Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 47
Filter
1.
Sci Total Environ ; 922: 171212, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38428605

ABSTRACT

Within the framework of the recent approval of the National Plan Against Radon by the Council of Ministers of the Spanish Government, one of its five axes focuses on the delimitation of priority action areas. In line with this objective, this paper presents the indoor radon risk maps of the Canary Islands. Due to the volcanic origin of the Canary Islands, there is a great deal of geological heterogeneity in the soils on which buildings settle, making it very difficult to delimit radon-risk areas in the process of creating maps. Following a methodology developed in previous works for a study area formed of a set of representative municipalities, this paper presents radon risk maps of the Canary Islands based on lithostratigraphic information and high-resolution terrestrial gamma radiation maps. The goodness of fit of these maps is verified based on a statistical analysis of indoor radon concentration measurements carried out at representative building enclosures. In order to analyse the level of risk to the population, these maps were combined with built up areas (urban fabric) maps and estimations of the annual effective doses due to radon was obtained by applying a dosimetric model. This methodology improves the capability to delimit indoor radon risk areas, with a greater margin of safety. In this respect, it is estimated that areas classified as low risk have indoor radon concentrations 41 % below the current reference level of 300 Bq/m3 established by national regulations in compliance with the precepts laid down in the European EURATOM Directive.

2.
Sci Total Environ ; 885: 163761, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37146802

ABSTRACT

The transposition of the European EURATOM directive into the regulations of the different member states of the European Union involved governments making great efforts to define priority action maps against indoor radon exposure in buildings over a short time period. In Spain, the Technical Building Code established 300 Bq/m3 as a reference level and set up a classification of municipalities in which remediation measures should be adopted for radon exposure in buildings. Oceanic volcanic islands, such as the Canary Islands, present high geological heterogeneity in a small space due to their volcanic origin. This variability poses a challenge to the elaboration of radiological risk maps, which makes it necessary to have a high density of data to collect local variations. This paper presents a methodology to obtain accurate radon risk maps based on geological criteria and terrestrial gamma radiation. The predictive efficiency of these maps is statistically verified using indoor radon concentration data measured in buildings. Other radiological variables, which are commonly used as criteria for radon risk prediction found in the literature, were also applied, such as the geogenic radon potential and the activity concentration of natural radioisotopes in soils. The higher resolution of the maps obtained allows for a more detailed classification of radon risk zones in the study area than the current risk maps published in the Spanish building regulations.

3.
Sci Total Environ ; 788: 147709, 2021 Sep 20.
Article in English | MEDLINE | ID: mdl-34029827

ABSTRACT

The recommendations of the European Atomic Energy Community (EURATOM) have recently been incorporated into Spanish regulations in the Basic Document of Health Standards of the Technical Building Code (CTE), section HS6, on protection against radon exposure. This further accentuates the need to delimit radon prone areas as a strategy to address measures which minimise the effects of this gas on the population. In this research, measurements of terrestrial gamma radiation and indoor radon of dwellings have been carried out in the same location to delimit these risk areas. A new methodology has been developed including a definition of a Representative Building Enclosure (RBE) and it is proposed a Building Storey Index (IBS) which allows normalizing measurements of indoor radon activity concentration taken in different levels from the ground to the RBE. The results show the need to consider the type of contact that exists between the building and the ground as a determining factor of radon risk. Terrestrial gamma radiation is used as a proxy for radioisotopic composition of soils to characterise the indoor radon risk at different geological formation.

4.
RNA Biol ; 16(3): 295-308, 2019 03.
Article in English | MEDLINE | ID: mdl-30734641

ABSTRACT

Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques. However, direct data about their native tertiary structure remain scarce. Here we have applied atomic force microscopy (AFM) to image at single-molecule resolution different variant RNAs of three representative viroids: potato spindle tuber viroid (PSTVd, family Pospiviroidae), peach latent mosaic viroid and eggplant latent viroid (PLMVd and ELVd, family Avsunviroidae). Our results provide a direct visualization of their native, three-dimensional conformations at 0 and 4 mM Mg2+ and highlight the role that some elements of tertiary structure play in their stabilization. The AFM images show that addition of 4 mM Mg2+ to the folding buffer results in a size contraction in PSTVd and ELVd, as well as in PLMVd when the kissing-loop interaction that stabilizes its 3D structure is preserved.


