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Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental abnormalities. Although intrauterine hyperglycemia has been implicated in excessive fetal growth, the effects of maternal AGEs on fetal development remain unclear. We evaluated the differentiation regulators and cellular signaling in the skeletal muscles of infants born to control mothers (ICM), diabetic mothers (IDM), and diabetic mothers supplemented with either cis-palmitoleic acid (CPA) or trans-palmitoleic acid (TPA). Cell viability, reactive oxygen species levels, and myotube formation were assessed in AGE-exposed C2C12 cells to explore potential mitigation by CPA and TPA. Elevated receptors for AGE expression and decreased Akt and AMPK phosphorylation were evident in rat skeletal muscles in IDM. Maternal palmitoleic acid supplementation alleviated insulin resistance by downregulating RAGE expression and enhancing Akt phosphorylation. The exposure of the C2C12 cells to AGEs reduced cell viability and myotube formation and elevated reactive oxygen species levels, which were attenuated by CPA or TPA supplementation. This suggests that maternal hyperglycemia and plasma AGEs may contribute to skeletal muscle disorders in offspring, which are mitigated by palmitoleic acid supplementation. Hence, the maternal intake of palmitoleic acid during pregnancy may have implications for fetal health.
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Ácidos Grasos Monoinsaturados , Productos Finales de Glicación Avanzada , Músculo Esquelético , Especies Reactivas de Oxígeno , Receptor para Productos Finales de Glicación Avanzada , Ácidos Grasos Monoinsaturados/farmacología , Productos Finales de Glicación Avanzada/metabolismo , Femenino , Animales , Embarazo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Ratas , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ratones , Suplementos Dietéticos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estrés Oxidativo/efectos de los fármacos , Resistencia a la Insulina , Humanos , Fosforilación , Ratas Sprague-Dawley , Embarazo en Diabéticas/metabolismo , Embarazo en Diabéticas/tratamiento farmacológico , Masculino , Desarrollo Fetal/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: Transabdominal ultrasonography [TAUS] appears comparable to colonoscopy for evaluating ulcerative colitis [UC] activity, but it has low accuracy in rectal evaluation. In this study, the accuracy of transperineal ultrasonography [TPUS] for evaluating rectal activity was compared to that of colonoscopy in paediatric UC cases. METHODS: Faecal calprotectin [FCP] values and TPUS and colonoscopic findings were compared prospectively in paediatric UC cases. Rectal wall thickening [RWT] and rectal wall flow [RWF] on power Doppler evaluated by TPUS were compared with the colonoscopy findings and were also measured on TAUS and assessed for the concordance rate of each finding. RESULTS: Thirty Mayo endoscopic sub-score [MES] 0-1 UC cases and 57 MES 2-3 UC cases were enrolled. FCP, RWT and RWF showed significant differences between the two groups [pâ <â 0.05]. RWT and RWF were independent predictors of UC endoscopic activity, showing sensitivity of 95.8% and specificity of 100% with RWTâ ≥â 4.5 mm and positive RWF. The concordance rates between TPUS and TAUS findings in MES 2-3 were moderate to fair, whereas those in MES 0-1 were fair to poor. The concordance rates between ultrasonic examiners were good for both TAUS and TPUS. CONCLUSIONS: TPUS may evaluate rectal activity of UC with accuracy comparable to endoscopy. If accurate ultrasonic screening for the total colon can be performed by TPUS and TAUS, repeated evaluation of short-term treatment response may be possible.
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Colitis Ulcerosa , Niño , Humanos , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/patología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Colonoscopía , Ultrasonografía , Complejo de Antígeno L1 de LeucocitoRESUMEN
BACKGROUND: The diagnosis of Yersinia enterocolitica (Ye) enteritis is not easy because detection from stool culture is more difficult for Ye than for other bacterial enteritides. The establishment of characteristic ultrasonographic findings for Ye enteritis would help improve the detection rate of Ye enteritis along with performance of several cold cultures. This would facilitate appropriate selection of antibiotics based on antimicrobial susceptibility testing and contribute to a more accurate understanding of local public health. This study aimed to retrospectively compare ultrasonographic findings and clinical features between children with Ye enteritis and other bacterial enteritides. METHODS: We identified patients treated for Ye enteritis (Ye group; n = 27) or other bacterial enteritides (Other enteritis group; n = 29) between 2014 and 2018. Ultrasonographic findings (including mean maximum diameter and mean major-minor axis ratio of ileocecal lymph nodes, wall thickness of the terminal ileum, and presence of a pericecal hyperechoic region), clinical symptoms, and laboratory findings at first visit were compared between groups. RESULTS: No difference in mean maximum diameter of ileocecal lymph nodes was seen between groups. However, mean major-minor axis ratio of ileocecal lymph nodes was lower in the Ye group than in the Other enteritis group (p < 0.001). Presence of a pericecal hyperechoic region was more frequent in the Ye group than in the Other enteritis group (p < 0.001). The combined presence of a mean ileocecal lymph node major-minor axis ratio <1.51 and a pericecal hyperechoic region offered 100% sensitivity. CONCLUSION: Characteristic ultrasonographic findings identified in this study may improve ultrasonographic differentiation of Y. enterocolitica enteritis from other bacterial enteritides.
