RESUMEN
BACKGROUND AND OBJECTIVE: The association between vitamin D levels and disease activity has been established in patients with several autoimmune rheumatic diseases. We aimed to examine the association between vitamin D and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Fifty-four AAV patients and 50 age- and sex-matched healthy controls without vitamin D supplements were included. Clinical and laboratory data were evaluated during the assessment of vitamin D levels. Two different forms of vitamin D in the sera-25(OH)D, which is the sum of 25(OH)D2 and 25(OH)D3, and 25(OH)D3, which only includes 25(OH)D in its D3 form-were measured, and the relationship between vitamin D and the obtained data was assessed. Variations in vitamin D levels relative to the season were also evaluated. RESULTS: Patients with AAV demonstrated considerably lower 25(OH)D serum levels than healthy controls (16.0 vs. 20.4â¯ng/mL, pâ¯= 0.016), and the proportion of individuals with vitamin D deficiency was higher in patients with AAV than in healthy controls (68.5% vs. 48.0%, pâ¯= 0.035). Both serum 25(OH)D and 25(OH)D3 were positively associated with the 36-item Short-form Health Survey (SF-36) physical component summary and SF-36 mental component summary (MCS) scores. A negative correlation was observed between 25(OH)D and 25(OH)D3 serum levels and Birmingham vasculitis activity score (BVAS), Creactive protein (CRP), and white blood cell count. Linear regression analysis indicated haemoglobin and 25(OH)D levels to be independently associated with BVAS and CRP and 25(OH)D levels with SF-36 MCS score. No seasonal variations were observed in vitamin D levels. CONCLUSION: The results from this study suggest that vitamin D levels could provide clinically useful information in AAV.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Humanos , Estudios Prospectivos , Calidad de Vida , Vitamina DRESUMEN
The primary objective of this study was to determine the effect of delaying the first colostrum feeding on small intestinal histomorphology and serum insulin-like growth factor-1 (IGF-1) concentrations, and the secondary objective was to characterize the ultrastructure of the small intestine of neonatal calves at 51 h of life. Twenty-seven male Holstein calves were fed pooled, pasteurized colostrum (7.5% of birth body weight; 62 g of IgG/L) at 45 min (0H, n = 9), 6 h (6H, n = 9), or 12 h (12H, n = 9) after birth. At 12 h after their respective colostrum feeding, calves were fed milk replacer at 2.5% of birth body weight per meal and every 6 h thereafter. Blood samples were collected every 6 h using a jugular catheter and analyzed for serum IGF-1 concentrations using an automated solid-phase chemiluminescent immunoassay. At 51 h of life, calves were euthanized to facilitate collection of the duodenum, proximal and distal jejunum, and ileum. All segments of the small intestine were assessed for histomorphology, whereas scanning electron and transmission electron microscopy analyses were conducted only for the proximal jejunum and ileum. The results revealed that there was no overall effect of colostrum feeding time on serum IGF-1 concentrations; however, serum IGF-1 concentrations were influenced by time. Specifically, concentrations of serum IGF-1 at 48 h were 29% greater than concentrations at 0 h of life (312.8 ± 14.85 vs. 241.9 ± 14.06 ng/mL). Although there was no overall effect of colostrum feeding time on all histomorphological measures assessed, treatment × segment interactions were observed. Villi height was 1.4 times greater in the distal jejunum of 0H calves than in 6H and 12H calves, and 0H calves tended to have 1.2 times greater ileal villus height than 12H calves. In addition, 0H calves had 1.2 and 1.3 times greater ileal crypt depth than 6H and 12H calves, respectively, and 1.3 times greater surface area index than 12H calves in the distal jejunum. Qualitative ultrastructural evaluation of small intestinal enterocytes conducted irrespective of colostrum treatment revealed the presence of large vacuoles of electron-dense material, apical mitochondria, and apical canalicular systems in the jejunum and ileum. These results indicate that the calf intestine at 51 h of life contains unique enterocyte characteristics similar to fetal enterocytes and that delaying colostrum feeding may negatively influence intestinal growth and development.
