Biwa. Using genetics and fossil records, we inferred that the ancestors of these lake-endemic Semisulcospira snails historically colonized the riverine habitats at least three times during the Middle Pleistocene. Each colonization resulted in the formation of a new lineage that was genetically and morphologically distinct from other lineages. Further, one of these colonizations was followed by hybridization with a cosmopolitan riverine species, which potentially facilitated the population persistence of the colonizers in the new environment. Despite their complex histories, all these colonizers were currently grouped within a single species, Semisulcospira kurodai, suggesting cryptic diversity in this species. This study highlights the significance of the riverine colonizations of the lake species to fully understand the diversification history of freshwater fauna in and around the ancient lakes.


Asunto(s)
Evolución Biológica , Lagos , Animales , Filogenia , Caracoles/genética , Caracoles/anatomía & histología , Ecosistema
6.
Microorganisms ; 11(11)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-38004633

RESUMEN

Epstein-Barr-virus-associated gastric cancer (EBVaGC) represents almost 7% of all GC and is a distinct subtype of GC with extreme DNA hypermethylation. EBVaGC is a tumor-infiltrating lymphocyte-rich tumor with little lymph-node metastasis in its early stage and with a relatively favorable prognosis in its advanced stage. Using upper gastrointestinal endoscopy, we recognize EBVaGC as a mainly depressed type with SMT-like protrusion in the upper part of the stomach near the gastric mucosal atrophic border or remnant stomach. The EBVaGC recognition rate of 21.4% with the endoscopic motif is not high, and further progress in endoscopic diagnosis of EBVaGC is needed. As less invasive endoscopic therapy, the extension of the criteria of endoscopic submucosal dissection (ESD) for early EBVaGC with little lymph-node metastasis should be discussed. Endoscopic diagnosis of EBVaGC may be relevant for the selection of patients who could benefit from endoscopic treatment or chemotherapy.

7.
Genome Biol Evol ; 15(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38014863

RESUMEN

Semisulcospira habei is a freshwater snail species endemic to the Lake Biwa drainage and belongs to a species group radiated within the lake system. We report the chromosome-scale genome assembly of S. habei, including eight megascaffolds larger than 150 Mb. The genome assembly size is about 2.0 Gb with an N50 of 237 Mb. There are 41,547 protein-coding genes modeled by ab initio gene prediction based on the transcriptome data set, and the BUSCO completeness of the annotated genes was 92.2%. The repeat elements comprise approximately 76% of the genome assembly. The Hi-C contact map showed seven well-resolved scaffolds that correspond to the basic haploid chromosome number of S. habei inferred from the preceding karyotypic study, while it also exhibited one scaffold with a complicated mosaic pattern that is likely to represent the complex of multiple supernumerary chromosomes. The genome assembly reported here represents a high-quality genome resource in disentangling the genomic background of the adaptive radiation of Semisulcospira and also facilitates evolutionary studies in the superfamily Cerithioidea.


Asunto(s)
Lagos , Caracoles , Animales , Caracoles/genética , Cromosomas/genética , Genómica , Tamaño del Genoma
8.
Gastric Cancer ; 26(1): 116-122, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36040575

RESUMEN

BACKGROUND AND STUDY AIMS: The diagnostic ability of endoscopists to determine invasion depth of early gastric cancer is not favorable. We designed an artificial intelligence (AI) classifier for differentiating intramucosal and submucosal gastric cancers and examined it to establish a diagnostic method based on cooperation between AI and endoscopists. PATIENTS AND METHODS: We prepared 500 training images using cases of mainly depressed-type early gastric cancer from 250 intramucosal cancers and 250 submucosal cancers. We also prepared 200 test images each of 100 cancers from another institution. We designed an AI classifier to differentiate between intramucosal and submucosal cancers by deep learning. We examined the performance of the AI classifier and the majority vote of the endoscopists as high confidence and low confidence diagnostic probability, respectively, and cooperatively combined them to establish a diagnostic method providing high accuracy. RESULTS: Internal evaluation of the training images showed that accuracy, sensitivity, specificity, and F1 measure by the AI classifier were 77%, 76%, 78%, and 0.768, and those of the majority vote of the endoscopists were 72.6%, 53.6%, 91.6%, and 0.662, respectively. A diagnostic method based on cooperation between AI and the endoscopists showed that the respective values were 78.0%, 76.0%, 80.0%, and 0.776 for the test images. The value of F1 measure was especially higher than those by AI or the endoscopists alone. CONCLUSIONS: Cooperation between AI and endoscopists improved the diagnostic ability to determine invasion depth of early gastric cancer.


