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PubMed1998

Advanced practice nursing in Texas: the interface of accreditation, regulation, and certification.

The rapidity and degree of development of regulation by boards of nursing of advanced practice nurses (APNs) and programs for their preparation has varied from state to state over the past 20 years. In general, boards have authority only to regulate advanced practice through the recognition of APNs and the setting of standards and scope of their practice. In the early 1990s, lack of consistent APN educational program standards and experiences and criteria for recognition of APNs was problematic at the levels of accreditation, certification, and regulation. The interdependency of these concepts as well as the necessity and difficulty of linking them in a consistent, effective manner has become increasingly evident. The Texas Board of Nurse Examiners has been involved in deriving a model designed to ensure the education and recognition of APNs with emphasis on both professionalism and public safety. Because Texas is unique in size and geography, it mirrors many problems and issues of both large and small states.

Certification↗

PubMedDate not supplied

Considerations of glaucoma in patients undergoing corneal refractive surgery.

Glaucoma patients present a unique set of challenges to physicians performing corneal refractive surgery. Corneal thickness, which is modified during corneal refractive surgery, plays an important role in monitoring glaucoma patients because of its effect on the measured intraocular pressure. Patients undergo a transient but significant rise in intraocular pressure during the laser-assisted in situ keratomileusis (LASIK) procedure with risk of further optic nerve damage or retinal vein occlusion. Glaucoma patients with filtering blebs are also at risk of damage to the bleb by the suction ring. Steroids, typically used after refractive surgery, can increase intraocular pressure in steroid responders, which is more prevalent among glaucoma patients. Flap interface fluid after LASIK, causing an artificially low pressure reading and masking an elevated pressure has been reported. The refractive surgeon's awareness of these potential complications and challenges will better prepare them for proper management of glaucoma patients who request corneal refractive surgery.

Cornea↗

PubMed1997

Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): a jungle of cell-cell interactions or a therapeutic opportunity?

Lipid-derived mediators play critical roles in inflammation and other multicellular vascular processes, including atherosclerosis and thrombosis. The lipoxins (LXs) were first isolated in 1984, and have continued to show intriguing and potentially important biological roles. These compounds carry a trihydroxytetraene structure and are both structurally and functionally unique among arachidonic acid-derived bioactive products. The availability of synthetic materials for evaluation of bioactions as well as appropriate methods of detection to determine when and where LX are generated has, in recent studies, catapulted our understanding of the formation and actions of the lipoxins. This mini-review addresses new concepts in the formation and biological roles of these lipid-derived mediators and considers whether the lipoxins and the newly discovered aspirin-triggered lipoxins (ATL) represent novel approaches for therapeutic opportunities. Recent findings indicate that select cytokines and aspirin initiate and regulate LX biosynthetic events. These circuits involve cell-cell interfacing that facilitates transcellular events to form LX that display anti-inflammatory actions in both in vitro and in vivo models. These recent results suggest that LX biosynthetic circuits assemble to evoke anti-inflammatory actions and generate LX that can serve as "stop signals" in appropriate microenvironments.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

The retinoid X receptor and its ligands: versatile regulators of metabolic function, cell differentiation and cell death.

Retinoid X Receptors (RXRs) consist of a family of nuclear receptors that target and regulate multiple signalling pathways. The early evolutionary emergence of RXRs in comparison to other nuclear receptors may have allowed for the development of unique properties as transcriptional regulators. Indeed, the complexity of these receptors is derived from their ability to activate transcription as homodimers or as obligate heterodimeric partners of a multitude of other nuclear receptors. In addition, RXRs can regulate gene expression in a ligand-dependent (forming permissive heterodimeric complexes) or - independent (forming non-permissive heterodimeric complexes) manner. Given that ligand binding is a critical component of RXR function, this review will focus on the ligand dependent functions of RXR. The remarkably conserved ligand binding domain of RXR is a multi-functional structure that in addition to ligand binding, serves as a homo- and heterodimeric interface, and a region to bind coactivactor and corepressor molecules. RXRs have a small ligand binding pocket and therefore bind their ligands (such as 9-cis RA) with both high affinity and specificity. In the presence of ligand, permissive RXR heterodimers bind coactivators, but nonpermissive complexes can bind coactivators or corepressors depending on the activation of the RXR's heterodimeric partner. Physiologically, the temporal and tissue specific pattern of RXRs as well as the presence of phenotypic abnormalities in receptor knockout studies (most severe in RXRa -/- animals) demonstrate the important role for these receptors both during development (morphogenesis) and in adult differentiated tissues (cell proliferation, cell differentiation, cell death). These receptors also play an important regulatory role metabolic signaling pathways (glucose, fatty acid and cholesterol metabolism), including metabolic disorders such as type 2 diabetes, hyperlipidemia and atherosclerosis. RXRs function as master regulators producing diverse physiological effects through the activation of multiple nuclear receptor complexes. RXRs represent important targets for pharmacologic interventions and therapeutic applications.

