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At least 1,027 records · Page 57Linked to original sources
PubMed2006

Personality prototypes in eating disorders based on the Big Five model.

A three factor model of personality pathology was investigated in a clinical sample of 335 female eating disordered patients. Cluster analysis of the Big Five NEO-FFI scales (Costa & McCrae, 1992) yielded three distinct personality profiles, which were consistent with previous studies: (1) a resilient/high functioning cluster with no clinical elevations on the NEO-FFI scales; (2) an undercontrolled/emotionally dysregulated cluster with elevated scores on the Neuroticism scale and low scores on Conscientiousness and Agreeableness; (3) an overcontrolled/constricted cluster showing high scores on Neuroticism and Conscientiousness and low scores on Openness to Experience. Comparing the three personality prototypes with respect to Axis I and Axis II disorders,resilients reported systematically less clinical and personality problems than both undercontrollers and overcontrollers. Compared to the latter, undercontrollers showed more impulsive personality features and behaviors. Finally, cluster membership was not clearly associated with eating disorder subtypes, suggesting that there is considerable variance in personality features and/or pathology within the various eating disorder categories.

Adolescent↗
PubMed2005

Modeling flexible loops in the dark-adapted and activated states of rhodopsin, a prototypical G-protein-coupled receptor.

Conformational possibilities of flexible loops in rhodopsin, a prototypical G-protein-coupled receptor, were studied by modeling both in the dark-adapted (R) and activated (R*) states. Loop structures were built onto templates representing the R and R* states of the TM region of rhodopsin developed previously (G. V. Nikiforovich and G. R. Marshall. 2003. Biochemistry. 42:9110). Geometrical sampling and energy calculations were performed for each individual loop, as well as for the interacting intracellular loops IC1, IC2, and IC3 and the extracellular loops EC1, EC2, and EC3 mounted on the R and R* templates. Calculations revealed that the intra- and extracellular loops of rhodopsin possess low-energy structures corresponding to large conformational movements both in the R and R* states. Results of these calculations are in good agreement with the x-ray data available for the dark-adapted rhodopsin as well as with the available experimental biophysical data on the disulfide-linked mutants of rhodopsin. The calculated results are used to exemplify how the combined application of the results of independent calculations with emerging experimental data can be used to select plausible three-dimensional structures of the loops in rhodopsin.

Adaptation, Physiological↗
PubMed2004

Prototype epicardial crawling device for intrapericardial intervention on the beating heart.

The development and preliminary testing of a device for facilitating minimally invasive beating-heart intrapericardial interventions are described. We propose the concept of an endoscopic robotic device that adheres to the epicardium by suction and navigates by crawling like an inchworm to any position on the surface under the control of a surgeon. This approach obviates cardiac stabilization, lung deflation, differential lung ventilation, and reinsertion of laparoscopic tools for accessing different treatment sites, thus offering the possibility of reduced trauma to the patient. The device has a working channel through which various tools can be introduced for treatment. The current prototype demonstrated successful prehension, turning, and locomotion on beating hearts in a limited number of trials in a porcine model.

Animals↗
PubMed1998

Effect of mouse intestinal bacteria on incidence of colorectal tumors induced by 1,2-dimethylhydrazine injection in gnotobiotic transgenic mice harboring human prototype c-Ha-ras genes.

We produced transgenic (Tg) gnotobiotic (GB) mice carrying human prototype c-Ha-ras genes and compared the incidence of colorectal tumors induced by 1,2-dimethylhydrazine (DMH) injection. At 7 to 11 weeks of age, germfree (GF) CB6F1-Tg Hras2 mice were inoculated with various mouse fecal suspensions or mixtures of bacteria isolated from mouse feces. Three weeks after bacterial inoculation, DMH was administered by subcutaneous injection at 20 mg per kg body weight for 20 weeks. Mice were euthanized 5 weeks after the last injection to investigate the number of colorectal tumors. The incidence of colorectal tumors was high in both Tg- and non-Tg-GF mice (100%). In Tg-specific pathogen-free (SPF) mice and Tg-GB-4 mice associated with basic mouse flora consisting of Escherichia coli, lactobacilli, Bacteroides and clostridia, the incidence of colorectal tumors was as high as that in GF mice. In Tg-SPF mice, the tumor score was higher than in Tg-GF mice (p < 0.01), but no colorectal tumors were detected in non-Tg groups of SPF, and the tumor incidence was remarkably low in non-Tg-GB-4 mice. The tumor incidence and score in Tg- and non-Tg-GB mice varied depending on the bacterial combination in their intestine. These results indicate that the presence of human c-Ha-ras genes and intestinal bacteria substantially modify colorectal tumorigenesis induced by DMH.

