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Information Systems↗
Biomedical subjects
S M Smith
Publications and source records attributed to S M Smith.
Conditional reduction of human immunodeficiency virus type 1 replication by a gain-of-herpes simplex virus 1 thymidine kinase function.
The development of an effective vaccine for human immunodeficiency virus type 1 (HIV-1) would be a major advance toward controlling the AIDS pandemic. Several disparate strategies for a safe and effective HIV vaccine have been proposed. Recent data suggest that loss-of-function live-attenuated virus could be a safe lentivirus vaccine. Here, we propose a gain-of-function approach that can complement loss-of-function in enhancing the safety profile of a live-attenuated virus. We describe an example in which ganciclovir (GCV) was used to treat effectively nef(-)HIV-1 engineered to express herpes simplex virus (HSV-1) thymidine kinase (TK). This treatment was found to be highly efficient in controlling HIV-1 spread in tissue culture and in a small animal (hu-PBL-SCID) model. We demonstrate that one distinct advantage of GCV-HSV-TK treatment is the elimination of integrated proviruses, a goal not easily achieved with other antiretrovirals.
AIDS Vaccines↗
Potato D-enzyme catalyzes the cyclization of amylose to produce cycloamylose, a novel cyclic glucan.
Potato D-enzyme was purified from recombinant Escherichia coli, and its action on synthetic amylose (average Mr of 320,000) was analyzed. D-enzyme treatment resulted in a decrease in the ability of the amylose to form a blue complex with iodine. Analysis of the products indicated that the enzyme catalyzes an intramolecular transglycosylation reaction on amylose to produce cyclic alpha-1,4-glucan (cycloamylose). Confirmation of the cyclic structure was achieved by demonstrating the absence of reducing and nonreducing ends, resistance to hydrolysis by glucoamylase (an exoamylase), and by "time of flight" mass spectrometry. The degree of polymerization of cycloamylose products was determined by time of flight mass spectrometry analysis and by high-performance anion-exchange chromatography following partial acid hydrolysis of purified cycloamylose molecules and was found to range from 17 to several hundred. The yield of cycloamylose increased with time and reached >95%. D-enzyme did not act upon purified cycloamylose, but if glucose was added as an acceptor molecule, smaller cyclic and linear molecules were produced. The mechanism of the cyclization reaction, the possible role of the enzyme in starch metabolism, and the potential applications for cycloamylose are discussed.
Chromatography, Gel↗
Distinct cis-acting elements direct the germination and sugar responses of the cucumber malate synthase gene.
The malate synthase gene (ms) promoter in cucumber (Cucumis sativus L.) was investigated with the aim of distinguishing DNA sequences mediating regulation of gene expression by sugar, and expression following seed germination. Promoter deletions were constructed and their ability to direct expression of the beta-glucuronidase (gus) reporter gene was investigated in transgenic Nicotiana plumbaginifolia. Gene expression was assayed in germinating seeds and developing seedlings (the germination response) and in seedlings transferred from light into darkness with and without sucrose (the sugar response). As progressively more of the promoter was deleted from the 5' end, first the sugar response and then the germination response was lost. Thus, distinct regions of the promoter are required for carbohydrate control and for regulation of gene expression in response to germination. Sequence comparisons of the ms promoter with that of the isocitrate lyase gene (icl) of cucumber have previously identified four IMH(ICL-MS-Homology) sequences. One such sequence, IMH2, is shown here to be implicated in the sugar response of the ms gene. The 17 bp sequences which when deleted from the ms gene results in loss of the germination response, contains a 14 bp sequence which is similar to a sequence in the icl promoter, which we refer to as IMH5. Furthermore, this sequence has similarity with amdI9-like sequences in filamentous fungi, which confer facB-mediated acetate inducibility on several genes, including those encoding ICL and MS.
Base Sequence↗
Calcium kinetics with microgram stable isotope doses and saliva sampling.
Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.
Administration, Oral↗
Selective regulation of cardiomyocyte gene expression and cardiac morphogenesis by retinoic acid.
Early heart development is known to be sensitive to retinoid concentrations; a specific pattern of malformations is observed in both vitamin A-deficiency and retinoid-toxicity states. While the influence of retinoids on early cardiac morphogenesis has been described previously, the effect of retinoids upon cardiomyocyte differentiation and gene expression is largely uncharacterized. We have established an in ovo chick embryo model in which slow-release retinoic acid (RA) induces four distinct cardiac malformations in a dose-dependent fashion. Late primitive streak-stage chick embryos were treated with all-trans-retinoic acid released from anion exchange beads placed on the embryo's left side and then allowed to develop further for 20-24 hr. At low doses (10 and 25 micrograms/ml RA) an abnormal loop structure was observed. At higher doses (50 and 100 micrograms/ml RA) cardia bifida and clustered heart tissue were noted. Situs inversus only occurred after treatment with 100 micrograms/ml RA. RA-treated embryos were subsequently analyzed for appropriate cardiac myocyte differentiation using antibody staining and ELISA analysis to detect sarcomeric myosin heavy chain, tropomyosin, titin, and alpha-actinin protein expression. Alpha-actinin expression was significantly decreased in RA-treated embryos, as compared to DMSO-treated controls. Also, heart contraction rate was depressed after RA exposure. RA exposure did not alter the protein expression levels of sarcomeric myosin heavy chain or tropomyosin. The observed alterations are consistent with suggestions that retinoids may affect both morphogenesis and myofibril formation in the developing heart.