Subject(s)
Microscopy, Atomic Force , Nucleic Acid Conformation , RNA, Viral/chemistry , Single Molecule Imaging , Viroids/genetics , Microscopy, Atomic Force/methods , Plant Viruses/genetics , Plant Viruses/ultrastructure , Single Molecule Imaging/methods
5.
International Journal of Dermatology ; 58(Suppl 1): 4-28, 2019.
Article in English | BIGG - GRADE guidelines | ID: biblio-1052798

ABSTRACT

This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non-biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque-psoriasis, which was summarized in Tables ad-hoc. The main end-points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0-1 and significant improvement of healthrelated quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.


Subject(s)
Phototherapy , Psoriasis/drug therapy , PUVA Therapy , Biological Products/therapeutic use , Arthritis, Psoriatic/drug therapy , Psoriasis/therapy , Ultraviolet Therapy , Arthritis, Psoriatic/therapy
6.
Medwave ; 18(6): e7314, 2018.
Article in English, Spanish | LILACS | ID: biblio-948393

ABSTRACT

Resumen Introducción La facoéresis es el procedimiento en que se extrae quirúrgicamente el cristalino para tratar las cataratas. La pérdida endotelial corneal es una complicación reconocida. Si bien se han descrito diversos factores asociados a este daño, la experiencia del cirujano ha sido poco explorada. Objetivos Evaluar la asociación entre la experiencia del cirujano y otras variables asociadas a la pérdida celular endotelial en el contexto de la facoéresis. Métodos Se analizaron registros clínicos de 198 cirugías de cataratas, evaluando el efecto de la experiencia del cirujano y otras variables asociadas: energía disipada acumulada, tipo de viscoelástico empleado, uso de azul tripán, cantidad de fluídica, tiempo de ultrasonido, energía de facoemulsificación combinada y recuento celular endotelial pre y postoperatorio. Resultados No se observaron diferencias en el conteo postoperatorio de células endoteliales. Los oftalmólogos con más de cinco años de experiencia presentaron menor uso de azul tripán pero mayor cantidad de energía disipada acumulada en cada procedimiento, mientras que los oftalmólogos con menor experiencia utilizaron mayor cantidad de fluídica. Conclusiones Aunque hubo diferencias en el manejo de algunos factores influyentes sobre la pérdida endotelial cornal según la experiencia de los oftalmólogos, no se hallaron diferencias en relación a dicha pérdida como resultado final.


Abstract Introduction Phacoeresis is the procedure through which the lens is surgically removed to treat cataracts. A corneal endothelial loss is a recognized sequel. Although several factors associated with this harm have been described, the surgeon's prior experience has been scarcely evaluated. Objectives To assess the association between the surgeon's experience and other variables associated with a corneal endothelial cell loss in the context of phacoeresis. Methods Clinical records of 198 patients undergoing cataract operations were prospectively reviewed. The experience of the surgeon and other variables were recorded, including cumulative dissipated energy, viscoelastic type, the use of trypan blue, amount of fluidics, ultrasound time, combined phacoemulsification energy, and pre- and postoperative corneal endothelial cell counts. Results No differences were observed in the postoperative corneal endothelial cell count between surgeons with more or less than five years of experience. Nevertheless, ophthalmologists with more than five years' experience used less trypan blue, but more cumulative dissipated energy in each procedure, while less experienced ophthalmologists used less fluidics. Conclusions Although there were differences in the surgical management regarding the surgeons' experience in factors known to influence corneal endothelial cell loss, no differences in endothelial cell loss were observed as an outcome.