1,2-Dimethylhydrazine↗
PubMed1990

Studies on the development of an ELISA kit for microbiological monitoring. 2. Improvement of the prototype ELISA kit with special references to mouse hepatitis virus antigen.

Improvement of the mouse hepatitis virus (MHV) antigen in a prototype ELISA kit was performed. Equivalent divalent antigens of MHV Nu-67 and S strains with a protein concentration of 10 micrograms/ml showed the best sensitivity and specificity for the detection of MHV and sialodacryoadenitis/Parker's rat coronavirus antibodies in mice and rats, respectively. An increase in the reliability of macroscopic evaluation of both antibody tests is expected by using the newly manufactured kit with the improved antigen.

Animals↗
PubMedDate not supplied

Structure and photoreaction of photoactive yellow protein, a structural prototype of the PAS domain superfamily.

Photoactive yellow protein (PYP) is a water-soluble photosensor protein found in purple photosynthetic bacteria. Unlike bacterial rhodopsins, photosensor proteins composed of seven transmembrane helices and a retinal chromophore in halophilic archaebacteria, PYP is a highly soluble globular protein. The alpha/beta fold structure of PYP is a structural prototype of the PAS domain superfamily, many members of which function as sensors for various kinds of stimuli. To absorb a photon in the visible region, PYP has a p-coumaric acid chromophore binding to the cysteine residue via a thioester bond. It exists in a deprotonated trans form in the dark. The primary photochemical event is photo-isomerization of the chromophore from trans to cis form. The twisted cis chromophore in early intermediates is relaxed and finally protonated. Consequently, the chromophore becomes electrostatically neutral and rearrangement of the hydrogen-bonding network triggers overall structural change of the protein moiety, in which local conformational change around the chromophore is propagated to the N-terminal region. Thus, it is an ideal model for protein conformational changes that result in functional change, responding to stimuli and expressing physiological activity. In this paper, recent progress in investigation of the photoresponse of PYP is reviewed.

Archaea↗
PubMed2006

Artificial lung: progress and prototypes.

Lung disease is the fourth leading cause of death (one in seven deaths) in the USA. Acute respiratory distress syndrome (ARDS) affects approximately 150,000 patients a year in the USA, and an estimated 16 million Americans are afflicted with chronic lung disease, accounting for 100,000 deaths per year. Medical management is the standard of care for initial therapy, but is limited by the progression of disease. Chronic mechanical ventilation is readily available, but is cumbersome, expensive and often requires tracheotomy with loss of upper airway defense mechanisms and normal speech. Lung transplantation is an option for less than 1100 patients per year since demand has steadily outgrown supply. For the last 15 years, the authors' group has studied ARDS in order to develop viable alternative treatments. Both extracorporeal gas exchange techniques, including extracorporeal membrane oxygenation, extracorporeal and arteriovenous CO(2) removal, and intravenous oxygenation, aim to allow for a less injurious ventilatory strategy during lung recovery while maintaining near-normal arterial blood gases, but precludes ambulation. The paracorporeal artificial lung (PAL), however, redefines the treatment of both acute and chronic respiratory failure with the goal of ambulatory total respiratory support. PAL prototypes tested on both normal sheep and the absolute lethal dose smoke/burn-induced ARDS sheep model have demonstrated initial success in achieving total gas exchange. Still, clinical trials cannot begin until bio- and hemodynamic compatibility challenges are reconciled. The PAL initial design goals are for a short-term (weeks) bridge to recovery or transplant, but eventually, for long-term support (months).

Animals↗
PubMed2003

Comparative immunological recognition of proteins from New Guinea "C" dengue virus type 2 prototype and from a dengue virus type 2 strain isolated in the State of Rio de Janeiro, Brazil.

The protein profiles of the New Guinea "C" dengue virus type 2 (DENV-2)prototype and those of a Brazilian DENV-2 isolated in the State of Rio de Janeiro in 1995 were compared. SDS-PAGE analysis showed that the virus from Rio de Janeiro expresses NS5 (93.0 kDa), NS3 (66.8 kDa) E (62.4 kDa) and NS1 (41.2 kDa) proteins differently from the New Guinea "C" virus. The immunoblot revealed specificity and antigenicity for the NS3 protein from DENV-2 Rio de Janeiro mainly in primary infections, convalescent cases, and in secondary infections in both cases and only antigenicity for E and NS1 proteins for both viruses in primary and secondary infections.

Animals↗
PubMed1980

A prototype apparatus for microexplosion cystolithotripsy.

We developed a prototype apparatus for microexplosion lithotripsy in the urinary bladder according to our original idea. A model calculus in a pig bladder was successfully crushed by the apparatus and was removed by aspiration.

Animals↗
PubMed2001

Lack of modifying effects of eugenol on development of lung proliferative lesions induced by urethane in transgenic mice carrying the human prototype c-Ha-ras gene.

