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PubMed2005

Immunology of preeclampsia.

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Cytokines↗

PubMed1976

Oxygen tension and the selective tropism of K-virus for mouse pulmonary endothelium.

This study focused on the unique nature of K-virus pneumonitis in suckling mice. This process, rather than being a conventional pneumonitis, is characterized by viral replication and cytopathic effects restricted exclusively to pulmonary endothelium. The selective viral attack on this air-blood interface suggests that K-virus is an endotheliotrope that requires a richly oxygenated intracellular milieu for replication. This possibility has been explored by studies of the course of K-virus infection in suckling mice under conditions of normal (21 per cent), increased (40 per cent), and decreased (10 per cent) 02 content of inspired air. The absence of critical modulating influences of these varied environmental conditions rules out a significant role of tissue 02 concentrations as determinants of the selective tropism of K-virus.

Animals↗

PubMed2005

Interactions between catalytic and inhibitory subunits of PDE6.

Rod and cone photoreceptor guanosine 3'5'-cyclic-monophosphate phosphodiesterases (PDEs) are classified into the PDE6 family of cyclic nucleotide PDEs. A unique feature of the PDE6 enzymes is the presence of inhibitory gamma-subunits (Pgamma). The inhibitory interaction between Pgamma and the rod PDE6alphabeta catalytic subunits is critically important for understanding the mechanism of phototransduction. Recent insights into the molecular interface between Pgamma and PDE6alphabeta have been achieved using mutagenesis of Pgamma, fluorescence labeling, and crosslinking approaches.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1999

Restricted natural language processing for case simulation tools.

For Interactive Patient II, a multimedia case simulation designed to improve history-taking skills, we created a new natural language interface called GRASP (General Recognition and Analysis of Sentences and Phrases) that allows students to interact with the program at a higher level of realism. Requirements included the ability to handle ambiguous word senses and to match user questions/queries to unique Canonical Phrases, which are used to identify case findings in our knowledge database. In a simulation of fifty user queries, some of which contained ambiguous words, this tool was 96% accurate in identifying concepts.

Computer Simulation↗

PubMed1984

A versatile computer-controlled biological stimulus sequencer.

A computer-controlled stimulus sequencer has been developed. This device can be controlled by several commonly available, inexpensive 8-bit microcomputers in which the address, data, and control lines are externally accessible. Although the Apple implementation has been described, a similar interface has also been devised for the Radio Shack Color Computer. The hardware relies on the Rockwell Versatile Interface Adapter (VIA) chip (which has two 16-bit timers capable of functioning as frequency dividers, event counters, or one-shots) and a 12-bit digital-to-analog converter (DAC) chip. This hardware combination, along with software written in Basic and machine language (stored in an EPROM for turn-key operation), allows creation of a large number of unique trains that can be chained together in any sequence. This is aided by storing the train characteristics economically in the computer memory and chaining different train parameters in a link-list. Several train parameters can be incremented or decremented manually by a pair of keys. The amplitude of the train can be changed manually or under program control. Once created, the trains can be edited on the run or deleted from the sequence. The device also generates a trigger pulse that can be referenced to any pulse in a train and can be used to pretrigger an oscilloscope. The software has provision for detecting an external signal, and this information can be used to modify train parameters. The interface is interrupt driven and therefore does not require continuous use of the Basic interpreter.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

PubMedDate not supplied

The Anesthesia Simulator Consultant: simulation plus expert system.

The Anesthesia Simulator Consultant was designed to provide anesthesiologists the opportunity to practice the management of anesthesia-critical incidents. The program simulates the operating room environment in a graphic display on the screen of a personal computer. Physiologic models predict the patient responses and an automated record-keeping system produces a detailed summary of the case. An expert system provides interpretations of patient information, differential diagnosis, and treatment for abnormal patient conditions. The coupling of the simulator, recorder, and expert system creates a unique self-study and evaluation environment.

Anesthesiology↗

PubMedDate not supplied

Expert systems as computer assisted instruction systems for nursing education and training.