Asunto(s)
Inteligencia Artificial , Neoplasias Gástricas , Humanos , Detección Precoz del Cáncer , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirugía , Endoscopía , Aprendizaje Profundo
9.
Mol Phylogenet Evol ; 175: 107563, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35809852

RESUMEN

Accurate species identification is of primary importance in ecology and evolutionary biology. For a long time, the unionid mussels Beringiana and Sinanodonta have puzzled researchers trying to unravel their diversity because of their poorly discernible morphologies. A recent study conducted species delineation of unionid mussels based on mitochondrial DNA variation, opening up a new avenue to grasp species diversity of the mussels. However, mtDNA-based classification may not align with species boundaries because mtDNA is prone to introgression and incomplete lineage sorting that cause discordance between species affiliation and gene phylogeny. In this study, we evaluated the validity of the mtDNA-based classification of unionid mussels Beringiana and Sinanodonta in Japan using mitochondrial sequence data, double digest restriction site-associated DNA library (ddRAD) sequencing, and morphological data. We found significant inconsistencies in the mitochondrial and nuclear DNA phylogenies, casting doubt on the reliability of the mtDNA-based classification in this group. In addition, nuclear DNA phylogeny revealed that there are at least two unionid lineages hidden in the mtDNA phylogeny. Although molecular dating technique indicates that Beringiana and Sinanodonta diverged >35 million years ago, their shell morphologies are often indistinguishable. Specifically, morphological analyses exhibited the parallel appearance of nearly identical ball-like shell forms in the two genera in Lake Biwa, which further complicates species identification and the morphological evolution of unionid mussels. Our study adds to a growing body of literature that accurate species identification of unionid mussels is difficult when using morphological characters alone. Although mtDNA-based classification is a simple and convenient way to classify unionid mussels, considerable caution is warranted for its application in ecological and evolutionary studies.


Asunto(s)
Bivalvos , Unionidae , Animales , Bivalvos/genética , ADN Mitocondrial/genética , Japón , Filogenia , Reproducibilidad de los Resultados , Unionidae/genética
10.
Sci Rep ; 12(1): 2119, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35136087

RESUMEN

Molecular studies based on the high resolution genetic markers help us to grasp the factor shaping the genetic structure of marine organisms. Ecological factors linking to life history traits have often explained the process of genetic structuring in open and connectable oceanic environments. Besides, population genetic divergence can be affected by fragmented habitat, oceanic current, and past geographical events. In the present study, we demonstrated the genetic differentiation of marine gastropod Monodonta sp. within a narrow range of peripheral oceanic islands, the Ogasawara Islands. Genetic analyses were performed not only with a mitochondrial DNA marker but also with a high-throughput SNPs dataset obtained by ddRAD-seq. The results of the mtDNA analyses did not show genetic divergence among populations, while the SNPs dataset detected population genetic differentiation. Population demographic analyses and gene flow estimation suggested that the genetic structure was formed by sea level fluctuation associated with the past climatic change and regulated by temporal oceanographic conditions. These findings provide important insights into population genetic patterns in open and connectable environments.