Animals↗

PubMed1994

Freeze-fracture and thin section study of the rough ER-Golgi interface in the pancreatic acinar cell. Resemblance between the intramembranal architecture of the outermost Golgi cisterna and the post-rough ER vesicular and tubular elements.

Post-ER membranous structures are clearly observed in pancreases fixed with aldehydes and subsequently with reduced osmium. Close to the transitional rough ER, clusters of vesicles of approximately 56 nm diameter are consistently present. In some cells, tortuous tubules appear enmeshed by the approximately 56 nm vesicles and by irregular, vesicular formations. In freeze-fracture replicas, the membranes of the bulges and tubules that protrude from the transitional rough ER differ from those of the donor compartment. These protrusions are herein designated as the budding chamber of the transitional rough ER. Quantitative and qualitative observations performed previously and in the present study show that the P and E freeze-fracture faces of the outermost Golgi cisternal membrane possess patterns of texture that are unique among membranes. The P-face exhibits a very high density of intramembranous particles of dimensions among the smallest yet described; E-faces show rugosities and an unusually high density of intramembranous particles of normal size. The membranes of the budding chamber, the putative transport vesicles of approximately 56 nm diameter, the sinuous tubules and the vesicles of irregular size and shape exhibit P and E fracture faces with textures indistinguishable from those of the corresponding P and E faces of the outermost Golgi cisterna.

Animals↗

PubMed2005

Avidin related protein 2 shows unique structural and functional features among the avidin protein family.

BACKGROUND: The chicken avidin gene family consists of avidin and several avidin related genes (AVRs). Of these gene products, avidin is the best characterized and is known for its extremely high affinity for D-biotin, a property that is utilized in numerous modern life science applications. Recently, the AVR genes have been expressed as recombinant proteins, which have shown different biotin-binding properties as compared to avidin. RESULTS: In the present study, we have employed multiple biochemical methods to better understand the structure-function relationship of AVR proteins focusing on AVR2. Firstly, we have solved the high-resolution crystal structure of AVR2 in complex with a bound ligand, D-biotin. The AVR2 structure reveals an overall fold similar to the previously determined structures of avidin and AVR4. Major differences are seen, especially at the 1-3 subunit interface, which is stabilized mainly by polar interactions in the case of AVR2 but by hydrophobic interactions in the case of AVR4 and avidin, and in the vicinity of the biotin binding pocket. Secondly, mutagenesis, competitive dissociation analysis and differential scanning calorimetry were used to compare and study the biotin-binding properties as well as the thermal stability of AVRs and avidin. These analyses pinpointed the importance of residue 109 for biotin binding and stability of AVRs. The I109K mutation increased the biotin-binding affinity of AVR2, whereas the K109I mutation decreased the biotin-binding affinity of AVR4. Furthermore, the thermal stability of AVR2(I109K) increased in comparison to the wild-type protein and the K109I mutation led to a decrease in the thermal stability of AVR4. CONCLUSION: Altogether, this study broadens our understanding of the structural features determining the ligand-binding affinities and stability as well as the molecular evolution within the protein family. This novel information can be applied to further develop and improve the tools already widely used in avidin-biotin technology.

Amino Acid Sequence↗

PubMed2001

The traumatization of grief? A conceptual framework for understanding the trauma-bereavement interface.

