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PubMed1999

Human immunodeficiency virus type 1 and mucosal humoral defense.

Mucosal sites serve as the principle venues through which primary human immunodeficiency virus type 1 (HIV-1) infections are transferred from donor to host. These moist tissues, which provide the interface with the external environment, also provide access to many of the secondary opportunistic infections that aggravate and may accelerate HIV-1 disease. Antibodies to HIV-1, particularly of the IgG rather than the IgA class, have been detected in virtually all mucosal fluids from HIV-1-infected patients. However, the ability of such patients to generate de novo humoral responses to new mucosal pathogens is impaired. Current studies are directed to characterizing the functional role of natural and infection-derived antibodies in control of HIV-1 infection as well as the impact of HIV-1 disease on mucosal B cell responses to immunization and infection.

Female↗
PubMed1977

Immune responses of BALB/c mice to the idiotype of T15 and of other myeloma proteins of BALB/c origin: implications for an immune network and antibody multispecificity.

Normal adult BALB/c mice are virtually unresponsive to the idiotype of myeloma protein T15 when immunized with purified T15. However, antibodies to the T15 idiotype can be elicited by T15 in BALB/c mice that are reared in a germ-free environment or injected as newborns with an alloantiserum to the idiotype. Some germ-free and neonatally suppressed mice also produce helper cells (presumably T helpers) that enhance B-cell production of anti-DNP antibodies in response to DNP-T15. Taken together with previous studies, the present results mean that so far there are no exceptions to the rule that BALB/c mice have B and T cells that can respond to idiotypes of myeloma proteins of BALB/c origin. There appears to be a reciprocal relation between the natural prevalence of an immunoglobulin's idiotype and its immunogenicity in isologous individuals. The findings support proposals for an immune network of idiotypes and anti-idiotypes. Besides binding one or more extrinsic antigens, it is likely that each immunoglobulin also binds the idiotype of some other immunoglobulin. An immune network therefore implies multispecificity of antibodies.

Animals↗
PubMed1994

Universal barrier to lateral spread of specific genes among microorganisms.

A genetic circuit to suppress the lateral spread of cloned genes from recombinant to indigenous microorganisms in the environment has been developed. It is based on the endonucleolytic activity of the bacterial toxin colicin E3, which has a distinct target at the 3' end of the 16S ribosomal RNA; this sequence is conserved in virtually all prokaryotic and many eukaryotic genera. Cleavage at this sequence separates the mRNA binding sites from the remainder of the 16S rRNA, thereby inhibiting protein synthesis. While host bacteria carrying the genes for both colicin production and colicin immunity are perfectly viable, lateral transfer of the E3 gene to non-immune recipients results in killing of such recipients. This genetic circuit decreases operational transfer frequencies of cloned genes linked to the E3 gene among a variety of bacterial genera by four to five orders of magnitude. In combination with transposon cloning vectors, the circuit is predicted to reduce the rate of lateral spread of specific genes to ecologically insignificant levels. This system therefore represents a useful tool both to explore the evolutionary and ecological consequences of experimentally reducing lateral gene spread among microorganisms, and to increase the ecological predictability of novel recombinant microorganisms.

Bacteria↗
PubMed1967

The effects of chronic hypoxemia on electrolyte and acid-base equilibrium: an examination of normocapneic hypoxemia and of the influence of hypoxemia on the adaptation to chronic hypercapnia.

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid-base and electrolyte equilibrium. During the first phase of observation we produced a state of "pure" hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO(2) tension (PCO(2)) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition. During the second phase of observation we subjected the hypoxemic dogs to stepwise increments in arterial carbon dioxide tension in order to evaluate the effects of the low oxygen tension on the acid-base adjustments to a chronic state of hypercapnia. At least 6 days was allowed for extracellular composition to reach a new steady state at each level of inspired carbon dioxide. The data demonstrate a rise in both plasma bicarbonate concentration and renal acid excretion that was not significantly different from that which has been described previously for hypercapnia without hypoxemia. Just as in these earlier studies, plasma hydrogen ion concentration rose with each increment in carbon dioxide tension, each millimeter Hg increment in PCO(2) leading to an increase in hydrogen ion concentration of 0.32 nmole per L. It thus appears that the chronic"carbon dioxide response curve" is not significantly influenced by moderately severe hypoxemia.

