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1.
Eur Rev Med Pharmacol Sci ; 25(18): 5636-5652, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34604956

RESUMEN

OBJECTIVE: Lung cancer is one of the leading causes of morbidity and mortality in the world. In the past decade, numerous studies focus on the prognostic nutritional index (i.e., a measure of serum albumin and lymphocyte in peripheral circulation) as a possible biomarker to predict the survival outcomes in cancer patients undergoing chemotherapy. Prognostic nutritional index can reliably predict the survivability outcomes by effectively quantifying the nutritional and immunological status of cancer patients. To date, only one review has attempted to evaluate the impact of the prognostic nutritional index on the survival outcomes in lung cancer patients with certain limitations. The goal of the present systematic review and meta-analysis is to bridge the gap in the literature and evaluate the capacity of the prognostic nutritional index for predicting the survivability outcomes in lung cancer patients undergoing chemotherapy. The aim of the study is to evaluate the impact of prognostic nutritional index scoring on survival outcomes in lung cancer patients undergoing chemotherapy. MATERIALS AND METHODS:  A systematic academic literature search was performed based on the PRISMA guidelines across Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE databases. A random-effect meta-analysis was performed to evaluate the impact of prognostic nutritional index scoring (i.e., high/low) on survival outcomes (i.e., progression-free survival, overall survival) in lung cancer patients undergoing chemotherapy. RESULTS:  From 963 studies, 16 eligible studies with 4250 lung cancer patients (62.32 ± 5.08 years) undergoing chemotherapy were included. Our meta-analysis revealed worse mortality outcomes in terms of progression-free survival (HR: 1.31) and overall survival (1.21) for the group with a low prognostic nutritional index score as compared to the group with a high prognostic nutritional index score in lung cancer patients undergoing chemotherapy. Subsequent subgroup analyses further demonstrated markedly worse outcomes for progression-free survival (1.32) and overall survival (1.52) in non-small lung cancer patients with lower prognostic nutritional index scores. CONCLUSIONS:  We provide preliminary evidence suggesting that lower prognostic nutrition index scores are associated with worse survivability outcomes (progression-free survival and overall survival) in lung cancer patients undergoing chemotherapy. We also show that lower prognostic nutrition index scores correlate with even worse survival outcomes in patients with non-small lung cancer histological subtype of lung cancer. These findings should help clinicians to stratify the risks associated with the chemotherapeutic management of lung cancer patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/fisiopatología , Evaluación Nutricional , Estado Nutricional , Anciano , Femenino , Predicción , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia
2.
Eur Rev Med Pharmacol Sci ; 18(8): 1142-50, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24817287

RESUMEN

OBJECTIVE: To compare the effects of the pretreatment and treatment with recombinant human interleukin-11 (rhIL-11) on acute liver failure induced by D-galactosamine (D-GalN). METHODS: The Sprague Dawley (SD) male rats were randomly divided into five groups: control, model, pretreatment, treatment and repeated treatment groups. The acute liver failure model was established by intraperitoneal injections with D-GalN (1400 mg/kg). The pretreatment, treatment and repeated treatment groups were injected subcutaneously with rhIL-11 (500 µg/kg). The rats were killed 24, 48, or 72 h after the D-GalN injection. The symptoms and survival rate of the rats were analysed. Liver injury was assessed by serum ALT and AST levels and by histological analysis. The percentage of Proliferating Cell Nuclear Antigen (PCNA+) cells in the liver tissue was evaluated by immunohistochemistry. RESULTS: Compared with the model group, the survival rate of the pretreatment group improved markedly, and these rats were protected from severe hepatic injury, as shown by the decreased serum ALT and AST levels and improved histological results. In the pretreatment group, the percentage of PCNA+ cells was significantly increased in the late stage. In contrast, the treatment and repeated treatment groups did not show improved survival rates or the prevention of severe hepatic injury, as shown by the absence of any decrease in the serum ALT and AST levels and the lack of any improvement in the histological results.The treatment and repeated treatment groups also have a significant increase in the percentage of PCNA+ cells in the late stage. CONCLUSIONS: The pretreatment with rhIL-11 can reduce acute liver failure and protect the liver. In contrast, the treatment with rhIL-11 cannot reduce acute liver failure or protect the liver.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Galactosamina , Interleucina-11/administración & dosificación , Fallo Hepático Agudo/prevención & control , Hígado/efectos de los fármacos , Sustancias Protectoras/administración & dosificación , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Proliferación Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Esquema de Medicación , Humanos , Hígado/enzimología , Hígado/patología , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/patología , Masculino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas Sprague-Dawley , Proteínas Recombinantes/administración & dosificación , Factores de Tiempo
3.
Eur Rev Med Pharmacol Sci ; 18(5): 703-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24668712

