RESUMEN
INTRODUCTION AND HYPOTHESIS: Venous injury may occur during exposure of the anterior longitudinal ligament at the anterior sacral promontory (SP). We aimed to quantitatively measure the extent of the vascular window (VW) in front of the SP in patients with internal iliac vein (IIV) variations using preoperative three-dimensional computed tomography angiography (3DCTA). We hypothesized that patients with IIV variations would have a narrow VW. METHODS: This prospective observational study included patients scheduled for laparoscopic sacrocolpopexy (LSC) between July 2022 and April 2023 who underwent preoperative 3DCTA. The primary endpoint was the VW measurement in the standard and variant IIV groups using 3DCTA before LSC. The secondary endpoint was the difference between the two IIV groups adjusted for age, body mass index, hypertension, and diabetes using an analysis of covariance (ANCOVA) model. Multiple regression analysis was performed to analyze the effect of factors on the distance from the SP to great vascular bifurcations. RESULTS: There were 20 cases of IIV variation (20.2%). VW was 28.8 ± 12.4 mm in the variant group and 39.6 ± 12.6 mm in the standard group (p = 0.001). In the ANCOVA model, IIV variations affected VW (coefficient, -11.8; 95% confidence interval [CI], -18.4 to -5.08, p < 0.001). Multivariate analysis revealed that the aorta-SP distance decreased with age (coefficient, -0.44; 95% CI, -0.77 to -0.11, p = 0.009). CONCLUSIONS: One in five women has a vascular variant at the SP that restricts the "safe" zone of fixation to < 3 cm.
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Laparoscopía , Prolapso de Órgano Pélvico , Humanos , Femenino , Vena Ilíaca/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Tomografía Computarizada por Rayos X/métodos , Sacro/diagnóstico por imagen , Sacro/cirugía , Sacro/irrigación sanguínea , Laparoscopía/métodos , Prolapso de Órgano Pélvico/cirugía , Procedimientos Quirúrgicos GinecológicosAsunto(s)
Conducto Auditivo Externo/patología , Pérdida Auditiva Conductiva/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Discoide/complicaciones , Piel/patología , Administración Oral , Anciano , Audiometría , Biopsia , Femenino , Pérdida Auditiva Conductiva/diagnóstico , Pérdida Auditiva Conductiva/etiología , Humanos , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/patología , Resultado del TratamientoRESUMEN
The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.
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Linfocitos T CD4-Positivos/metabolismo , Dermatitis Atópica/inmunología , Receptores Inmunológicos/metabolismo , Adulto , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Proliferación Celular , Quimiocina CCL17/sangre , Quimiocina CCL17/inmunología , Dermatitis Atópica/sangre , Femenino , Citometría de Flujo , Voluntarios Sanos , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Receptores Inmunológicos/inmunología , Piel/inmunologíaAsunto(s)
Anticuerpos Monoclonales/efectos adversos , Mucina-1/sangre , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Biomarcadores/sangre , Biomarcadores/metabolismo , Humanos , Interleucina-17/antagonistas & inhibidores , Estudios Longitudinales , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Mucina-1/metabolismo , Psoriasis/sangre , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Estudios RetrospectivosAsunto(s)
Linfocitos B Reguladores/inmunología , Dermatitis Atópica/sangre , Interleucina-10/metabolismo , Adolescente , Adulto , Linfocitos B Reguladores/metabolismo , Estudios de Casos y Controles , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Femenino , Voluntarios Sanos , Humanos , Interleucina-10/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Strain B-9, which has a 99% similarity to Sphingosinicella microcystinivorans strain Y2, is a Gram-negative bacterium with potential for use in the degradation of microcystin-related compounds and nodularin. We attempted to extend the application area of strain B-9 and applied it to mycotoxins produced by fungi. Among the tested mycotoxins, only ochratoxin A was completely hydrolyzed to provide the constituents ochratoxin α and l-phenylalanine, and levels of fumonisin B1 gradually decreased after 96 h. However, although drugs including antibiotics released into the aquatic environment were applied for microbial degradation using strain B-9, no degradation occurred. These results suggest that strain B-9 can only degrade amino acid-containing compounds. As expected, the tested compounds with amide and ester bonds, such as 3,4-dimethyl hippuric acid and 4-benzyl aspartate, were readily hydrolyzed by strain B-9, although the sulfonamides remained unchanged. The ester compounds were characteristically and rapidly hydrolyzed as soon as they came into contact with strain B-9. Furthermore, the degradation of amide and ester compounds with amino acids was not inhibited by the addition of ethylenediaminetetraacetic acid (EDTA), indicating that the responsible enzyme was not MlrC. These results suggest that strain B-9 possesses an additional hydrolytic enzyme that should be designated as MlrE, as well as an esterase.