Scientific opinion differs on whether pathological (or complicated, traumatic) grief is an entity distinct from post-traumatic stress disorder. Some argue that it is different, and for the creation of a new category of pathological grief for the DSM system, while others consider bereavement and associated grief reactions to fall within the category of traumatic life events, for which the existing system would offer adequate classification. Although investigators have begun to explore similarities and differences in the trauma and bereavement domains, there is still confusion and lack of consensus about definitions and basic concepts. A conceptual framework, suggested here, may help bring clarity to the area. Our analysis shows that the lack of consensus about the nature of reactions and disorders of bereavement is due to concentration on different parts of the framework. Furthermore, the lack of differentiation between traumatic and non-traumatic bereavement has caused neglect of the unique features of non-traumatic grief reactions. These components need further exploration, especially since extension of DSM classification is currently under consideration.

Adaptation, Psychological↗

PubMed2005

DATF: a database of Arabidopsis transcription factors.

UNLABELLED: We have probably developed the most comprehensive database of Arabidopsis transcription factors (DATF). The DATF contains known and predicted Arabidopsis transcription factors (1827 genes in 56 families) with the unique information of 1177 cloned sequences and many other features including 3D structure templates, EST expression information, transcription factor binding sites and nuclear location signals. AVAILABILITY: DATF is freely available at http://datf.cbi.pku.edu.cn

Amino Acid Sequence↗

PubMed2006

Organisation of the mouse sinoatrial node: structure and expression of HCN channels.

OBJECTIVE: To reveal the structural characteristics of the sinoatrial node (SAN) and the distribution of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) in the SAN in the mouse. METHODS: The structure of the SAN and the distribution of HCN channels in the SAN in the mouse were studied by histology and immunolabelling of ANP, Cx43 and HCN channels. RESULTS: The mouse SAN is a comma-shaped structure with a length of approximately 1.5 mm parallel to the crista terminalis and is separated from atrial muscle by connective tissue at the border both with the crista terminalis and the atrial septum. A unique compact nodal structure with densely-packed nodal cells was identified at the head of the comma-shaped SAN. Cell size and fibre orientation vary regionally in the SAN: the cells in the compact node are small and are orientated perpendicular to the crista terminalis, whereas the cells in the more inferior part are larger and more loosely-packed and are orientated parallel to the crista terminalis. All SAN cells exhibited labelling of HCN4, but no cell exhibited detectable labelling of HCN1, HCN2, ANP and Cx43, while surrounding atrial cells exhibited labelling of ANP and Cx43, but not HCN1, HCN2 and HCN4. A specialised interface between the SAN and surrounding atrial muscle was also identified: strands of HCN4-positive nodal cells protrude into the atrial muscle and strands of Cx43-positive atrial cells protrude into the SAN; thus, there are interdigitations between the SAN and atrial muscle. CONCLUSIONS: In the mouse, (i) the SAN is structurally complex with a densely-packed head and loosely-packed tail; (ii) HCN4 is the only HCN isoform detectable and is present throughout the SAN; and (iii) there is a specialised interface between the SAN and surrounding atrium that may be necessary for the SAN to drive the more hyperpolarized atrial muscle.

Action Potentials↗

PubMed1998

Noninvasive positive-pressure ventilation in chronic obstructive pulmonary disease.

Interest in noninvasive positive-pressure ventilation both as an alternative to intubation and mechanical ventilation and as a unique therapy has grown over recent years. Clinical and patient acceptance is highest in neuromuscular deficits, but supporting evidence for its use in chronic obstructive pulmonary disease is highly dependent on the application. This review considers the clinical implementation of noninvasive positive-pressure ventilation in acute respiratory failure, as a postextubation weaning alternative, in stable severe hypercapnic chronic obstructive pulmonary disease, in overlap syndrome, and for nocturnal oxygen desaturation. Some applications are well supported, leading to a cautious recommendation for its utilizatip4, whereas for others evidence is starkly conflicting. The clinical efficacy of noninvasive positive-pressure ventilation is vastly dependent on equipment, equipment-patient interface, pressure settings, physician's bedside manner, and experience of the center. Interpretation of the studies must take into account the foregoing factors along with the various ventilatory techniques and differing primary outcome measures. Generalizations can be made regarding indications and contraindications, but this is an area rife with exceptions. The subtle message from the clinical studies describes the importance of the clinical art applied from the palette of science and technology.

