PubMed Health⌕ Search

Biomedical subjects

J Badger

Publications and source records attributed to J Badger.

30 records · Page 2Linked to original sources
PubMed1991

Water structure in cubic insulin crystals.

The electron density distribution of the solvent in the cubic insulin crystal structure, which occupies 65% of the volume, has been mapped from 1.7-A resolution diffraction data by an iterative difference Fourier method, using the previously determined protein structure as the refinement restraint. Starting with phases from the protein and a flat solvent model, the difference map calculated from the data was added outside the protein envelope, and the modified map was then used to recalculate phases for the iterative refinement. Tests of the method with model data, with the experimental data and a variant protein model, and by carrying out a partial refinement of the solvent map demonstrate that the refinement algorithm produces reliable values for the solvent density within the noise level of the data. Fluctuations in density are observed throughout the solvent space, demonstrating that nonrandom arrangements of the water molecules extend several layers from the well-ordered hydration shell in contact with the protein surface. Such ordering may account for the hydration force opposing close approach of hydrophilic surfaces and other long-range water-dependent interactions in living structures.

Fourier Analysis↗
PubMed1991

Psychiatric morbidity following implantation of the automatic implantable cardioverter defibrillator.

The automatic implantable cardioverter defibrillator (AICD) has found a place in the treatment of sustained ventricular tachycardia and in survivors of sudden arrhythmic death. However, little is known about the psychological impact of this device on patients and their families. In a group of 20 AICD recipients, examined between 3 and 21 months post-implantation, the prevalence of psychiatric disorder was 50%. Following implantation, six patients suffered from adjustment disorder; three suffered from major depression; and one developed panic disorder. Psychiatric morbidity in patients was associated with psychopathology in family members, peri-operative AICD shocks, and social support that was perceived to be inadequate.

Adaptation, Psychological↗
PubMed1990

Panic disorder in cardiac outpatients.

The prevalence of and nature of panic disorder were investigated in an ambulatory cardiology practice. Questionnaires about panic symptoms were mailed to 414 patients, and possible or definite panic disorder was found in 104 of the 310 respondents. Interviews with 52 of the 104 patients substantiated diagnoses of panic disorder, for a prevalence of 9.2% of the total sample population of 414. Comparison of patients grouped by duration of panic disorder revealed that long-duration panic disorder had its onset before age 30 and followed a chronic course. Short-duration panic disorder developed at an older age following the appearance of cardiac disease.

Anxiety Disorders↗
PubMed1989

Three-dimensional structures of drug-resistant mutants of human rhinovirus 14.

Mutants of human rhinovirus 14 were isolated and characterized by searching for resistance to compounds that inhibit viral uncoating. The portions of the RNA that code for amino acids that surround the antiviral compound binding site were sequenced. X-ray analysis of two of these mutants, 1188 Val----Leu and 1199 Cys----Tyr, shows that these were single-site substitutions which would sterically hinder drug binding. Differences in the resistance of mutant viruses to various antiviral compounds may be rationalized in terms of the three-dimensional structures of these mutants. Predictions of the structures of mutant rhinovirus 14 with the substitutions 1188 Val----Leu, 1199 Cys----Tyr and 1199 Cys----Trp in VP1 were made using a molecular dynamics technique. The predicted structure of the 1199 Cys----Tyr mutant was consistent with the electron density map, while the 1188 Val----Leu prediction was not. Large (up to 1.4 A) conformational differences between native rhinovirus 14 and the 1199 Cys----Tyr mutant occurred in main-chain atoms near the mutation site. These changes, as well as the orientation of the 1199 tyrosine side-chain, were correctly predicted by the molecular dynamics calculation. The structure of the predicted 1199 Cys----Trp mutation is consistent with the drug-resistant properties of this virus.

Chromosome Aberrations↗
PubMed1989

Structural analysis of antiviral agents that interact with the capsid of human rhinoviruses.

X-Ray diffraction data have been obtained for nine related antiviral agents ("WIN compounds") while bound to human rhinovirus 14 (HRV14). These compounds can inhibit both viral attachment to host cells and uncoating. To calculate interpretable electron density maps it was necessary to account for (1) the low (approximately 60%) occupancies of these compounds in the crystal, (2) the large (up to 7.9 A) conformational changes induced at the attachment site, and (3) the incomplete diffraction data. Application of a density difference map technique, which exploits the 20-fold noncrystallographic redundancy in HRV14, resulted in clear images of the HRV14:WIN complexes. A real-space refinement procedure was used to fit atomic models to these maps. The binding site of WIN compounds in HRV14 is a hydrophobic pocket composed mainly from residues that form the beta-barrel of VP1. Among rhinoviruses, the residues associated with the binding pocket are far more conserved than external residues and are mostly contained within regular secondary structural elements. Molecular dynamics simulations of three HRV14:WIN complexes suggest that portions of the WIN compounds and viral protein near the entrance of the binding pocket are more flexible than portions deeper within the beta-barrel.

