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OBJECTIVES: We aimed to identify associations between patterns of large-vessel lesions of large-vessel giant cell arteritis (LV-GCA) and treatment outcomes. METHODS: We extracted data on 68 newly diagnosed patients with LV-GCA from a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014. Patients with aortic lesions were identified based on the findings from contrast-enhanced computed tomography, magnetic resonance imaging, or positron emission tomography-computed tomography (Group 2, n = 49). Patients without aortic lesions were subdivided into LV-GCA with or without subclavian lesions defined as Group 1 (n = 9) or Group 3 (n = 10), respectively. The primary outcome evaluation was failure to achieve clinical remission by Week 24 and/or relapse within 104 weeks. RESULTS: The mean age and proportion of patients with cranial lesions and polymyalgia rheumatica in Group 2 were numerically lower than in the other two groups. Large-vessel lesions in Group 3 included carotid, pulmonary, renal, hepatic, or mesenteric lesions. The cumulative rate of poor treatment outcomes >2 years was 11.1%, 55.3%, and 88.0% in Groups 1, 2, and 3, respectively (by Kaplan-Meier analysis). The mean time to poor outcome was significantly different between the groups. CONCLUSIONS: Classification by subclavian and aortic lesions may be useful to determine treatment strategy.
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Arteritis de Células Gigantes , Polimialgia Reumática , Humanos , Arteritis de Células Gigantes/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
In this study, we investigated the mechanistic features and kinetics of the thermal decomposition of solids accompanied by liquefaction as exemplified by the thermal dehydration reactions of monosodium L-glutamate monohydrate (MSG-MH). The thermal dehydration of MSG-MH occurs via two mass-loss processes comprising the elimination of crystalline water and intramolecular dehydration. Multistep kinetic behaviors and the liquefaction during both thermal dehydration processes were evidenced by systematic thermoanalytical measurements and in situ microscopic observations. During the thermal dehydration of crystalline water, the liquefaction of the surface product layer occurred midway through the reaction, and the subsequent reaction proceeded with a geometrical constraint, where the solid reactant was covered by a liquid surface layer, affording a solid anhydride. The intramolecular dehydration of the solid anhydride yielded a liquid product on the surface of the reacting particles, and the internal solid reactant dissolved in the liquid product. Subsequently, the intramolecular dehydration proceeded in the liquid phase to afford liquid sodium pyroglutamate. The net kinetic behavior of the physico-geometrical reaction steps in each thermal dehydration process was revealed using kinetic approaches based on cumulative and conjunct kinetic equations. The advanced kinetic approaches employed to reveal the specific kinetic features of the heterogeneous reaction processes in solid-liquid-gas systems are described in this article.
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Among organic-inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), using a cell culture system. DPDTe exhibited strong cytotoxicity against vascular endothelial cells and fibroblasts along with high intracellular accumulation but showed no cytotoxicity and had less accumulation in vascular smooth muscle cells and renal epithelial cells. The cytotoxicity of DPDTe decreased when intramolecular tellurium atoms were replaced with selenium or sulfur atoms. Electronic state analysis revealed that the electron density between tellurium atoms in DPDTe was much lower than those between selenium atoms of diphenyl diselenide and sulfur atoms of diphenyl disulfide. Moreover, diphenyl telluride did not accumulate and exhibit cytotoxicity. The cytotoxicity of DPDTe was also affected by substitution. p-Dimethoxy-DPDTe showed higher cytotoxicity, but p-dichloro-DPDTe and p-methyl-DPDTe showed lower cytotoxicity than that of DPDTe. The subcellular distribution of the compounds revealed that the compounds with stronger cytotoxicity showed higher accumulation rates in the mitochondria. Our findings suggest that the electronic state of tellurium atoms in DPDTe play an important role in accumulation and distribution of DPDTe in cultured cells. The present study supports the hypothesis that nucleophilic organometallic compounds, as well as electrophilic organometallic compounds, exhibit cytotoxicity by particular mechanisms.