Acute Disease↗

PubMed2004

Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity.

The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in human malignancies, resulting in the formation of oncogenic ETV6 gene fusions. Many of the known partner genes encode protein tyrosine kinases (PTKs), generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN), comprised of the ETV6 SAM domain fused to the NTRK3 PTK, is unique among ETV6 chimeric oncoproteins, as it is expressed in cancers of multiple lineages. We initially hypothesized that, similar to other ETV6-PTK chimeras, SAM-mediated dimerization of EN leads to constitutive activation of the PTK and downstream signaling cascades. However, when the EN SAM domain was replaced with an inducible FK506 binding protein (FKBP) dimerization system, resulting FKBP-NTRK3 chimeras failed to transform NIH 3T3 cells even though PTK activation was preserved. It was recently shown that the ETV6 SAM domain has two potential interacting surfaces, raising the possibility that this domain can mediate protein polymerization. We therefore mutated each EN SAM binding interface in a manner shown previously to abolish self-association of wild-type ETV6. Each mutation completely blocked the ability of EN to polymerize, to activate its PTK, and to transform NIH 3T3 cells. Furthermore, EN itself formed large polymeric structures within cells while mutant EN proteins were present only as monomers. Finally, we observed a dominant negative effect on the transformation of isolated SAM domains coexpressed in EN-transformed cells. Taken together, our results suggest that higher-order polymerization may be a critical requirement for the transformation activity of EN and possibly other ETV6-PTK fusion proteins.

Animals↗

PubMed2002

Group for research in pathology education online resources to facilitate pathology instruction.

BACKGROUND: The Group for Research in Pathology Education (GRIPE) is an organization of pathology educators whose purpose is to promote and facilitate excellence in pathology education. One important function of GRIPE is the maintenance of image and multiple-choice test question data banks. These resources have recently been made available online via the GRIPE Digital Library Web site. The purpose of the GRIPE Digital Library project was to develop an online searchable database that would facilitate access to the GRIPE resources for pathology education. DESIGN: The GRIPE image bank--containing approximately 3000 peer-reviewed gross and microscopic pathologic images along with textual descriptions--was linked with the GRIPE test question bank using Gossamer Thread's DBMan Web database management program. The search and display templates create a functional user interface that integrates images, image descriptions, and test questions into a single online digital library. Using any Web browser, faculty can access the GRIPE Digital Library and search for images and/or test items that can be used in teaching. RESULTS: In the first 18 months (February 2000 through July 2001), users at 40 GRIPE member institutions signed up and used the GRIPE Digital Library to perform more than 6000 individual searches and view more than 37500 images. These digital images were used to produce lectures and laboratory modules that were posted on Web pages and made available to students remotely. CONCLUSIONS: The GRIPE Digital Library provides a unique resource that can facilitate development of educational materials for pathology instruction and helps to fulfill the educational mission of GRIPE.

Computer Communication Networks↗

PubMed2001

Optimizing brain tumor resection. Midfield interventional MR imaging.

