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1.
Addict Behav ; 36(8): 874-7, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21481543

ABSTRACT

BACKGROUND: Benzodiazepine (BZD) dependence is a condition generally circumscribed to a therapeutic framework. Up to 44% of chronic users become dependent. The widespread use of BZD in psychiatry requires the evaluation of psychometric properties of self-reported instruments to characterize this phenomenon. OBJECTIVE: To examine the reliability, construct and criterion validity of the Benzodiazepine Dependence Questionnaire (BDEPQ) in Mexican psychiatric patients. METHOD: Patients were included if they met DSM-IV criteria for any Axis I disorder and were BZD users. A total of 150 patients were recruited. Diagnoses were made with the SCID-I and BZD dependence was determined with an adaptation of the substance dependence section of the SCID-I. All patients answered the BDEPQ. RESULTS: Almost half of the patients met criteria for BZD dependence. The BDEPQ showed adequate factor loadings with strong alpha values for the subscales and total score. A cut-off value of 23 reached the most stable sensitivity and specificity values. CONCLUSIONS: Psychometric properties of the BDEPQ in Mexican psychiatric patients support its utility as a tool for the clinical work and research as it shows to be a useful instrument for the early recognition of BZD dependence in clinical populations.


Subject(s)
Anti-Anxiety Agents/adverse effects , Benzodiazepines/adverse effects , Mental Disorders/drug therapy , Substance-Related Disorders/diagnosis , Surveys and Questionnaires/standards , Adult , Aged , Anti-Anxiety Agents/therapeutic use , Benzodiazepines/therapeutic use , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Mexico , Middle Aged , Psychiatric Status Rating Scales , Psychometrics , Reproducibility of Results , Sensitivity and Specificity , Substance-Related Disorders/complications , Young Adult
2.
Rev. chil. infectol ; 26(5): 413-419, oct. 2009. tab
Article in Spanish | LILACS | ID: lil-532131

ABSTRACT

Introduction: In the past few years, an increase in methicillin resistant-not multiresistant Staphylococcus aureus was observed in Uruguay among children with community acquired infections. Recommendations for empiric antibiotic treatment required adjustments and new national guidelines were recommended in July 2004. Adherence to these guidelines was indirectly performed by monitoring antibiotic consumption and antimicrobial susceptibility patterns in Uruguay. Objective: To describe and compare antibiotic consumption and antimicrobial susceptibility of Staphylococcus aureus in a Pediatric Hospital of the Centro Hospitalario Pereira Rossell (PH-CHPR) between 2001 and 2006. Methods: Antibiotic consumption in hospitalized children was calculated using the Defined Daily Dose per 100 bed-days (DDD/100). Reference valúes were obtained from the World Health Organization Collaborating Center for Drug Statistics Methodology of. Consumption. Data were obtained using the WinPharma programme of the Pharmacy Department of CHPR. The fraction of annual occupancy of hospital beds was obtained from the Statistic División of CHPR. Antibiotic consumption was evaluated netween 2001 and 2006 and expressed as DDD/100 and percent change. Antimicrobial susceptibility was evaluated using CHPR's Microbiology Laboratory data during the same time period. Results: After 2003 a significant increase in consumption of clindamycin, ceftriaxone, trimethoprim-sulphamethoxazole, cefuroxime, vancomycin and gentamycin was observed, except for cephradine. Consumption of clindamycin, ceftriaxone and trimethoprim-sulphamethoxazole showed the highest increase (6.15 percent; 1.44 percent and 1.17 percent respectively). Detection of Staphylococcus aureus increased significantly mostly from skin and soft tissue infections. Oxacillin susceptibility of S aureus strains obtained from different sites had a significant and persistent decrease after 2003 (from 81 percent during year ...