Animals↗
Effects of cytosine arabinoside on human leukemia cells.
Cytosine arabinoside (Ara-C) is used to treat leukemias, with complete remission induced by combination chemotherapy in approximately 70% of cases of acute myelogenous leukemia (AML). Ara-CTP acts as a competitive inhibitor of DNA polymerase and may also be incorporated into DNA. Accumulation of deoxyribonucleoside triphosphates (dNTPs) induced by Ara-C may indicate disruption of DNA synthesis in susceptible leukemia cells. A procedure has been developed for the quantification of Ara-CTP and dNTPs from small samples of leukaemia cells from patients (4 x 10(7) cells) activated with concanavalin A (10 micrograms/ml, 48 hr) and grown in the presence of [32P]orthophosphate (1.1 microM, 9 x 10(6) Ci/mol, 16 hr). The susceptibilities to Ara-C of the human leukemia cell lines CCRF-CEM (IC50 = 6.30 nM), CCRF-HSB-2 (IC50 = 10.4 nM) and MOLT-4 (IC50 = 10.0 nM) may be correlated with their abilities to accumulate high concentrations of Ara-CTP (> 1000 amol/cell) with increases of between 1.3- and 3.4-fold in dATP, dGTP and dTTP for the four cell lines, while dCTP decreased between 0.23- and 0.78-fold. By contrast, an Ara-C-resistant derivative of HL-60 cells (IC50 = 400 nM) accumulated only low concentrations of Ara-CTP (71 amol/cell) without significant changes in dNTPs. High concentrations of Ara-CTP in leukemia cells induce accumulations of dATP, dGTP and dTTP due to inhibition of DNA synthesis, and depletion of dCTP. This imbalance in the pools of the four dNTPs could lead to genetic miscoding and cell death.
Aged↗
Does imitation enhance memory for faces? Four converging studies.
Four multimethod studies probed the hypothesis, derived from the Zajonc-Markus motor theory of emotion, that facial recognition is enhanced by imitation of the faces. In all studies, participants were (a) randomly assigned to imitate or to concentrate on a set of faces presented on slides; (b) covertly videotaped, or measured for facial electromyographic responses, to assess facial motor responsiveness; (c) asked to recognize faces previously seen from a larger set; and (d) asked to complete individual difference measures relevant to imitation or memory. The major dependent variable was the percentage of faces accurately recognized. Across variations in procedure, persons who initially imitated faces later recognized fewer faces than did persons in various control conditions. No evidence was found for individual difference moderators of this general conclusion. Results call into question the adequacy of the Zajonc-Markus motoric theory explanation of memory for faces.
Adult↗
Treatment of vancomycin-resistant Enterococcus faecium infections with an investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of fifteen cases.
New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are urgently needed. We describe the treatment of 15 patients with VREF infection with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin antibiotic. Primary infections treated were bacteremia (4), urinary tract (4), intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64 micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all bactericidal titers were less than 1:2. Development of resistance to quinupristin/dalfopristin during therapy was not observed. The only drug-related adverse effect noted was phlebitis in 4 patients; all had received quinupristin/dalfopristin by peripheral venous infusion. Three patients had clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery of VREF from infected sites in post-treatment cultures. Ten patients died of severe underlying disease; VREF was believed to contribute directly to the death of only 1 patient. While evaluation of clinical efficacy was complicated by the severity of underlying disease in patients with VREF infection, our experience suggests that quinupristin/dalfopristin is a safe and potentially useful agent for the treatment of VREF infections.
Adult↗
The influence of insurance status and income on health care use among the nonmetropolitan elderly.
The objective of this research is to examine the influence of income and type of insurance coverage on the use of health services among the nonmetropolitan elderly. A model of health services utilization is used as the foundation for examining this issue with data from a telephone survey of a randomly selected sample of residents from four nonmetropolitan counties in Pennsylvania. Results indicated that those elders with Medicaid coverage were less likely to visit a doctor than respondents with private insurance or Medicare only, even after controlling for income and other relevant factors. Further, lower income respondents with Medicare were less likely to visit the dentist than those with private insurance (Medicare does not cover dental care). In contrast, neither income nor insurance predicted hospital use. As such, the health and dental care needs of many lower income nonmetropolitan elders may potentially be going unmet. In general, findings highlight the continued relevance of economic barriers to the use of such services among the nonmetropolitan elderly.
Aged↗
Biological control with Trichogramma: advances, successes, and potential of their use.