Antiviral Agents↗
PubMed1989

Genetic and molecular analyses of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound.

Spontaneous mutants of human rhinovirus 14 resistant to WIN 52084, an antiviral compound that inhibits attachment to cells, were isolated by selecting plaques that developed when wild-type virus was plated in the presence of high (2 micrograms/ml) or low (0.1 to 0.4 micrograms/ml) concentrations of the compound. Two classes of drug resistance were observed: a high-resistance (HR) class with a frequency of about 4 x 10(-5), and a low-resistance (LR) class with a 10- to 30-fold-higher frequency. The RNA genomes of 56 HR mutants and 13 LR mutants were sequenced in regions encoding the drug-binding site. The HR mutations mapped to only 2 of the 16 amino acid residues that form the walls of the drug-binding pocket. The side chains of these two residues point directly into the pocket and were invariably replaced by bulkier groups. These findings, and patterns of resistance to related WIN compounds, support the concept that HR mutations may hinder the entry or seating of drug within the binding pocket. In contrast, all of the LR mutations mapped to portions of the polypeptide chain near the canyon floor that move when the drug is inserted. Because several LR mutations partially reverse the attachment-inhibiting effect of WIN compounds, these mutants provide useful tools for studying the regions of the capsid structure involved in attachment. This paper shows that the method of escape mutant analysis, previously used to identify antibody binding sites on human rhinovirus 14, is also applicable to analysis of antiviral drug activity.

Antiviral Agents↗
PubMed1988

Structural comparison of the prokaryotic ribosomal proteins L7/L12 and L30.

The structures of two prokaryotic ribosomal proteins, the carboxyterminal half of L7/L12 from Escherichia coli (L12CTF) and L30 from Bacilus stearothermophilus display a remarkably similar fold in which alpha-helices pack onto one side of an antiparallel, three-stranded, beta-pleated sheet. A detailed comparison of the structures by least-squares methods reveals that more than two-thirds of the alpha carbons can be superimposed with a root mean square distance of 2.33 A. The principal difference is an extra alpha-helix in L12CTF. The sequences of the proteins display a distinct conservation in regions which are crucial to the common fold, in particular the hydrophobic core. It is proposed that the similarity is a result of divergent evolution.

Amino Acid Sequence↗
PubMed1988

Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.

The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.

Antiviral Agents↗
PubMed1986

Crystal structure of a prokaryotic ribosomal protein.

The structure of ribosomal protein L30 from Bacillus stearothermophilus has been solved to a resolution of 2.5 A. The molecule is somewhat elongated and contains two helices and a three-stranded, anti-parallel beta-pleated sheet. The protein fold, in which helices pack on the same side of the sheet, generates a simple helix-sheet, two-layered motif. It is possible to distinguish three hydrophobic patches on the molecular surface, and one end has six isolated arginine and lysine residues. It is proposed that these reflect sites of protein-protein and protein-RNA interaction, respectively. The protein fold is very similar to that of the only other known ribosomal protein structure, L7/L12 from Escherichia coli, and, based on this similarity, an attempt is made to align the amino acid sequences of the two proteins.

Crystallography↗
PubMed1977

Thyrotropin binding and long acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates.

The ability of various thyroid subcellular fractions to bind [125I]iodo TSH and to absorb long-acting thyroid stimulator (LATS) and thyroid stimulating immunoglobulins (TSI) activities was examined. Membranes purified from thyroid homogenates or isolated thyroid cells absorbed LATS/TSI activities and specifically bound [125I]iodo TSH. Purified thyroglobulin, nuclei, mitochondria and ribosomes did not bind [125I]iodo TSH nor did they absorb LATS/TSI activities. Cell sap obtained by gentle lysis of isolated thyroid cells failed to absorb LATS/TSI activities and to bind labeled hormone. However, freeze-thawing of the cells fragmented the membranes, releasing [125I]iodo TSH binding as well as LATS/TSI absorbing activities into the soluble (cell sap) fraction. The results suggest that the LATS/TSI antigen is of cell surface origin, includes the TSH receptor or larger membrane fragments containing the receptor, and that its release into the soluble fraction is due to the fragmentation of the thyroid membrane during homogenization and preparative procedures.

Animals↗
PubMedDate not supplied

HIV and psoriasis.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