Introducción: En Uruguay, Staphylococcus aureus resistente a meticilina no multi-resistente se instaló como patógeno en las infecciones comunitarias del niño. Objetivo: Describir la evolución de la susceptibilidad in vitro de S. aureus y su relación con el consumo de antimicrobianos en el Centro Hospitalario Pereira Rossell (CHPR) entre 2001-2006. Metodología: Se estimó el consumo de antimicrobianos mediante el cálculo de la Dosis Diaria Definida por 100 camas-día. Los valores de referencia fueron obtenidos del Collaborating Centre for Drug Statistics Methodology of World Health Organiza-tion. Los datos de consumo fueron extraídos del programa WinFarma del Dpto de Farmacia de CHPR. El porcentaje de ocupación de camas/año se obtuvo de la División de Estadísticas del CHPR. Se analizó la susceptibilidad antimicrobiana de S. aureus de aislados de piel, tejidos blandos y sitios normalmente estériles. Se analizó la evolución del consumo y la susceptibilidad in vitro en el período 2001-2006. Resultados: Desde el año 2003, el consumo de clindamicina, ceftriaxona y cotrimoxazol aumentó y la susceptibilidad a oxacilina disminuyó significativamente. Entre 2004 y 2006 el "efecto D" disminuyó su frecuencia desde 28 a 21 por ciento. No se observaron diferencias en el patrón de susceptibilidad antimicrobiana en función del sitio de aislamiento. Conclusiones: Staphylococcus aureus resistente a meticilina no multi-resistente se ha introducido en forma significativa como un patógeno causante de infecciones en la comunidad en niños uruguayos. La vigilancia del consumo de antimicrobianos y de la epidemiología local es indispensable para actualizar las guías de antibioterapia empírica.


Subject(s)
Humans , Anti-Bacterial Agents/administration & dosage , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Microbial Sensitivity Tests , Staphylococcal Infections/microbiology , Uruguay
3.
Arch Cardiol Mex ; 75(1): 49-54, 2005.
Article in Spanish | MEDLINE | ID: mdl-15909740

ABSTRACT

AIM: To review the results of myocardial perfusion during rest and post-pharmacological stress induced by dipyridamole and analyze the SPECT images in patients with complete left bundle branch block LBBB, comparing the results in the presence of a normal coronary angiographic study and with critical coronary obstructions. METHODS: Results from 50 studies of myocardial perfusion of patients with complete block of the LBBB were reviewed and segmental perfusion was analyzed comparing these results with those obtained with those from the diagnostic coronariography. RESULTS: From the 15 studied patients, divided in two groups, 9 with angiographically normal coronaries and 6 with significant coronary lesions, it was not possible to establish a typical perfusion pattern due to the small size of the sample, revealing that the perfusion defects cannot be explained only by the electrocardiographic alterations since other factors participate, such as left ventricular telediastolic hypertension on the interventricular septum as a consequence of the loss of synchrony in ventricular contraction. CONCLUSIONS: Regional myocardial perfusion in patients with complete block of the LBBB is altered in 95% of the cases without relation with the presence of significant coronary alterations.


Subject(s)
Bundle of His , Dipyridamole , Heart Block/diagnostic imaging , Radiopharmaceuticals , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Vasodilator Agents , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Perfusion
4.
Arch. cardiol. Méx ; 75(1): 49-54, ene.-mar. 2005. graf
Article in Spanish | LILACS | ID: lil-631871

ABSTRACT

Propósito del trabajo: Revisar los resultados de perfusión miocárdica en reposo y post estrés farmacológico con dipiridamol e imágenes SPECT en pacientes con Bloqueo Completo de Rama Izquierda del Haz de His y comprar resultados cuando se tienen coronarias angiográficamente normales y con obstrucciones coronarias críticas. Método: Se revisaron los resultados de 50 estudios de perfusión miocárdica de los pacientes con Bloqueo de Rama Izquierda del Haz de His y se analizó la perfusión segmentaria comparándola con la coronariografía diagnóstica. Resultados: De los 15 pacientes estudiados, divididos en 2 grupos, 9 con coronarias angiográficamente normales y 6 con lesiones coronarias significativas, no es posible establecer un patrón de perfusión típico para cada entidad por el pequeño tamaño de la muestra y pone de manifiesto que los defectos de perfusión no se explican únicamente por las alteraciones electrocardiográficas pues influyen factores como la hipertensión telediastólica ventricular izquierda sobre el septum interventricular como consecuencia de la pérdida de sincronía en la contracción ventricular. Conclusiones: La perfusión miocárdica regional en pacientes con BRIHH está alterada en el 95% de los casos sin relación a la presencia de lesiones coronarias significativas.