The ever-increasing specialization of nursing care may require nursing professionals to provide nursing care outside of their specialty. Nurses will have to familiarize themselves with a new specialization area at short notice. Fortunately, expert-systems technology can prove particularly helpful in achieving this familiarity. As such, this technology can prove a valuable tool for education and training of nursing professionals and students. This article describes the unique edge that expert systems technology provides in this context. Using VP-Expert, an expert system shell, the authors present two examples to illustrate the development of a computer aided instruction system and the unique benefits such a system offers.

Computer-Assisted Instruction↗

PubMedDate not supplied

Evolution of the multidomain protein wheat germ agglutinin.

We compared the homologous amino acid sequences of hevein and each of the four domains (A, B, C, and D) of wheat germ agglutinin and used them to construct a pseudophylogenetic tree relating these sequences to a hypothetical common ancestor sequence. In the crystal structure of the wheat germ agglutinin dimer, six pseudo-two-fold rotational symmetry axes have previously been located in addition to the true twofold axis. Four of these relate two nonidentical domains to each other in each of the four possible pairs constituting the sugar-binding sites (A1D2, A2D1, B1C2, and B2C1). The remaining two relate contiguous unique pairs of sugar-binding sites to each other (A1D2 to B1C2, and A2D1 to B2C1). These latter two sets of pairs are related to each other by the true twofold axis. Side chains that mediate sugar binding in the interfaces of each of the four pairs were found to be largely conserved. The sequence homology, taken together with these pseudo-symmetry elements in the dimer structure, suggests a pathway for the evolution of the four-domain molecule from a single-domain dimer that can be correlated with simultaneous development of the saccharide-binding sites.

Amino Acid Sequence↗

PubMed1992

Effect of amplitude of micromotion on bone ingrowth into titanium chambers implanted in the rabbit tibia.

The micromotion chamber for implantation in the rabbit tibia consists of two titanium components that have a 1 mm contiguous pore for bone ingrowth. The fixed, outer cylinder of the chamber contains a movable inner core that can be manually rotated. The model is unique because specific, discrete, daily periods of motion of a predetermined amplitude and frequency can be delivered to the ingrowing tissue. In the present study, we compared the histological and scintigraphic results of bone ingrowth into chambers having a congruently shaped interface that was moved 20 cycles/d with an amplitude of either 0.5 or 0.75 mm. Histological sections from both amplitude groups contained extensive new woven and trabecular bone, embedded in a fibrovascular network. However, the chambers with a larger amplitude of motion yielded less bone ingrowth than those with a smaller amplitude. These studies suggest that short, discrete periods of motion can stimulate the formation of fibrous tissue rather than bone using the parameters chosen in this model.

Animals↗

PubMed2005

Direct determination of effective interfacial optical constants by nonlinear optical null ellipsometry of chiral films.

Nonlinear optical null ellipsometry (NONE) measurements of chiral interfaces allowed direct experimental measurement of the linear interfacial optical constants in surface second harmonic generation (SHG) measurements. Since phase information is retained in NONE measurements, the real and imaginary components of the interfacial refractive index (n and k, respectively) were uniquely obtained from the measured chiral chi((2)) tensor elements of a fluorescein-labeled bovine serum albumin film. The sensitivity of the calculated chi((2)) tensor elements on the assumed values of the interfacial optical constants allowed measurements of n and k to four significant figures with no additional adjustable parameters and independent of molecular symmetry. The optical constants measured by SHG agreed within a relative error of 0.8% with values predicted independently using a simple effective medium approximation, also with no adjustable parameters. Additionally, those same optical constants produced relationships between the achiral chi((2)) tensor elements in excellent agreement with predictions for systems exhibiting weak orientational order. This study suggests that the far-field intensity and polarization state of the nonlinear optical beam may be largely independent of the near-field optical constants within the interfacial layer in the limit of a film thickness much less than the wavelength of light.

Journal Article↗

PubMed2003

Total protein measurement using a fiber-optic evanescent wave-based biosensor.

