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BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.
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Globulinas , Desnutrición , Neoplasias , Biomarcadores/metabolismo , Proteína C-Reactiva/análisis , Estudios de Cohortes , Globulinas/metabolismo , Glucosa/metabolismo , Humanos , Inflamación/complicaciones , Liderazgo , Linfocitos/química , Linfocitos/metabolismo , Masculino , Desnutrición/complicaciones , Neoplasias/complicaciones , Evaluación Nutricional , Estado Nutricional , Estudios Prospectivos , Calidad de Vida , Estudios RetrospectivosRESUMEN
OBJECTIVE: To elucidate the role of histone deacetylase inhibitor Trichostatin A (TSA) in affecting metastasis of breast carcinoma, and its molecular mechanism. PATIENTS AND METHODS: LPAR5 levels in breast carcinoma tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its expression pattern was further verified in breast carcinoma cell lines. The relationship between LPAR5 and prognosis of breast carcinoma patients was analyzed. After TSA induction (100-400 nmol/L) for 6-48 h, the proliferative and migratory abilities of SKBR3 and MDA-MB-231 cells in overexpressing LPAR5 were examined by cell counting kit-8 (CCK-8), transwell and wound healing assay. By constructing a xenograft model in nude mice, the influences of TSA and LPAR5 on in vivo growth of breast carcinoma were examined. RESULTS: LPAR5 was upregulated in breast carcinoma samples. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as lower overall survival and progression-free survival in breast carcinoma patients. LPAR5 level was dose-dependently downregulated in TSA-induced SKBR3 and MDA-MB-231 cells. In addition, TSA induction dose-dependently declined proliferative ability, and time-dependently attenuated migratory ability in breast carcinoma cells. In vivo overexpression of LPAR5 in nude mice reversed the inhibitory effect of TSA on breast carcinoma growth. CONCLUSIONS: TSA induction can suppress proliferative and migratory abilities in breast carcinoma by downregulating LPAR5.
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Neoplasias de la Mama/tratamiento farmacológico , Regulación hacia Abajo/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Animales , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Desnudos , Persona de Mediana Edad , Receptores del Ácido Lisofosfatídico/genética , Receptores del Ácido Lisofosfatídico/metabolismoRESUMEN
The prevalence of hepatitis E virus (HEV) in domestic swine threats the public health, due to the risk of zoonotic transmission. In this study, we investigated the prevalence and genetic features of HEV in swine, in Gansu, which is geographically an important province in China. 377 fecal samples were collected from pig farms in Gansu province of China and tested for HEV RNA by RT-PCR. The prevalence rate is about 23% in pig farms of Gansu province. By RT-nPCR, 5' and 3' RACE methods, a whole genome with 7,284 nt in length, termed as swCH189, was obtained and investigated by nucleotide, codon and amino acid usage analyses. Phylogenetic tree analysis classified swCH189 strain into genotype 4e. Although this subtype has never been reported in the local population, genotype 4 is known as zoonotic and more pathogenic than other genotypes. According to the synonymous codon usage patterns of the three open reading frames (ORFs) of swCH189, compositional constraint mainly influences usage patterns of synonymous codons with A-end, while natural selections dominate in usage patterns of synonymous codons with G, C and U-ends. Genetic diversities of each ORFs, in respect to codon and amino acid usage patterns, are closely related to other members of genotype 4 in general, but with distinct features. Thus, the prevalence rate and the genetic features of HEV determined by this study are important for the prevention of zoonotic transmission of HEV from swine to human in this region as well as in China.