Major contributions to the release of Trichogramma for biological control of lepidopterous pests have been made in the past 20 years. Most trials have used only five species of Trichogramma against two pests; Ostrinia in corn is considered the most universally feasible. All Trichogramma programs must address the following four aspects to be successful commercially. Selection of the appropriate population is based on inter- and intraspecific variation, as well as on current definitions of parasitoid quality. Mass rearing is comprised of both host and parasitoid components, although major emphasis is now on developing artificial systems. Effective distribution of Trichogramma requires supportive extension and advanced technology. Strategies for use in the field vary according to the approach desired (inundative or inoculative), the timing, frequency and rate of release, and the multiple factors that affect release, such as the weather, crop, host, predation, pesticides, and dispersal. The past difficulty in assessing the efficacy of Trichogramma should be improved with new guidelines for standardizing terminology and measurements.
Journal Article↗
Regulation of body fluid compartments during short-term spaceflight.
The fluid and electrolyte regulation experiment with seven subjects was designed to describe body fluid, renal, and fluid regulatory hormone responses during the Spacelab Life Sciences-1 (9 days) and -2 (14 days) missions. Total body water did not change significantly. Plasma volume (PV; P < 0.05) and extracellular fluid volume (ECFV; P < 0.10) decreased 21 h after launch, remaining below preflight levels until after landing. Fluid intake decreased during weightlessness, and glomerular filtration rate (GFR) increased in the first 2 days and on day 8 (P < 0.05). Urinary antidiuretic hormone (ADH) excretion increased (P < 0.05) and fluid excretion decreased early in flight (P < 0.10). Plasma renin activity (PRA; P < 0.10) and aldosterone (P < 0.05) decreased in the first few hours after launch; PRA increased 1 wk later (P < 0.05). During flight, plasma atrial natriuretic peptide concentrations were consistently lower than preflight means, and urinary cortisol excretion was usually greater than preflight levels. Acceleration at launch and landing probably caused increases in ADH and cortisol excretion, and a shift of fluid from the extracellular to the intracellular compartment would account for reductions in ECFV. Increased permeability of capillary membranes may be the most important mechanism causing spaceflight-induced PV reduction, which is probably maintained by increased GFR and other mechanisms. If the Gauer-Henry reflex operates during spaceflight, it must be completed within the first 21 h of flight and be succeeded by establishment of a reduced PV set point.
Adult↗
Breast pseudoaneurysm after core biopsy.
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Aneurysm, False↗
Adenocarcinoma of a foregut cyst: detection with positron emission tomography.
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Adenocarcinoma, Mucinous↗
Endocrine, renal, and circulatory influences on fluid and electrolyte homeostasis during weightlessness: a joint Russian-U.S. project.
Microgravity is known to have a substantial effect on fluid homeostasis. The research described here was planned as part of the first joint Russian-U.S. science program carried out during a Shuttle flight. The aim of the program was to study the nature of the changes in fluid homeostasis induced by microgravity, as well as to determine the possible mechanisms underlying the regulation of fluid balance under conditions of spaceflight. To determine the effects of spaceflight on the homeostasis of fluid and electrolytes, measurements were taken of total body water, extracellular fluid plasma volumes, levels of regulatory hormones, and nutrient consumption before, during, and after a nine-day flight. Changes in renal function were studied before and after the flight. In these 2 subjects, weightlessness was not associated with a decreased extracellular fluid volume. However, there were the characteristic decreases in plasma atrial natriuretic peptide concentrations, and increases in plasma and urinary cortisol. Results indicated decreased urine volume, even through the first 48 hours of flight. Fluid volumes and glomerular filtration rate were increased after landing, probably related to the saline-loading countermeasure used by Shuttle crewmembers. The information obtained as a result of this research will facilitate the development of future research programs, as well as preventive measures for future long-duration spaceflights.
Body Water↗
Control of red blood cell mass during spaceflight.
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Aerospace Medicine↗
Independent nurse practitioner. Advanced nursing practice in Brisbane, Australia.
Within the last decade, changes have been witnessed in nursing practice, including Queensland, Australia. These changes occurred when nursing underwent restructuring in most states of Australia. The result was that the focus moved to recognize clinical expertise rather than years of service. This change in focus provided a career path for professional nursing practice. The author presents her own experiences and discusses all of the important aspects of advanced practice nursing in this country.
Australia↗
Feeling-of-knowing judgments from the subject's perspective.
We examined the manner in which subjects interpret experimenter-provided feeling-of-knowing (FOK) definitions. The original FOK definition proposed by Hart (1965) is a composite of two criteria: (1) A feeling that the sought-after information is known and (2) a feeling that the sought-after information can be correctly identified on a later criterion test. We hypothesized that subjects may use one or both of these criteria in reporting FOK states. We found that Goodman-Kruskal gamma correlations (Goodman & Kruskal, 1954) were substantially large when subjects attended to the predictive aspect of FOK definitions relative to subjects who assessed what they believed they knew. We argue that FOKs are more accurate when task-relevant information is incorporated into the judgment. Finally, these data weaken a cue-familiarity interpretation of the FOK phenomenon.
Adult↗