AIM: To review the results of myocardial perfusion during rest and post-pharmacological stress induced by dipyridamole and analyze the SPECT images in patients with complete left bundle branch block LBBB, comparing the results in the presence of a normal coronary angiographic study and with critical coronary obstructions. Methods: Results from 50 studies of myocardial perfusion of patients with complete block of the LBBB were reviewed and segmental perfusion was analyzed comparing these results with those obtained with those from the diagnostic coronariography. Results: From the 15 studied patients, divided in two groups, 9 with angiographically normal coronaries and 6 with significant coronary lesions, it was not possible to establish a typical perfusion pattern due to the small size of the sample, revealing that the perfusion defects cannot be explained only by the electrocardiographic alterations since other factors participate, such as left ventricular telediastolic hypertension on the interventricular septum as a consequence of the loss of synchrony in ventricular contraction. Conclusions: Regional myocardial perfusion in patients with complete block of the LBBB is altered in 95% of the cases without relation with the presence of significant coronary alterations.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bundle of His , Dipyridamole , Heart Block , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon , Vasodilator Agents , Perfusion
5.
Biochemistry ; 34(16): 5351-63, 1995 Apr 25.
Article in English | MEDLINE | ID: mdl-7537090

ABSTRACT

When the single-stranded RNA genome of HIV-1 is copied into double-stranded DNA, the viral enzyme reverse transcriptase (RT) catalyzes the addition of approximately 20,000 nucleotides; however, the precise mechanism of nucleotide addition is unknown. In this study, we attempt to integrate the genetic data and biochemical mechanism of DNA polymerization with the structure of HIV-1 RT complexed with a dsDNA template-primer. The first step of polymerization involves the physical association of a polymerase with its nucleic acid substrate. A comparison of the structures of HIV-1 RT in the presence and absence of DNA indicates that the tip of the p66 thumb moves approximately 30 A upon DNA binding. This conformational change permits numerous interactions between residues of alpha-helices H and I in the thumb subdomain and the DNA. Measurements of DNA binding affinity for nucleic acids with double-stranded DNAs that have an increasing number of bases in the template overhang and molecular modeling suggest that portions of beta 3 and beta 4 within the fingers subdomain bind single-stranded regions of the template. Measurements of nucleotide incorporation efficiency (kcat/Km) show that the binding and incorporation of the next complementary nucleotide are not dependent on the length of the template overhang. Molecular modeling of an incoming nucleotide triphosphate (dTTP), based in part on the position of mercury atoms in a RT/DNA/Hg-UTP/Fab structure, suggests that portions of secondary structural elements alpha C-beta 6, alpha E, beta 11b, and beta 9-beta 10 determine the topology of the dNTP-binding site. These results also suggest that nucleotide incorporation is accompanied by a protein conformational change that positions the dNTP for nucleophilic attack. Nucleophilic attack by the oxygen atom of the 3'-OH group of the primer strand could be metal-mediated, and Asp185 may be directly involved in stabilizing the transition state. The translocation step may be characterized by rotational as well as translational motions of HIV-1 RT relative to the DNA double helix. Some of the energy required for translocation could be provided by dNTP hydrolysis and could be coupled with conformational changes within the nucleic acid. A structural comparison of HIV-1 RT, Klenow fragment, and T7 RNA polymerase identified regions within T7 RNA polymerase which are not present in the other two polymerases that might help this polymerase to remain bound with nucleic acids and contribute to the ability of the T7 RNA polymerase to polymerize processively.