Asunto(s)
Flujo Génico , Caracoles/genética , Distribución Animal , Animales , Cambio Climático , ADN Mitocondrial , Japón , Filogeografía , Polimorfismo de Nucleótido Simple
11.
Clin Case Rep ; 10(2): e05372, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35154721

RESUMEN

We report a case of fever of unknown origin in a patient with MDS associated with IgM-MGUS. The patient was positive for MYD88 mutation, and chemotherapy for LPL/WM improved the fever. Analysis of MYD88 and the effect of chemotherapy on LPL/WM finally revealed the latent LPL/WM in this case.

12.
Int J Mol Med ; 49(4)2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35119085

RESUMEN

Anti­CD19 chimeric antigen receptor (CAR)­T cell therapy against refractory B­cell malignancies shows excellent therapeutic effects. However, there are some obstacles to be overcome in this treatment. Since current CAR­T cells target a single cell­surface protein on tumor cells, the CAR­T cells also attack normal cells expressing the protein. This is one of the major adverse effects of this therapy. To improve target­cell­specificity of this therapy, we established a novel CAR system, in which T­cell activation was controlled by expression patterns of proteins on target cells. Our novel CAR­T cells had two distinct CARs consisting of a 'Signal­CAR', recognizing a protein on tumor cells, and a 'Scissors­CAR', recognizing another protein on normal cells. The signal­CAR had a peptide sequence which was cleaved by the Scissors­CAR, and functional domains for cellular activation. The Scissors­CAR had a protease domain that cleaved its recognition peptide sequence in the Signal­CAR. When tumor cells expressed only the protein recognized by the Signal­CAR, the tumor cells were attacked. By contrast, normal cells expressing both the proteins induced inactivation of the Signal­CAR through cleavage of the recognition site when getting in contact with the CAR­T cells. To establish this system, we invented a Scissors­CAR that was dominantly localized on cell membranes and was activated only when the CAR­T cells were in contact with the normal cells. Using a T­cell line, Jurkat, and two proteins, CD19 and HER2, as target proteins, we showed that the anti­CD19­Signal­CAR was cleaved by the anti­HER2­Scissors­CAR when the CAR­T cells were co­cultivated with cells expressing both the proteins, CD19 and HER2. Furthermore, we demonstrated that primary CAR­T cells expressing both the CARs showed attenuated cytotoxicity againsT cells with both the target proteins. Our novel system would improve safety of the CAR­T cell therapy, leading to expansion of treatable diseases by this immunotherapy.


Asunto(s)
Receptores Quiméricos de Antígenos , Antígenos CD19/genética , Antígenos CD19/metabolismo , Proteínas de la Membrana/metabolismo , Péptido Hidrolasas/metabolismo , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/metabolismo
13.
J Parasitol ; 108(1): 44-52, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-35038324

RESUMEN

Two cases of human philophthalmosis have been reported in Japan. Gravid flukes removed from the eyes of the patients were broken, but their morphological characteristics suggest that an unknown species of the genus Philophthalmus is involved as a pathogen for humans. The mitochondrial DNA barcode of the human eye fluke enabled us to discover its larval stage from the Japanese mud snail, Batillaria attramentaria. The discovered cercaria had previously been temporarily described as "Philophthalmid sp. I." In this study, we examined the infection status of B. attramentaria with Philophthalmid sp. I found on a muddy seashore of the Seto Inland Sea, Japan, and the resulting metacercariae were experimentally administered to Japanese quails to develop them into the gravid adult stage. The complete specimens of the adult and larval stages allowed us to describe a new species. Based on morphological and molecular analyses, Philophthalmus hechingeri n. sp. is proposed for the human-infecting eye fluke in Japan. The natural definitive hosts of the new species are unknown. However, the habitat of B. attramentaria suggests that shorebirds (seagulls, sandpipers, and plovers) might be the possible candidates.


