Biomedical subjects

S Curry

Publications and source records attributed to S Curry.

At least 37 records · Page 2Linked to original sources

PubMed2005

Locating high-affinity fatty acid-binding sites on albumin by x-ray crystallography and NMR spectroscopy.

Human serum albumin (HSA) is a versatile transport protein for endogenous compounds and drugs. To evaluate physiologically relevant interactions between ligands for the protein, it is necessary to determine the locations and relative affinities of different ligands for their binding site(s). We present a site-specific investigation of the relative affinities of binding sites on HSA for fatty acids (FA), the primary physiological ligand for the protein. Titration of HSA with [(13)C]carboxyl-labeled FA was used initially to identify three NMR chemical shifts that are associated with high-affinity binding pockets on the protein. To correlate these peaks with FA-binding sites identified from the crystal structures of FA-HSA complexes, HSA mutants were engineered with substitutions of amino acids involved in coordination of the bound FA carboxyl. Titration of [(13)C]palmitate into solutions of HSA mutants for either FA site four (R410A/Y411A) or site five (K525A) within domain III of HSA each revealed loss of a specific NMR peak that was present in spectra of wild-type protein. Because these peaks are among the first three to be observed on titration of HSA with palmitate, sites four and five represent two of the three high-affinity long-chain FA-binding sites on HSA. These assignments were confirmed by titration of [(13)C]palmitate into recombinant domain III of HSA, which contains only sites four and five. These results establish a protocol for direct probing of the relative affinities of FA-binding sites, one that may be extended to examine competition between FA and other ligands for specific binding sites.

Binding Sites↗

PubMed2005

Evidence for B+ --> K0K+ and B0 --> K0K0, and measurement of the branching fraction and search for direct CP violation in B+ --> K0pi+.

We present evidence for the b --> d penguin-dominated decays B+ --> K0K+ and B0 --> K0K0 in 227 x 10(6) Y(4S) --> BB decays collected with the BABAR detector. We measure the branching fractions B(B+ --> K0K+) = (1.5 +/- 0.5 +/- 0.1) x 10(-6)(< 2.4 x 10(-6)) and B(B0 --> K0K0) = [formula: see text], where the uncertainties are statistical and systematic, respectively. We also present improved measurements of the charge-averaged branching fraction B(B+ --> K0pi+) = (26.0 +/- 1.3 +/- 1.0) x 10(-6) and CP-violating charge asymmetry A(CP) (K0pi+) = -0.09 +/- 0.05 +/- 0.01), where the uncertainties are statistical and systematic, respectively.

Journal Article↗

PubMed2005

Observation of a broad structure in the pi+ pi- J/psi mass spectrum around 4.26 GeV/c2.

We study initial-state radiation events, e+ e- --> gammaISR pi+ pi- J/psi, with data collected with the BABAR detector. We observe an accumulation of events near 4.26 GeV/c2 in the invariant-mass spectrum of pi+ pi- J/psi. Fits to the mass spectrum indicate that a broad resonance with a mass of about 4.26 GeV/c2 is required to describe the observed structure. The presence of additional narrow resonances cannot be excluded. The fitted width of the broad resonance is 50 to 90 MeV/c2, depending on the fit hypothesis.

Journal Article↗

PubMed2005

Cerebral folate deficiency with developmental delay, autism, and response to folinic acid.

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral folate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills.

Adaptation, Physiological↗

PubMed2003

Using three-dimensional imaging to assess treatment outcomes in orthodontics: a progress report from the University of the Pacific.

Past research in integrated three-dimensional (3D) craniofacial mapping at the Craniofacial Research Instrumentation Laboratory (CRIL) of the University of the Pacific is summarized in narrative form. The advantages and limitations of recent commercial developments in the application of cone beam geometry volumetric X-ray scanners in dentistry and surface digital mapping of study casts are discussed. The rationale for methods currently in development at CRIL for merging longitudinal information from existing 3D study casts and two-dimensional lateral X-ray cephalograms in studies of orthodontic treatment outcome is presented.

Cephalometry↗

PubMed2001

Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids.