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Infecciones Bacterianas , Enteritis , Yersiniosis , Yersinia enterocolitica , Estudios de Casos y Controles , Niño , Enteritis/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Ultrasonografía , Yersiniosis/diagnóstico por imagen , Yersiniosis/microbiologíaRESUMEN
INTRODUCTION: Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. METHODS: Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. RESULTS: The microarray results indicated significantly higher expression levels of cancer-related genes PIM2 and SPI1 in the active group than in the remission and control groups (p < 0.05). Real-time PCR confirmed that PIM2 and SPI1 expression levels were significantly higher, whereas TP53 and APC expression levels were significantly lower, in the active-phase group than in the remission and control groups (p < 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. CONCLUSIONS: Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.
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Colitis Ulcerosa , Síndrome del Colon Irritable , Adulto , Niño , Colitis Ulcerosa/patología , Humanos , Mucosa Intestinal/patología , Síndrome del Colon Irritable/patologíaRESUMEN
BACKGROUND: Granulomatosis with polyangiitis (GPA) is a syndrome of refractory vasculitis involving the upper respiratory tract, lungs, kidneys, and systemic small and medium-sized arteries that affects all age groups. No pediatric case with a bloody pericardial effusion resulting in cardiac tamponade and co-existing hematochezia has been reported. CASE PRESENTATION: A 14-year-old boy was referred for evaluation of prolonged fever, chest pain, and intermittent hematochezia. Diagnostic imaging showed a prominent pericardial effusion. Immediately after admission, his systolic blood pressure decreased. Emergent pericardiocentesis resulted in aspiration of a massive amount of bloody pericardial fluid. This was diagnosed as cardiac tamponade because his blood pressure recovered immediately after the drainage. The patient had an elevated serine proteinase 3-anti-neutrophil cytoplasmic antibody (PR3-ANCA) level on serological examination. Head MRI showed thickening of nasal and sinusoidal mucosa and a cystic mass in the left sphenoid sinus. After ruling out malignancy based on the cytology of the effusion, chest MRI, and gallium scintigraphy, total colonoscopy showed multiple irregular-shaped aphthae from the right transverse colon to the cecum on the contralateral side of the mesenteric attachments. Biopsy specimens of aphthous lesions confirmed necrotizing granulomatous inflammation. A diagnosis of GPA was made based on these findings, and oral prednisolone (PSL) and azathioprine were started. The hematochezia disappeared rapidly, and no recurrence of pericardial effusion was seen after PSL tapering was completed. The PR3-ANCA level decreased into the normal range immediately after the initial therapy. CONCLUSIONS: Pericarditis is a common cardiac complication of GPA, but there have been no reports of resultant cardiac tamponade. This is the first case of pediatric GPA with cardiac and gastrointestinal complications preceding the common symptoms such as respiratory or renal symptoms. A case of pediatric GPA with hematochezia is also extremely rare. In conclusion, serial measurement of ANCA levels is important in patients with persistent fever and bloody stool, such as in inflammatory bowel disease, to make the diagnosis of a vasculitic syndrome.
