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Biomedical subjects

S Curry

Publications and source records attributed to S Curry.

At least 19 recordsLinked to original sources
PubMed1998

Titration calculations of foot-and-mouth disease virus capsids and their stabilities as a function of pH.

Foot-and-mouth disease virus (FMDV), a non-enveloped picornavirus, is sensitive to acidic conditions. At pH values below 7 the icosahedral virus capsid, formed from 60 copies of a protomer containing four polypeptides (VP1 to 4), dissociates into 12 pentamers, releasing the viral RNA. Evidence suggests that this acid lability may assist FMDV cell entry via an endosomal pathway. Calculations of titration curves and pH-stability profiles are presented for three different strains of FMDV, O1BFS, A10(61) and A22 Iraq, and compared with experimental data for complete virions and empty capsids (which lack RNA). The finite difference Poisson-Boltzmann method was used for the calculation of electrostatic free energies with the solvent treated as a dielectric continuum. The inter-pentamer interface in the virus is formed by two protomers related by 2-fold icosahedral symmetry. As a simple model for inter-pentamer interactions, a dimer and two separate protomers were compared. The association free energy was computed by integrating the difference between the titration curves of the two species. The calculations reproduced the observed decrease in capsid stability at acidic pH but not the difference in pH sensitivities of the two type A viruses. It is shown that only residues within 15 A of the interface play a significant role in determining acid lability. For the experimentally studied pH range (5 to 7.6), histidine residues were found to dominate the pH-dependence of the stability. Two histidine residues in VP3, H142 and H145, are shown to have the greatest effect by virtue of their interactions with many polar residues across the inter-pentamer interface; the interaction of H142 with an alpha-helix in the opposite pentamer contributes only a small proportion of the destabilization energy.

Aphthovirus↗
PubMed1998

Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites.

Human serum albumin (HSA) is the most abundant protein in the circulatory system. Its principal function is to transport fatty acids, but it is also capable of binding a great variety of metabolites and drugs. Despite intensive efforts, the detailed structural basis of fatty acid binding to HSA has remained elusive. We have now determined the crystal structure of HSA complexed with five molecules of myristate at 2.5 A resolution. The fatty acid molecules bind in long, hydrophobic pockets capped by polar side chains, many of which are basic. These pockets are distributed asymmetrically throughout the HSA molecule, despite its symmetrical repeating domain structure.

Amino Acid Sequence↗
PubMed1998

Vulvar cancer.

Historically, nearly all vulvar cancer is managed by ultraradical surgery. Currently, individualized and more surgically conservative approaches achieve equivalent outcomes with far less morbidity and cosmetic disfiguration. Microinvasive disease can be cured with local excision only. Lateral lesions are usually managed with local excision and ipsilateral groin node dissection only. Advanced disease responds remarkably to chemoradiation.

Chemotherapy, Adjuvant↗
PubMed1998

Recidivism in convicted rapists.

Factors associated with recidivism in 86 men convicted of rape were studied. These men had been out of prison for up to 12 years (mean, 7.6 years). The majority of the men had been assessed in a sexual behaviors clinic of a general psychiatric hospital at the time of their conviction. Almost 50 percent of the group had committed some offense by the fifth year out of prison. The recidivism rates for sexual, violent, and any criminal recidivism were 16 percent, 26 percent, and 53 percent, respectively. The ability to predict sexual and violent recidivism in this population of rapists was rather poor. More sexual recidivists, compared with nonrecidivists, had been removed from their family home prior to age 16. Violent recidivists compared with nonrecidivists were also more frequently removed from their homes prior to 16 years of age, and they showed significantly more problems with alcohol. In terms of any criminal recidivism, recidivists compared with nonrecidivists were younger and scored higher on the Michigan Alcohol Screening Test (MAST). They also had more previous charges and/or convictions for violent offenses and more charges and/or convictions for any criminal acts. The combination of age and MAST scores was able to predict 92.6 percent of the nonrecidivists and 53.3 percent of the recidivists. The outstanding feature of the total group of rapists was their poor sexual adjustment as indicated on the Derogatis Sexual Functioning Inventory, on which they scored at approximately the seventh percentile of the population at large. There was also an indication that rapists have problems with hostility, as measured by the Buss-Durkee Hostility Inventory. Furthermore, the range of scores on the MAST indicated that the total group of rapists has serious problems with alcohol. The inability of phallometric assessments and psychopathy as measured by the Psychopathy Checklist-R to predict recidivism are discussed.

Adult↗
PubMed1997

Structural studies of poliovirus mutants that overcome receptor defects.