Acid-Base Equilibrium↗
PubMed2004

Video capture virtual reality as a flexible and effective rehabilitation tool.

Video capture virtual reality (VR) uses a video camera and software to track movement in a single plane without the need to place markers on specific bodily locations. The user's image is thereby embedded within a simulated environment such that it is possible to interact with animated graphics in a completely natural manner. Although this technology first became available more than 25 years ago, it is only within the past five years that it has been applied in rehabilitation. The objective of this article is to describe the way this technology works, to review its assets relative to other VR platforms, and to provide an overview of some of the major studies that have evaluated the use of video capture technologies for rehabilitation.

Journal Article↗
PubMed2005

NEOBASE: databasing the neocortical microcircuit.

Mammals adapt to a rapidly changing world because of the sophisticated perceptual and cognitive function enabled by the neocortex. The neocortex, which has expanded to constitute nearly 80% of the human brain seems to have arisen from repeated duplication of a stereotypical template of neurons and synaptic circuits with subtle specializations in different brain regions and species. Determining the design and function of this microcircuitry is therefore of paramount importance to understanding normal and abnormal higher brain function. Recent advances in recording synaptically-coupled neurons has allowed rapid dissection of the neocortical microcircuitry thus yielding a massive amount of quantitative anatomical, electrical and gene expression data on the neurons and the synaptic circuits that connect the neurons. Due to the availability of the above mentioned data, it has now become imperative to database the neurons of the microcircuit and their synaptic connections. The NEOBASE project, aims to archive the neocortical microcircuit data in a manner that facilitates development of advanced data mining applications, statistical and bioinformatics analyses tools, custom microcircuit builders, and visualization and simulation applications. The database architecture is based on ROOT, a software environment that allows the construction of an object oriented database with numerous relational capabilities. The proposed architecture allows construction of a database that closely mimics the architecture of the real microcircuit, which facilitates the interface with virtually any application, allows for data format evolution, and aims for full interoperability with other databases. NEOBASE will provide an important resource and research tool for studying the microcircuit basis of normal and abnormal neocortical function. The database will be available to local as well as remote users using Grid based tools and technologies.

Animals↗
PubMed1976

Platelet cyclic 3':5'-nucleotide phosphodiesterase released by thrombin and calcium ionophore.