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OBJECTIVES: Progressive supranuclear palsy (PSP) is an uncommon progressive neurodegenerative disease with no effective cure at present. The initial symptoms resemble those of Parkinson's disease; however, the prevalence of PSP is about one-tenth that of Parkinson's disease. In many cases, dysphagia is severe, and the development of dysphagia is an early predictor of life expectancy. The aim of the current study was to define the effects of Lee Silverman Voice Treatment (LSVT LOUD) on swallowing and voice/speech in seven patients with PSP. METHODS: : Each patient underwent swallowing and voice/speech evaluations before and after 4 weeks of LSVT. Swallowing motility disorders were defined, temporal measures of swallowing were determined by videofluoroscopic evaluation, and voice measures of maximum phonation and speech intelligibility in reading and monologue were examined. RESULTS: After LSVT, the median duration of opening of the upper esophageal sphincter (from the beginning of the posterior movement of the bolus to upper esophageal sphincter opening) on videofluoroscopy was significantly shortened from 0.42 to 0.38 s (Wilcoxon signed-rank test P=0.016). The oral transit duration was decreased in five patients, but the decrease was not significant. Voice changes after LSVT included increases in voice intensity and in sustained duration were not significant. CONCLUSION: In this small study, it was found that LSVT may improve swallowing functions in patients with PSP.
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INTRODUCTION: Anal fistulae have a significant impact on the quality of life of patients with Crohn's disease (CD). In this cross-sectional study, we aimed to determine whether biological agents were effective in treating anal fistulae in patients with CD. METHODS: Fifty-three patients diagnosed with CD were retrospectively enrolled. Their data regarding symptoms, treatments, and disease progression from January 2007 to December 2016 were reviewed from the medical records. Fifteen (28%) patients with CD were complicated by anal fistulae. RESULTS: The male-to-female ratio was 13:2, and the mean age at onset was 11 years and 6 months. Among the 15 patients, 14 (93%) had anal fistulae as an initial symptom. Almost all patients were treated by providing elemental diet, 5-aminosalicylic acid, and steroids as induction therapy. Biological agents were used in 8 patients (53.3%), and fistula closure was confirmed in all of them. Among the 7 patients not treated with biological agents, 1 (14.3%) had a recurrent anal fistula, while another had incomplete fistula closure. Regarding surgical management, 2 patients were treated using the seton method, and no patients required a colostomy. CONCLUSION: Treatment with biological agents is highly effective concerning the closure of anal fistulae in patients with CD, and reducing pain may improve their quality of life.
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Enfermedad de Crohn , Fístula Rectal , Factores Biológicos , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Masculino , Calidad de Vida , Fístula Rectal/tratamiento farmacológico , Fístula Rectal/etiología , Fístula Rectal/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infection causes chronic gastritis, duodenal and to a lesser extent, gastric ulcers, and gastric cancer. Most H. pylori infections are acquired in childhood, and effective treatment of childhood infection is very important. Esophagogastroduodenoscopy (EGD) is useful for endoscopic diagnosis, mucosal tissue biopsy, and culture examination for H. pylori in children and adults. In this paper, we report results of susceptibility tests and eradication rates in H. pylori-positive children who underwent EGD over a 12-year period. MATERIALS AND METHODS: The subjects were H. pylori-positive pediatric patients who had gastrointestinal symptoms and underwent EGD in the Department of Pediatrics, Juntendo University Hospital (January 2007-December 2018). Patients underwent serum IgG antibody tests, fecal antigen tests, or urea breath tests, and subsequently, culture tests by gastric mucosal biopsy during EGD. H. pylori positivity was defined as a positive result on both tests. Patients received triple therapy for 14 days using our regimen, and eradication was assessed at 2, 6, and 12 months after therapy. RESULTS: Forty-five patients were H. pylori-positive, and the overall clarithromycin (CAM) resistance rate was 71.1 % (32/45). The CAM resistance rate for the 2013-2018 period was significantly higher than the 2007-2012 period (52.6% vs. 84.6%, P < 0.05). According to the results of the antimicrobial susceptibility test, we prescribed effective antibiotics, and this resulted in a primary eradication rate of 97.7%. CONCLUSIONS: We suggest that antimicrobial susceptibility testing can significantly improve rates of primary eradication of H. pylori infection.