Subject(s)
DNA Replication , HIV-1/enzymology , Protein Conformation , RNA-Directed DNA Polymerase/chemistry , RNA-Directed DNA Polymerase/metabolism , Amino Acid Sequence , Base Sequence , Binding Sites , DNA Primers , DNA, Viral/biosynthesis , DNA, Viral/chemistry , Genome, Viral , HIV Reverse Transcriptase , HIV-1/genetics , Kinetics , Models, Molecular , Molecular Sequence Data , Nucleic Acid Conformation , Protein Structure, Secondary , RNA, Viral/genetics , Templates, Genetic
6.
J Mol Biol ; 243(3): 369-87, 1994 Oct 28.
Article in English | MEDLINE | ID: mdl-7525966

ABSTRACT

The locations of HIV-1 RT nucleoside and non-nucleoside inhibitor-binding sites and inhibitor-resistance mutations are analyzed in the context of the three-dimensional structure of the enzyme and implications for mechanisms of drug inhibition and resistance are discussed. In order to help identify residues that may play a role in inhibitor binding, solvent accessibilities of amino acids that comprise the inhibitor-binding sites in the structure of HIV-1 RT complexed with a dsDNA template-primer are analyzed. While some mutations that cause resistance to nucleoside analogs, such as AZT, ddI, and ddC, are located near enough to the dNTP-binding site to directly interfere with binding of nucleoside analogs, many are located away from the dNTP-binding site and more likely confer resistance by other mechanisms. Many of the latter mutations are located on the surface of the DNA-binding cleft and may lead to altered template-primer positioning or conformation, causing a distortion of the geometry of the polymerase active site and consequent discrimination between normal and altered dNTP substrates. Other nucleoside analog-resistance mutations located on the periphery of the dNTP-binding site may exert their effects via altered interactions with dNTP-binding site residues. The structure of the hydrophobic region in HIV-1 RT that binds non-nucleoside inhibitors, for example, nevirapine and TIBO, has been analyzed in the absence of bound ligand. The pocket that is present when non-nucleoside inhibitors are bound is not observed in the inhibitor-free structure of HIV-1 RT with dsDNA. In particular it is filled by Tyr181 and Tyr188, suggesting that the pocket is formed primarily by rotation of these large aromatic side-chains. Existing biochemical data, taken together with the three-dimensional structure of HIV-1 RT, makes it possible to propose potential mechanisms of inhibition by non-nucleoside inhibitors. One such mechanism is local distortion of HIV-1 RT structural elements thought to participate in catalysis: the beta 9-beta 10 hairpin (which contains polymerase active site residues) and the beta 12-beta 13 hairpin ("primer grip"). An alternative possibility is restricted mobility of the p66 thumb subdomain, which is supported by the observation that structural elements of the non-nucleoside inhibitor-binding pocket may act as a "hinge" for the thumb.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Antiviral Agents/pharmacology , HIV-1/enzymology , Protein Conformation , RNA-Directed DNA Polymerase/chemistry , Reverse Transcriptase Inhibitors , Amino Acid Sequence , Binding Sites , Drug Resistance, Microbial/genetics , HIV Reverse Transcriptase , Humans , Models, Molecular , Molecular Sequence Data , Mutation/physiology
7.
J Mol Recognit ; 7(2): 157-61, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7530020

ABSTRACT

The p66/p51 human immunodeficiency virus type 1 reverse transcriptase is a heterodimer with identical N-terminal amino acid sequences. The enzyme contains two polymerization domains and one RNase H domain, which is located at the C-terminus of the p66 subunit. Both polymerization domains fold into four individual subdomains that are not arranged in a similar fashion, forming an unusually asymmetric dimer. The complexity of the RT p66/p51 heterodimer structure is simplified using solvent-accessibility surface areas to describe the buried surface area of contact among the different subdomains. In addition, the RT/DNA contacts in the recently published RT/DNA/Fab structure [Jacobo-Molina et al., Proc. Natl Acad. Sci. USA, 90, 6320-6324 (1993)] are described using the same approach. Finally, the RT/DNA complex is compared with other dimeric DNA-binding proteins. It was found that the size of the protein and the extent of the dimer interface were not directly related to the extent of contact between the protein and the DNA. Furthermore, RT, the only protein that is not a sequence-specific DNA binding protein in this analysis, had the largest surface of interaction with the nucleic acid.