Contact of rat platelets with thrombin or the divalent cation ionophore A-23187, in the presence of extracellular calcium, resulted in the secretion of adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) phosphodiesterases. Significant association of calcium with platelets occurred during platelet surface contact with thrombin. Thrombin concentration to induce association of calcium virtually agreed with that to release the enzyme. The finding that A-23187 (5 to 20 muM) also provoked a rapid and marked association of extracellular calcium with platelets suggests that calcium mobilization into the intracellular environment may account, at least in part, for this association between platelet and calcium. Two different phosphodiesterases, a relatively specific cyclic AMP and a relatively specific cyclic GMP phosphodiesterase were secreted from platelets into the plasma in soluble form. The amounts of the phosphodiesterases secreted were dose- or time-dependent on thrombin (0.1 to 2 units) or A-23187 (5 to 20 muM) within 30 min. The enzyme release by thrombin was completely inhibited by heparin but the release by A-23187 was not. The two phosphodiesterases secreted seemed to correspond to the two enzymes isolated from platelet homogenates in many respects. Rat platelets contained, at least, three cyclic 3':5'-nucleotide phosphodiesterases, namely, two relatively specific cyclic AMP phoshodiesterases and a relatively specific cyclic GMP phosphodiesterase which were clearly separated from each other by Sepharose 6B or DEAE-cellulose column chromatography or sucrose gradient centrifugation. The two platelet cyclic AMP phosphodiesterase (Mr = 180,000 and 280,000) had similar apparent Km values of 0.69 and 0.75 muM with different sedimentation coefficient values of 4.9 S and 7.1 S, respectively. They did not hydrolyze cyclic GMP significantly. A cyclic GMP phosphodiesterase (Mr - 260,000) exhibited abnormal kinetics for cyclic GMP with an apparent Km value of 1.5 muM and normal kinetics for cyclic AMP with a Km of 300 muM. The properties of a platelet cyclic AMP phosphodiesterase (Mr = 180,000) and a platelet cyclic GMP phosphodiesterase were found to agree with those of the two phosphodiesterases released from platelets by thrombin or A-23187. Depletion of extracellular calcium by an addition of citrate, EDTA, or ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) to the blood or platelet suspension resulted in a loss of the activity of the smaller form of platelet cyclic AMP phosphodiesterase (Mr = 180,000) and addition of calcium restored the activity of this cyclic AMP phosphodiesterase. Thus, calcium seemed to be involved in the mechanism of an occurrence of this smaller form of cyclic AMP phosphodiesterase as well as the secretion of this enzyme. Contact of human platelets with thrombin also resulted in the secretion of cyclic nucleotide phosphodiesterase which was dependent on the concentration of calcium. No species difference was observed in this respect.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Well-designed and well-administered executive incentive plans do work.

Executive incentive plans in the health-care industry, virtually unheard of a decade ago, are becoming a critical part of the overall integrated management system. These plans are necessary today to drive improved performance and overall success in the increasingly difficult health-care environment. This article describes (1) incentive growth, (2) the components of a successful executive incentive program, (3) how an incentive program drives business strategies, performance, and philosophy, and (4) the overall benefits of a well-designed and well-administered program.

Communication↗
PubMed2005

Partitioning respiration of C3-C4 mixed communities using the natural abundance 13C approach--testing assumptions in a controlled environment.

Contributions of C3 and C4 plants to respiration of C3-C4 ecosystems can be estimated on the basis of their contrasting 13C discrimination. But accurate partitioning requires accurate measurements of the isotope signature of whole system respiratory CO2 (deltaR), and of its members (delta3 and delta4). Unfortunately, experimental determination of representative delta3 and delta4 values is virtually impossible in nature, generating a need for proxies (surrogates) of delta3 and delta4 values (e.g., the delta of leaf biomass). However, recent evidence indicates that there may be systematic differences among the delta of respiratory and biomass components. Thus, partitioning may be biased depending on the proxy. We tested a wide range of biomass- and respiration-based delta proxies for the partitioning of respiration of mixed Lolium perenne (C3) - Paspalum dilatatum (C4) stands growing at two temperatures inside large 13CO2/ 12CO2 gas exchange chambers. Proxy-based partitioning was compared with results of reference methods, including (i) the delta of whole plant respiratory CO2 (delta3 and delta4) or (ii) respiration rate of intact C3 and C4 plants. Results of the reference methods agreed near perfectly. Conversely, some proxies yielded erroneous partitioning results. Partitioning based on either the delta of shoot or root respiratory CO2 produced the worst bias, because shoot respiratory CO2 was enriched in 13C by several per thousand and root respiratory CO2 was depleted by several per thousand relative to whole plant respiratory CO2. Use of whole plant or whole shoot biomass delta gave satisfactory partitioning results under the constant conditions of the experiments, but their use in natural settings is cautioned if environmental conditions are variable and the time scales of respiration partitioning differ strongly from the residence time of C in biomass. Other biomass-based proxies with faster turnover (e.g., leaf growth zones) may be more useful in changing conditions.