Asunto(s)
Infecciones Parasitarias del Ojo/parasitología , Gastrópodos/parasitología , Trematodos/clasificación , Infecciones por Trematodos/parasitología , Animales , Enfermedades de las Aves/parasitología , Código de Barras del ADN Taxonómico , ADN Ribosómico/química , Complejo IV de Transporte de Electrones/genética , Variación Genética , Humanos , Japón , Funciones de Verosimilitud , Filogenia , Codorniz , ARN Ribosómico 28S/genética , Alineación de Secuencia , Trematodos/genética , Trematodos/crecimiento & desarrollo , Trematodos/aislamiento & purificación
14.
In Vivo ; 35(6): 3407-3411, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34697176

RESUMEN

BACKGROUND: Neurotoxicity is one of the dangerous complications of chimeric antigen receptor (CAR) T-cell therapy, while its pathophysiology remains to be fully understood. Motor weakness not associated with central nervous system (CNS) toxicity has rarely been reported after CAR T-cell therapy. CASE REPORT: A 42-year-old female with a refractory diffuse large B-cell lymphoma received tisagenlecleucel (tisa-cel) and developed cytokine release syndrome (CRS) on day 3. She was treated with tocilizumab and methylprednisolone, which resolved CRS promptly. On day 7, motor weakness in lower extremities appeared, and she gradually became unable to walk without showing any other symptoms attributed to CNS disturbances. Whereas dexamethasone and tocilizumab were ineffective, neuropathy improved after high dose chemotherapy followed by autologous stem cell transplantation. Nerve conduction study (NCS) in lower extremities showed a decline in compound muscle action potential amplitude along with worsening of motor weakness, which was restored after improvement of symptoms. Based on symptoms and NCS, her motor weakness was thought to be due to disturbance in peripheral nerves. CONCLUSION: This study reports a patient who developed severe motor weakness due to disturbance in peripheral nerves after tisa-cel therapy. Neurotoxicity of non-CNS origin should also be noted in CAR T-cell therapy.


Asunto(s)
Inmunoterapia Adoptiva/efectos adversos , Debilidad Muscular/inducido químicamente , Nervios Periféricos , Receptores de Antígenos de Linfocitos T , Adulto , Síndrome de Liberación de Citoquinas/inducido químicamente , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/fisiopatología , Trasplante Autólogo
15.
Int J Hematol ; 114(4): 424-440, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34165774

RESUMEN

Ruxolitinib (RUX), a JAK1/2-inhibitor, is effective for myeloproliferative neoplasm (MPN) with both JAK2V617 F and calreticulin (CALR) mutations. However, many MPN patients develop resistance to RUX. Although mechanisms of RUX-resistance in cells with JAK2V617 F have already been characterized, those in cells with CALR mutations remain to be elucidated. In this study, we established RUX-resistant human cell lines with CALR mutations and characterized mechanisms of RUX-resistance. Here, we found that RUX-resistant cells had high levels of MPL transcripts, overexpression of both MPL and JAK2, and increased phosphorylation of JAK2 and STAT5. We also found that mature MPL proteins were more stable in RUX-resistant cells. Knockdown of MPL in RUX-resistant cells by shRNAs decreased JAK/STAT signaling. Immunoprecipitation assays showed that binding of mutant CALR to MPL was increased in RUX-resistant cells. Reduction of mutated CALR decreased proliferation of the resistant cells. When resistant cells were cultured in the absence of RUX, the RUX-resistance was reversed, with reduction of the mutant-CALR/MPL complex. In conclusion, MPL overexpression induces higher levels of a mutant-CALR/MPL complex, which may cause RUX-resistance in cells with CALR mutations. This mechanism may be a new therapeutic target to overcome RUX-resistance.