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Aminoácidos/metabolismo , Bacterias Gramnegativas/metabolismo , Microcistinas/metabolismo , Antifúngicos/farmacología , Biodegradación Ambiental , Inhibidores Enzimáticos/farmacología , Esterasas/química , Micotoxinas/metabolismo , Péptido Hidrolasas/química , Péptidos Cíclicos/farmacología , Sulfonamidas/química , Microbiología del AguaRESUMEN
Signaling through coinhibitory receptors downregulates the immune response to prevent excessive immune activation and maintain optimal immunity and tolerance. The aim of this study was to examine the levels of the soluble forms of coinhibitory receptors and their ligands, namely, galectin-9 (the ligand of T-cell immunoglobulin and mucin domain 3) and CD155 (the ligand of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), and their association with clinical features in patients with systemic sclerosis (SSc). The serum levels of galectin-9 and soluble sCD155 were examined by enzyme-linked immunosorbent assays in patients with SSc, and the results were evaluated with respect to clinical features. Patients with SSc exhibited raised serum levels of galectin-9, but not sCD155. Serum galectin-9 levels were raised not only in patients with diffuse cutaneous SSc but also in patients with limited cutaneous SSc. Furthermore, serum galectin-9 levels correlated positively with the erythrocyte sedimentation rate. In addition, increased serum galectin-9 levels tended to be associated with higher mortality and serious organ involvement. These results suggest that galectin-9, but not CD155, may be involved in the pathogenesis of SSc. In addition, the measurement of serum galectin-9 levels could be used to predict serious organ involvement and high mortality in patients with SSc.
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Galectinas/sangre , Receptores Virales/sangre , Esclerodermia Sistémica/metabolismo , Piel/patología , Adolescente , Adulto , Anciano , Sedimentación Sanguínea , Niño , Humanos , Persona de Mediana Edad , Pronóstico , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/mortalidad , Transducción de Señal , Análisis de Supervivencia , Adulto JovenRESUMEN
The bacterial strain Sphingosinicella sp. B-9 was originally discovered to have the ability to degrade cyanobacterial cyclic peptides (microcystins), and has three hydrolytic enzymes (MlrA, MlrB, and MlrC). The purpose of this study was to examine in detail the degradation of glucagon/vasoactive intestinal polypeptide (VIP) family peptides by B-9, and to investigate the substrate specificity of B-9 proteases and the possibility of using a B-9 protease as a novel protease for peptide quantification by using a surrogate peptide and mass spectrometry (MS). The effective use of inhibitors revealed the following hydrolytic capability of B-9: One of the B-9 proteases (presumably MlrB) that was not inhibited by ethylenediaminetetraacetic acid (EDTA) cleaved bioactive peptides into medium-sized peptides with broad selectivity, similar to neutral endopeptidase, and another protease that was not inhibited by phenylmethylsulfonyl fluoride (PMSF) corresponded to MlrC and cleaved the resulting medium-sized peptides to smaller peptides or amino acids. The former property was desirable to obtain a suitable surrogate peptide, which was used successfully to quantify peptide using liquid chromatography (LC)-MS. Thus, the present study verified that one of the B-9 proteases has broad cleavage selectivity and cleavage sites, not seen in commercially available proteases, and is applicable to protein and peptide quantification using LC-MS.
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Sphingomonadaceae/metabolismo , Péptido Intestinal Vasoactivo/análisis , Péptido Intestinal Vasoactivo/metabolismo , Aminoácidos/metabolismo , Cromatografía Liquida , Hidrólisis/efectos de los fármacos , Espectrometría de Masas , Péptido Hidrolasas/metabolismo , Fluoruro de Fenilmetilsulfonilo/farmacología , Inhibidores de Proteasas/farmacología , Sphingomonadaceae/enzimología , Péptido Intestinal Vasoactivo/químicaRESUMEN
The reaction of some physiologically active peptides with bacterial strain B-9 has been investigated. Bradykinin, ß-endorphin, and [Leu(5)]enkephalin were quickly degraded, with half-lives of <5 min. Somatostatin, substance P, and angiotensin I were degraded relatively smoothly, with half-lives of 10 min to 1 h, whereas oxytocin and insulin were slowly degraded, with half-lives of 1 and 4 days, respectively. Vasopressin was barely degraded, with a half-life of >7 days. Linearized vasopressin, prepared by the reductive cleavage of the disulfide bond followed by alkylation with iodoacetamide, was degraded significantly faster than intact vasopressin, with a half-life of 2.5 h. A loop formed by disulfide bond formation was regarded as one of the degradation-resistant factors. Hydrolysis of the peptides in this study took place through cleavage of various peptide bonds, and the strain B-9 may bear similarities to the neutral endopeptidase in terms of its broad selectivity.
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Bacterias/metabolismo , Péptidos/metabolismo , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Datos de Secuencia Molecular , Péptidos/química , Espectrofotometría UltravioletaRESUMEN
MOTIVATION: Although a huge amount of mammalian genomic data does become publicly available, there are still hurdles for biologists to overcome before such data can be fully exploited. One of the challenges for gaining biological insight from genomic data has been the inability to cross-reference transcriptomic and proteomic data using a single informational platform. To address this, we constructed an open-access database that enabled us to cross-reference transcriptomic and proteomic data obtained from immune cells. RESULTS: The database, named RefDIC (Reference genomics Database of Immune Cells), currently contains: (i) quantitative mRNA profiles for human and mouse immune cells/tissues obtained using Affymetrix GeneChip technology; (ii) quantitative protein profiles for mouse immune cells obtained using two-dimensional gel electrophoresis (2-DE) followed by image analysis and mass spectrometry and (iii) various visualization tools to cross-reference the mRNA and protein profiles of immune cells. RefDIC is the first open-access database for immunogenomics and serves as an important information-sharing platform, enabling a focused genomic approach in immunology. AVAILABILITY: All raw data and information can be accessed from http://refdic.rcai.riken.jp/. The microarray data is also available at http://cibex.nig.ac.jp/ under CIBEX accession no. CBX19, and http://www.ebi.ac.uk/pride/ under PRIDE accession numbers 2354-2378 and 2414.