Carbon↗
PubMed2004

The challenge of using virtual reality in telerehabilitation.

Continuing advances in virtual reality (VR) technology along with concomitant system cost reductions have supported the development of more useful and accessible VR systems that can uniquely target a wide range of physical, psychological, and cognitive rehabilitation concerns and research questions. VR offers the potential to deliver systematic human testing, training, and treatment environments that allow for the precise control of complex dynamic three-dimensional stimulus presentations, within which sophisticated interaction, behavioral tracking, and performance recording is possible. The next step in this evolution will allow for Internet accessibility to libraries of VR scenarios as a likely form of distribution and use. VR applications that are Internet deliverable could open up new possibilities for home-based therapy and rehabilitation. If executed thoughtfully, they could increase client involvement, enhance outcomes and reduce costs. However, before this vision can be achieved, a number of significant challenges will need to be addressed and solved. This article will first present three fictional case vignettes that illustrate the ways that VR telerehabilitation might be implemented with varying degrees of success in the future. We then describe a system that is currently being used to deliver virtual worlds over the Internet for training safety skills to children with learning disabilities. From these illustrative fictional and reality-based applications, we will then briefly discuss the technical, practical, and user-based challenges for implementing VR telerehabilitation, along with views regarding the future of this emerging clinical application.

Adult↗
PubMed1984

Effects of luminance and flicker on ocular dominance shift in kitten visual cortex.

We raised monocularly deprived kittens in visual environments with low level illumination that was either steady or flickering. With steady scotopic luminance ocular dominance shifted as it does in normal photopic lighting. In flickering light with an average frequency of 2 Hz there was virtually no ocular dominance shift, while in flickering light averaging 0.1 Hz there was a significant shift. Recordings from the 2 Hz flicker-reared were similar to the dark-reared recordings. The flickering illumination was produced in one case by a high contrast-low brightness TV near the cage, and in another case, by a low voltage incandescent bulb driven by a pseudo-random sequence generator. This circuit delivered either a maximum ON time of 1.7 s or a maximum of 40 s, for the 2 Hz and 0.1 Hz respectively. Both the TV and flickering bulb produced average illumination comparable to the dim (0.01 cd/m2) steady scotopic illumination. We conclude that dim flickering light is not a sufficient stimulus for promoting ocular dominance shift in kittens in the critical period unless the flicker rate approaches 0.1 Hz. Furthermore results from the TV rearing suggest that flicker may be capable of preventing an ocular dominance shift expected from a concurrent steady low light level background.

Animals↗
PubMed2001

Engineering the pH-optimum of a triglyceride lipase: from predictions based on electrostatic computations to experimental results.

The optimisation of enzymes for particular purposes or conditions remains an important target in virtually all protein engineering endeavours. Here, we present a successful strategy for altering the pH-optimum of the triglyceride lipase cutinase from Fusarium solani pisi. The computed electrostatic pH-dependent potentials in the active site environment are correlated with the experimentally observed enzymatic activities. At pH-optimum a distinct negative potential is present in all the lipases and esterases that we studied so far. This has prompted us to propose the "The Electrostatic Catapult Model" as a model for product release after cleavage of the ester bond. The origin of the negative potential is associated with the titration status of specific residues in the vicinity of the active site cleft. In the case of cutinase, the role of Glu44 was systematically investigated by mutations into Ala and Lys. Also, the neighbouring Thr45 was mutated into Proline, with the aim of shifting the spatial location of Glu44. All the charge mutants displayed altered titration behaviour of active site electrostatic potentials. Typically, the substitution of the residue Glu44 pushes the onset of the active site negative potential towards more alkaline conditions. We, therefore, predicted more alkaline pH optima, and this was indeed the experimentally observed. Finally, it was found that the pH-dependent computed Coulombic energy displayed a strong correlation with the observed melting temperatures of native cutinase.

Amino Acid Sequence↗
PubMed1998

Integrated medical informatics with small group teaching in medical education.