RESUMEN

OBJECTIVES: Ghrelin is an octanoylated peptide hormone with multiple and diverse physiologic functions including an important role in energy homeostasis and reproduction. In this study, the adjustment effects of different postnatal nutritional status on puberty onset and the expression of hypothalamic ghrelin and gonadotrophin-releasing hormone (GnRH) were examined in 1 day-old female Sprague-Dawley rats. MATERIALS AND METHODS: Animals were randomly assigned into four groups: overnutrition group (Group O), normal group (Group N, control group), and undernutrition groups (Group U and U2). Western blot analysis and immunohistochemistry were used to analyze the expression of hypothalamic ghrelin and GnRH. RESULTS: With a low level expression of hypothalamic ghrelin, the appearance of puberty onset and secretion peak of GnRH in Group O was earlier than the other groups. CONCLUSIONS: Undernutrition delayed puberty onset and the GnRH peak, at the same time, promoted the expression of hypothalamic ghrelin.While, the expression of hypothalamic ghrelin was suppressed at puberty onset.


Asunto(s)
Ghrelina/biosíntesis , Hormona Liberadora de Gonadotropina/biosíntesis , Hipotálamo/metabolismo , Estado Nutricional/fisiología , Maduración Sexual/fisiología , Animales , Animales Recién Nacidos , Femenino , Regulación de la Expresión Génica , Gonadotropinas/metabolismo , Desnutrición/metabolismo , Ratas , Ratas Sprague-Dawley
4.
Genet Mol Res ; 13(1): 590-7, 2014 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-24615024

RESUMEN

We investigated genetic susceptibility to coronary artery disease (CAD) by studying the association of MKL1 gene polymorphisms with CAD in the Chinese Han population. We performed a case-control study with 476 unrelated CAD patients and 325 non-CAD controls. All SNPs were genotyped with a TaqMan SNP genotyping assay. The distribution of MKL1-184C>T gene polymorphism in each group was in Hardy-Weinberg equilibrium. The frequency of the MKL1 T allele in the CAD group was significantly higher than in the control group (38.6 vs 30.8%). After logistic regression models adjusted for CAD risk factors, the risk of CAD among CT genotypes was 1.765 times higher than among the CC genotypes [odds ration (OR) = 1.765, 95% confidence interval (CI) = 1.246-2.5], and for TT genotypes it was 1.806 times higher than for the CC genotypes (OR = 1.806, 95%CI = 1.203-2.71). In summary, genotypes with at least one T allele (CT or TT genotypes) had a significantly increased CAD risk than the CC genotypes, with a ratio of 1.78 to 1 (OR = 1.780, 95%CI = 1.311-2.418). There was a close association between -184 T allele and 3VD (OR = 1.614, 95%CI = 1.259-2.07, P < 0.05). We conclude that the -184C>T of MKL1 is an important susceptibility factor for CAD in the Han Chinese in Henan Province. Homozygosity for the T allele is not only associated with an increased risk for CAD, it is also correlated with severity of stenosis in the Chinese Han population.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Proteínas de Unión al ADN/genética , Estudios de Asociación Genética , Proteínas de Fusión Oncogénica/genética , Adulto , Anciano , Anciano de 80 o más Años , China , Enfermedad de la Arteria Coronaria/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Transactivadores
5.
Asian Pac J Cancer Prev ; 14(10): 5905-10, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24289598

RESUMEN

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.


Asunto(s)
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 Cultivadas
6.
Transfus Med ; 23(1): 42-47, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23106135