Asunto(s)
Regulación de la Expresión Génica , Proteínas de Interacción con los Canales Kv/genética , Proteínas de Interacción con los Canales Kv/metabolismo , Mutación , Trastornos Mieloproliferativos/genética , Receptores de Trombopoyetina/genética , Receptores de Trombopoyetina/metabolismo , Animales , Calreticulina , Línea Celular Tumoral , Análisis Mutacional de ADN , Manejo de la Enfermedad , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Resistencia a Antineoplásicos , Humanos , Inmunohistoquímica , Janus Quinasa 2/genética , Megacariocitos/metabolismo , Ratones , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/tratamiento farmacológico , Nitrilos , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/metabolismo , Unión Proteica , Pirazoles/farmacología , Pirazoles/uso terapéutico , Pirimidinas
16.
Int J Mol Sci ; 22(7)2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33810223

RESUMEN

DNA can adopt various structures besides the B-form. Among them, cruciform structures are formed on inverted repeat (IR) sequences. While cruciform formable IRs (CFIRs) are sometimes found in regulatory regions of transcription, their function in transcription remains elusive, especially in eukaryotes. We found a cluster of CFIRs within the mouse Pou5f1 enhancer. Here, we demonstrate that this cluster or some member(s) plays an active role in the transcriptional regulation of not only Pou5f1, but also Sox2, Nanog, Klf4 and Esrrb. To clarify in vivo function of the cluster, we performed genome editing using mouse ES cells, in which each of the CFIRs was altered to the corresponding mirror repeat sequence. The alterations reduced the level of the Pou5f1 transcript in the genome-edited cell lines, and elevated those of Sox2, Nanog, Klf4 and Esrrb. Furthermore, transcription of non-coding RNAs (ncRNAs) within the enhancer was also upregulated in the genome-edited cell lines, in a similar manner to Sox2, Nanog, Klf4 and Esrrb. These ncRNAs are hypothesized to control the expression of these four pluripotency genes. The CFIRs present in the Pou5f1 enhancer seem to be important to maintain the integrity of ES cells.


Asunto(s)
Elementos de Facilitación Genéticos , Células Madre Embrionarias de Ratones/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Animales , Línea Celular , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Ratones , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Conformación de Ácido Nucleico , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Activación Transcripcional , Regulación hacia Arriba
17.
Int J Hematol ; 113(6): 910-920, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33683652

RESUMEN

We have recently reported a new method for detecting T-cell-derived extracellular vesicles (EVs), CD3+CD4+EVs,CD3+CD8+EVs, and CD3+HLA-DR+EVs. In our previous study, CD3+HLA-DR+EVs were released profusely by CD8+T cells, only moderately by T helper1 (Th1) CD4+T cells, and very little from Th2 CD4+T cells in vitro. EVs were measured sequentially in patients undergoing hematopoietic stem cell transplantation (HSCT), and their relationship to GVHD was investigated in comparison with other conventional biomarkers. We analyzed peripheral blood samples from 20 patients (13 children and 7 adults) who underwent HSCT at Tokyo Medical and Dental University Hospital. CD3+CD4+EV and CD3+CD8+EV levels specifically correlated with the CD4+ and CD8+T lymphocyte counts, respectively. CD3+CD8+EVs and CD3+HLA-DR+EVs increased in GVHD and reflected the persistence of GVHD more specifically than soluble IL-2 receptor (sIL-2R). In engraftment syndrome, sIL-2R was markedly elevated, but CD3+HLA-DR+EVs were not. Furthermore, ferritin and sIL-2R markedly increased in hemophagocytic syndrome (HPS) that developed before engraftment; however, the change in CD3+HLA-DR+EVs was marginal. CD3+CD4+, CD3+CD8+, and CD3+HLA-DR+EVs efficiently reflect the cell-mediated immune response, and CD3+CD8+EVs and CD3+HLA-DR+EVs are more useful than other conventional biomarkers, such as sIL-2R, for monitoring and evaluation of acute GVHD.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Vesículas Extracelulares/metabolismo , Enfermedad Injerto contra Huésped/sangre , Enfermedad Aguda , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico
18.
Rinsho Ketsueki ; 61(10): 1469-1475, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33162442