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Derivados del Benceno/farmacología , Células Endoteliales/efectos de los fármacos , Compuestos Organometálicos/farmacología , Compuestos de Organoselenio/farmacología , Telurio/farmacología , Animales , Derivados del Benceno/química , Derivados del Benceno/metabolismo , Bovinos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/metabolismo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Células LLC-PK1 , Modelos Químicos , Estructura Molecular , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Compuestos Organometálicos/química , Compuestos Organometálicos/metabolismo , Compuestos de Organoselenio/química , Compuestos de Organoselenio/metabolismo , Porcinos , Telurio/químicaRESUMEN
Objectives: To identify the prognostic predictive factor of complete renal response (CR) at week 12 by focusing on the plasma mycophenolic acid (MPA) concentration in induction therapy in lupus nephritis.Methods: We prospectively enrolled patients with biopsy-proven LN class III/IV who were hospitalized between 2016 and 2017. As an induction therapy, mycophenolate mofetil was continuously introduced at 2000 mg/day. We measured the MPA plasma concentration at two time points depending on the induction therapy phase, early (week 4) or middle (week 12). The association between these concentrations and CR rate at week 12 was evaluated.Results: Ten patients were enrolled. A significantly higher AUC0-12 between 0 and 12 h of MPA at the early phase was observed in the patients with CR at week 12 than in those without (p = .03). All the patients with high MPA-AUC0-12 (> 40 mg h/L) at the early phase achieved CR at week 12, but no such association was found at the middle phase. The multivariate analysis revealed that MPA-AUC0-12 was selected as an independent predictive factor of CR at week 12 (odds ratio: 1.12; 95% confidence interval: 1.01-1.45, p = .02).Conclusion: The high AUC0-12 of MPA at the early phase of induction therapy may predict good renal response.
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Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Ácido Micofenólico/sangre , Inducción de Remisión/métodos , Adulto , Biomarcadores/sangre , Femenino , Humanos , Nefritis Lúpica/sangre , Masculino , Persona de Mediana EdadRESUMEN
A 49-year-old woman with primary Sjögren syndrome initially developed pulmonary venous hypertension (PVH) due to heart failure with preserved ejection fraction. Endomyocardial biopsy specimens showed mild myocardial fibrosis. Pulmonary arterial hypertension (PAH) was revealed after the treatment with diuretics. During the treatment for PAH using upfront combination with pulmonary vasodilators and immunosuppressants, the patient developed combined disease with PAH and PVH. A careful hemodynamic assessment is necessary in such cases.
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Insuficiencia Cardíaca/complicaciones , Hipertensión Pulmonar/complicaciones , Síndrome de Sjögren/complicaciones , Volumen Sistólico/fisiología , Cateterismo Cardíaco , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertensión Pulmonar/fisiopatología , Persona de Mediana Edad , Síndrome de Sjögren/fisiopatologíaRESUMEN
OBJECTIVE: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52. METHODS: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed. RESULTS: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119). CONCLUSIONS: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.
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Aminoacil-ARNt Sintetasas/inmunología , Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Dermatomiositis/inmunología , Ribonucleoproteínas/inmunología , Adulto , Anciano , Enfermedades Autoinmunes/sangre , Dermatomiositis/sangre , Dermatomiositis/complicaciones , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Persona de Mediana EdadAsunto(s)
Cardiología/normas , Vasculitis/terapia , Consenso , Técnicas de Diagnóstico Cardiovascular/normas , Medicina Basada en la Evidencia/normas , Humanos , Valor Predictivo de las Pruebas , Factores de Riesgo , Síndrome , Resultado del Tratamiento , Vasculitis/diagnóstico , Vasculitis/epidemiología , Vasculitis/fisiopatologíaRESUMEN
OBJECTIVE: To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP). METHODS: We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10â years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients. RESULTS: Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan. CONCLUSIONS: FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.