In order to better understand the process of cell entry for non-enveloped viruses, we have solved the crystal structures of five poliovirus mutants which can infect cells expressing mutant poliovirus receptors. Four of these structures have been solved from frozen crystals using cryocrystallographic data collection methods. The mutations have a range of structural consequences, from small local perturbations to significant loop rearrangements. All of the mutant viruses are more labile to conversion to an apparent cell entry intermediate, suggesting that these mutant viruses could compensate for the suboptimal receptors by lowering the thermal energy required to undergo the receptor-mediated conformational change.

Capsid↗
PubMed1997

Lower molar and incisor displacement associated with mandibular remodeling.

The purpose of this study was to quantify the amount of alveolar modeling at the apices of the mandibular incisor and first molar specifically associated with appositional and resorptive changes on the lower border of the mandible during growth and treatment. Cephalometric data from superimpositions on anterior cranial base, mandibular implants of the Björk type, and anatomical "best fit" of mandibular border structures were integrated using a recently developed strategy, which is described. Data were available at annual intervals between 8.5 and 15.5 years for a previously described sample of approximately 30 children with implants. The average magnitudes of the changes at the root apices of the mandibular first molar and central incisor associated with modeling/remodeling of the mandibular border and symphysis were unexpectedly small. At the molar apex, mean values approximated zero in both anteroposterior and vertical directions. At the incisor apex, mean values approximated zero in the anteroposterior direction and averaged less than 0.15 mm/year in the vertical direction. Standard deviations were roughly equal for the molar and the incisor in both the anteroposterior and vertical directions. Dental displacement associated with surface modeling plays a smaller role in final tooth position in the mandible than in the maxilla. It may also be reasonably inferred that anatomical best-fit superimpositions made in the absence of implants give a more complete picture of hard tissue turnover in the mandible than they do in the maxilla.

Adolescent↗
PubMed1997

Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus.

Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been proposed to be involved in the cleavage of VP0. A comparison of the putative active sites in FMDV and poliovirus suggests a structural explanation for the sequence specificity of the cleavage reaction.

Aphthovirus↗
PubMed1996

Protective effect of dichloroacetate in a rat model of forebrain ischemia.

Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex (PDHC), and improves the recovery of cerebral pH, lactate, ATP, and PCr following reperfusion in animal models of forebrain ischemia. In order to determine whether this results in neuroprotection, rats were administered NaDCA (100 mg/kg or 10mg/kg i.v.) 10 min before 12 min of normothermic forebrain ischemia (bilateral carotid artery occlusion plus systemic hypotension, 45 mmHg). Neuronal injury assessed histopathologically 7 days post-ischemia was significantly reduced in the CA1 region of the hippocampus, the dorsal lateral striatum, and the neocortex, in rats treated with 100 mg/kg NaDCA, but not in rats treated with 10 mg/kg NaDCA.

Adenosine Triphosphate↗
PubMed1996

Perturbations in the surface structure of A22 Iraq foot-and-mouth disease virus accompanying coupled changes in host cell specificity and antigenicity.

BACKGROUND: Foot-and-mouth disease virus (FMDV) is an extremely infectious and antigenically diverse picornavirus of cloven-hoofed animals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the structural basis of this phenomenon we have determined the structures of two variants of an A22 virus. RESULTS: The structures of monolayer- and suspension-cell-adapted A22 FMDV have been determined by X-ray crystallography. Picornaviruses comprise four capsid proteins, VP1-4. The major antigenic loop of the capsid protein VP1 is flexible in both variants of the A22 subtype but its overall disposition is distinct from that observed in other FMDV serotypes (O and C). A detailed structural comparison between A22 FMDV and a type O virus suggests that different conformations in a portion of the major antigenic loop of VP1 (the GH loop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gly) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VP1 GH loop. CONCLUSION: The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibility is important in both antigenic variability and structural communication with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across the virion surface: the change in the VP3 GH loop caused by the VP1 GH loop and the Glu82-->Gly change in VP2 which we believe perturbs the GH loop of VP1. In the latter case, the amplification of the sequence changes leads to differences, between the monolayer- and suspension-cell-adapted viruses, in host-cell interactions and antigenicity.

Antigens, Viral↗
PubMed1996

Partitioning the components of maxillary tooth displacement by the comparison of data from three cephalometric superimpositions.