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Antibacterianos , Farmacorresistencia Bacteriana , Infecciones por Helicobacter , Pruebas de Sensibilidad Microbiana , Antibacterianos/uso terapéutico , Pruebas Respiratorias , Niño , Claritromicina/uso terapéutico , Quimioterapia Combinada , Mucosa Gástrica , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , HumanosRESUMEN
PURPOSE: In cases of unilateral vocal fold paralysis (UVFP), voice disorders caused by glottic insufficiency can lead to a considerable reduction in the patient's quality of life. Voice therapy (VT) is an effective treatment that must be started early after the onset of vocal fold paralysis. This study examined the effect of early VT for patients with UVFP occurring after esophagectomy. MATERIALS AND METHODS: Patients who had residual UVFP at 1 month postoperatively after esophagectomy for esophageal cancer between November 2014 and March 2017 were evaluated. Seventeen patients were divided into the VT group (n = 6) and non-VT group (n = 11). We compared these two groups and retrospectively examined the effect of early VT. The study endpoints included aerodynamic tests, laryngeal endoscopy, laryngeal stroboscopy, and glottal closure. All of these evaluations were performed at preoperatively and at 1 and 3 months postoperatively. RESULTS: Subglottal pressure reduced notably in the VT group, and both the mean flow rate and maximum phonation time tended to improve after VT. Conversely, there were no significant differences in MFR and MPT in the non-VT group. Furthermore, although UVFP remained after VT, we achieved glottal closure for all three patients. Conversely, only two of the six patients with glottic insufficiency in the non-VT group achieved glottal closure. CONCLUSION: VT may be effective for improving impaired vocal function in patients with UVFP. It is reasonable to expect that VT can be initiated 1 month after the onset of vocal fold paralysis.
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Glotis/fisiopatología , Complicaciones Posoperatorias/terapia , Presión , Parálisis de los Pliegues Vocales/terapia , Entrenamiento de la Voz , Anciano , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fonación , Complicaciones Posoperatorias/etiología , Recuperación de la Función , Estudios Retrospectivos , Factores de Tiempo , Parálisis de los Pliegues Vocales/diagnóstico , Parálisis de los Pliegues Vocales/etiología , Parálisis de los Pliegues Vocales/fisiopatologíaRESUMEN
The aim of this study was to investigate whether a dual endothelin receptor antagonist bosentan modulates the kinetics of bone marrow-derived stem cells in inhibiting the development of pulmonary hypertension. Bone marrow chimeric mice, transplanted with enhanced green fluorescent protein (eGFP)-positive bone marrow mononuclear cells, were exposed to hypobaric hypoxia or kept in the ambient air, and were daily treated with bosentan sodium salt or saline for 21 days. After the treatment period, right ventricular pressure was measured and pulmonary vascular morphometry was conducted. Incorporation of bone marrow-derived cells was analyzed by immunohistochemistry. Gene expression and protein level in the lung tissue were evaluated by quantitative real-time PCR and western blotting, respectively. The results showed that, in hypoxic mice, right ventricular pressure and the percentage of muscularized vessel were increased and pulmonary vascular density was decreased, each of which was reversed by bosentan. Bone marrow-derived endothelial cells and macrophages in lungs were increased by hypoxia. Bosentan promoted bone marrow-derived endothelial cell incorporation but inhibited macrophage infiltration into lungs. Quantitative real-time PCR analysis revealed that interleukin 6, stromal cell-derived factor-1, and monocyte chemoattractant protein-1 were upregulated by hypoxia, in which interleukin 6 and monocyte chemoattractant protein-1 were downregulated and stromal cell-derived factor-1 was upregulated by bosentan. Protein level of endothelial nitric oxide synthase (eNOS) in the whole lung was significantly upregulated by hypoxia, which was further upregulated by bosentan. Bosentan modulated kinetics of bone marrow-derived ECs and macrophages and related gene expression in lungs in ameliorating pulmonary hypertension in mice. Altered kinetics of bone marrow-derived stem cells may be a novel mechanism of the endothelin receptor blockade in vivo and confer a new understanding of the therapeutic basis for pulmonary hypertension.
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Esophagectomy for esophageal cancer is invasive thoracic surgery with a high incidence rate of postoperative complications and prolongation of hospitalization, even if the standardized clinical pathway improves the outcome (mortality and morbidity). Postoperative recurrent nerve paralysis (RNP) is related to respiratory complications concomitant with prolonged hospitalization. However, it has not been elucidated which factors affect the incidence and recovery of RNP. To detect the predictive factor for postoperative RNP, we focused on preoperative serum albumin. Patients who had esophageal cancer with standard esophagectomy were evaluated. In total, 94 patients were divided into three groups depending on the presence of RNP (46 in patients without RNP, 29 in those with transient RNP who recovered within 6 months follow-up and 19 in those with residual RNP). We retrospectively investigated factors associated with residual RNP. Preoperative lower serum albumin was associated with residual RNP. In addition, days to the resumption of oral intake and duration of stay in the hospita postoperatively were delayed in the group of residual RNP. Multiple regression analysis indicated that preoperative serum albumin was a predictive factor for residual RNP. Preoperative lower serum albumin level might be linked to residual RNP which could prolong the resumption of postoperative oral intake and shorten the period of stay at the hospital after esophagectomy, leading to unfavorable outcomes for patients.