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Postoperative Complications/pathology , Cataract Extraction/adverse effects , Phacoemulsification/adverse effects , Corneal Endothelial Cell Loss/etiology , Cataract/pathology , Cataract Extraction/methods , Prospective Studies , Phacoemulsification/methods , Ophthalmologists
7.
Rev Gastroenterol Mex ; 80(1): 21-6, 2015.
Article in English, Spanish | MEDLINE | ID: mdl-25747884

ABSTRACT

BACKGROUND: Gastric cancer is the second cause of death by cancer worldwide. Histologic classification may predict tumor biology, clinical behavior, and outcome. According to the Lauren classification, the disease is divided into 2 types, diffuse and intestinal, and the latter has a better prognosis. AIM: To determine the frequency of gastric adenocarcinoma and compare the histopathologic characteristics of intestinal and diffuse-type gastric adenocarcinoma in Mexican patients treated at a tertiary referral hospital. METHODOLOGY: A retrospective study evaluated the pathology reports of patients with gastric adenocarcinoma corresponding to the time frame of January 2003 to December 2012. Adenocarcinomas of the gastric cardia were excluded. Frequencies were expressed as percentages and the categorical variables were compared with the chi-square test. Statistical significance was set at a P<.05. RESULTS: A total of 417 cases of gastric adenocarcinoma were found, 230 (55.2%) of which were diffuse-type and 118 (28.2%) were intestinal-type. The mean age of the patients with diffuse type gastric cancer was 54.02±14.93 and 119 (51.3%) of those patients were men. The mean age of the patients with intestinal-type gastric cancer was 63.43±13.78, and 69 (62.2%) were men. Ninety-two of the diffuse-type patients were under the age of 50 years, compared with 22 of the patients with intestinal-type carcinoma. CONCLUSIONS: This is the first study on the Mexican population to analyze the differences in the histologic types of adenocarcinoma. Diffuse-type gastric carcinoma was the most frequent subtype in our study population and it is associated with worse outcome.


Subject(s)
Adenocarcinoma/pathology , Stomach Neoplasms/pathology , Adenocarcinoma/epidemiology , Adult , Aged , Female , Humans , Male , Mexico/epidemiology , Middle Aged , Retrospective Studies , Stomach Neoplasms/epidemiology
8.
Geobiology ; 12(1): 34-47, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24237661

ABSTRACT

The Iberian Pyrite Belt (IPB, southwest of Spain), the largest known massive sulfide deposit, fuels a rich chemolithotrophic microbial community in the Río Tinto area. However, the geomicrobiology of its deep subsurface is still unexplored. Herein, we report on the geochemistry and prokaryotic diversity in the subsurface (down to a depth of 166 m) of the Iberian Pyritic belt using an array of geochemical and complementary molecular ecology techniques. Using an antibody microarray, we detected polymeric biomarkers (lipoteichoic acids and peptidoglycan) from Gram-positive bacteria throughout the borehole. DNA microarray hybridization confirmed the presence of members of methane oxidizers, sulfate-reducers, metal and sulfur oxidizers, and methanogenic Euryarchaeota. DNA sequences from denitrifying and hydrogenotrophic bacteria were also identified. FISH hybridization revealed live bacterial clusters associated with microniches on mineral surfaces. These results, together with measures of the geochemical parameters in the borehole, allowed us to create a preliminary scheme of the biogeochemical processes that could be operating in the deep subsurface of the Iberian Pyrite Belt, including microbial metabolisms such as sulfate reduction, methanogenesis and anaerobic methane oxidation.


Subject(s)
Bacteria/classification , Biota , Euryarchaeota/classification , Methane/metabolism , Soil Microbiology , Soil/chemistry , Sulfates/metabolism , Bacteria/genetics , Bacteria/immunology , Bacteria/metabolism , Euryarchaeota/genetics , Euryarchaeota/immunology , Euryarchaeota/metabolism , In Situ Hybridization, Fluorescence , Microarray Analysis , Oligonucleotide Array Sequence Analysis , Oxidation-Reduction , Protein Array Analysis , Spain
9.
Mem. Inst. Invest. Cienc. Salud (Impr.) ; 10(2): 30-37, dic. 2012. tab, ilus
Article in Spanish | LILACS, BDNPAR | ID: lil-685739