Subject(s)
DNA/metabolism , HIV-1/enzymology , RNA-Directed DNA Polymerase/chemistry , RNA-Directed DNA Polymerase/metabolism , Binding Sites , DNA Primers , HIV Reverse Transcriptase , Humans , In Vitro Techniques , Macromolecular Substances , Models, Molecular , Molecular Structure , Molecular Weight , Protein Conformation , Substrate Specificity
8.
Proc Natl Acad Sci U S A ; 91(11): 4882-6, 1994 May 24.
Article in English | MEDLINE | ID: mdl-7515182

ABSTRACT

Analysis of the three-dimensional structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) complexed with double-stranded DNA indicates that while many nucleoside-resistance mutations are not at the putative dNTP binding site, several are in positions to interact with the template-primer. Wild-type HIV-1 RT and two nucleoside-resistant variants, Leu74-->Val and Glu89-->Gly, have been analyzed to determine the basis of resistance. The ability of the wild-type enzyme to incorporate, or reject, a 2',3'-dideoxynucleoside triphosphate (ddNTP) is strongly affected by interactions that take place between the enzyme and the extended template strand 3-6 nt beyond the polymerase active site. Inspection of a model of the enzyme with an extended template suggests that this interaction involves the fingers subdomain of the p66 subunit in the vicinity of Leu74. These data provide direct evidence that the fingers subdomain of the p66 subunit of HIV-1 RT interacts with the template strand. The wild-type enzyme is resistant to ddITP if the template extension is 3 nt or less and becomes sensitive only when the template extends more than 3 or 4 nt beyond the end of the primer strand. However, the mutant enzymes are resistant with both short and long template extensions. Taken together with the three-dimensional structure of HIV-1 RT in complex with double-stranded DNA, these data suggest that resistance to the dideoxynucleotide inhibitors results from a repositioning or change in the conformation of the template-primer that alters the ability of the enzyme to select or reject an incoming dNTP.


Subject(s)
Dideoxynucleosides/pharmacology , RNA-Directed DNA Polymerase/drug effects , Base Sequence , DNA, Viral , Drug Resistance, Microbial/genetics , HIV Reverse Transcriptase , Molecular Sequence Data , Protein Conformation , RNA-Directed DNA Polymerase/chemistry , RNA-Directed DNA Polymerase/genetics , Templates, Genetic
9.
Proc Natl Acad Sci U S A ; 90(13): 6320-4, 1993 Jul 01.
Article in English | MEDLINE | ID: mdl-7687065

ABSTRACT

The crystal structure of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) heterodimer (p66/p51), a 19-base/18-base double-stranded DNA template-primer, and a monoclonal antibody Fab fragment has been determined at 3.0 A resolution. The four individual subdomains of RT that make up the polymerase domains of p66 and p51 are named fingers, palm, thumb, and connection [Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A. & Steitz, T. A. (1992) Science 256, 1783-1790]. The overall folding of the subdomains is similar in p66 and p51 but the spatial arrangements of the subdomains are dramatically different. The template-primer has A-form and B-form regions separated by a significant bend (40-45 degrees). The most numerous nucleic acid interactions with protein occur primarily along the sugar-phosphate backbone of the DNA and involve amino acid residues of the palm, thumb, and fingers of p66. Highly conserved regions are located in the p66 palm near the polymerase active site. These structural elements, together with two alpha-helices of the thumb of p66, act as a clamp to position the template-primer relative to the polymerase active site. The 3'-hydroxyl of the primer terminus is close to the catalytically essential Asp-110, Asp-185, and Asp-186 residues at the active site and is in a position for nucleophilic attack on the alpha-phosphate of an incoming nucleoside triphosphate. The structure of the HIV-1 RT/DNA/Fab complex should aid our understanding of general mechanisms of nucleic acid polymerization. AIDS therapies may be enhanced by a fuller understanding of drug inhibition and resistance emerging from these studies.