To investigate the modifying effects of eugenol (EUG), a component of cigarette smoke, on lung carcinogenesis, male and female transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 250 mg/kg urethane (UR) or saline, followed by a diet containing 6,000 ppm EUG or basal diet for 26 weeks. Their non-transgenic CB6F1 littermates (non-Tg mice) were also treated in the same manner. In both male and female rasH2 mice, alveolar/bronchiolar hyperplasias, adenomas and carcinomas were observed in all UR-treated groups. However, there were no significant intergroup differences in the incidences and multiplicities of these lesions between the UR alone and UR + EUG groups. In non-Tg mice, alveolar/bronchiolar hyperplasias, adenomas or carcinomas were sporadically observed in UR-treated groups of both sexes, with no significant differences in the incidences and multiplicities between the UR alone and UR + EUG groups. There were no intergroup differences between them in the PCNA-positive ratios of adenomas or carcinomas and the areas of adenomas or carcinomas to the whole lung area examined. The present results suggest that the EUG treatment does not exert modifying effects on lung carcinogenesis induced by UR in both male and female rasH2 mice and non-Tg mice.

Adenoma↗
PubMed2006

Prediction of in vivo drug-drug interactions from in vitro data : factors affecting prototypic drug-drug interactions involving CYP2C9, CYP2D6 and CYP3A4.

BACKGROUND: Quantitative predictions of in vivo drug-drug interactions (DDIs) resulting from metabolic inhibition are commonly made based upon the inhibitor concentration at the enzyme active site [I] and the in vitro inhibition constant (K(i)). Previous studies have involved the use of various plasma inhibitor concentrations as surrogates for [I] along with K(i) values obtained from published literature. Although this approach has resulted in a high proportion of successful predictions, a number of falsely predicted interactions are also observed. OBJECTIVES: To focus on three issues that may influence the predictive value of the [I]/K(i) ratio approach: (i) the use of unbound K(i) (K(i,u)) values generated from standardised in vitro experiments compared with literature values; (ii) the selection of an appropriate [I]; and (iii) incorporation of the impact of intestinal metabolic inhibition for cytochrome P450 (CYP) 3A4 predictions. To this end we have selected eight inhibitors of CYP2C9, CYP2D6 and CYP3A4 and 18 victim drugs from a previous database analysis to allow prediction of 45 clinical DDI studies. METHODS: In vitro kinetic and inhibition studies were performed in human liver microsomes using prototypic probe substrates of CYP2C9 and CYP2D6, with various inhibitors (miconazole, sulfaphenazole, fluconazole, ketoconazole, quinidine, fluoxetine, fluvoxamine). The K(i) estimates obtained were corrected for non-specific microsomal binding, and the K(i,u) was incorporated into in vivo predictions using various [I] values. Predictions for CYP3A4 were based upon in vitro data obtained from a previous publication within our laboratory, and an assessment of the impact of the interaction in the gut wall is included. Predictions were validated against 45 in vivo studies and those within 2-fold of the in vivo ratio of area under the plasma concentration-time curve of the substrate, in the presence and absence of the inhibitor (AUC(i)/AUC) were considered successful. RESULTS: Predictions based upon the average systemic total plasma drug concentration ([I](av)) [incorporating the effects of parallel drug elimination pathways] and the K(i,u) value resulted in 91% of studies predicted to within 2-fold of the in vivo AUC(i)/AUC. This represents a 35% improvement in prediction accuracy compared with predictions based upon total K(i) values obtained from various published literature sources. A corresponding reduction in bias and an increase in precision were also observed compared with the use of other [I] surrogates (e.g. the total and new unbound maximum hepatic input plasma concentrations). No significant improvement in prediction accuracy was observed by incorporating consideration of gut wall inhibition for CYP3A4. CONCLUSION: DDI predictions based upon the use of K(i,u) data obtained under a set of optimal standardised conditions were significantly improved compared with predictions using in vitro data collated from various sources. The use of [I](av) as the [I] surrogate generated the most successful predictions as judged by several criteria. Incorporation of either plasma protein binding of inhibitor or gut wall CYP3A4 inhibition did not result in a general improvement of DDI predictions.

Algorithms↗
PubMed2000

Gossypol: prototype of inhibitors targeted to dinucleotide folds.

Gossypol, a disesquiterpene from cottonseed, exhibits multiple biological properties, including male antifertility activity and anticancer activity. Gossypol also inhibits the growth of numerous parasitic organisms and shows antiviral activity against a number of enveloped viruses, including the AIDS virus. Derivatives of gossypol, in which the aldehyde functional groups that contribute to toxicity have been modified, retain or even show enhanced biological activity. Ring substituted 2,3-dihydroxy-1-naphthoic acids, which are structural analogs of gossypol, share with gossypol the ability to complex with dehydrogenases at the dinucleotide fold (Rossmann fold) with selectivity, suggesting that gossypol may be considered the prototype of a new class of drugs targeted to dehydrogenases. Most of the biological activities of gossypol and related compounds may result from inhibition of dehydrogenases.