RESUMEN

OBJECTIVES/AIMS: This work aims to develop a multiplex polymerase chain reaction combined with DNA pooling for mass screening for rare blood types. BACKGROUND: The differences in most blood group antigens are associated with single-nucleotide polymorphisms (SNPs), which are used in detecting blood antigen expression at the molecular level. However, all existing sequence-specific primers polymerase chain reaction (PCR-SSP) assays for blood typing genotype one or several SNPs individually. DNA pooling is a way that reduces the amount of genotyping required. METHODS: A sensitive multiplex PCR-SSP assay testing pooled DNA was established to detect the rare Fy(b) and S alleles. It was applied to screen a total of 4490 donor samples via testing 898 DNA pools. The samples in the positive pools were further tested individually. Then the positive samples, including Fy(a-b+)/Fy(a+b+) and S+s-/S+s+ genotypes, were tested via two PCR-SSP assays for alleles Fy(a) and s. The rare genotypes Fy(a-b+) and S+s- were verified using serologic tests and sequencing analysis. RESULTS: Two hundred and fifty-four donors were tested positive for the Fy(b) allele, whereas 101 donors were positive for the S allele. Among the 254 Fy(b+) donors, 5 were Fy(a-b+) and 249 were Fy(a+b+). Among the 101 S+ donors, 3 were S+s- and 98 were S+s+. The rare Fy(b) and S alleles comprised 2·28 and 1·16%, respectively. The PCR-SSP assays were confirmed by sequencing analysis and serological test. CONCLUSION: A multiplex PCR assay was combined with DNA pooling to reduce the number of tests required, making large-scale screening feasible.


Asunto(s)
Sistema del Grupo Sanguíneo Duffy/genética , Pruebas Genéticas/métodos , Técnicas de Genotipaje , Reacción en Cadena de la Polimerasa Multiplex/métodos , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/genética , Alelos , Donantes de Sangre , Incompatibilidad de Grupos Sanguíneos/prevención & control , Transfusión Sanguínea , Análisis Costo-Beneficio , Cartilla de ADN , Pruebas Genéticas/economía , Técnicas de Genotipaje/economía , Humanos , Reacción en Cadena de la Polimerasa Multiplex/economía , Manejo de Especímenes
7.
J Hum Hypertens ; 27(4): 265-70, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22648266

RESUMEN

Elevated levels of circulating triglycerides and increased arterial stiffness are associated with cardiovascular disease. Numerous studies have reported an association between levels of circulating triglycerides and arterial stiffness. We used Mendelian randomization to test whether this association is causal. We investigated the association between circulating triglyceride levels, the apolipoprotein A-V (ApoA5) -1131T>C single nucleotide polymorphism and brachial-ankle pulse wave velocity (baPWV) by examining data from 4421 subjects aged 18-74 years who were recruited from the Chinese population. baPWV was significantly associated with the levels of circulating triglycerides after adjusting for age, sex, body mass index (BMI), systolic blood pressure, heart rate, waist-to-hip ratio, antihypertensive treatment and diabetes mellitus status. The -1131C allele was associated with a 5% (95% confidence interval 3-8%) increase in circulating triglycerides (adjusted for age, sex, BMI, waist-to-hip ratio, diabetes mellitus and antihypertensive treatment). Instrumental variable analysis showed that genetically elevated levels of circulating triglycerides were not associated with increased baPWV. These results do not support the hypothesis that levels of circulating triglycerides have a causal role in the development of arterial stiffness.


Asunto(s)
Índice Tobillo Braquial , Apolipoproteínas A/genética , Enfermedades Cardiovasculares/genética , Polimorfismo de Nucleótido Simple , Análisis de la Onda del Pulso , Triglicéridos/sangre , Rigidez Vascular , Adolescente , Adulto , Anciano , Apolipoproteína A-V , Pueblo Asiatico/genética , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etnología , Enfermedades Cardiovasculares/fisiopatología , Distribución de Chi-Cuadrado , China/epidemiología , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Valor Predictivo de las Pruebas , Análisis de Regresión , Medición de Riesgo , Factores de Riesgo , Regulación hacia Arriba , Adulto Joven
8.
Vox Sang ; 97(2): 139-46, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19490579