Subject(s)
DNA/chemistry , RNA-Directed DNA Polymerase/chemistry , Base Sequence , Computer Graphics , Crystallization , HIV Reverse Transcriptase , Models, Molecular , Molecular Sequence Data , Nucleic Acid Conformation , Protein Conformation , Protein Folding , Protein Structure, Secondary , Ribonuclease H/metabolism , X-Ray Diffraction
10.
J Mol Biol ; 230(3): 857-67, 1993 Apr 05.
Article in English | MEDLINE | ID: mdl-8386772

ABSTRACT

SCH 38057 (1-[6-(2-chloro-4-methoxyphenoxy)-hexyl]imidazole hydrochloride) is a new, water-soluble antiviral compound that has inhibitory activities against a number of picornavirus infections. The structure of the human rhinovirus 14 (HRV14) complex with SCH 38057 was determined at 3.0 A resolution by single-crystal diffraction techniques using synchrotron X-radiation. SCH 38057 was found to bind at the innermost end of the hydrophobic pocket within the capsid protein VP1, a locus of binding of other antipicornaviral agents; however, the complex differs from previously reported complexes in two important aspects. It leaves a considerable volume near the entrance to the binding pocket unoccupied. In addition, the alterations in the conformation of the VP1 polypeptide are similar to, but more extensive than those observed in HRV14 complexes with other antiviral agents. Although only 9 amino acids of VP1 have close contacts with the SCH 38057 molecule (within 3.6 A), at least 36 amino acids from both VP1 and VP3 have significantly altered conformations (C alpha movement > 0.5 A versus native). The structures of complexes of HRV14 with SCH 38057 and WIN 51711 are compared. Aromatic ring interactions between picornavirus capsid residues and antiviral inhibitors are proposed to be among the major determinants for positioning of these compounds.


Subject(s)
Antiviral Agents/chemistry , Imidazoles/chemistry , Rhinovirus/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Capsid/chemistry , Capsid/metabolism , Computer Simulation , Electrons , Humans , Imidazoles/metabolism , Models, Molecular , Molecular Structure , Protein Conformation , Rhinovirus/drug effects , Rhinovirus/metabolism , X-Ray Diffraction
11.
Nature ; 357(6373): 85-9, 1992 May 07.
Article in English | MEDLINE | ID: mdl-1374166

ABSTRACT

AIDS, caused by human immunodeficiency virus (HIV), is one of the world's most serious health problems, with current protocols being inadequate for either prevention or successful long-term treatment. In retroviruses such as HIV, the enzyme reverse transcriptase copies the single-stranded RNA genome into double-stranded DNA that is then integrated into the chromosomes of infected cells. Reverse transcriptase is the target of the most widely used treatments for AIDS, 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), but resistant strains of HIV-1 arise in patients after a relatively short time. There are several nonnucleoside inhibitors of HIV-1 reverse transcriptase, but resistance to such agents also develops rapidly. We report here the structure at 7 A resolution of a ternary complex of the HIV-1 reverse transcriptase heterodimer, a monoclonal antibody Fab fragment, and a duplex DNA template-primer. The double-stranded DNA binds in a groove on the surface of the enzyme. The electron density near one end of the DNA matches well with the known structure of the HIV-1 reverse transcriptase RNase H domain. At the opposite end of the DNA, a mercurated derivative of UTP has been localized by difference Fourier methods, allowing tentative identification of the polymerase nucleoside triphosphate binding site. We also determined the structure of the reverse transcriptase/Fab complex in the absence of template-primer to compare the bound and free forms of the enzyme. The presence of DNA correlates with movement of protein electron density in the vicinity of the putative template-primer binding groove. These results have important implications for developing improved inhibitors of reverse transcriptase for the treatment of AIDS.