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Enfermedades de los Nervios Craneales/etiología , Neoplasias Esofágicas/sangre , Esofagectomía/efectos adversos , Parálisis/etiología , Complicaciones Posoperatorias/etiología , Nervio Laríngeo Recurrente , Albúmina Sérica/análisis , Anciano , Enfermedades de los Nervios Craneales/epidemiología , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Parálisis/epidemiología , Complicaciones Posoperatorias/epidemiología , Periodo Preoperatorio , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to examine whether acute non-perforated appendicitis (ANPA) can be safely triaged by a pediatrician for conservative management (CM) using gray-scale ultrasonography with power Doppler (GSPD). METHOD: Seventy five cases of ANPA assessed by a pediatrician with GSPD (2013-2015) were reviewed. GSPD grading for ANPA was: I: slightly irregular wall/normal blood flow; II: irregular wall/increased blood flow; III: irregular wall/decreased blood flow; and IV: absence of wall/blood flow. Grades I/II were managed conservatively with intravenous antibiotics then encouraged to book for interval appendectomy (IA). Grades III/IV were reviewed for emergency appendectomy (EA) by a pediatric surgeon. RESULTS: GSPD grading was I (n=26), II (n=36), III (n=9), and IV (n=4). EA was required for 5 cases, one grade III, and four grade IV cases. One grade IV case was treated conservatively after surgical review but EA was unavoidable. Of the remaining 70 cases discharged well after a mean of 5.7days hospitalization, 25/70 had IA with chronic inflammation on histology, 6/70 had recurrence of ANPA treated successfully by EA, and 39/70 remain asymptomatic at least 10months after declining IA. Overall, GSPD triaging with CM was cheaper than surgery. CONCLUSIONS: GSPD performed by pediatricians appears to be safe/effective for triaging ANPA. LEVEL OF EVIDENCE: Level III.
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Apendicitis/diagnóstico por imagen , Pediatras , Triaje/métodos , Ultrasonografía Doppler Dúplex/métodos , Enfermedad Aguda , Adolescente , Apendicitis/terapia , Niño , Preescolar , Tratamiento Conservador , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP)(+)CD45(-) cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4). Because the vast majority of EGFP(+)CD45(-) cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs). EGFP(+) PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2) and Ang II type 1 receptor (AT1R), were expressed on Ly6C(high) monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+)F4/80(+)CCR2(+) monocytic cells and EGFP(+) PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+) bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+) PaSCs in injured mice. We propose that CCR2(+) monocytes migrate into the pancreas possibly via the MCP-1/CCR2 pathway and give rise to PaSCs.
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Diferenciación Celular , Quimiocina CCL2/metabolismo , Quimiotaxis , Monocitos/citología , Páncreas/citología , Células Estrelladas Pancreáticas/citología , Receptores CCR2/metabolismo , Traslado Adoptivo , Angiotensinógeno/biosíntesis , Animales , Compuestos de Bifenilo/farmacología , Tetracloruro de Carbono/farmacología , Diferenciación Celular/efectos de los fármacos , Quimiotaxis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Fluorescentes Verdes/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/efectos de los fármacos , Irbesartán , Antígenos Comunes de Leucocito/deficiencia , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Células Estrelladas Pancreáticas/efectos de los fármacos , Receptor de Angiotensina Tipo 1/metabolismo , Transducción de Señal/efectos de los fármacos , Tetrazoles/farmacologíaRESUMEN
Oncogenic transformation requires unlimited self-renewal. Currently, it remains unclear whether a normal capacity for self-renewal is required for acquiring an aberrant self-renewal capacity. Our results in a new conditional transgenic mouse showed that a mixed lineage leukemia (MLL) fusion oncogene, MLL-ENL, at an endogenous-like expression level led to leukemic transformation selectively in a restricted subpopulation of hematopoietic stem cells (HSCs) through upregulation of promyelocytic leukemia zinc finger (Plzf). Interestingly, forced expression of Plzf itself immortalized HSCs and myeloid progenitors in vitro without upregulation of Hoxa9/Meis1, which are well-known targets of MLL fusion proteins, whereas its mutant lacking the BTB/POZ domain did not. In contrast, depletion of Plzf suppressed the MLL-fusion-induced leukemic transformation of HSCs in vitro and in vivo. Gene expression analyses of human clinical samples showed that a subtype of PLZF-high MLL-rearranged myeloid leukemia cells was closely associated with the gene expression signature of HSCs. These findings suggested that MLL fusion protein enhances the self-renewal potential of normal HSCs to develop leukemia, in part through a Plzf-driven self-renewal program.