The development of the intraoperative MR imager represents an important example of creative vision and interdisciplinary teamwork. The result is a remarkable tool for neurosurgical applications. MRT allows surgical manipulation under direct visualization of the intracranial contents through the eye of the surgeon and through the volumetric images of the MR imaging system. This technology can be applied to cranial and spinal cases, and forseeably can encompass application to the entire gamut of neurosurgical efforts. The author's experience has been that this device is easy and comfortable for the surgeon to use. Image acquisition, giving views in the plane of choice, lasts no more than 2 to 60 seconds (depending on the imaging method), and does not increase the duration of a given procedure substantially. The author believes that the information received through intraoperative MR imaging scanning ultimately will contribute to decreasing the duration of surgery. Future possibilities include combining the intraoperative MR imager with other technologies, such as the endoscope, focused ultrasound, robotics, and the evaluation of brain function intraoperatively. The development of the intraoperative MR imager marks a significant advance in neurosurgery, an advance that will revolutionize intraoperative visualization as fully as the operating microscope. The combination of intraoperative visualization and precise surgical navigation is unparalleled, and its enhancement of surgical applications will be widespread. Considering the remarkable potential of the intraoperative MR imager for neurosurgical applications, optimal magnet design, image quality, and navigational methods are necessary to capitalize on the advantages of this revolutionary tool. The intraoperative MR imaging system that the author's team has developed and used has combined these features, and allows the performance of open surgical procedures without the need of patient or magnet repositioning. By using advanced navigational tools and computer technology, it represents an integration of frameless stereotactic methods with real-time interactive imaging. The midfield imager provides sufficient spatial and temporal resolution and image quality to assess anatomy and pathology adequately, to monitor a surgical procedure, and make image-based decisions. The intraoperative use of this unique system is not limited to biopsies or limited-access procedures. The entire range of neurosurgical procedures can be performed, if the requisite instrumentation is available. Much work remains to be done, however. The team did not develop this system only to enable the performance of current neurosurgical procedures. Forty years ago, the operating microscope enabled not only the performance of undreamt-of procedures but opened the door to entire new subspecialties. The entire landscape of neurosurgery will change at a fundamental level as the full ramifications of this exciting idea come to fruition. The holy grail of image-guided surgery is a seamless interface between the eye and hand in the purest sense (i.e., the mind's eye and hand). Ideally, this seamless interface represents effortless flow between the procedural goal compared with the present situation and the manipulation of the tools available to accomplish the task, whether they be the scalpel, drill, laser, ultrasonic aspirator, phased array focused ultrasound, microrobot, or high-dose irradiator. As in the realm of high-performance military jet fighters, the physical limits of the human being demarcate the confining boundary of the system. Those limits are much tighter around the domain of tool manipulation, where the surgeon will yield, early on, to the enhanced performance of robotics and other technical adjuncts. The era of large open magnet imaging systems for surgical procedures then will come to a close; however, the grander era of the surgeon's integration of precision-guided, multimodality therapeutics will just be beginning. The future will be very bright, indeed.

Adult↗

PubMedDate not supplied

Glass ionomer cement, an intelligent material.

The main task of a dental filling material is to permanently seal the dentinal wound and to restore the anatomy. In particular with respect to the former requirement, glass-ionomer cements exhibit, thanks to it's ingenious composition, unique properties, which allows it to react on external information in such a way that the cement automatically and adequately fulfills it's function as a proper restorative material. Because of it's setting mechanism, glass-ionomer cement restorations have a better perspective to seal the tissue than amalgam or resin composites do. As resistance to wear of glass ionomers is inferior to resin composites it proves to be a better dentin replacement, than a substitute for tooth enamel. Restorations made in a combination of glass-ionomer cement and resin composite, the so called sandwich restorations, have shown to function excellently, both at the tooth interface as well as the outer surface. As any leakage still cannot be excluded, the fluoride release at the margins of the restoration forms a wellcome contribution to the prevention of secondary caries. Once more, glass-ionomer cement shows to be intelligent by automatically activating an advantageous process when the environment requires it.

Dental Bonding↗

PubMed1993

The policy-research interface: an insider's view.

This paper is a summary of some illuminating comments made by the author when invited to discuss some of the above papers in the area of liquor licensing and availability. Prior to his appointment as the Director and Government Printer of State Print in South Australia, the author had been the first Director of Liquor Licensing in Western Australia. In that capacity he was responsible for undertaking a major review of the Liquor Act in Western Australia and in implementing a new administrative structure. He was subsequently appointed as the Chief Executive Officer of the Western Australian Totalisator Agency Board (which is responsible for off-course betting on horse and greyhound racing) before returning to South Australia. The author's experience of reviewing liquor licensing legislation in both South Australia and Western Australia, and his administration of a licensing authority provides him, in the Editors' view, with unique insights into the working of governments and the formulation of policy in this area. His paper is presented here in the form in which it was given at the conference.