A novel method and instrumental system to determine the total protein concentration in a liquid sample is described. It uses a fiber optic total protein sensor (FOPS) based on the principles of fiber optic evanescent wave spectroscopy. The FOPS applies a dye-immobilized porous glass coating on a multi-mode optical fiber. The evanescent waves at the fiber optic core-cladding interface are used to monitor the protein-induced changes in the sensor element. The FOPS offers a single-step method for quantifying protein concentrations without destroying the sample. The response time and reusability of the FOPS are evaluated. This unique sensing method presents a sensitive and accurate platform for the quantification of protein.

Biosensing Techniques↗

PubMed1999

Structural characterization by computer experiments of the lipid-free LDL-receptor-binding domain of apolipoprotein E.

The structure and dynamics of the lipid-free LDL-receptor-binding domain of apolipoprotein E (apoE-RBD) has been investigated by Molecular Dynamics Simulations. ApoE-RBD in its monomeric lipid-free form is a singular four-helix bundle made up of four elongated amphipathic helices. Analysis of one 1.5 ns molecular dynamics trajectory of apoE-RBD performed in water indicates that the lipid-free domain adopts a structure that exhibits characteristics found in native proteins: it has very stable helices and presents a compact structure. Yet its interior exhibits a larger number of transient atomic-size cavities relative to that found in other proteins of similar size and its apolar side chains are more mobile. The latter features distinguish the elongated four-helix bundle as a slightly disordered structure, which shows a structural likeness with some de novo designed four-helix bundle proteins and shares with the latter a leucine-rich residue composition. We anticipate that these unique properties compared with other native helix bundles may be related to the postulated ability of apoE-RBD to undergo an opening of its bundle upon interaction with phospholipids. The distribution of empty cavities computed along the trajectory in the interface regions between the different pairs of helices reveals that the tertiary contacts in one of the interfaces are weaker suggesting that this particular interface could be more easily ruptured upon lipid association.

Algorithms↗

PubMed2002

G proteins and olfactory signal transduction.

The olfactory system sits at the interface of the environment and the nervous system and is responsible for correctly coding sensory information from thousands of odorous stimuli. Many theories existed regarding the signal transduction mechanism that mediates this difficult task. The discovery that odorant transduction utilizes a unique variation (a novel family of G protein-coupled receptors) based upon a very common theme (the G protein-coupled adenylyl cyclase cascade) to accomplish its vital task emphasized the power and versatility of this motif. We now must understand the downstream consequences of this cascade that regulates multiple second messengers and perhaps even gene transcription in response to the initial interaction of ligand with G protein-coupled receptor.

Animals↗

PubMed2004

THUMP: an immersive haptic console for surgical simulation and training.

Telerobotic systems are revolutionizing minimally invasive surgery (MIS), giving the surgeon complete control over precise dexterous movements of tiny robotic instruments. Such 'surgery-by-wire' approaches also create unique opportunities for simulation and training, as the surgeon operates at a computer-mediated haptic console. Possible extensions include offline training in simulated environments and advanced guidance and mentoring during actual operations. To explore these options and further improve telerobotic interfaces, we have constructed a two-handed, fully articulating haptic console that provides force and torque feedback as well as a stereoscopic display.

Computer Simulation↗

PubMed1997

HPLC/MS determination of buprenorphine and norbuprenorphine in biological fluids and hair samples.