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Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Células Madre Hematopoyéticas/patología , Factores de Transcripción de Tipo Kruppel/metabolismo , Leucemia/etiología , Células Progenitoras Mieloides/patología , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Fusión Oncogénica/genética , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Western Blotting , Diferenciación Celular , Proliferación Celular , Transformación Celular Neoplásica/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Humanos , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Factores de Transcripción de Tipo Kruppel/genética , Leucemia/metabolismo , Leucemia/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Progenitoras Mieloides/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteína de la Leucemia Promielocítica con Dedos de Zinc , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: We previously reported that hepatic stellate cells (HpSCs) are of hematopoietic origin in liver injury. However, the immediate precursors of HpSCs remain unknown. This study was conducted to elucidate whether terminally differentiated blood cells can differentiate into HpSCs. MATERIALS AND METHODS: We adoptively transferred a variety of cells isolated from enhanced green fluorescent protein (EGFP)-transgenic mice into carbon tetrachloride (CCl(4))-treated nontransgenic mice twice weekly for 2 weeks. We examined the presence of EGFP(+) HpSCs in the injured liver using immunofluorescence analysis. RESULTS: Monocytes, neutrophils, eosinophils, B cells, or T cells from EGFP mice were transferred into CCl(4)-treated mice. Thirty percent of EGFP(+) cells in the livers of mice given Ly6C(high)c-kit(-) monocytes were negative for CD45, but were positive for glial fibrillary acidic protein, desmin, CD146, ADAMTS13, and α-smooth muscle actin, well-known markers of HpSCs. EGFP(+)CD45(-) cells were predominantly positive for glial fibrillary acidic protein. Although 48% of EGFP(+) cells were positive for procollagen type I, half of them were CD45(-). In the livers of mice given neutrophils, eosinophils, B cells, or T cells, all of the EGFP(+) cells were CD45(+). The majority of EGFP(+) cells in the nonparenchymal cell fraction purified from the livers of mice given Ly6C(high)c-kit(-) monocytes contained lipid droplets and were positive for glial fibrillary acidic protein, desmin, ADAMTS13, and procollagen type I. When Ly6C(+) monocyte-depleted peripheral blood total nucleated cells were adoptively transferred into CCl(4)-treated mice, we found no EGFP(+)CD45(-) cells in the liver. CONCLUSIONS: These results suggest that Ly6C(+) monocytes can become HpSCs in the injured liver.