Subject(s)
DNA-Binding Proteins/chemistry , HIV-1/enzymology , RNA-Directed DNA Polymerase/chemistry , Base Sequence , Binding Sites , Crystallization , DNA/metabolism , HIV Reverse Transcriptase , Immunoglobulin Fab Fragments , Methylmercury Compounds , Models, Molecular , Molecular Sequence Data , Organomercury Compounds , Protein Conformation , Structure-Activity Relationship , Uridine Triphosphate/analogs & derivatives , X-Ray Diffraction
12.
Acta Crystallogr B ; 48 ( Pt 2): 217-27, 1992 Apr 01.
Article in English | MEDLINE | ID: mdl-1515111

ABSTRACT

1-Methyluracil (1-methyl-2,4-dioxopyrimidine), C5H6-N2O2, M(r) = 126.12, orthorhombic, Ibam, a = 13.188 (6), b = 13.175 (5), c = 6.214 (3) A, V = 1079.7 (8) A3, Z = 8, Dx = 1.552 g cm-3, lambda (Mo K alpha) = 0.7107 A, mu = 1.317 cm-1, F(000) = 528, T = 123 K, R(F2) = 0.068 for 2996 reflections with sin theta/lambda less than 1.08 A-1. The electronic charge-density distribution has been analyzed in terms of Stewart's rigid pseudoatom model, using restricted Slater radial functions and angular multipole terms extending to octapoles for C, N and O, and quadrupoles for H pseudoatoms. Three different structure refinements have been carried out based on two X-ray diffraction data sets from different crystals collected at temperatures differing by about 20 K. The molecular dipole moment is 6.4 (27) D. Maps of the electrostatic potential for a molecule isolated from the crystal show that atoms O2 and O4 confer overall electro-negativity on one side of the molecule while the CH groups and the C1 methyl group confer electropositivity on the other. For the centrosymmetric hydrogen-bonded dimer (N3-H3...O4'; H...O distances 1.77 A) the electrostatic potential shows electropositive bridges between the molecules. These features are lacking for the C-H...O interactions (distances H6...O2, 2.37; H11...O4, 2.34 A). The electron density and its Laplacian have been determined at the intramolecular bond-critical points and also for the intermolecular H...O interactions. Values for the former are characteristic of covalent bonds. Values of the electron density and Laplacian for the C-H...O interactions are very small and have little or no significance in terms of their e.s.d.'s. The electrostatic energy of interaction for the N-H...O hydrogen-bonded dimer is -10 (12) kJ mol-1. The attractive electrostatic energy increases to -67 (33) kJ mol-1 for a centrosymmetric planar tetramer in which the C-H...O interactions are also formed.


Subject(s)
Uracil/analogs & derivatives , Calorimetry , Electrochemistry , Molecular Conformation , Uracil/chemistry , X-Ray Diffraction
13.
Proc Natl Acad Sci U S A ; 88(23): 10895-9, 1991 Dec 01.
Article in English | MEDLINE | ID: mdl-1720554

ABSTRACT

Two crystal forms of complexes have been grown that contain human immunodeficiency virus type 1 reverse transcriptase and a monoclonal antibody Fab fragment. One of the crystal forms (form II, space group P3112, a = 168.7 A, c = 220.3 A) diffracts x-rays to 3.5-A resolution and appears suitable for moderate-resolution structure determination. The form II crystals have the unusual property that their maximum resolution of diffraction and resistance to radiation damage are enhanced by either crystallization in the presence of or soaking with double-stranded DNA primer-template mimics. These crystals may permit structural studies of catalytically relevant complexes and eventually enable us to experimentally observe successive steps in the reverse transcription process.


Subject(s)
Antibodies, Monoclonal , HIV-1/enzymology , Immunoglobulin Fab Fragments , Oligodeoxyribonucleotides/chemistry , RNA-Directed DNA Polymerase/chemistry , Antibodies, Monoclonal/isolation & purification , Base Sequence , Escherichia coli/genetics , Immunoglobulin Fab Fragments/isolation & purification , Molecular Sequence Data , Oligodeoxyribonucleotides/metabolism , Protein Binding , RNA-Directed DNA Polymerase/immunology , RNA-Directed DNA Polymerase/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , X-Ray Diffraction/methods
14.
Mycopathologia ; 93(1): 9-12, 1986 Jan.
Article in English | MEDLINE | ID: mdl-3485770

ABSTRACT

A mycotic keratitis case which was caused by Curvularia lunata var. aeria in a patient with an injury in the eye is described. The diagnosis was based on the mycologic analysis of several samples taken from the ulcer of cornea. In vitro tests of the sensitivity of the isolated species to several antifungal drugs were made. The results were related to the response in vivo to the treatment.