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Neuropatías Amiloides Familiares/patología , Trasplante de Hígado/efectos adversos , Adulto , Amiloide/análisis , Colorantes , Rojo Congo , Femenino , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Miocardio/química , Prealbúmina/análisis , Médula Espinal/química , Factores de Tiempo , Lengua/químicaRESUMEN
OBJECTIVES: We aimed to identify a serum biomarker for evaluating the disease activity of relapsing polychondritis (RP). METHODS: We measured and compared serum levels of 28 biomarkers potentially associated with this disease, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), high-sensitivity C-reactive protein (hs-CRP), and cartilage oligomeric matrix protein (COMP), in 15 RP patients and 16 healthy donors (HDs). We divided the 15 RP patients into active RP (n = 8) and inactive RP (n = 7) groups, depending on the extent of the disease, and compared candidate markers between groups. The localization of membrane-bound TREM-1 in the affected tissue was examined by immunohistochemistry. RESULTS: Serum levels of sTREM-1, interferon-γ, chemokine (C-C motif) ligand 4, vascular endothelial growth factor, and matrix metalloproteinases-3 were significantly higher in RP patients than HDs. Among these markers, sTREM-1 had the highest sensitivity and specificity (86.7 and 86.7 %, respectively). Furthermore, the serum level of sTREM-1 was significantly higher in active RP patients than inactive RP patients (p = 0.0403), but this was not true for hs-CRP or COMP. TREM-1 was expressed on endothelial cells in RP lesions. CONCLUSIONS: The serum level of sTREM-1 may be a useful marker of disease activity in RP.
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Glicoproteínas de Membrana/sangre , Policondritis Recurrente/sangre , Receptores Inmunológicos/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Receptor Activador Expresado en Células Mieloides 1RESUMEN
Purpose: To identify molecular signatures specific for ocular graft-versus-host disease (GVHD) by proteomic analysis of corneas from mice with GVHD. Methods: We identified differentially expressed proteins (DEPs) in corneal samples from GVHD model mice and syngeneic control mice 4 weeks after bone marrow transplantation. Data-independent acquisition analysis was performed on individual samples, and the roles of DEPs in biological pathways related to GVHD were evaluated via bioinformatics and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Three important signaling pathways were upregulated in the cornea in mice with GVHD: (1) the necroptosis pathway, (2) the mitogen-activated protein kinase (MAPK) pathway, and (3) as previously reported, the neutrophil extracellular trap (NET) pathway. In those signaling pathways, we identified new upregulated molecules, including (1) receptor-interacting protein kinase 1 (RIPK1), RIPK3, interferon regulatory factor 9, the interferon-induced double-stranded RNA-activated protein kinase lipoxygenase, and high mobility group box1 (HMGB1) which are damage-associated molecular patterns (DAMPs) in the necroptosis pathway; (2) the sequentially upregulated interleukin 1 (IL-1) receptor-associated kinase (IRAK), an evolutionarily conserved signaling intermediate in the Toll pathway (ECSIT), and p38, which is downstream of the IL-1 receptor and increased CDC42/Rac (Rac2), a Rho family GTPase in the MAPK pathway; and (3) the integrin components CR3 and macrophage-1 antigen (MAC-1), which are DAMPs, and the pyroptosis-related protein gasdermin D (GSDMD) in the NET pathway. Conclusions: These novel molecules may help researchers elucidate the pathogenesis of GVHD and identify new therapeutic targets for corneal changes in patients with ocular GVHD.
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Córnea , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped , Ratones Endogámicos C57BL , Necroptosis , Proteómica , Transducción de Señal , Regulación hacia Arriba , Animales , Ratones , Necroptosis/fisiología , Enfermedad Injerto contra Huésped/metabolismo , Córnea/metabolismo , Córnea/patología , Transducción de Señal/fisiología , Femenino , Trasplante de Médula ÓseaRESUMEN
Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.
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Tasa de Filtración Glomerular , Pacientes Ambulatorios , Farmacéuticos , Potasio , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Insuficiencia Renal Crónica/dietoterapia , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Estudios Prospectivos , Anciano , Potasio/sangre , Persona de Mediana Edad , Japón , Hiperpotasemia/prevención & control , Hiperpotasemia/sangre , Hiperpotasemia/dietoterapia , Potasio en la Dieta/administración & dosificación , Anciano de 80 o más AñosRESUMEN
PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.