Asunto(s)
Alimentación Animal , Bovinos , Calostro , Factor I del Crecimiento Similar a la Insulina/metabolismo , Intestino Delgado/ultraestructura , Animales , Animales Recién Nacidos , Duodeno , Femenino , Mucosa Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Intestino Delgado/crecimiento & desarrollo , Masculino , Leche , EmbarazoRESUMEN
Conflicting reports exist on whether prolonged IgG consumption can further increase serum IgG in neonatal calves. Given that higher serum IgG in neonates has lifelong benefits, our objective was to determine whether serum IgG can be increased by providing multiple meals containing IgG to neonatal calves. Twenty-seven Holstein bulls were all fed 1 colostrum meal (7.5% body weight; 62 g of IgG/L) at 2 h after birth and randomly assigned to be fed (5% body weight) colostrum (COL; n = 9), whole milk (WM; n = 9), or a 1:1 colostrum:whole milk mixture (MX; n = 9) every 12 h from 12 to 72 h. Serum IgG was measured at 1, 2, 3, 6, 9, 11, and 12 h after birth. After the 12-h meal, IgG was determined at 0.5-h intervals until 16 h and then at 1-h intervals from 16 to 24 h. Serum IgG was then measured at 27 h, then every 6 h from 30 to 60 h. From 60 to 64 h, IgG was measured every 0.5 h, then at 65 and 66 h, and then every 2 h until 72 h. Serum IgG increased rapidly between 2 and 12 h for all calves. A treatment × time interaction occurred as serum IgG began to diverge between treatments after they were fed at 12 h; the interaction was greatest over the entire period for COL compared with both MX and WM and was greater for MX than for WM. Maximum IgG concentrations (Cmax) were 30.4 ± 0.8, 27.2 ± 0.8, and 23.9 ± 0.8 g/L for COL, MX, and WM, respectively. Although MX Cmax was equivalent to both COL and WM Cmax, COL Cmax was greater than WM Cmax. Feeding COL and MX also prolonged the time to reach Cmax. Respectively, these calves achieved Cmax at 29.5 and 27.0 ± 3.4 h, whereas WM IgG peaked at 13.4 ± 3.4 h. No differences were observed for apparent efficiency of absorption between treatments from 0 to 12 h and 0 to 24 h. Immunoglobulin G area under the curve (AUC) was the same for COL and MX calves over the entire experimental period and from when treatments were fed. The IgG AUC for 0 to 72 h for WM calves was 27.4% lesser than that for COL calves but not different from MX calves. However, the IgG AUC for 12 to 72 h for WM calves differed relative to that for both COL (30.8% less) and MX (19.6% less) calves. Serum IgG concentrations were more persistent when COL (88.2 ± 2.4%) and MX (91.2 ± 2.4%) were fed rather than WM (75.3 ± 2.4%). Prolonged IgG consumption increased serum IgG concentrations, corresponding to the mass of IgG fed, and improved apparent IgG persistency in Holstein bulls. Neonatal calves should be fed at least 62 g of IgG at 12 h after birth to further increase serum IgG concentrations.
Asunto(s)
Bovinos/inmunología , Calostro/inmunología , Inmunoglobulina G/sangre , Leche/inmunología , Animales , Animales Recién Nacidos , Peso Corporal , Bovinos/sangre , Femenino , Inmunidad Materno-Adquirida , Masculino , Parto , EmbarazoRESUMEN
This study evaluated how feeding colostrum- or a colostrum-milk mixture for 3 d postnatal affects plasma glucagon-like peptide-2 (GLP-2), serum insulin-like growth factor-1 (IGF-1), and small intestinal histomorphology in calves. Holstein bulls (n = 24) were fed colostrum at 2 h postnatal and randomly assigned to receive either colostrum (COL), whole milk (WM), or a 1:1 COL:WM mixture (MIX) every 12 h from 12 to 72 h. A jugular venous catheter was placed at 1 h postnatal to sample blood frequently for the duration of the experiment. Samples were collected at 1, 2, 3, 6, 9, 11, and 12 h. Following the 12-h meal, blood was collected at half-hour intervals until 16 h and then at 1-h intervals from 16 to 24 h. A 27-h sample was taken, then blood was sampled every 6 h from 30 to 60 h. Again, blood was taken at half-intervals from 60 to 64 h, then at 65 and 66 h, following which, a 2-h sampling interval was used until 72 h. Plasma GLP-2 (all time points) and serum IGF-1 (at time points: 1, 6, 12, 18, 24, 36, 48, and 72 h) were both analyzed. Duodenal, jejunal, and ileal tissues were collected at 75 h of age to assess histomorphology and cellular proliferation. Feeding COL, rather than WM, increased plasma GLP-2 by 60% for 2 h and tended to increase GLP-2 by 49.4% for 4 h after the 60-h meal. Insulin-like growth factor-1 area under the curve (from 12 to 72 h) tended to be 27% greater for COL than WM calves but was otherwise unaffected by treatment. Ileal crypts tended to proliferate more with MIX than WM, whereas ileal crypt proliferation did not differ for COL compared with MIX or WM and was not different between treatments in the proximal jejunum. Villi height was increased 1.8 and 1.5× (COL and MIX vs. WM) in the proximal and distal jejunum, respectively, whereas MIX duodenal and ileal villi height tended to be 1.5 and 1.4× that of WM. Crypt depth did not differ in any region. Surface area of the gastrointestinal tract was reduced for WM by 60 and 58% (proximal jejunum) and 38 and 52% (ileum) relative to COL and MIX and was 54% less than MIX in the distal jejunum. Overall, extended COL feeding minimally increased plasma GLP-2 and serum IGF-1 compared with WM feeding. As COL and MIX similarly promoted small intestinal maturation, feeding calves transition milk to promote intestinal development could be a strategy for producers.