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Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/veterinaria , Enfermedades de los Porcinos/virología , Animales , China/epidemiología , Heces/virología , Variación Genética , Genotipo , Hepatitis E/epidemiología , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Virus de la Hepatitis E/genética , Sistemas de Lectura Abierta , Filogenia , Porcinos , Enfermedades de los Porcinos/epidemiologíaRESUMEN
OBJECTIVE: MEK1/2 (mitogen-activated protein kinase 1 and 2)/ERK1/2 (extracellular signal-regulated kinase 1 and 2) is important transducers of external signals for cell growth, survival, and apoptosis in acute myeloid leukemia cells (AML). In this study, we analyzed the effect of MEK inhibitor CI-1040 on the survival of AML cells. MATERIALS AND METHODS: Using ELISA and MTT we studied the cytotoxic effects of CI-1040 on AML U-937 cells. We studied the changes induced by CI-1040 on PUMA and p53 expression in U-937 cells by Western blotting assay. Moreover, we analyzed the cytotoxic effect of CI-1040 in U-937 cells with deleted PUMA, wt-p53 by wt-p53 siRNA and PUMA siRNA transfection. RESULTS: CI-1040 induced apoptosis and inhibited proliferation in U-937 cells in a dose and time-dependent manner. CI-1040 induced a significant increase in PUMA mRNA and protein levels. Importantly, we show that knockdown of PUMA by PUMA siRNA transfection inhibited CI-1040-induced apoptosis and proliferation inhibition in U-937 cells. Moreover, CI-1040 induced apoptosis and proliferation inhibition was irrespective of wt-P53 status. CONCLUSIONS: These results demonstrate that CI-1040 induce apoptosis of U-937 cells and might be a new therapeutic option for the treatment of AML.
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Apoptosis/efectos de los fármacos , Benzamidas/farmacología , Leucemia Mieloide Aguda , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Células Tumorales CultivadasRESUMEN
OBJECTIVE: The etiology of Major depressive disorder (MDD) is multifactorial but the genetic risk is an important factor. Previous studies have shown a significant interaction between serotonin and brain-derived neurotrophic factor (BDNF) in brain function. The serotonin transporter protein promoter polymorphism (5-HTTLPR) and BDNF (rs6265) are two of the most studied candidate gene polymorphisms in relation to MDD. However, the effect of 5-HTTLPR-BDNF (rs6265) interaction on MDD-risk is not consistent. PATIENTS AND METHODS: This study recruited 459 patients with MDD and 412 healthy volunteers in a Chinese Han population. Polymerase chain reaction (PCR)-based genotyping was used to detect polymorphisms. Logistic regression was applied to estimate the effect of polymorphisms of 5-HTTLPR, BDNF (rs6265), and their interaction. RESULTS: We observed a significant correlation between the heterozygous genotype of 5-HTTLPR and MDD [odds ratio (OR) = 1.42, 95% CI: 1.05~1.91; p = 0.02]. The BDNF (rs6265) polymorphism showed that there is no correlation with MDD. When interaction with BDNF was modeled, for individuals with BDNF (rs6265), genotype GG, cases in the heterozygous group had even higher odds of MDD than those in the combined homozygous group of 5-HTTLPR polymorphism (OR = 2.92, 95% CI: 1.43-5.95; p = 0.003). CONCLUSIONS: Our results suggested that 5-HTTLPR, may be associated with the susceptibility of MDD in an overdominant mode, and there may be a significant interaction between 5-HTTLPR and BDNF (rs6265) polymorphisms in relation to MDD.
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Trastorno Depresivo Mayor/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Pueblo Asiatico , Factor Neurotrófico Derivado del Encéfalo/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Heat shock protein 90 (Hsp90) is a highly conserved chaperone protein that interacts with various client proteins to mediate their folding and stability. The Broad-Complex-Tramtrack-Bric-a-brac (BTB) domain, also known as poxvirus and zinc finger (POZ) domain, exists widely in different proteins and is highly conserved. However, the stability mechanism of BTB domain-containing proteins has not been fully understood. Co-immunoprecipitation and a protein pull-down assay were performed to investigate the interaction between Hsp90 and the transcription factor Broad isoform Z7 (BrZ7) in vivo and in vitro. The middle domain of Hsp90 directly associated with the BTB domain of BrZ7. The Hsp90 inhibitor 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) interrupted the interaction between Hsp90 and BrZ7 and decreased the protein level of BrZ7 but did not affect the mRNA level of BrZ7. The addition of the proteasome inhibitor peptide aldehyde Cbz-leu-leu leucinal suppressed the 17-AAG-induced degradation of BrZ7. BTB domain deletion and 17-AAG treatment resulted in inhibition of BrZ7 function in gene expression in the 20-hydroxyecdysone and juvenile hormone pathways. These results reveal that the middle domain of Hsp90 associates with the BTB domain of BrZ7 to prevent BrZ7 degradation and maintain BrZ7 function in gene expression in the lepidopteran insect Helicoverpa armigera.