An original method, based upon HPLC (high performance liquid chromatography)/Ionspray-MS, has been developed for the identification of buprenorphine (BUP) and norbuprenorphine (norBUP) in biological fluids and hair samples. Biological fluids (2 mL) are extracted at pH 8.4 by CHCl3/2-propanol/n-heptane (25:10:65, v/v) after addition of deuterated BUP (BUP-d4, 10 ng). Hair samples (40 mg) are extracted in the same conditions after decontamination by CH2Cl2, mechanical pulverization, addition of BUP-d4 (1 ng), acidic incubation (1 mL 0.1 N HCl, 56 degrees C overnight), then neutralization by NaOH. Analytes are separated on a 4-microns NovaPak C18 (Waters) column (150 by 2.0 mm, ID) with a mobile phase of acetonitrile/2 mM NH4COOH buffer, pH 3.0 (80:20, v/v; flow rate 200 microL/min; post column split 1:3). Detection is done by a Perkin-Elmer Sciex API-100 mass analyzer equipped with an ISP interface (nebulizing and curtain gas:99.95-% N2; main settings: orifice + 50 V, electron multiplier + 2400 V). The mean retention times for BUP, BUP-d4, and norBUP are 5.84, 5.79, and 4.42 min, respectively. For all compounds, mass spectra exhibit a unique, protonated molecular ion [M + H]+ at m/z 414 (norBUP), 468 (BUP), and 472 (BUP-d4), without any significant fragmentation. The lower limits of detection are 0.10 and 0.05 ng/mL blood, and 4 and 2 pg/mg hair for BUP and norBUP, respectively. BUP and norBUP concentrations measured in hair from six addicts under substitutive therapy by BUP ranged from 4 to 140 pg/mg, and from nondetected to 67 pg/mg, respectively. The good performances of this method in terms of both sensitivity and specificity make it a convenient alternative to HPLC/coulometry and GC/MS for the separate analysis of BUP and norBUP in biological samples.

Adult↗

PubMed1998

Cutaneous injuries in women athletes.

Positioned at the interface between the athlete and her sports environment, the skin bares the brunt of multiple forces, many of which result in cutaneous trauma. Although this subject has been reviewed in considerable detail, we wish to focus on those injuries which are unique to women competitors and fitness advocates either exclusively, or more commonly, with equal or greater frequency than their male counterparts. We hope that these topics will be of value to dermatology nurses in answering questions on the subject both in and out of the clinical setting.

Athletic Injuries↗

PubMed1994

Structure of a unique twofold symmetric haem-binding site.

Bacterioferritin of Escherichia coli, also known as cytochrome b1, is a hollow, nearly spherical shell made up of 24 identical protein subunits and 12 haems. We have solved this structure in a tetragonal crystal form at 2.9 A resolution. We find that each haem is bound in a pocket formed by the interface between a pair of symmetry-related subunits. The quasi-twofold axis of the haem is closely aligned with the local twofold axis relating these subunits. The axial ligands of the haem are sulphurs of two equivalent methionyl residues (Met 52) from the symmetry-related subunits. A cluster of four water molecules is trapped in the gap between the upper edge of the haem and two extended protein loops which close off the haem from the outer aqueous environment. This is the first structure of a bis-methionine ligated haem-binding site and the first case of a twofold symmetric haem-binding site.

Bacterial Proteins↗

PubMed2001

Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria.

Indolicidin, an antimicrobial peptide with a unique amino acid sequence (ILPWKWPWWPWRR-NH(2)) is found in bovine neutrophils. A derivative of indolicidin, CP10A, has alanine residues substituted for proline residues and has improved activity against Gram-positive organisms. Transmission electron microscopy of Staphylococcus aureus and Staphylococcus epidermidis treated with CP10A showed mesosome-like structures in the cytoplasm. The peptide at 2-fold the minimal inhibitory concentration did not show significant killing of S. aureus ISP67 (a histidine, uridine, and thymidine auxotroph) but did show an early effect on histidine and uridine incorporation and, later, an effect on thymidine incorporation. Upon interaction with liposomes, detergents, and lipoteichoic acid, CP10A was shown by circular dichroism spectroscopy to undergo a change in secondary structure. Fluorescence spectroscopy indicated that the tryptophan residues were located at the hydrophobic/hydrophilic interface of liposomes and detergent micelles and were inaccessible to the aqueous quencher KI. The three-dimensional structure of CP10A in the lipid mimetic dodecylphosphocholine was determined using two-dimensional NMR methods and was characterized as a short, amphipathic helical structure, whereas indolicidin was previously shown to have an extended structure. These studies have introduced a cationic peptide with a unique structure and an ability to interact with membranes and to affect intracellular synthesis of proteins, RNA, and DNA.

Antimicrobial Cationic Peptides↗