Alcohol Drinking↗

PubMed1999

The variable and conserved interfaces of modeled olfactory receptor proteins.

The accumulation of hundreds of olfactory receptor (OR) sequences, along with the recent availability of detailed models of other G-protein-coupled receptors, allows us to analyze the OR amino acid variability patterns in a structural context. A Fourier analysis of 197 multiply aligned olfactory receptor sequences showed an alpha-helical periodicity in the variability profile. This was particularly pronounced in the more variable transmembranal segments 3, 4, and 5. Rhodopsin-based homology modeling demonstrated that the inferred variable helical faces largely point to the interior of the receptor barrel. We propose that a set of 17 hypervariable residues, which point to the barrel interior and are more extracellularly disposed, constitute the odorant complementarity determining regions. While 12 of these residues coincide with established ligand-binding contact positions in other G-protein-coupled receptors, the rest are suggested to form an olfactory-unique aspect of the binding pocket. Highly conserved olfactory receptor-specific sequence motifs, found in the second and third intracellular loops, may comprise the G-protein recognition epitope. The prediction of olfactory receptor functional sites provides concrete suggestions of site-directed mutagenesis experiments for altering ligand and G-protein specificity.

Amino Acid Sequence↗

PubMed2003

Structural analysis of lipid complexes of GM2-activator protein.

The GM2-activator protein (GM2-AP) is a small lysosomal lipid transfer protein essential for the hydrolytic conversion of ganglioside GM2 to GM3 by beta-hexosaminidase A. The crystal structure of human apo-GM2-AP is known to consist of a novel beta-cup fold with a spacious hydrophobic interior. Here, we present two new structures of GM2-AP with bound lipids, showing two different lipid-binding modes within the apolar pocket. The 1.9A structure with GM2 bound shows the position of the ceramide tail and significant conformational differences among the three molecular copies in the asymmetric unit. The tetrasaccharide head group is not visible and is presumed to be disordered. However, its general position could be established through modeling. The structure of a low-pH crystal, determined at 2.5A resolution, has a significantly enlarged hydrophobic channel that merges with the apolar pocket. Electron density inside the pocket and channel suggests the presence of a trapped phospholipid molecule. Structure alignments among the four crystallographically unique monomers provide information on the potential role for lipid binding of flexible chain segments at the rim of the cavity opening. Two discrete orientations of the S130-T133 loop define an open and a closed configuration of the hydrophobic channel that merges with the apolar pocket. We propose: (i) that the low-pH structure represents an active membrane-binding conformation; (ii) that the mobile S130-T133 loop serves as a gate for passage of ligand into the apolar pocket; and (iii) that this loop and the adjacent apolar V59-W63 loop form a surface patch with two exposed tryptophan residues that could interface with lipid bilayers.

Apoproteins↗

PubMed1999

Touch-pad technology: immediate feedback for resident educators in teenage reproductive health.

OBJECTIVE: To describe a program for residents in obstetrics and gynecology to design, research, and present an innovative teaching activity to secondary-school students in reproductive health. METHODS: An interactive 3-hour assembly was held for 285 grade-9 and -10 students. Six residents chose topics that encompassed key areas in adolescent health (menstruation, contraception, risk-taking behaviors, sexuality, and sexually transmitted diseases [STDs]). Each gave an interactive presentation designed to address issues identified through anonymous questions submitted by the students in advance. Touch-pad technology was used throughout the presentations to ascertain the students' knowledge about, and attitudes toward, a range of reproductive health issues. Each resident participant completed a follow-up questionnaire. RESULTS: Touch-pads provided a unique format, allowing teens to respond candidly to sensitive topics anonymously while providing important feedback to resident educators to help them focus their presentations and address areas of greatest need. Resident participants reported that by preparing these presentations, they honed their knowledge about contraception, STDs, and teen sexuality; identified important community resources for teens; and were sensitized to issues unique to teen sexual-health counseling. CONCLUSION: This project provided an opportunity for residents to improve their knowledge of teenage sexuality and to develop skills as teachers, while forging a valuable link between the community and the university.

Computer-Assisted Instruction↗