ABSTRACT

Existe abundante literatura respecto a parámetros antropométricos en población indígena chilena, sin embargo, todas se centran en población infantil y mapuche. El objetivo del presente estudio es caracterizar antropométricamente a la población adulta pehuenche, comuna de Alto Biobio, y ver la influencia del mestizaje y el cambio generacional sobre estos parámetros. Este estudio corresponde a un análisis secundario de la base de datos del Proyecto “Küme Mongüen Pehuenche”, la muestra corresponde a 314 adultos (56 mestizos y 162 mujeres), las variables estudiadas corresponden a: sexo, edad, etnia, peso, talla, perímetro de cintura e índice de masa corporal (IMC). Los promedios generales corresponden a 70,66 ±11,87 Kg para peso, 1,58 ±0,08 m para talla, 91,37 ±9,41 cm para perímetro de cintura y 28,15 ±4,49 Kg/m2 para IMC. El peso y talla son significativamente mayores en hombres, pero el IMC lo es en mujeres, no se encontraron otras diferencias estadísticamente significativas por etnia o edad, existe una fuerte correlación entre perímetro de cintura e IMC. Los resultados del presente estudio dan cuenta de una población caracterizada por una estatura menor al promedio nacional, aunque superior al de población indígena chilena, con una tendencia al sobrepeso y obesidad que tiende a desaparecer en los adultos mayores, así como una gran uniformidad, sin cambios producto del mestizaje (etnia) ni el cambio generacional (edad).


Subject(s)
Anthropometry , Body Height , Body Weight , Indigenous Peoples
10.
Rev. chil. enferm. respir ; 25(1): 25-28, 2009. ilus, tab
Article in Spanish | LILACS | ID: lil-520478

ABSTRACT

The acute neurogenic pulmonary edema (NPE) is a kind of pulmonary edema that occurs as a result of a variety of injuries of the central nervous system. Usually it is underdiagnosed. It has been reported in many diseases and direct injuries of the central nervous system. We present the clinical case of a middle age women with a neurogenic pulmonary edema secondary to a epileptic seizure. We made a review of the literature with special emphasis on clinical implications and treatment.


El edema pulmonar agudo neurogénico (EPN) es un tipo de edema pulmonar que ocurre como consecuencia de una variada gama de lesiones del sistema nervioso central. Generalmente es subdiagnosticado. Se ha reportado en múltiples patologías y lesiones directas del sistema nervioso central. Presentamos el caso clínico de una mujer de mediana edad, con edema pulmonar agudo secundario a una crisis convulsiva epiléptica. Se realiza una revisión de la literatura con especial énfasis en las implicancias clínicas y tratamiento.


Subject(s)
Humans , Female , Adult , Pulmonary Edema/diagnosis , Pulmonary Edema/etiology , Pulmonary Edema/therapy , Epilepsy, Tonic-Clonic/complications , Central Nervous System Diseases/complications
12.
Biosens Bioelectron ; 22(9-10): 1926-32, 2007 Apr 15.
Article in English | MEDLINE | ID: mdl-16996729

ABSTRACT

We present a DNA biosensor based on self-assembled monolayers (SAMs) of thiol-derivatized peptide nucleic acid (PNA) molecules adsorbed on gold surfaces. Previous works have shown that PNA molecules at an optimal concentration can be self-assembled with their molecular axes normal to the surface. In such structural configuration BioSAMs of PNAs maintain their capability for recognizing complementary DNA. We describe the combined use of PM-RAIRS and synchrotron radiation XPS for the detection and spectroscopic characterization of PNA-DNA hybridization process on gold surfaces. RAIRS and XPS are powerful techniques for surface characterization and molecular detection, which do not require a fluorescence labeling of the target. We present a characterization of the spectroscopic IR and XPS features, some of them associated to the phosphate groups of the DNA backbone, as an unambiguous signature of the PNA-DNA heteroduplex formation. The N(1s) XPS core level peak after DNA hybridization is decomposed in curves components, and every component assigned to different chemical species. Therefore, the results obtained by means of two complementary structural characterization techniques encourage the use of PNA-based biosensors for the detection of DNA molecules on natural samples.