Animals↗
PubMed2026

Development of a Blockchain-Based Platform to Enable Indigenous Data Sovereignty and Shared Research Participation With Indigenous Communities: Technology Prototyping and Community Engagement Study.

BACKGROUND: Historic and ongoing problematic practices regarding the collection, storage, and use of Indigenous health data have led to the need to ensure principles of Indigenous Data Sovereignty (IDS) are followed in research practices and technology development. OBJECTIVE: This project, a partnership between UC San Diego and the Native BioData Consortium (NativeBio), sought to explore the practical application of blockchain technology and its potential to facilitate Indigenous-led research collaboration. METHODS: This project first undertook purposeful relationship building with NativeBio to form a Community Advisory Board (CAB) for identifying community and technology needs for a blockchain research collaboration platform with an initial focus on genomic data. Over a 2-year project period, a series of public meetings and presentations at Indigenous-led conferences introduced the concept of exploring compatibility between blockchain and IDS principles, followed by iterative prototyping and co-design of a blockchain platform with NativeBio, using Ethereum as the underlying protocol. RESULTS: Direct engagement with NativeBio and the CAB informed the initial design and development of a "b-IDS" proof-of-concept (POC) blockchain platform. The POC consists of three main components: (1) the web front-end layer, (2) the Ethereum network that executes the smart contract and blockchain storage aspects of the framework, and (3) the back-end database that stores off-chain interactions and data for future use with external genomic data repositories. After refinement of the POC, a community-based participatory research (CBPR) use case aligned with IDS principles was identified as a practical workflow and incorporated into the design of the POC for implementation. CONCLUSIONS: The findings from this project demonstrated the potential use of operationalizing IDS through blockchain technology with proactive and sustained engagement with Indigenous partners. Blockchain technology may have certain advantages over other data governance approaches and systems, facilitating timely oversight, shared decision-making and consent structures, and direct involvement of Indigenous communities in technology design, respecting the core principles of IDS and CBPR. Future development of the blockchain-IDS POC will need to incorporate other research practices and ethics frameworks to expand its use to other public health and biomedical research use cases.

Blockchain↗
PubMed1976

Computed tomography of the body: initial clinical trial with the EMI prototype.

A review of the first 400 cases examined on one of three prototype EMI body scanners is presented. During the initial evaluation phases, it became obvious that computed tomography of the body has tremendous potential in the evaluation of various organs and disease states. The technique has been most useful in evaluating patients with known or suspected abdominal neoplasm, particularly lesions of liver, pancreas, retroperitoneum, and kidney. Too few cases have been studied to realistically quantitate its impact on the total field of medical diagnostic imaging.

Abdominal Neoplasms↗
PubMed1982

Clinical experience with a prototype real-time dedicated breast scanner.

The evaluation of 1,003 sonomammographic examinations on a predominantly symptomatic population using a prototype real-time dedicated breast scanner is presented. Interpretations were initially made by one of four experienced radiologists without knowledge of clinical data (i.e., symptoms, age, physical findings, or other imaging modality interpretations). A second interpretation was subsequently made with this information. Pathologic confirmation was available on 262 lesions, including 71 carcinomas and 191 benign biopsies. Of the carcinomas, 19 were smaller than 2.0 cm in diameter. The sensitivity of sonographic detection of breast cancer on initial readings was 0.76 and on second readings with clinical data was 0.85. The specificity for a benign reading on sonography was 0.80 on initial interpretation and 0.81 on the second interpretation.

Adolescent↗
PubMed2005

Clinical potentials for dynamic contrast-enhanced hepatic volumetric cine imaging with the prototype 256-MDCT scanner.

OBJECTIVE: To achieve dynamic contrast-enhanced hepatic volumetric cine imaging, we developed a prototype 256-MDCT scanner. This study examined the feasibility of the technique for human hepatic imaging in three hepatocellular carcinoma patients. CONCLUSION: Volumetric cine imaging successfully visualized dynamic contrast enhancement of the hepatocellular carcinoma. It is helpful to evaluate the phase of contrast enhancement or for functional studies of the head, renal artery, coronary artery, and liver.

Aged↗
PubMed1985

Effects of presentation schedule on retention and prototype formation for kinesthetically presented figures.

This study assessed the influence of blocked, random, and serial acquisition schedules on the learning of kinesthetically presented geometric patterns. Measures of both retention and prototype formation did not indicate an influence for type of presentation order. This nonsignificant finding is consistent with theories which purport that benefits of random and serial practice schedule result from the active involvement of the learner in both movement planning and the analysis of error information.

Adult↗