Subject(s)
Cornea/pathology , Keratitis/microbiology , Mitosporic Fungi/isolation & purification , Mycoses/microbiology , Aged , Eye Injuries/complications , Humans , Keratitis/pathology , Male , Miconazole/pharmacology , Mitosporic Fungi/drug effects , Mycoses/pathology , Natamycin/pharmacology , Nystatin/pharmacology
15.
Carbohydr Res ; 137: 21-30, 1985 Mar 29.
Article in English | MEDLINE | ID: mdl-3986848

ABSTRACT

The crystal structure of alpha,alpha-trehalose (alpha-D-glucopyranosyl alpha-D-glucopyranoside), C12H22O11, is monoclinic, P2(1), Z = 2, with unit cell dimensions at -150 degrees [20 degrees] of a = 12.971(5) [13.003(5)], b = 8.229(4) [8.252(4)], c = 6.789(3) [6.799(3)] A, beta = 98.12(4) [98.33(4)]. The crystal structure was solved by using MULTAN, and refined to R = 0.059, Rw = 0.048 for 1564 intensities, measured with MoK alpha radiation. The molecular structure is very similar to that observed in the dihydrate crystals. It has approximate C2 symmetry. Both glucopyranosyl groups are in the 4C1 conformation. The linkage torsion angles, O-5-C-1-O-1-C-1, are +60.8 degrees and +60.1 degrees. The primary alcohol groups are oriented gauche/gauche and gauche/trans, as in the dihydrate structure. A comparison of the cross-polarization, magic-angle-spinning (c.p.-m.a.s.), 13C-n.m.r. spectra for powders of the crystalline anhydrous and dihydrate forms shows differences in resonances assigned to C-1 and C-4 that would not be anticipated from the results of the crystal-structure analyses.


Subject(s)
Disaccharides , Trehalose , Crystallization , Freezing , Magnetic Resonance Spectroscopy , Models, Molecular
16.
Quad Sclavo Diagn ; 15 Suppl 1: 793-802, 1979 Jun.
Article in Italian | MEDLINE | ID: mdl-400258

ABSTRACT

The distribution of the O-groups of E. coli isolated in rivers (Arno, Serchio) and other surface waters is compared with the distribution of those isolated in urinary tract infections. The "chi square" test indicates a good correlation between the observed and expected frequencies in these two distributions, for all the O-groups, but six. Two of these (08 and 019) are significantly more frequent in the waters than in urinary isolates and four (02, 01, 018 and 075) viceversa. The O-group 6 its the most frequent in both, however the observed frequency in urine is greater than the expected one as regards the frequency in water isolates. These results would confirm, with the mentioned exceptions, the prevalence theory. The different patterns of resistance to the antibiotics suggest us to research a possible correlation between the antibotic resistance and the most frequent isolated O-groups. But no evidence of such correlation is demonstrated.


Subject(s)
Escherichia coli Infections/microbiology , Escherichia coli/isolation & purification , Urinary Tract Infections/microbiology , Water Microbiology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Escherichia coli/classification , Italy , Serotyping , Species Specificity
17.
Radiol Med ; 64(11): 1267-73, 1978 Nov.
Article in Italian | MEDLINE | ID: mdl-217041

ABSTRACT

A case of cholangiocarcinoma observed in a woman of 38 following carotidographic examination with Thorotrast is described: the presence of radioactivity was also demonstrated by gamma spectrometry. The high mean dose absorbed by the liver (estimated at about 3,000 rad) together with the high relative biological effectiveness of the alpha contribution and the time lapse justify the hypothesis that the neoplasia was caused by irradiation.


Subject(s)
Adenoma, Bile Duct/etiology , Bile Duct Neoplasms/etiology , Brain Neoplasms/diagnostic imaging , Cerebral Angiography/adverse effects , Liver Diseases/etiology , Neoplasms, Radiation-Induced , Splenic Diseases/etiology , Thorium Dioxide/adverse effects , Atrophy , Female , Glioma/diagnostic imaging , Humans , Middle Aged
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