The primary ligands of human serum albumin (HSA), an abundant plasma protein, are non-esterified fatty acids. In vivo, the majority of fatty acids associated with the protein are unsaturated. We present here the first high-resolution crystal structures of HSA complexed with two important unsaturated fatty acids, the monounsaturated oleic acid (C18:1) and the polyunsaturated arachidonic acid (C20:4). Both compounds are observed to occupy the seven binding sites distributed across the protein that are also bound by medium and long-chain saturated fatty acids. Although C18:1 fatty acid binds each site on HSA in a conformation almost identical with that of the corresponding saturated compound (C18:0), the presence of multiple cis double bonds in C20:4 induces distinct binding configurations at some sites. The observed restriction on binding configurations plausibly accounts for differences in the pattern of binding affinities for the primary sites between polyunsaturated fatty acids and their saturated or monounsaturated counterparts.

Arachidonic Acid↗

PubMed2001

Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I.

Human serum albumin (HSA) is an abundant transport protein found in plasma that binds a wide variety of drugs in two primary binding sites (I and II) and can have a significant impact on their pharmacokinetics. We have determined the crystal structures at 2.5 A-resolution of HSA-myristate complexed with the R-(+) and S-(-) enantiomers of warfarin, a widely used anticoagulant that binds to the protein with high affinity. The structures confirm that warfarin binds to drug site I (in subdomain IIA) in the presence of fatty acids and reveal the molecular details of the protein-drug interaction. The two enantiomers of warfarin adopt very similar conformations when bound to the protein and make many of the same specific contacts with amino acid side chains at the binding site, thus accounting for the relative lack of stereospecificity of the HSA-warfarin interaction. The conformation of the warfarin binding pocket is significantly altered upon binding of fatty acids, and this can explain the observed enhancement of warfarin binding to HSA at low levels of fatty acid.

Albumins↗

PubMed2001

Motivations for healthful dietary change.

OBJECTIVE: To describe scales that measure motivations for changing dietary behaviour, and to examine associations of these scales with current diet and dietary change. DESIGN: A secondary analysis of a randomised trial of a self-help intervention to promote lower fat and higher fruit and vegetable consumption. PARTICIPANTS AND SETTING: Participants were 1205 adults selected at random from enrolees of a large Health Maintenance Organization. At baseline, data were collected on motives for changing diet, fruit and vegetable intake, fat-related dietary habits, and demographic characteristics. Participants were then randomised to receive the intervention or to receive no materials. A follow-up survey was administered at 12 months. RESULTS: A majority of participants reported that it was very important to make dietary changes to feel better (72%) and to control an existing medical problem (57%), but very few (4%) were motivated by pressure from others. Factor analysis of the diet motivation items yielded two intrinsic ('self-image' and 'personal health') and one extrinsic ('social pressure') scales with fair internal consistency reliabilities (Cronbach's alpha = 0.59 to 0.68). Motivation scales were statistically significantly associated with demographic characteristics and baseline diet. For example, desire for a better self-image was a stronger motivator for changing diet among females, while personal health was more important to older persons and men (P < 0.001). Social pressure to change diet was statistically significantly associated with higher fat intake (r = 0.11) and self-image was associated with lower fat intake (r = -0.14, both P < 0.001). Motivation by social pressure and self-image were both significantly associated with greater fat reduction at 12 months post-intervention (P < 0.05). CONCLUSIONS: The intrinsic and extrinsic motivation scales were weakly associated with current diet and predicted response to dietary intervention. More research is needed to better characterise and measure motives for dietary change, and to test whether tailoring interventions based on individuals' motives for dietary change would improve intervention effectiveness.

Adolescent↗

PubMed2001

Epidemiology and hospital course of rattlesnake envenomations cared for at a tertiary referral center in Central Arizona.