Asunto(s)
Alimentación Animal , Bovinos , Calostro , Péptido 2 Similar al Glucagón/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Intestino Delgado/crecimiento & desarrollo , Leche , Animales , Animales Recién Nacidos , Bovinos/sangre , Dieta/veterinaria , Íleon/crecimiento & desarrollo , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Yeyuno/crecimiento & desarrollo , Yeyuno/metabolismo , MasculinoRESUMEN
Glucagon-like peptide-1 (GLP-1) plays a role in the regulation of glucose homeostasis via the stimulation of insulin secretion. The objective of this study was to evaluate the effect of extended colostrum feeding on plasma concentration of GLP-1. Holstein bull calves (n = 27) were fed pooled colostrum at 7.5% of birth body weight at 2 h after birth and then fed mature milk (M), a 50:50 mixture of pooled colostrum and milk (CM), or pooled colostrum (C; n = 9 for each treatment) at 5% of birth body weight at 12 h after birth and every 12 h thereafter until 72 h after birth. Blood samples were obtained before (1 and 2 h after birth) and after (until 72 h after birth; 42 time points) the first colostrum feeding, and plasma concentrations of glucose, insulin, and GLP-1 were measured. Data were analyzed by ANOVA of JMP 13 (SAS Institute Inc., Cary, NC) with treatment, time, and treatment × time interaction as fixed effects. Treatment × time interaction was observed for plasma insulin and glucose concentrations, which were mainly the result of lower concentrations from 1 to 2 d after birth for C compared with M. Conversely, on d 3 after birth, the difference between treatments was not observed for insulin and glucose. For the entire experimental period, plasma GLP-1 concentration was higher for C (2.25 ng/mL) compared with M (1.41 ng/mL) and tended to be higher compared with CM (1.58 ng/mL). A treatment × time interaction was observed for GLP-1, but unlike glucose and insulin, this was mainly the result of higher concentrations from 54 to 72 h after birth (on d 3 after birth) for C compared with M or CM. Postprandial plasma concentration of glucose was not correlated with that of GLP-1 but was positively correlated with that of insulin for the 4-h period after feeding on d 1 (r = 0.30) and d 3 after birth (r = 0.33). Postprandial plasma concentration of GLP-1 was positively correlated with that of insulin for the 4-h period after feeding on d 3 after birth (r = 0.20). These results indicate that extended colostrum feeding may increase plasma GLP-1 concentrations, especially 3 d after birth, but further study is necessary to determine the effect on plasma insulin and glucose concentrations.
Asunto(s)
Glucemia , Calostro/fisiología , Péptido 1 Similar al Glucagón/sangre , Insulina/sangre , Leche/fisiología , Animales , Animales Recién Nacidos , Bovinos , Dieta/veterinaria , Femenino , Masculino , Parto , Periodo Posprandial , EmbarazoRESUMEN
OBJECTIVE: The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. METHODS: We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. RESULTS: The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. CONCLUSION: The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients.