Subject(s)
Biosensing Techniques/instrumentation , DNA/analysis , Gold , Peptide Nucleic Acids , Spectrophotometry, Infrared
13.
Langmuir ; 21(21): 9510-7, 2005 Oct 11.
Article in English | MEDLINE | ID: mdl-16207029

ABSTRACT

We have characterized self-assembled monolayers (SAMs) of thiol-derivatized peptide nucleic acid (PNA) chains adsorbed on gold surfaces by using reflection absorption infrared spectroscopy (RAIRS) and X-ray photoemission spectroscopy (XPS) techniques. We have found that the molecular orientation of PNAs strongly depends on surface coverage. At low coverage, PNA chains lie flat on the surface, while at high coverage, PNA molecules realign their molecular axes with the surface normal and form SAMs without the need of co-immobilization of spacers or other adjuvant molecules. The change in the molecular orientation has been studied by infrared spectroscopy and it has been confirmed by atomic force microscopy (AFM). PNA immobilization has been followed by analyzing the N(1s) XPS core-level peak. We show that the fine line shape of the N(1s) core-level peak at optimal concentration for biosensing is due to a chemical shift. A combination of the above-mentioned techniques allow us to affirm that the structure of the SAMs is stabilized by molecule-molecule interactions through noncomplementary adjacent nucleic bases.


Subject(s)
Cysteine , Gold , Peptide Nucleic Acids/chemistry , Chromatography, High Pressure Liquid , Microscopy, Atomic Force , Models, Molecular , Molecular Conformation , Oligodeoxyribonucleotides/chemistry , Oligodeoxyribonucleotides/isolation & purification , Spectrophotometry , Spectrophotometry, Infrared
14.
Phys Rev Lett ; 93(20): 208103, 2004 Nov 12.
Article in English | MEDLINE | ID: mdl-15600975

ABSTRACT

We report on the formation of ordered self-assembled monolayers (SAMs) of single-stranded peptide nucleic acids (ssPNA). In spite of their remarkable length (7 nm) thiolated PNAs assemble standing up on gold surfaces similarly to the SAMs of short alkanethiols. SAMs of ssPNA recognize complementary nucleic acids, acting as specific biosensors that discriminate even a point mutation in target ssDNA. These results are obtained by surface characterization techniques that avoid labeling of the target molecule: x-ray photoemission, x-ray absorption and atomic force microscopy.


Subject(s)
DNA, Single-Stranded/chemistry , Peptide Nucleic Acids/chemistry , Microscopy, Atomic Force , Models, Molecular , Spectrometry, X-Ray Emission , Sulfhydryl Compounds/chemistry
16.
Ginecol Obstet Mex ; 69: 65-71, 2001 Feb.
Article in Spanish | MEDLINE | ID: mdl-11339176

ABSTRACT

OBJECTIVE: Evaluate the prognostic value of the early response of the serum estradiol FSH y LH action of leuprolide acetate during the folicular phase, used as an adjuvant to ovarian stimulation in IVF-ET. STUDY DESIGN: Were analyzed 31 cycles of stimulation in 26 patients with sterility primary and secondary. Where measured estradiol, FSH, LH on cycle day 2 to 5 for to establish the patterns of response to GnRHa administration. Were compared the response patterns in relation to the number of oocyte captured, estradiol in the day of application of hCG, number of embryos and fertilization rate using (t-student, wilcoxon test and X2). RESULTS: Where observed four distincts patterns of response of estradiol. Pattern A: 133 cycles, presented a prompt elevation of estradiol, followed by a fall on the 4th cycle's day. Pattern B: 9 cycles delayed elevation of the estradiol, followed by a fall on the 6th cycles day. Pattern C: 7 cycles showed persistent elevation of the estradiol. Pattern D: 2 cycles no response of the estradiol (canceled cycles). Was found a significative difference in the estradiol level the day of application of hCG, number of captured oocytes and number of embrions in the pattern A in relation with B and C. No significative difference were found in the fertilization rate. The seric level of FSH and LH were no predictives. We concluded that the response pattern of the estradiol to the leuprolide acetate is the good prognosis indicator of the results of IVF-ET.