RESUMEN

BACKGROUND AND OBJECTIVES: The purpose of the work was to analyse the genotype of D-elute (DEL) samples and to elucidate whether there were novel DEL alleles in Chinese population. MATERIALS AND METHODS: D-negative samples were identified by an indirect antiglobulin test (IAT), and absorption\elution tests to screen weak D, partial D and DEL phenotypes. DELs were further analysed by multiplex PCR, PCR-sequence-specific primers (PCR-SSP) and sequencing. Some of the DEL samples were determined to show RHD zygosity by PCR-restriction fragment length polymorphism or real-time quantitative PCR. RESULTS: Of 400 253 samples from individual donations, 1585 (0.40%) were typed as D negative. Among these D-negative samples, 279 DELs were observed. Two hundred and sixty-eight DELs were confirmed to have the RHD (K409 K) allele. Three DELs seemed to have RHD-CE-D hybrid alleles, including one RHD-CE(4-9)-D, one RHD-CE(2-5)-D and one suspected RHD(1-9)-CE. Five novel RHD alleles were found among the rest of the DEL samples, including four RHD 3 g > a, one RHD (R10W), one RHD (L18P), one RHD (L84P) and one RHD (A137E). Eighty-four DELs were analysed for Rhesus box zygosity, there were 77 RHD+/RHD-and seven RHD+/RHD+. CONCLUSION: About 4.35% apparent D negative Chinese individuals were weak D or partial D, while 17.60% were DEL. Novel DEL alleles are rare, and all but 11 of the 279 DELs were due to the most common DEL allele, RHD (K409 K). The RHD 3G > A might be the second most frequent DEL allele in Chinese. Exploration of a complete molecular basis for DEL in Chinese ethnic groups is a long-term endeavour.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Sistema del Grupo Sanguíneo Rh-Hr/genética , Alelos , China , Genotipo , Fenotipo , Polimorfismo de Nucleótido Simple
9.
J Fish Biol ; 75(5): 1092-100, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20738600

RESUMEN

It has been demonstrated that growth hormone (GH) transgenic fish often posses a trait for fast growth. Here, we investigated the growth of F(4)'all-fish' GH transgenic carp Cyprinus carpio and their serum GH levels for a year. The results showed that F(4) all-fish GH transgenic carp were significantly larger in body mass (c. two-fold, P < 0.001) and body length (c. 1.3 fold, P < 0.001), compared with the non-transgenic group. The discrepancy of serum GH levels between the transgenic carp group and control group is 54 fold, when the water temperature was 12-34 degrees C. When the water temperature decreased to 3.5 degrees C in January, the discrepancy was 256 fold. The serum GH level of the transgenic group was relatively constant, while that of control varied greatly based on month and water temperature. The changes of growth rates between the transgenic group and the control group were similar for a year. Taken together, the results indicated that F(4) all-fish GH transgenic carp had not only higher and constant serum GH levels but also a significant fast-growing effect, compared with the control. To our knowledge, this is the first report on a one-year investigation of growth trait and serum growth hormone level in F(4) all-fish GH transgenic carp.


Asunto(s)
Tamaño Corporal/genética , Carpas/sangre , Carpas/crecimiento & desarrollo , Hormona del Crecimiento/sangre , Animales , Animales Modificados Genéticamente , Femenino , Hormona del Crecimiento/genética , Masculino , Temperatura
10.
Phytomedicine ; 16(2-3): 215-21, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18951001

RESUMEN

Guan-Xin-Er-Hao (GXEH) is a Chinese medicine formula for treating ischemic heart diseases (IHD) and has a favorable effect. Our aim was to examine whether or not acute oral GXEH could protect the heart against myocardial infarction and apoptosis in acute myocardial ischemic rats. If so, we would explain the antioxidative mechanism involved. The left anterior descending coronary artery was occluded to induce myocardial ischemia in hearts of Sprague-Dawley rats. At the end of the 3h ischemic period (or 24h for infarct size), we measured the myocardial infarct size, myocardial apoptosis and the activities of antioxidative enzymes. GXEH reduced infarct size, myocardial apoptosis and the serum level of malondialdehyde (MDA), increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and GSH-peroxidase (GPX) activities and the serum level of glutathione (GSH). GXEH exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidation and antilipid peroxidative properties, and thus may be used as a promising agent for both prophylaxis and treatment of IHD.


Asunto(s)
Antioxidantes/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Isquemia Miocárdica/tratamiento farmacológico , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Malondialdehído/metabolismo , Infarto del Miocardio/prevención & control , Isquemia Miocárdica/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo
11.
Transfus Med ; 18(3): 199-203, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18598284

RESUMEN

The D antigen is the most antigenic in the Rh blood group system. Variation in the D antigen may have the potential to cause alloimmunization. D variant may have different molecular backgrounds in people of different ethnic groups. The aim of this study was to investigate serological and molecular differences related to the D antigen among Chinese ethnic groups. Blood samples of six different races in Xinjiang were screened for D variants using serological test. The suspected D variants were further analyzed by using polymerase chain reaction and sequencing to determine the RHD genotype. Fourteen D elute phenotypes (DELs), included 11 Han, 2 Uigur and 1 Hui, were detected together with two weak Ds, one in the Han and one in the Uigur. The 14 DELs possessed the RHD (K409K) allele. The weak D found in the Han was of type 15, but the Uigur phenotype was of weak D type 5. Our results suggest that the Uigur population has both Han and Caucasian characteristics in the Rh blood group system, but the RHD genotypes of other minorities settled in China need to be further studied. A different strategy for Rh typing based on ethnic specificity should be used to detect D variants.