National Taiwan University College of Medicine (NTUCM) introduced small groups of teaching and basic-clinical integrated courses for medical students in 1992. By using computer network and multimedia techniques, this study tried to overcome barriers to learning in small group teaching. The Department of Medical Informatics of NTUCM established campus networking and computer classrooms and provided Internet and intranet network services including mail, netnews, bulletin board systems (BBS), world wide web (WWW), gopher, ftp and local file servers. To implement an interactive learning environment, the authors first tried mail lists, newsgroups and BBS. Next an integrated learning system prototype on the WWW was developed to provide functions including online syllabus, discussion boards simulated to BBS, online talk, interactive case studies, virtual classroom with video on demand (VOD) and Internet medical resources. The results showed that after the medical students completed the required course of medical informatics and had good network access using a network to communicate with each other became a daily practice. In the future, the system will extend to the tutoring of clinical practice and continuing medical education. The authors expect a national medical education network and more international cooperation and exchange.

Curriculum↗
PubMed2001

Predicting long-range transport: a systematic evaluation of two multimedia transport models.

The United Nations Environment Program has recently developed criteria to identify and restrict chemicals with a potential for persistence and long-range transport (persistent organic pollutants or POPs). There are many stakeholders involved, and the issues are not only scientific but also include social, economic, and political factors. This work focuses on one aspect of the POPs debate, the criteria for determining the potential for long-range transport (LRT). Our goal is to determine if current models are reliable enough to support decisions that classify a chemical based on the LRT potential. We examine the robustness of two multimedia fate models for determining the relative ranking and absolute spatial range of various chemicals in the environment. We also consider the effect of parameter uncertainties and the model uncertainty associated with the selection of an algorithm for gas-particle partitioning on the model results. Given the same chemical properties, both models give virtually the same ranking. However, when chemical parameter uncertainties and model uncertainties such as particle partitioning are considered, the spatial range distributions obtained for the individual chemicals overlap, preventing a distinct rank order. The absolute values obtained for the predicted spatial range or travel distance differ significantly between the two models for the uncertainties evaluated. We find that to evaluate a chemical when large and unresolved uncertainties exist, it is more informative to use two or more models and include multiple types of uncertainty. Model differences and uncertainties must be explicitly confronted to determine how the limitations of scientific knowledge impact predictions in the decision-making process.

Decision Making↗
PubMed2006

A pair-rule gene circuit defines segments sequentially in the short-germ insect Tribolium castaneum.

In Drosophila, a hierarchy of maternal, gap, pair-rule, and segment polarity gene interactions regulates virtually simultaneous blastoderm segmentation. For the last decade, studies have focused on revealing the extent to which Drosophila segmentation mechanisms are conserved in other arthropods where segments are added sequentially from anterior to posterior in a cellular environment. Despite our increased knowledge of individual segmentation genes, details of their interactions in non-Drosophilid insects are not well understood. We analyzed the Tribolium orthologs of Drosophila pair-rule genes, which display pair-rule expression patterns. Tribolium castaneum paired (Tc-prd) and sloppy-paired (Tc-slp) genes produced pair-rule phenotypes when their transcripts were severely reduced by RNA interference. In contrast, similar analysis of T. castaneum even-skipped (Tc-eve), runt (Tc-run), or odd-skipped (Tc-odd) genes produced severely truncated, almost completely asegmental phenotypes. Analysis of interactions between pair-rule components revealed that Tc-eve, Tc-run, and Tc-odd form a three-gene circuit to regulate one another as well as their downstream targets, Tc-prd and Tc-slp. The complement of primary pair-rule genes in Tribolium differs from Drosophila in that it includes Tc-odd but not Tc-hairy. This gene circuit defines segments sequentially in double segment periodicity. Furthermore, this single mechanism functions in the early blastoderm stage and subsequently during germ-band elongation. The periodicity of the Tribolium pair-rule gene interactions reveals components of the genetic hierarchy that are regulated in a repetitive circuit or clock-like mechanism. This pair-rule gene circuit provides insight into short-germ segmentation in Tribolium that may be more generally applicable to segmentation in other arthropods.