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Antígenos Ly/inmunología , Hígado/citología , Monocitos/citología , Traslado Adoptivo , Animales , Citometría de Flujo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Monocitos/inmunologíaRESUMEN
The purpose of the present study was to investigate the long-term compliance with salt restriction and blood pressure (BP) control status in Japanese hypertensive outpatients. Subjects included 103 patients, 59 women and 44 men, mean age 67 +/- 9 years, who underwent successful 24-h home urine collection more than 10 times over an interval of 5 years. Urinary salt, potassium, and creatinine were measured. During the follow-up period (average 8.6 years), participants underwent urine collection 11.4 times in average. Urinary salt excretion at the last visit was significantly lower than that of the first visit (8.2 +/- 3.1 vs. 9.6 +/- 3.7 g/day; p < 0.01). The achievement of urinary salt excretion <6 g/day increased from 18.5% at the first visit to 26.2% at the last visit. Similarly, BP at the last visit was significantly lower than that of the first visit (130 +/- 14/69 +/- 11 vs. 145 +/- 17/86 +/- 12 mmHg; p < 0.01). The achievement rate of BP <140/90 mmHg and <130/85 mmHg also increased significantly during this period (39.2% to 70.8% and 13.7% to 39.6%, respectively, p < 0.01). Results suggest that urinary salt excretion decreased by repeated measurements using 24-h home urine collection. Lifestyle modification including weight loss as well as the intensive antihypertensive treatment contributed to the improved BP control during this period.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dieta Hiposódica , Hipertensión/dietoterapia , Hipertensión/orina , Pacientes Ambulatorios , Cooperación del Paciente , Anciano , Algoritmos , Antihipertensivos/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial , Creatinina/orina , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Estilo de Vida , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Potasio/orina , Estudios Retrospectivos , Cloruro de Sodio/orina , Factores de Tiempo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
A 55-year-old woman was admitted to our hospital because of fever and renal impairment. The patient had undergone a tooth extraction 11 months prior to admission. Echocardiography demonstrated vegetation on the mitral valve, and Streptococcus mitis was detected on blood culture. Accordingly, infectious endocarditis (IE) was diagnosed. Renal biopsy showed crescentic glomerulonephritis. Based on the negative staining for immunoglobulins and complement components in immunofluorescence study and lack of dense deposits on electron microscopy, the renal involvement was considered to be of the pauci-immune type. Subarachnoid hemorrhage (SAH) and subdural hematoma (SDH) developed simultaneously following commencement of antibiotic therapy. The intracranial involvement improved by conservative therapy. Antibiotic treatment resulted in gradual control of IE infection and improvement of renal function. A repeated renal biopsy, performed about 5 months after the first biopsy, showed amelioration of glomerular injury and interstitial damage. To our knowledge, our case was the second to report simultaneous developments of both SAH and SDH secondary to IE. We postulate that the glomerular injury was associated with IE. We report here a rare case of IE-associated crescentic glomerulonephritis with complications of SAH and SDH.
Asunto(s)
Endocarditis Bacteriana/complicaciones , Glomerulonefritis/etiología , Hematoma Subdural/etiología , Hemorragia Subaracnoidea/etiología , Antibacterianos/uso terapéutico , Biopsia , Endocarditis Bacteriana/tratamiento farmacológico , Femenino , Glomerulonefritis/patología , Humanos , Riñón/patología , Persona de Mediana EdadRESUMEN
We investigated the usefulness of measuring urinary salt excretion by using a self-monitoring device. Subjects were 34 hypertensive patients who underwent successful 24-h home urine collection five times and 25 volunteers. Four volunteers were diagnosed as having hypertension based on home blood pressure (BP) readings. All subjects were asked to measure daily urinary salt excretion for 30 days by using a self-monitoring device which estimates 24-h salt excretion by overnight urine. The mean urinary salt excretion during the 30 days was 8.36 +/- 1.52 g/day and the range (maximum-minimum value) was 5.47 +/- 20.05 g/day in all subjects. Mean urinary salt excretion decreased from 8.52 +/- 1.63 g/day for the first 10 days to 8.31 +/- 1.54 g/day for the last 10 days (p < 0.05). The mean urinary salt excretion determined by a self-monitoring device using overnight urine was positively associated with that determined by 24-h home urine for five times in the hypertensive subjects (r = 0.63, p < 0.01). Results indicate that a self-monitoring device seems to be useful to monitor daily salt intake and to guide salt restriction.
Asunto(s)
Hipertensión/orina , Monitoreo Ambulatorio/instrumentación , Sales (Química)/orina , Autocuidado , Urinálisis/instrumentación , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Estudios de Casos y Controles , Ritmo Circadiano , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio/métodos , Potasio/orina , Reproducibilidad de los Resultados , Sodio/orina , Urinálisis/métodosRESUMEN
Autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered the standard therapy for younger patients with multiple myeloma, however, survival curve doesn't reach plateau. On the other hand, allogeneic reduced-intensity stem cell transplantation (RIST) with graft-versus-myeloma (GVM) effects is expected to be the curable therapy. We had three cases received RIST (one case as a salvage therapy for relapse after tandem auto-PBSCT, and two cases as an intentional RIST after achieving partial response by auto-PBSCT). All of three cases relapsing or progressing after RIST showed disease type of plasmacytoma without plasma cells in the bone marrow. That may be because conditioning regimen doesn't include total body irradiation, or GVM is ineffective in plasmacytoma, but effective in bone marrow. Here, we report clinical course of these three cases with some consideration.