Using roentgenographic cephalograms from a sample of subjects with metallic implants, appropriately superimposed tracings were used to distinguish developmental and treatment-associated displacements of the maxillary central incisor and first molar associated "local" changes within the periodontium from "secondary" changes which reflect sutural and appositional growth at more distant osseous loci. Tracings were superimposed on anterior cranial base (ACB), on the maxillary implants only (IMP_MAX), and according to the best fit of maxillary anatomic structures without reference to the implants (A_MAX). Using the IMP_MAX superimposition, one could measure total local displacement at any landmark taking into consideration the effects of all appositional and resorptive changes on the superior and anterior surfaces of the palate, whereas using the A_MAX superimposition one could measure local displacement without consideration of surface appositional and resorptive changes. If the second of these measurements were subtracted from the first, the result would be a direct measurement of the effects of surface appositional and resorptive changes as they are expressed at that particular landmark. This strategy has enabled us to quantify and report the amount of accommodation which occurs at the location of each dental landmark in association with the resorptive and appositional changes which occur through time on the superior and anterior surfaces of the hard palate.

Adolescent↗
PubMed1996

The poliovirus 135S particle is infectious.

The molecular mechanism of cell entry by unenveloped viruses is poorly understood. The picornaviruses poliovirus, human rhinovirus, and coxsackievirus convert to an altered form (the 135S or A particle) upon interaction with receptors on susceptible cells at 37 degrees C. The 135S particle is thought to be a necessary intermediate because it accumulates inside susceptible cells soon after infection and drugs which inhibit conversion of the virus to this form also prevent infection. However, since a variable fraction of the altered 135S particles is reported to elute unproductively from the surface of susceptible cells, their precise role remains unclear. We have found that poliovirus 135S particles can infect Chinese hamster ovary (CHO) and murine L cells, neither of which are susceptible to infection by native poliovirus. The infectivity of the particles in tissue culture appears to be between 10(3) to 10(5) times less than that of poliovirus on HeLa cells. The 135S particle infectivity was not sensitive to RNase but was greatly reduced by proteolytic treatment. Proteolysis specifically removed the newly exposed N terminus of VP1, a feature which has previously been shown to mediate interactions of the particle with lipid membranes. These results demonstrate that although the infectivity of the 135S particle appears to be receptor independent, it nonetheless requires some property associated with the protein coat. In particular, the N terminus of VP1 plays an important role in the infection process. Our findings are consistent with the hypothesis that the 135S particle is an intermediate in the normal cell entry pathway of poliovirus infection.

Animals↗
PubMed1996

Are pedophiles with aggressive tendencies more sexually violent?

Pedophiles use varying degrees of persuasion, coercion, and physical force in their sexual assaults. Pedophiles may also display aggressiveness and characteristics of hostility in nonsexual areas of their behavior. This study (N = 263) investigates the relationship between pedophiles with aggressive tendencies and the degree of sexual violence in their pedophilic acts. The degree of sexual violence was rated subjectively after a comprehensive psychiatric and psycho-sexual assessment and obtaining collateral information from police reports and witness statements. The degree of sexual violence was also rated more objectively using the penile plethysmography. Strict DSM-IV pedophilic disorder criteria were adopted for this study. The authors discuss whether sexual violence in a pedophilic population is focused to sexual areas or tends to be more generalized in other physically aggressive and hostile areas.

Adult↗
PubMed1996

Co-morbidity of alcoholism and the paraphilias.

Alcoholism has been related to a wide variety of crimes. Various authors have studied the prevalence of alcoholism in relationship to incest, rape and pedophilia. This study evaluates the co-morbidity of alcoholism and the specific paraphilias including sexual sadism, fetishism, incest, pedophilia, exhibitionism and transvestism. Rapists were included although by definition it is not strictly a paraphilic disorder. Seven hundred and twenty eight paraphilic individuals were evaluated. More than 50% of sexual sadists were alcoholics. Alcoholism in association with sexual sadists was statistically significant as compared to transvestites, rapists, pedophiles, and incest offenders. Transvestism had the lowest relative rate of alcoholism. The authors discuss these findings and the role alcoholism plays in causing violent sexual behavior in individuals with paraphilias.

Adult↗
PubMed1996

A comparison of treatment of paraphilias with three serotonin reuptake inhibitors: a retrospective study.

Treatment of the paraphilic disorders using behavioral, cognitive, pharmacological, and social interventions has been shown to have limited success with poorly motivated or noncompliant patients. Researchers have speculated on the role of the serotonergic system in the paraphilic disorders. Recent anecdotal studies have reported successful results with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of the paraphilic disorders. This retrospective study evaluates and compares the effectiveness of three SSRIs in a group of paraphilics (N = 58). The individual effectiveness of fluvoxamine, fluoxetine, and sertraline were examined and compared. Results found that the severity of fantasies decreased and that there were no significant differences in the reported efficacy between fluvoxamine, fluoxetine, and sertraline. Although double blind placebo crossover studies are still needed to assess the efficacy of these agents, this study further supports the growing body of literature on the potential use of these drugs in the treatment of the paraphilias.

1-Naphthylamine↗