OBJECTIVE: To describe the demographics and primary inpatient treatment of victims of rattle-snake bites (RSBs) referred to a teritiary referral poison treatment center in central Arizona, and to compare the frequency of local tissue complications and hematologic toxicity during hospitalization in children with those for adults. METHODS: This was a chart review of patients diagnosed as having RSB by a toxicology service between July 1994 and April 2000. Data collected included: age, sex, date, bite location, time to and length of hospitalization, time to and amount of antivenin, serial hematologic studies, and inpatient complications. RESULTS: Of 241 patients admitted, 236 charts met inclusion criteria. The majority of RSB victims were male (81%). Children (< or =13 years) represented 22%. Most RSBs (78%) occurred between April and September. Mean time (+/-SEM) to presentation was 1.7 +/- 0.2 hours. Antivenin was administered to 77% of patients, with an average (+/-SEM) of 28.5 +/- 0.9 vials administered. Hematologic abnormalities included: coagulopathy (60%), hypofibrinogenemia (49%), and thrombocytopenia (33%). No statistically significant difference in the above parameters was detected between upper- and lower-extremity envenomations, or between children and adults. Immediate antivenin reactions occurred in 36% of patients. Hemorrhagic bullae formation occurred in 22%, occurring most frequently in upper extremities. Operative procedures were required in 3.4% of patients. Hospitalization averaged 2.5 +/- 0.1 days. There was no fatality. CONCLUSIONS: In Arizona, RSB victims were typically adult males with upper-extremity bites. Hematologic abnormalities were common. Local tissue complications were more common with upper-extremity envenomations. No statistically significant difference was detected in frequency of hematologic disorders or local tissue complications when children were compared with adults.

Adolescent↗

PubMed2000

Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures.

Human serum albumin (HSA) is one of the most abundant proteins in the circulatory system and plays a key role in the transport of fatty acids, metabolites, and drugs. For many drugs, binding to serum albumin is a critical determinant of their distribution and pharmacokinetics; however, there have as yet been no high resolution crystal structures published of drug-albumin complexes. Here we describe high resolution crystal structures of HSA with two of the most widely used general anesthetics, propofol and halothane. In addition, we describe a crystal structure of HSA complexed with both halothane and the fatty acid, myristate. We show that the intravenous anesthetic propofol binds at two discrete sites on HSA in preformed pockets that have been shown to accommodate fatty acids. Similarly we show that the inhalational agent halothane binds (at concentrations in the pharmacologically relevant range) at three sites that are also fatty acid binding loci. At much higher halothane concentrations, we have identified additional sites that are occupied. All of the higher affinity anesthetic binding sites are amphiphilic in nature, with both polar and apolar parts, and anesthetic binding causes only minor changes in local structure.

Anesthetics, General↗

PubMed2000

Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin.

Human serum albumin (HSA) is an abundant plasma protein that is responsible for the transport of fatty acids. HSA also binds and perturbs the pharmacokinetics of a wide range of drug compounds. Binding studies have revealed significant interactions between fatty acid and drug-binding sites on albumin but high-resolution structural information on ligand binding to the protein has been lacking. We report here a crystallographic study of five HSA-fatty acid complexes formed using saturated medium-chain and long-chain fatty acids (C10:0, C12:0, C14:0, C16:0 and C18:0). A total of seven binding sites that are occupied by all medium-chain and long-chain fatty acids have been identified, although medium-chain fatty acids are found to bind at additional sites on the protein, yielding a total of 11 distinct binding locations. Comparison of the different complexes reveals key similarities and significant differences in the modes of binding, and serves to rationalise much of the biochemical data on fatty acid interactions with albumin. The two principal drug-binding sites, in sub-domains IIA and IIIA, are observed to be occupied by fatty acids and one of them (in IIIA) appears to coincide with a high-affinity long-chain fatty acid binding site.

Binding Sites↗

PubMed2000

Structure of tandem RNA recognition motifs from polypyrimidine tract binding protein reveals novel features of the RRM fold.