Animals↗
PubMed1951

Determination of inherited traits of H. influenzae by desoxyribonucleic acid fractions isolated from type-specific cells.

Change of non-typable (R) strains of H. influenzae into the specific type of origin or new types (S) has been effected in vitro in a predictable fashion within a single 24 hour growth period, by a desoxyribonucleic acid-containing fraction isolated from type-specific cells of the type desired. Only a small proportion of the population of R cells are susceptible to the change induced in inherited characteristics by the desoxyribonucleic acid fraction. The data suggest that the number of susceptible cells present in any given population size varies with the specific type of origin of the R cells; a lesser degree of variation in different independent cultures of the same strain and population size has been demonstrated. The results suggest that the R H. influenzae cells which are susceptible to transformation arise as the result of mutation. It has been demonstrated that the reaction necessary for transformation takes place virtually immediately if susceptible cells are present. Furthermore it has been shown that the change which enables an R cell to form a colony of type-specific organisms has been completed within 15 minutes in an environment which does not permit cell multiplication.

DNA↗
PubMed2001

Fine-needle aspiration biopsy.

OBJECTIVES: Fine-needle aspiration biopsy (FNAB) is a technique in which a fine needle is introduced into a mass, cellular material is aspirated, and a cytological diagnosis is rendered. It separates reactive and inflammatory processes that do not require surgical intervention from neoplasia and benign from malignant tumors. FNAB lends itself to the diagnosis of palpable head and neck masses, in particular, those that persist following antibiotic treatment. STUDY DESIGN/METHODS: This clinical state-of-the-art review article is intended to provide an overview of the clinical use of FNAB in the management of head and neck masses. Relevant case histories are used to illustrate this point. RESULTS: Fine-needle aspiration biopsy has a high overall diagnostic accuracy of 95% for all head and neck masses, 95% for benign lesions, and 87% for malignant ones. CONCLUSIONS: There are virtually no contraindications, and complications are minimal. Advantages of FNAB are that it is safe and simple, it can be performed as an outpatient procedure, and it is well tolerated by patients. In the present managed care environment, it also proves cost-effective. The diagnosis is readily known to the clinician, and appropriate treatment modalities can be discussed with the patient. It is recommended as a first line of investigation in palpable head and neck masses.

Adult↗
PubMed2006

Exploring the listening experiences during guided imagery and music therapy of outpatients with depression.

The purpose of this preliminary study was to explore the listening experiences of outpatient depression sufferers who underwent guided imagery and music therapy (GIM). A purposive sampling method was performed at the psychiatric outpatient clinic of a medical center in southern Taiwan from April 2003 to June 2004. The five subjects in this study all underwent a total of eight sessions of individual GIM therapy. The researcher invited a therapist to implement the GIM therapy sessions. Researchers conducted a semi-structured, in-depth telephone interview with each subject within 24 to 48 hours after each therapy session. Eight interviews were accomplished and transcribed for each case, and then subject to content analysis. The results showed a total of 55 important listening episodes, which could be categorized into the following 5 themes: (1) leisurely wandering in very natural sceneries; (2) creation of surreal virtual surroundings; (3) recollection of past life experiences; (4) submersion in thematic music melodies; and (5) experiencing various physical relaxation events. The triggering effect represented a combination of multiple factors, including music, the individual, the therapist and environment. The theme of each patient's imagery episode was a result of the effect of the four factors, with music having the greatest impact. This study hopes to present the listening experiences of depression sufferers in GIM therapy; to make suggestions for future investigations into subsequent impacts and changes that GIM has on patients; and to, perhaps, serve as references for future clinical practice or studies.

Adult↗