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Proteínas HSP90 de Choque Térmico/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Animales , Benzoquinonas/farmacología , Línea Celular , Dipéptidos , Ecdisterona/farmacología , Proteínas HSP90 de Choque Térmico/genética , Inmunoprecipitación , Proteínas de Insectos/metabolismo , Lactamas Macrocíclicas/farmacología , Unión Proteica , Isoformas de Proteínas/metabolismo , Factores de Transcripción/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: To investigate the preventive and therapeutic potential of garlic oil on human pancreatic carcinoma cells. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was performed to study the effects of garlic oil on three human pancreatic cancer cell lines, AsPC-1, Mia PaCa-2 and PANC-1. Cell cycle progression and apoptosis were detected by flow cytometry (FCM), staining with PI and annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI), respectively. Morphologic changes of pancreatic cancer cells were observed under transmission electron microscopy (TEM) after treatment with garlic oil at low inhibitory concentrations (2.5 µM and 10 µM) for 24 hours. RESULTS: Proliferation of the AsPC-1, PANC-1, and Mia PaCa-2 cells was obviously inhibited in the first 24 hours with the MTT assay. The inhibition effect was more significant after 48 hours. When cells were exposed to garlic oil at higher concentrations, an early change of the apoptotic tendency was detected by FCM and TEM. CONCLUSION: Garlic oil could inhibit the proliferation of AsPC-1, PANC-1, and Mia PaCa-2 cells in this study. Moreover, due to programmed cell death, cell cycle arrest, or both, pro-apoptosis effects on AsPC-1 cells were induced by garlic oil in a dose and time dependent manner in vitro.
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Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ajo/química , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Aceites de Plantas/farmacología , Citometría de Flujo , Humanos , Microscopía Electrónica de Transmisión , Células Tumorales CultivadasRESUMEN
PURPOSE: To evaluate the use of surgical treatment with amniotic membrane for long-term atopic keratoconjunctivitis. Damaged corneas were repaired with various techniques: amniotic membrane transplantations, amniotic membrane coverings, amniotic membrane fillings (AMFs), and amniotic membrane inlay fillings, the latter of which were combined with glycerol-preserved corneal transplants. METHODS: This retrospective study was conducted on 37 eyes belonging to 37 patients with atopic keratoconjunctivitis. Thirty-two patients were classified into four groups according to surgical technique. Five patients undergoing medical management served as controls. Surgical outcome was measured by recovery time and long-term visual improvement. RESULTS: In all surgical eyes, integrity of ocular tissues was effectively restored and symptoms were reduced at 24.4 ± 13 days post recovery. Mean best-corrected visual acuity improved from 0.6 ± 0.2 to 0.198 ± 0.16 logarithm of the minimum angle of resolution (P<0.001). There were no intraoperative or postoperative complications, with the exception of two recurring cases, both controlled by medication. Recovery time of the control groups lasted 52 ± 16 days. In controls, mean best-corrected visual acuity improved from 0.74 ± 0.15 to 0.54 ± 0.29 logarithm of the minimum angle of resolution (P ≤ 0.05). The vision improvement has significant difference for surgical treatment vs medical. (Mann-Whitney U-test, U = 119, P < 0.05, one tailed).Vision improvements remained stable during a mean follow-up period of 21.7 ± 3.8 months. CONCLUSION: Patients suffering from severe chronic atopic keratoconjunctivitis and its complications can benefit from suitable surgical treatments: transplants, covers, fillings, or corneal graft surgeries supplemented with AMFs.