Polypyrimidine tract binding protein (PTB), an RNA binding protein containing four RNA recognition motifs (RRMs), is involved in both pre-mRNA splicing and translation initiation directed by picornaviral internal ribosome entry sites. Sequence comparisons previously indicated that PTB is a non-canonical RRM protein. The solution structure of a PTB fragment containing RRMs 3 and 4 shows that the protein consists of two domains connected by a long, flexible linker. The two domains tumble independently in solution, having no fixed relative orientation. In addition to the betaalphabetabetaalphabeta topology, which is characteristic of RRM domains, the C-terminal extension of PTB RRM-3 incorporates an unanticipated fifth beta-strand, which extends the RNA binding surface. The long, disordered polypeptide connecting beta4 and beta5 in RRM-3 is poised above the RNA binding surface and is likely to contribute to RNA recognition. Mutational analyses show that both RRM-3 and RRM-4 contribute to RNA binding specificity and that, despite its unusual sequence, PTB binds RNA in a manner akin to that of other RRM proteins.

Amino Acid Motifs↗

PubMed2000

Testing reminder and motivational telephone calls to increase screening mammography: a randomized study.

BACKGROUND: Prospective randomized trials have demonstrated that motivational telephone calls increase adherence to screening mammography. To better understand the effects of motivational calls and to maximize adherence, we conducted a randomized trial among women aged 50-79 years. METHODS: We created a stratified random sample of 5062 women due for mammograms within the Group Health Cooperative of Puget Sound, including 4099 women with prior mammography and 963 without it. We recruited and surveyed 3743 (74%) of the women before mailing a recommendation. After 2 months, 1765 (47%) of the 3743 women had not scheduled a mammogram and were randomly assigned to one of three intervention groups: a reminder post-card group (n = 590), a reminder telephone call group (n = 585), and a motivational telephone call addressing barriers group (n = 590). The telephone callers could schedule mammography. We used Cox proportional hazards models to estimate the hazard ratio (HR) and 95% confidence interval (CI) for documented mammography use by 1 year. RESULTS: Women who received reminder calls were more likely to get mammograms (HR = 1.9; 95% CI = 1.6-2.4) than women who were mailed postcards. The motivational and reminder calls (average length, 8.5 and 3.1 minutes, respectively) had equivalent effects (HR = 0.97; 95% CI = 0.8-1.2). After we controlled for the intervention effect, women with prior mammography (n = 1277) were much more likely to get a mammogram (HR = 3.4; 95% CI = 2.7-4.3) than women without prior use (n = 488). Higher income, but not race or more education, was associated with higher adherence. CONCLUSIONS: Reminding women to schedule an appointment was as efficacious as addressing barriers. Simple intervention groups should be included as comparison groups in randomized trials so that we better understand more complex intervention effects.

Affect↗

PubMed2000

Recidivism of child molesters: a study of victim relationship with the perpetrator.

OBJECTIVE: To compare the rates among of recidivism or re-offense among convicted child molesters who offend against biological children, stepchildren, and relationships where the child is an extended family member, acquaintance or stranger to the victim. METHOD: Four hundred male subjects 18 years of age or older and at least 5 years older than the victim at the time of the index offense, were convicted of a hands on sexual offense against one or more children under the age of 16. Subjects were grouped into five categories according to the type of relationship the perpetrator had with the victim. The subjects records of criminal arrests and convictions was obtained from the national Royal Canadian Mounted Police data. Subjects were then followed-up for a period of up to 15 years after conviction when they were at risk to re-offend in the community. Survival outcome data after the index sexual offense was collected for all new sexual, violent, and any criminal offenses. RESULTS: A larger proportion of men ( 16.2%) who sexually offended against children who were acquaintances, were charged with a new sexual offense than men who sexually offended against biological (4.8%) or their stepchildren (5.1%). The percentage of men who were subsequently charged with any type of criminal offense and who offended against their biological children (19%) was smaller than men who offended against children where the relationship is an extended family member (40%), acquaintances (35.9%) or strangers (45.2%). CONCLUSIONS: When comparing the different categories of relationship the victim had with the perpetrator, the category of stranger has been highlighted as a group with a higher risk for re-offense. Our results have shown that comparatively, the risk of acquaintance group is a significantly higher risk category than was previously thought. Although professionals are principally concerned with sexual recidivism, general criminality appears to present in relatively large proportions of all child molesters with the stranger group at the highest risk level. While no single factor will predict recidivism in itself, the importance of defining the relationship between the perpetrator and victim is evident from this study.