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Senescencia Celular , Enfermedad Injerto contra Huésped , Disfunción de la Glándula de Meibomio , Glándulas Tarsales , Animales , Femenino , Masculino , Ratones , Compuestos de Anilina/farmacología , Trasplante de Médula Ósea/métodos , Senescencia Celular/fisiología , Enfermedad Crónica , Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped/patología , Inmunohistoquímica , Disfunción de la Glándula de Meibomio/metabolismo , Glándulas Tarsales/patología , Glándulas Tarsales/metabolismo , Ratones Endogámicos BALB C , Sulfonamidas/farmacologíaRESUMEN
OBJECTIVES: To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab. METHODS: We conducted a multicenter, retrospective, case-control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected. RESULTS: For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died. CONCLUSIONS: PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/diagnóstico , Adalimumab , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Persona de Mediana Edad , Neumonía por Pneumocystis/etiología , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Strong CTL response can be observed and associated with the control of proviral load in human T-lymphotropic virus type 1 (HTLV-1) infection. However, there are few details with regard to how HTLV-1 specific CTLs work against HTLV-1 infected cells and adult T-cell leukemia cells (ATLs). In this study, using Tax-specific CTL lines with high- and low-functional avidity developed from HLA-A2-transgenic mice, we showed that higher avidity CTLs specific for Tax expressing larger numbers of TCRs and better binding strength to the antigen-HLA-A2 complex are much more efficient at eliminating HTLV-1 infected cells and, in particular, ATL tumor cells with the ability of recognizing a latent level of Tax product detected only with a real-time PCR. These findings suggest that such higher avidity CTLs specific for Tax in HTLV-1 could be responsible for preventing the development of HTLV-1 infection by detecting trace amount of antigens.
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Productos del Gen tax , Antígeno HLA-A2/inmunología , Infecciones por HTLV-I/terapia , Virus Linfotrópico T Tipo 1 Humano/inmunología , Leucemia-Linfoma de Células T del Adulto/terapia , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Linaje de la Célula , Células Cultivadas , Pruebas Inmunológicas de Citotoxicidad , Ensayo de Inmunoadsorción Enzimática , Epítopos , Productos del Gen tax/antagonistas & inhibidores , Productos del Gen tax/genética , Productos del Gen tax/inmunología , Antígeno HLA-A2/genética , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/virología , Humanos , Leucemia-Linfoma de Células T del Adulto/etiología , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/prevención & control , Leucemia-Linfoma de Células T del Adulto/virología , Ratones , Ratones Transgénicos , Unión Proteica , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/metabolismo , Latencia del Virus/inmunologíaRESUMEN
Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid (AC-H) and its lithium salt (AC-Li) in chiral ionic liquid (CIL), (R)-1-(2,3-dihydroxypropyl)-3-methylimidazolium acetate {[(R)-GLYMI][AcO]}, gave a mixture of two head-to-tail (HT) and two head-to-head (HH) cyclodimers in HT/HH ratios of 1.3-1.7 (for AC-H) and 2.2-4.3 (for AC-Li) with low enantiomeric excesses (ee) of 0-3% for chiral syn-HT and anti-HH dimers. In contrast, irradiation of AC-H in an aqueous solution, containing cucurbit[8]uril (CB[8]) as a host and [(R)-GLYMI][AcO] or [(R)-GLYMI][Tf(2)N] as a modifier of CB portals, afforded the HH dimers in 91-99% selectivity, although the anti-HH dimer was totally racemic. Interestingly, irradiation of AC-H in a dichloromethane solution, containing [(R)-GLYMI][AcO] as a chiral template, led to the formation of the HH-dimers in 98% selectivity with chiral anti-HH dimer in -14% ee, presumably by the dual ligation of two ACs to a CIL through electrostatic and hydrogen-bonding interactions.
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Antracenos/química , Ácidos Carboxílicos/química , Líquidos Iónicos/química , Ciclización , Dimerización , Estructura Molecular , Procesos Fotoquímicos , Solventes/química , Electricidad Estática , EstereoisomerismoRESUMEN
Factor V deficiency is an extremely rare hematologic disorder with an incidence of one in one million. However, the risks related to cardiac surgery employing cardiopulmonary bypass in patients with factor V deficiency are not well established. Herein, we report the case of a 71-year-old male who was incidentally diagnosed with acquired factor V deficiency underwent mitral valve repair for severe mitral regurgitation. The patient was treated preoperatively with an adrenocorticosteroid immunosuppressant therapy; the procedure was performed safely with a positive outcome.