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Amnios/trasplante , Queratoconjuntivitis/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad Crónica , Trasplante de Córnea/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Agudeza Visual , Adulto JovenRESUMEN
INTRODUCTION: The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping. MATERIALS AND METHODS: Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared. RESULTS: One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary. CONCLUSIONS: Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing (AU)
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Neoplasias de la Mama/patología , Colorantes , Ganglios Linfáticos , Ganglios Linfáticos/patología , Metástasis Linfática , Terapia Neoadyuvante , Biopsia del Ganglio Linfático Centinela/métodos , Escisión del Ganglio Linfático , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Ganglios Linfáticos/cirugía , Azul de Metileno/químicaRESUMEN
The present study was to determine the protective effects of melatonin (MLT) against the damages of neuroendocrine-immune induced by lipopolysaccharide (LPS) in streptozotocin (STZ)-induced diabetic rats, and to analyze the parameters related to diabetes and oxidative stress. A total of 70 male Sprague-Dawley rats were assigned to this experiment. 10 of rats received STZ intraperitoneally (i.p.) alone as diabetic control; 40 of rats as the Diabetes+LPS received STZ plus LPS i.p. after induction of diabetes with STZ, then assigned to sub-groups as MLT (0.1) (mg), MLT (1) (mg), and Vehicle group, received two doses MLT and vehicle, i.p., respectively, q6 h for 12 h after LPS administration; and the remaining served as normal and LPS control. LPS significantly increased the serum levels of TNF-alpha and IL-6 in normal and diabetic rats; LPS also dramatically increased the plasma concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone. Both 0.1 and 1 mg/kg MLT doses significantly decreased the serum levels of TNF-alpha and IL-6. Significant inhibitory effects of MLT (1 mg/kg) were observed on the plasma concentrations of CRH, ACTH, and corticosterone of the HPA axis. The beneficial effects of MLT, such as the antioxidant activity and maintaining glucose homoeostasis, were also observed in this study, this resulted in a protective effect against the damages caused by LPS in STZ-induced diabetic rats. This finding probably provides a new approach for preventing the undesirable effects of the vicious cycle of hyperglycemia and stress factors such as severe infection in diabetic patients.
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Diabetes Mellitus Experimental/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inflamación/tratamiento farmacológico , Melatonina/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Análisis de Varianza , Animales , Antioxidantes/administración & dosificación , Corticosterona/sangre , Hormona Liberadora de Corticotropina/sangre , Diabetes Mellitus Experimental/inducido químicamente , Relación Dosis-Respuesta a Droga , Sistema Hipotálamo-Hipofisario/metabolismo , Inflamación/metabolismo , Interleucina-6/sangre , Lipopolisacáridos/toxicidad , Masculino , Neuroinmunomodulación/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Sistema Hipófiso-Suprarrenal/metabolismo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIMS: This study aimed to determine the microbial diversity in the starter of Fen Liquor. METHODS AND RESULTS: The plate method was used to enumerate the micro-organisms; meanwhile, the 16S rDNA of bacteria and the internal transcribed spacer of fungi were used to determine microbial diversity. Several genera were accordingly identified. Among the bacteria, Lactobacillales and Actinomycetales were detected only on the surface of the starter, whereas Bacillales was dominant within the starter. Among the fungi, Saccharomycopsis and Issatchenkia were the main genera in surface and interior starter, respectively; in addition, Thermomyces was found in interior starter, while other species of fungi were detected on the surface. CONCLUSIONS: The culture-dependent and polymerase chain reaction-based methods revealed the significant microbial diversity in different locations in the starter of Fen Liquor. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify the bacterial and fungal communities associated with the starter of Fen Liquor using both traditional and molecular methods; it is also the first to compare the microbial diversity on the surface of starter with that in the interior. The results enrich our knowledge on liquor-related micro-organisms, and can be used to promote the development of the traditional fermentation technology.