Asunto(s)
Detección Precoz del Cáncer , Prueba de Papanicolaou , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Displasia del Cuello del Útero/diagnóstico , Adulto , Anciano , Células Escamosas Atípicas del Cuello del Útero/patología , Citodiagnóstico , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Displasia del Cuello del Útero/patologíaRESUMEN
PURPOSE: The aim of this study was to elucidate the cytological characteristics and the diagnostic usefulness of intraoperative cytology (IOC) for papillary thyroid carcinoma (PTC). In addition, using decision tree analysis, effective features for accurate cytological diagnosis were sought. METHODS: We investigated cellularity, cytological features and diagnosis based on the Bethesda System for Reporting Thyroid Cytopathology in IOC of 240 conventional PTCs. The cytological features were evaluated in terms of nuclear score with nuclear features, and additional figures such as presence of swirling sheets, psammoma bodies, and multinucleated giant cells. The nuclear score (range 0-7) was made via seven nuclear features, including (1) enlarged, (2) oval or irregularly shaped nuclei, (3) longitudinal nuclear grooves, (4) intranuclear cytoplasmic pseudoinclusion, (5) pale nuclei with powdery chromatin, (6) nuclear membrane thickening, and (7) marginally placed micronucleoli. RESULTS: Nuclear scores in PTC, suspicious for malignancy, and atypia of undetermined significance cases were 6.18 ± 0.80, 4.48 ± 0.82, and 3.15 ± 0.67, respectively. Additional figures more frequent in PTC than in other diagnostic categories were identified. Cellularity of IOC significantly correlated with tumor size, nuclear score, and presence of additional figures. Also, IOCs with higher nuclear scores (4-7) significantly correlated with larger tumor size and presence of additional figures. In decision tree analysis, IOCs with nuclear score >5 and swirling sheets could be considered diagnostic for PTCs. CONCLUSIONS: Our study suggests that IOCs using nuclear features and additional figures could be useful with decreasing the likelihood of inconclusive results.
Asunto(s)
Carcinoma Papilar/diagnóstico , Citodiagnóstico/métodos , Árboles de Decisión , Neoplasias de la Tiroides/diagnóstico , Biopsia con Aguja Fina , Carcinoma Papilar/cirugía , Diagnóstico Diferencial , Humanos , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugíaRESUMEN
AIM: To evaluate the efficacy of prostatic artery embolisation (PAE) in lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) at short- and mid-term follow-up. MATERIALS AND METHODS: The current study included 484 BPH patients from seven eligible studies. A meta-analysis was performed to determine the mean differences in parameters associated with LUTS, including the international prostate symptom score (IPSS), peak urinary flow (Qmax), post-void residual volume (PVR), quality of life score (QoL), prostate-specific antigen level (PSA), and prostatic volume (PV), between baseline and follow-up periods. RESULTS: Nearly all parameters at follow-up of 3-24 months were significantly improved compared to the baseline. Mean differences in IPSS at 3, 6, 12, and 24 months were -14.06 (95% confidence interval [CI]: -16.47 to -11.64), -12.32 (95% CI: -15.57 to -9.08), -16.41 (95% CI: -19.81 to -13.02), and -17 (95% CI: -17.91 to -16.09), respectively. In addition, mean differences of Qmax, PVR, PV, and QoL between the follow-up period and baseline were improved significantly; however, there were no significant differences in PSA at 24 months. CONCLUSION: The present data shows that PAE could improve LUTS by BPH after short- and mid-term follow-up; however, more cumulative studies for long-term follow-up and comparison with other therapeutic modalities will be needed.
Asunto(s)
Embolización Terapéutica/estadística & datos numéricos , Síntomas del Sistema Urinario Inferior/epidemiología , Síntomas del Sistema Urinario Inferior/prevención & control , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/terapia , Anciano , Causalidad , Comorbilidad , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Próstata/irrigación sanguínea , Hiperplasia Prostática/diagnóstico por imagen , Factores de Riesgo , Resultado del TratamientoRESUMEN
UNLABELLED: This systematic review was performed to compare the diagnostic accuracy of vertebral fracture assessment (VFA) with that of spinal radiography for identification of vertebral fractures (VFs). VFA appeared to have moderate sensitivity and high specificity for detecting VFs when compared with spinal radiography. INTRODUCTION: VFs are recognized as the hallmark of osteoporosis, and a previous VF increases the risk of a future fracture. Therefore, the timely detection of VFs is important for prevention of further fractures. This systematic review examined the diagnostic accuracy of VFA using dual X-ray absorptiometry (DXA) to identify VFs. METHODS: We searched for potentially relevant studies using electronic databases, including Ovid-Medline, Ovid-EMBASE, Cochrane library, and four Korean databases, from their inception to May 2013. We compared the diagnostic accuracy of VFA with that of spinal radiography for detection of VFs by analyzing the sensitivity and specificity using a 2 × 2 contingency table. Subgroup analyses were also performed on studies with a low risk of bias and applicability. RESULTS: Twelve studies were analyzed for the diagnostic accuracy of VFA. The sensitivity and specificity were 0.70-0.93 and 0.95-1.00, respectively, analyzed on a per-vertebra basis, and 0.65-1.00 and 0.74-1.00 on a per-patient basis. The sensitivity and specificity of five studies in subgroups with a low risk of bias in the intervention test were 0.70-0.84 and 0.96-0.99, respectively. In studies with a low risk of bias in the patient selection, those based on a per-vertebra basis in three studies were 0.70-0.93 and 0.96-1.00, respectively. CONCLUSIONS: VFA had moderate sensitivity and high specificity for detecting VF when compared with spinal radiography. However, the present findings are insufficient to assess whether spinal radiography should be replaced by VFA.