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Procedimientos Quirúrgicos Cardíacos , Deficiencia del Factor V , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Anciano , Puente Cardiopulmonar , Deficiencia del Factor V/diagnóstico , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Masculino , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification criteria, or large vessel lesions (LVLs) detected by imaging based on the modified classification criteria. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as the absence of clinical signs and symptoms in cranial and large vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have a relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as a relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model. RESULTS: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had a relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5% and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p = 0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. CONCLUSION: The initial treatment intensity in the treatment algorithm of GCA could be determined based upon the presence or absence of LVLs detected by imaging at baseline.
Asunto(s)
Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Femenino , Arteritis de Células Gigantes/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: This study investigated the prognostic factors of cardiac death or cardiac failure using cardiac scintigraphy, echocardiography (UCG), and magnetic resonance imaging (MRI) in asymptomatic systemic sclerosis (SSc) patients. METHODS: We retrospectively evaluated SSc patients who had undergone cardiac scintigraphy using 99m thallium (99m Tl) and 123 I-ß-methyl-P-iodophenyl-pentadecanoic acid (123 I-BMIPP), UCG, and cardiac MRI. We calculated the mismatch score in scintigraphy by subtracting the uptake of 123 I-BMIPP from that of 99m Tl. Patients were divided into two groups according to whether they survived with no cardiac failure or subsequently proceeded to cardiac failure or death during the study period. We identified prognostic factors by analyzing 99m Tl and 123 I-BMIPP uptake, mismatch scores, UCG findings, and cardiac delayed enhancement on MRI. We also evaluated pathological evidence of myocardial fibrosis. RESULTS: Of 33 SSc cases, 11 proceeded to cardiac failure or death. There was no significant difference in UCG or MRI findings between the two groups. Low mismatch score in cardiac scintigraphy was the only predictive factor of cardiac failure or death by multivariate analysis (odds ratio, 6.48; 95% confidence interval, 1.22-423.2; P = 0.01). When patients were grouped according to high or low mismatch scores based on a cut-off using receiver operating characteristics curve analysis, the cumulative incidence of cardiac failure or death was higher in the low mismatch group than in the high mismatch group (P = 0.02). The percentage of fibrosis was significantly higher in deceased cases compared to surviving cases. CONCLUSIONS: Low mismatch score in cardiac scintigraphy was associated with cardiac death or cardiac failure in SSc patients.
Asunto(s)
Circulación Coronaria , Ácidos Grasos/administración & dosificación , Cardiopatías/diagnóstico por imagen , Radioisótopos de Yodo/administración & dosificación , Yodobencenos/administración & dosificación , Imagen de Perfusión Miocárdica/métodos , Radiofármacos/administración & dosificación , Esclerodermia Sistémica/complicaciones , Talio/administración & dosificación , Anciano , Enfermedades Asintomáticas , Causas de Muerte , Progresión de la Enfermedad , Ecocardiografía , Femenino , Fibrosis , Cardiopatías/etiología , Cardiopatías/mortalidad , Cardiopatías/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miocardio/patología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/mortalidadRESUMEN
BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is caused by a variant transthyretin (TTR), which is a serum protein secreted by the liver. Mass spectrometry (MS) is a useful tool that can detect variant TTRs in serum samples from patients with ATTRv amyloidosis. We previously reported several mass spectrometric methods to detect variant TTRs in serum samples. Those methods require cumbersome immunoprecipitation with anti-TTR antibodies and significant time to analyze the variant TTRs. In our study here, we developed a new simple and quick method to detect variant TTRs in serum samples by means of matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) MS without immunoprecipitation (direct MALDI). METHODS: By using direct MALDI, we analyzed 288 serum samples obtained from patients who were clinically suspected having amyloidosis to investigate the usefulness of this direct MALDI method to detect variant TTRs in serum samples. RESULTS: The method completed the process within 30 min. We successfully identified variant TTRs in serum samples from patients, except for a few patients with TTR Glu61Lys and Glu89Gln mutations because of the small mass shift of those variant TTRs from wild-type TTR. We also found that the mass shifts of variant TTRs measured by direct MALDI corresponded to theoretical mass changes. CONCLUSION: Our results suggest that the direct MALDI method is useful for the screening of ATTRv amyloidosis.