Subject(s)
Estradiol/blood , Follicle Stimulating Hormone/blood , Leuprolide/therapeutic use , Luteinizing Hormone/blood , Ovulation Induction/methods , Adult , Embryo Transfer , Female , Fertilization in Vitro , Humans , Prognosis , Time Factors
17.
J Acquir Immune Defic Syndr ; 26(2): 145-50, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11242181

ABSTRACT

OBJECTIVE: Transmission of drug-resistant HIV-1 strains is increasing with widespread use of antiretroviral drugs in developed countries. This study examined the prevalence of resistant viruses in recent seroconverters in Madrid, Spain. DESIGN: HIV isolates from 30 consecutive participants with positive or indeterminate HIV antibody test results and a negative test result at a mean of 6.6 months earlier were examined for HIV drug resistance. All study subjects admitted to having very recently engaged in high-risk practices. All were therapeutically naive and were recruited between 1997 and 1999 in a referring health care facility for sexually transmitted diseases. METHODS: Population-based sequencing of the viral reverse transcriptase (RT) and protease (PR) regions derived from plasma viral RNA was performed. Phenotypic resistance was assessed by a recombinant virus assay. RESULTS: Overall prevalence of genotypes associated with reduced susceptibility was 26.7% (8 of 30 participants). Resistance mutations were seen against nucleoside analogues in 7 (23.3%), nonnucleoside reverse transcriptase inhibitors in 1 (3.3%), and protease inhibitors in 2 (6.7%). Zidovudine-resistance mutations M41L and/or T215Y were the commonest, found in 20% (6 of 30 participants). Resistance mutations to at least two antiretroviral families (multidrug-resistance) were detected in 2 (6.7%) study subjects. A median infectious dose (IC50) increase of fourfold for any drug was found in 7 patients, and in 2 was > tenfold for zidovudine (genotype M41L + T215Y) and lamivudine (genotype M184V), respectively. CONCLUSIONS: Drug-resistant HIV variants were present in over one quarter of individuals recently diagnosed as infected in Madrid, Spain. Therefore, resistance testing at baseline should be considered for the optimal design of first-line antiretroviral combinations.


Subject(s)
Drug Resistance, Microbial/genetics , HIV Infections/virology , HIV Seropositivity/virology , HIV-1/genetics , Drug Resistance, Multiple/genetics , Genotype , HIV Infections/transmission , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV Seropositivity/epidemiology , HIV Seropositivity/transmission , HIV-1/drug effects , HIV-1/growth & development , Humans , Lamivudine/pharmacology , Mutation , Phenotype , Protease Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Spain/epidemiology , Viral Load , Zidovudine/pharmacology
18.
Intervirology ; 44(6): 339-43, 2001.
Article in English | MEDLINE | ID: mdl-11805439

ABSTRACT

The emergence of resistance to antiretroviral drugs represents one of the main reasons for treatment failure in HIV-infected persons. Resistance to multiple nucleoside analogues may result from rearrangements in the HIV pol gene, in particular one insertion of two amino acids at position 69. Herein, we examined the prevalence of this resistant genotype and its genetic heterogeneity in a group of 475 healthy pretreated HIV-positive subjects in Spain. Only 4 (0.8%) carried the codon 69 insertion. It was always found coupled to the T69S mutation. The extra amino acids were S-S in 2 subjects and S-G in the other 2. The presence of the insert was seen only in subjects previously exposed to AZT monotherapy for at least 6 months.