Asunto(s)
Donantes de Sangre , Polimorfismo Genético , Sistema del Grupo Sanguíneo Rh-Hr/genética , China/etnología , Etnicidad/genética , Genética de Población , Genotipo , Humanos , Reacción en Cadena de la Polimerasa
12.
Vox Sang ; 92(3): 242-6, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17348873

RESUMEN

BACKGROUND AND OBJECTIVES: RHD alleles are considered variable in the Chinese RhD-negative persons. The purpose of the present work was to elucidate the molecular bases of two novel RHD alleles identified in a survey of a Chinese RhD-negative population. MATERIALS AND METHODS: A total of 163 RhD-negative blood samples were investigated. The sequences of RHD exons were examined by RHD exon specific multiplex polymerase chain reaction (PCR) and PCR with sequence-specific primers (PCR-SSP). Characterizations of RHD intron 2 and Rhesus box were performed by PCR-PstI digestion. The DNA and cDNA sequences of the novel alleles were determined by PCR and reverse transcriptase-PCR (RT-PCR) sequencing analysis. A family study was performed to investigate the segregation of a novel RHD allele. RESULTS: One hundred and twenty-nine samples (79.1%) had no RHD gene. Twenty-seven samples (16.6%) carried RHD-CE-D hybrid alleles. The remainder seven samples (4.3%) appeared to have an intact RHD gene. Three of them were sequenced for RHD gene and two novel alleles, RHD 325del and RHD intron 2 1A, were identified. The deletion of a nucleotide A at position 325 in the allele RHD 325del resulted in a stop codon at amino acid position 118. The RHD intron 2 1A allele was generated from a splice mutation and its transcript sequence had no exon 2. Family study indicated that the RHD 325del allele was inherited with a Ce haplotype. CONCLUSION: This study provides the molecular bases of RHD alleles RHD 325del and RHD intron 2 1A. The existences of RHD 711del, RH (D1 CE2-9 D10), and RH (D1 CE2-9 D10) alleles in the Chinese population were confirmed. A PCR-SSP-based assay for rapid detection of RHD 325del and RHD intron 2 1A alleles was established and it could be used to predict the RHD genotype in the Chinese RhD-negative subjects.


Asunto(s)
Alelos , Pueblo Asiatico/genética , Mutación/genética , Sistema del Grupo Sanguíneo Rh-Hr/genética , Secuencia de Bases , Genotipo , Humanos , Datos de Secuencia Molecular , Fenotipo
13.
Mol Microbiol ; 43(6): 1387-400, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11952893

RESUMEN

To address the need for new approaches to antibiotic drug development, we have identified a large number of essential genes for the bacterial pathogen, Staphylococcus aureus, using a rapid shotgun antisense RNA method. Staphylococcus aureus chromosomal DNA fragments were cloned into a xylose-inducible expression plasmid and transformed into S. aureus. Homology comparisons between 658 S. aureus genes identified in this particular antisense screen and the Mycoplasma genitalium genome, which contains 517 genes in total, yielded 168 conserved genes, many of which appear to be essential in M. genitalium and other bacteria. Examples are presented in which expression of an antisense RNA specifically reduces its cognate mRNA. A cell-based, drug-screening assay is also described, wherein expression of an antisense RNA confers specific sensitivity to compounds targeting that gene product. This approach enables facile assay development for high throughput screening for any essential gene, independent of its biochemical function, thereby greatly facilitating the search for new antibiotics.


Asunto(s)
Proteínas Bacterianas/genética , Marcación de Gen , Genes Esenciales , Genoma Bacteriano , ARN sin Sentido , Staphylococcus aureus/genética , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Clonación Molecular , Biología Computacional/métodos , Mycoplasma/genética , Mycoplasma/metabolismo , Plásmidos , ARN Mensajero/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Transformación Bacteriana , Xilosa/farmacología
15.
Phys Rev D Part Fields ; 44(4): R942-R945, 1991 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-10014004
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