Adult↗

PubMed2000

Molecular tectonic model of virus structural transitions: the putative cell entry states of poliovirus.

Upon interacting with its receptor, poliovirus undergoes conformational changes that are implicated in cell entry, including the externalization of the viral protein VP4 and the N terminus of VP1. We have determined the structures of native virions and of two putative cell entry intermediates, the 135S and 80S particles, at approximately 22-A resolution by cryo-electron microscopy. The 135S and 80S particles are both approximately 4% larger than the virion. Pseudoatomic models were constructed by adjusting the beta-barrel domains of the three capsid proteins VP1, VP2, and VP3 from their known positions in the virion to fit the 135S and 80S reconstructions. Domain movements of up to 9 A were detected, analogous to the shifting of tectonic plates. These movements create gaps between adjacent subunits. The gaps at the sites where VP1, VP2, and VP3 subunits meet are plausible candidates for the emergence of VP4 and the N terminus of VP1. The implications of these observations are discussed for models in which the externalized components form a transmembrane pore through which viral RNA enters the infected cell.

Capsid↗

PubMed2000

Prediction of recidivism in extrafamilial child molesters based on court-related assessments.

One hundred ninety-two convicted extrafamilial child molesters were followed for an average of 7.8 years after their conviction. The percentage of men who had committed a sexual, a violent, or any criminal offense by the 12th year was 15.1, 20.3, and 41.6, respectively. The sexual recidivists, compared with the nonrecidivists; demonstrated more problems with alcohol and showed greater sexual arousal to assaultive stimuli involving children than to mutually consenting stimuli with children. The violent recidivists, compared with the nonrecidivists, were more likely to have a history of violence in the families in which they were raised and were rated significantly more psychopathic on the Psychopathy Checklist--Revised (PCL-R). They also showed more sexual arousal to stimuli depicting mutually consenting sexual interactions with children than to adult stimuli. In terms of any criminal recidivism, recidivists were younger, had completed fewer years of school, and were raised in psychologically more harmful family environments compared with nonrecidivists. They also reported that, before 16 years of age, they were more likely to have been physically abused and were more likely to have been removed from their homes compared to those that did not recidivate. In addition, recidivists demonstrated more general hostility on the Buss-Durkee Hostility Inventory and were rated significantly more psychopathic on the PCL-R. The phallometric assessments revealed, that the criminal recidivists, compared to the nonrecidivists, showed more sexual arousal to stimuli depicting coercive sexual activity with children than consenting sexual activities with children. In addition, they showed more sexual arousal to scenes depicting adult rape then adult mutually consenting sex. Finally, the recidivists also had more charges or convictions for violence and any criminal acts. The small number of significant differences between recidivists and nonrecidivists in the sexual and violent categories precluded an attempt to determine which combination of factors meaningfully predicted reoffending. However, for criminal recidivism, a stepwise discriminant function analysis to assess the combination of factors that most successfully distinguished between groups in terms of criminal recidivism was significant, with subjects' age, total number of criminal convictions, and pedophile assault index being retained for optimal prediction. The procedure correctly classified 70.6% of the original group, 82.8% of the nonrecidivists, and 52.6% of the recidivists. PCL-R Total Score alone was equally successful in a similar discriminant function.

Adolescent↗

PubMed2000

X-ray vision.

Explore the source record for details and available documents.

Cost Savings↗

PubMed2000

Development of a business plan for women's health services, using Malcolm Baldrige Performance Excellence Criteria.

A new process for business planning at Hartford Hospital was needed to achieve critical business results. This article describes the Hospital's use of the Malcolm Baldrige Performance Excellence Criteria as a way to standardize and improve business planning. Women's Health Services is one of Hartford Hospital's "centers for excellence" and one of the first to use these criteria to improve its service. Staff learned how to build their business plan upon a set of core values and concepts such as customer-driven quality, leadership that sets high expectations, continuous improvement and learning, valuing employees, faster response to market demands, management by fact, and a long-range view of the future.

Commerce↗