Subject(s)
Genetic Heterogeneity , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/enzymology , Anti-HIV Agents/therapeutic use , Didanosine/therapeutic use , Drug Resistance, Viral , Genetic Heterogeneity/drug effects , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/drug effects , HIV-1/genetics , Humans , Lamivudine/therapeutic use , Male , Mutagenesis , Prevalence , Reverse Transcriptase Inhibitors/therapeutic use , Spain/epidemiology , Zidovudine/therapeutic use
19.
EMBO J ; 19(21): 5752-61, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11060026

ABSTRACT

The 3'-azido-3'-deoxythymidine (AZT)-resistant pheno type of a heavily mutated human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) carrying a dipeptide (Ser-Ser) insertion between codons 69 and 70 as well as other mutations related to resistance to RT inhibitors has been studied. Recombinant virus carrying this variant RT (termed SS RT) showed reduced susceptibility to all nucleoside RT inhibitors in clinical use, particularly to AZT. In the presence of ATP, recombinant SS RT had an increased ability to remove the 3'-terminal nucleotide from AZT- terminated primers and extend the unblocked primer, compared with wild-type HIV-1 RT (BH10 isolate). Insertion of two serines in the sequence context of BH10 RT did not affect the ATP-dependent phosphorolytic activity of the enzyme, and had no influence in resistance to RT inhibitors. However, SS RT mutants lacking the dipeptide insertion or bearing a four-serine insertion showed reduced ATP-dependent phosphorolytic activity that correlated with increased AZT sensitivity, as determined using a recombinant virus assay. Therefore, the insertion appears to be critical to enhance AZT resistance in the sequence context of multidrug-resistant HIV-1 RT.


Subject(s)
HIV Reverse Transcriptase/chemistry , HIV Reverse Transcriptase/genetics , Reverse Transcriptase Inhibitors/pharmacology , Zidovudine/pharmacology , Amino Acid Sequence , Base Sequence , Codon/genetics , DNA Primers/genetics , Drug Resistance, Microbial/genetics , Genetic Variation , HIV Reverse Transcriptase/metabolism , HIV-1/enzymology , HIV-1/genetics , HIV-1/isolation & purification , Humans , Kinetics , Molecular Sequence Data , Mutation , Phenotype
20.
Nucleic Acids Res ; 28(22): 4497-505, 2000 Nov 15.
Article in English | MEDLINE | ID: mdl-11071938

ABSTRACT

The yeast ribosomal GTPase associated center is made of parts of the 26S rRNA domains II and VI, and a number of proteins including P0, P1alpha, P1beta, P2alpha, P2beta and L12. Mapping of the rRNA neighborhood of the proteins was performed by footprinting in ribosomes from yeast strains lacking different GTPase components. The absence of protein P0 dramatically increases the sensitivity of the defective ribosome to degradation hampering the RNA footprinting. In ribosomes lacking the P1/P2 complex, protection of a number of nucleotides is detected around positions 840, 880, 1100, 1220-1280 and 1350 in domain II as well as in several positions in the domain VI alpha-sarcin region. The protection pattern resembles the one reported for the interaction of elongation factors in bacterial systems. The results exclude a direct interaction of these proteins with the rRNA and are compatible with an increase in the ribosome affinity for EF-2 in the absence of the acidic P proteins. Interestingly, a sordarin derivative inhibitor of EF-2 causes an opposite effect, increasing the reactivity in positions protected by the absence of P1/P2. Similarly, a deficiency in protein L12 exposes nucleotides G1235, G1242, A1262, A1269, A1270 and A1272 to chemical modification, thus situating the protein binding site in the most conserved part of the 26S rRNA, equivalent to the bacterial protein L11 binding site.


Subject(s)
GTP Phosphohydrolases/metabolism , RNA, Ribosomal/metabolism , Ribosomal Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Antifungal Agents/metabolism , Antifungal Agents/pharmacology , Base Sequence , Binding Sites/genetics , Binding, Competitive , Endoribonucleases/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Indenes , Molecular Sequence Data , Molecular Structure , Mutagenesis , Mutation , Nucleic Acid Conformation/drug effects , Protein Binding , Protein Synthesis Inhibitors/metabolism , RNA, Ribosomal/chemistry , RNA, Ribosomal/genetics , Ribosomal Proteins/genetics , Ribosomes/chemistry , Ribosomes/genetics , Ribosomes/metabolism , Saccharomyces cerevisiae/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...