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Bebidas Alcohólicas/microbiología , Bacterias/aislamiento & purificación , Hongos/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , Bacterias/crecimiento & desarrollo , China , Recuento de Colonia Microbiana , Medios de Cultivo , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , ADN de Hongos/análisis , ADN de Hongos/aislamiento & purificación , ADN Espaciador Ribosómico/análisis , Ecosistema , Fermentación , Hongos/clasificación , Hongos/genética , Hongos/crecimiento & desarrollo , Datos de Secuencia Molecular , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
A nonviral gene carrier, calcium carbonate (CaCO3) nanoparticle, was evaluated for efficient in vitro and in vivo delivery of small interfering RNA (siRNA) targeting vascular endothelial growth factor-C (VEGF-C). The chemically synthesized CaCO3 nanoparticle has a 58 nm diameter and +28.6 mV positive surface charge. It is capable of forming a CaCO3 nanoparticle-DNA complex and transferring DNA into targeted cells with high transfection efficiency while effectively protecting the encapsulated DNA from degradation. Furthermore, the CaCO3 nanoparticle-DNA complex has no obvious cytotoxicity for SGC-7901 cells, while a liposome-DNA complex exhibited measurable cytotoxicity. SGC-7901 cells transfected with a VEGF-C-targeted siRNA via CaCO3 nanoparticle exhibit significantly reduced VEGF-C expression as measured by real-time PCR and enzyme-linked immunosorbent assay; whereas no decrease in VEGF-C expression is observed in cells treated by control transfection. Transfection of SGC-7901 cells with VEGF-C siRNA via CaCO3 nanoparticle also dramatically suppresses tumor lymphangiogenesis, tumor growth and regional lymph-node metastasis in subcutaneous xenografts. Significant downregulation of VEGF-C messenger RNA expression in a subcutaneous xenograft derived from VEGF-C siRNA-treated SGC-7901 cells was confirmed by real-time PCR as compared to controls. We conclude that CaCO3 nanoparticle is a novel and nonviral system for effective delivery of siRNA for cancer gene therapy.
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Carbonato de Calcio/química , Nanopartículas/química , ARN Interferente Pequeño/genética , Neoplasias Gástricas/terapia , Factor C de Crecimiento Endotelial Vascular/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/efectos de los fármacos , Ensayo de Cambio de Movilidad Electroforética , Terapia Genética/métodos , Humanos , Inmunohistoquímica , Linfangiogénesis , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Nanopartículas/ultraestructura , Plásmidos/administración & dosificación , Plásmidos/química , Plásmidos/genética , Interferencia de ARN , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Transfección , Factor C de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
AIMS: To identify a novel beta globin gene mutation found in a Chinese family, and also to assess its functional consequences. METHODS: Haematological analysis was performed on all family members. The 23 common mutations of beta thalassaemia found in Chinese populations were detected by means of a reverse dot blot method. Direct DNA sequencing of polymerase chain reaction (PCR) amplified complete beta globin gene was carried out to identify the novel mutation. A real time, one step reverse transcription PCR assay was used to measure beta globin mRNA in the reticulocytes of heterozygous patients. RESULTS: A novel frameshift mutation-an insertion of G between codons 15 and 16 in a homonucleotide run of four guanines-was determined, which generates a new premature chain terminator at the 22nd codon. Relative quantitative analysis of the beta globin mRNA in heterozygous subjects demonstrated a 39.83% reduction compared normal controls. CONCLUSIONS: The significantly lower amounts of beta globin mRNA found in mutation carriers is probably caused by the rapid nonsense mediated degradation of the mutant mRNA. These data, combined with haematological analysis, suggest that this novel mutation of CDs 15/16 (+G) results in a beta(0) thalassaemia phenotype.
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Mutación del Sistema de Lectura/genética , Globinas/genética , Talasemia beta/genética , Adulto , Secuencia de Bases , Preescolar , Codón sin Sentido/genética , Femenino , Genotipo , Globinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Talasemia beta/sangreRESUMEN
A 31 year old man was admitted to hospital for abrupt syncope. Two dimensional echocardiogram in the apical four chamber view showed Ebstein's malformation. This is the first documented case of Ebstein's malformation with atrial septal defect, right cor triatriatum, and a right overt accessory atrioventricular pathway.