Asunto(s)
Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Absorciometría de Fotón/métodos , Femenino , Humanos , Masculino , Osteoporosis Posmenopáusica/complicaciones , Fracturas Osteoporóticas/etiología , Radiografía , Sensibilidad y Especificidad , Fracturas de la Columna Vertebral/etiologíaRESUMEN
Fever is a common symptom of systemic lupus erythematosus (SLE), and because of this it is difficult to discriminate between SLE flare and infection. The delta neutrophil index (DNI), automatically determined by the ADVIA 2120 electronic cell analyzer, has been reported to reflect the fraction of circulating immature granulocytes and to be associated with the presence of infection. In this study, we investigated the utility of DNI in discriminating infections from SLE flares in febrile SLE patients. In total, 111 episodes in 92 febrile SLE patients were reviewed. The infection group showed significantly higher white blood cell counts, neutrophil counts, C-reactive protein and procalcitonin than the SLE flare group. Complement (C)3 and C4 levels were decreased significantly in the SLE flare group. Patients in the SLE flare group had significantly lower DNI than those in both infection groups, with or without bacteremia. In a multivariate logistic regression analysis, only DNI was a significant independent factor for the presence of infection (odds ratio (OR): 18.9). When we selected a DNI value of 2.8% as the cutoff for infection, SLE patients with DNI ≥ 2.8% were found to be at higher risk for infection than those with DNI <2.8% (relative risk 8.48-fold). Our data suggest that DNI may be a marker to differentiate infections from SLE flares in febrile SLE patients.
Asunto(s)
Fiebre/diagnóstico , Infecciones/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Neutrófilos/inmunología , Adulto , Bacteriemia/diagnóstico , Biomarcadores , Proteína C-Reactiva/análisis , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A fast microtomography system for high-resolution high-speed imaging has been developed using bright monochromatic x-rays at the BL29XU beamline of SPring-8. The shortest scan time for microtomography we attained was 0.25 s in 1.25 µm effective pixel size by combining the bright monochromatic x-rays, a fast rotating sample stage, and a high performance x-ray imaging detector. The feasibility of the tomography system was successfully demonstrated by visualization of rising bubbles in a viscous liquid, an interesting issue in multiphase flow physics. This system also provides a high spatial (a measurable feature size of 300 nm) or a very high temporal (9.8 µs) resolution in radiographs.
Asunto(s)
Microtecnología/instrumentación , Tomografía por Rayos X/instrumentación , Color , Estudios de Factibilidad , Imagenología Tridimensional , Rotación , Factores de TiempoRESUMEN
AIM: The aim of this study is to evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in the prediction of circumferential resection margin (CRM) and to determine whether each different MRI scan plane provides an accurate CRM assessment. METHOD: Fifty-seven consecutive patients with mid-rectal cancer were enrolled prospectively. The CRM measurement from each MRI plane according to tumor location was compared with CRM measurement on whole-mount sections with the definition of threatened CRM as 2 mm in distance. The difference in performance among the sagittal, axial and oblique MR images was analyzed by using receiver operating characteristic (ROC) curves (A(z)). RESULTS: For anterior tumors (n = 17), the A(z) of the sagittal, axial and oblique MR planes were 0.66, 0.83 and 0.79, respectively. For lateral tumors (n = 17), the A(z) of the sagittal, axial and oblique MR planes were 0.53, 0.66 and 0.78, respectively. For posterior tumors (n = 23), the A(z) of the sagittal, axial and oblique MR planes were 0.76, 0.82 and 0.97, respectively. CONCLUSIONS: MRI provides an accurate prediction of preoperative CRM. There exist differences in diagnostic accuracy according to each different scan plane of MRI and tumor location within the rectum.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Cuidados Preoperatorios , Estudios Prospectivos , Curva ROC , Neoplasias del Recto/cirugía , Sensibilidad y EspecificidadRESUMEN