RESUMEN

A 45-year-old man initially diagnosed with aplastic anemia had been receiving treatment for >4 years when he visited our hospital for a detailed examination. On admission, bone marrow (BM) aspiration showed erythroid dysplasia and chromosomal abnormalities, including trisomy 3 in 1/20 cells. After 3 months of observation, BM aspiration showed the involvement of 5% abnormal lymphocytes, and flow cytometry revealed a monoclonal B-cell phenotype. After a further 5 months of observation, his blood test showed a sudden elevation in white blood cell (WBC) count and the presence of villous lymphocytes. Fluorodeoxyglucose-positron emission tomography (FDG-PET) only revealed strong uptake by systemic BM, and BM aspiration showed the involvement of 76.4% abnormal lymphocytes, which were positive for CD19 and dim CD11c; negative for CD25, CD103, cyclin D1, and BRAF-V600E; and exhibited light chain restriction. The patient was diagnosed with marginal zone lymphoma-like primary bone marrow (BM) lymphoma. Treatment with R-CHOP and R-cladribine failed. He then underwent an allogeneic peripheral blood stem cell transplantation from a human leucocyte antigen (HLA)-identical sibling, and he has since remained in good health and without relapse for 9 years. Further clinical and biological analyses are necessary to establish an optimal treatment strategy for this disease.


Asunto(s)
Neoplasias Óseas , Linfoma de Células B de la Zona Marginal , Pancitopenia , Médula Ósea , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pancitopenia/complicaciones
19.
Rinsho Ketsueki ; 61(10): 1487-1491, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33162445

RESUMEN

This is a case of a 75-year-old man who was on maintenance hemodialysis for 10 years due to diabetic nephropathy and was prescribed polaprezinc due to a low serum zinc level (55 µg/dl) and dysgeusia. Three months after the polaprezinc treatment was initiated, the patient developed pancytopenia, which persisted even after the serum zinc level was normalized and medication was discontinued. He was referred to our institute so that the progression of pancytopenia could be assessed. A blood biochemical examination revealed a WBC count of 1,700/µl, Hb level of 8.9 g/dl, and Plt count of 9.5×104/µl. A bone marrow aspirate smear showed slight megaloblastic changes and ringed sideroblasts in addition to an elevated WT1 mRNA level (76 copies/µg RNA) in the peripheral blood. Although these findings mimicked those of myelodysplasia, low serum copper (<2 µg/dl) and ceruloplasmin levels (3 mg/dl) were suggestive of hematopoietic abnormalities due to zinc-induced copper deficiency. Treatment with cocoa, a compound generally known to be rich in copper, gradually improved the pancytopenia and dysplastic bone marrow histology. This case indicates that clinicians should consider the risk of zinc-induced copper deficiency and its complications when zinc supplementation is administered to patients with chronic kidney disease, particularly those undergoing hemodialysis.


Asunto(s)
Hematopoyesis , Anciano , Cobre , Suplementos Dietéticos , Humanos , Masculino , Diálisis Renal , Zinc
20.
Ecol Evol ; 10(15): 8186-8196, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32788971

RESUMEN

Biogeography and genetic variation of freshwater organisms are influenced not only by current freshwater connections but also by past drainage networks. The Seto Inland Sea is a shallow enclosed sea in Japan, but geological evidence showed that a large freshwater drainage had intermittently appeared in this area between the late Pliocene and Pleistocene. Here, we demonstrated that this paleodrainage greatly affected the genetic variation of the East Asian freshwater snails, Semisulcospira spp. We found that the mtDNA haplotypes originated in the Lake Biwa endemic Semisulcospira species at the upstream side of the paleodrainage were frequently observed in the riverine Semisulcospira species at its downstream side. The genome-wide DNA and morphological analyses consistently showed that there was no clear evidence of nuclear introgression between the Lake Biwa endemics and riverine species. These results suggest that the large paleodrainage had facilitated mitochondrial introgression and had broadly spread the introgressed mtDNA haplotypes to its downstream region around the Seto Inland Sea. Our study highlights the role of paleodrainages in shaping the genetic variation of freshwater organisms.

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