Apaf-1-interacting protein (APIP) was previously isolated as an inhibitor of mitochondrial cell death interacting with Apaf-1. Here, we report a hypoxia-selective antiapoptotic activity of APIP that induces the activation of AKT and extracellular signal-regulated kinase (ERK)1/2. Stable expression of APIP in C2C12 (C2C12/APIP) cells suppressed cell death induced by hypoxia and etoposide. Unlike etoposide, however, APIP induces the sustained activation of AKT and ERK1/2 and the phosphorylation of caspase-9 during hypoxia. Inhibition of AKT and ERK1/2 activation by the treatments with phosphatidylinositol 3'-kinase and mitogen-activated protein kinase kinase (MEK)1/2 inhibitors sensitized C2C12/APIP cells to hypoxic cell death and abolished the hypoxia-induced phosphorylation of caspase-9. Further, overexpression of phosphorylation-mimic caspase-9 mutants (caspase-9-T125E and caspase-9-S196D), but not phosphorylation-defective caspase-9 mutants (caspase-9-T125A and caspase-9-S196A), effectively suppressed hypoxia-induced death of C2C12 cells. These results elucidate a novel Apaf-1-independent antiapoptotic activity of APIP during hypoxic cell death, inducing the sustained activation of AKT and ERK1/2 and leading to caspase-9 phosphorylation.
Asunto(s)
Apoptosis , Factor Apoptótico 1 Activador de Proteasas/metabolismo , Caspasa 9/metabolismo , Hipoxia , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Factor Apoptótico 1 Activador de Proteasas/genética , Caspasa 9/genética , Caspasas/metabolismo , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Electroforesis en Gel Bidimensional , Activación Enzimática , Etopósido/farmacología , Humanos , Ratones , Mutación/genética , Fosforilación , Transducción de SeñalRESUMEN
We have examined differences in gene expression pattern between embryogenic callus (EC) and nonembryogenic callus (NEC) derived from mature seed embryo of rice (Oryza sativa L. cv Donggin). Three EC-specific transcripts were identified by differential display of amplified cDNAs. Specific expression of two partial cDNAs, designated as REC1 and REC2, respectively, was confirmed by a northern blot analysis. Partial nucleotide sequence of the clone REC1 showed no homology with any known genes, but partial amino acid sequence deduced from the clone REC2 exhibited 55-82% homology with nickel-cobalt-resistant proteins identified from a bacterium, Alcaligenes eutrophus CH34.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Oryza/embriología , Oryza/genética , Semillas/embriología , Semillas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Oryza/ultraestructura , Reacción en Cadena de la Polimerasa , Semillas/ultraestructuraRESUMEN
Capsaicin (CAP) has been known to inhibit some tumor development in vivo (J.J. Jang, S.H. Kim, T.K. Yun, Inhibitory effect of capsaicin on mouse lung tumor development, in vivo, J. Korean Med. Sci. 3 (1989) 49-53; J.J. Jang, K.J. Cho, Y.S. Lee, J.H. Bae, Different modifying responses of capsaicin in a wide-spectrum initiation model of F344 rat, J. Korean Med. 6 (1991) 31-36) [1,2] even though its mechanism of action is not well understood. The objectives of this study were to examine the effect of CAP on expression of tumor forming-related genes in a Korean stomach tumor cell, SNU-1. We used slot blot hybridization to investigate its effect on a wide spectrum of proto-oncogenes. It was found that CAP enhanced the transcripts of two proto-oncogenes (c-myc and c-Ha-ras) and tumor suppressor gene p53. While a low concentration of CAP (0.01 microM) did not significantly increase the level of p53 transcript in SNU-1, it did increase it by a factor of 3.5 at a 10 microM dose of CAP. Consequently, SNU-1 cells are sensitive to CAP in the overexpression of tumor suppressor gene, p53 and proto-oncogenes, c-myc and c-Ha-ras, but not those of c-erbB-2, c-jun and bcl-2 genes. Both cell death and DNA fragmentation were shown in SNU-1 cells with treatment of CAP. Our results suggest that CAP induces apoptotic cell death in human gastric cancer cells (SNU-1) in vitro which may be possibly mediated by the overexpression of p53 and/or c-myc genes. Because cell suicide is arguably the most potent natural defense against cancer, the correlation between the induction of apoptosis and the change of tumor forming-related gene expression after CAP treatment should be further studied in detail.