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At least 73 records · Page 4Linked to original sources

PubMed2004

Design and application of a novel brain slice system that permits independent electrophysiological recordings from multiple slices.

We describe a novel brain slice system 'SliceMaster' that allows electrophysiological recordings from eight brain slices independently. The system consists of two autonomous units each supporting four modular brain slice chambers enabling high signal-to-noise ratio recordings, each chamber has one stimulation electrode, one recording electrode, a twin camera system and a solution application system. The positioning of both electrodes and cameras are controlled from a remote user console. The software both acquires and performs on-line analysis of the data. We have demonstrated utility of this system in obtaining recordings of spontaneous firing activity and evoked synaptic activity from mouse hippocampal slices, with reduced variability within and between experiments. Furthermore, we show recordings of population spikes from the perirhinal cortex, indicating applicability of this system for further brain regions. In addition, stable recordings could be maintained until recording was terminated after 3 h, permitting investigation of the induction and maintenance of synaptic plasticity. Recordings of spontaneous and synaptic activity, and effects of pharmacological and electrophysiological manipulation, were consistent with reports using conventional methods. However, the described system permits concurrent and independent recordings from eight brain slices, thus improving throughput, statistical design, and reducing animal use.

Action Potentials↗

PubMed1989

Small-bowel transplantation permits survival in rats with lethal short-gut syndrome.

The functional integrity of transplanted bowel would most convincingly be demonstrated if transplantation after an otherwise lethal intestinal resection permitted survival and growth. In this experiment, we proposed to define the extent of bowel resection necessary for lethality and to show that transplantation allows salvage of these animals. Adult Brown-Norway rats (250 g) underwent extensive small-bowel resection (SBR) (ligament of Treitz to ileocecal valve) (n = 5), cecectomy only (CEC) (n = 3), SBR plus CEC (n = 6), or SBR plus CEC and syngeneic transplantation of 25 cm of jejunum (n = 6). All animals with SBR or CEC alone survived and grew; all animals with SBR plus CEC died within 2 weeks (mean, 6.4 days); and 6 of 6 animals with SBR plus CEC and transplant survived and grew. The difference in survival between the lethally resected rats and those with an intestinal transplant was highly significant (P less than 0.01). Dietary intake was similar in all groups. We conclude that in the rat, extensive small-bowel resection alone is not sufficient to be lethal; most of the small bowel and the cecum must be resected to obtain a lethal model. We have also shown that transplantation of small bowel into rats with an otherwise lethal extent of bowel resection will allow the animals to survive and grow. These results suggest the need for caution in correlating survival after intestinal transplantation in the rat with transplant function, since the preservation of too much native gut might permit survival even if the transplant has no nutritional function.

Animals↗

PubMed2003

The learner's permit.

PROBLEM: This paper considers the role and value of an extended learner's period in a graduated licensing system. METHOD: Review and synthesis of the literature. RESULTS: The learner's permit allows beginners to practice under supervision before attempting the road test for a driver's license. A learner's permit stage was an integral part of the "provisional" (graduated) licensing model initially formulated by NHTSA in the mid-1970s. Almost all Canadian provinces and U.S. states now have graduated licensing (GDL) programs that typically include an extended period of supervised driving. Most parents and teens favor the learner stage, and consistent with the intent of GDL, most learners are practicing and gaining driving experience under low-risk conditions. Research shows that very few learners crash while under supervision and that an extended learner stage has safety benefits. IMPACT ON RESEARCH, PRACTICE AND POLICY: Further research is needed on the safety benefits of an extended learner stage and on its optimal features.

Accidents, Traffic↗

PubMed1998

Controlling antimicrobial resistance: a proposed transferable permit market.

Resistance to antimicrobials results in those antimicrobials becoming ineffective in treating common bacterial infections. To prevent the spread of such resistance the use of antimicrobials requires control. The authors have previously argued that use of regulation or charges to control resistance would not be efficient. Regulation will not account for different marginal costs of reducing antimicrobial prescription amongst GPs, and charges, although based on sound economic concepts, are based on an unrealistic amount of required information. It was therefore argued that a system of tradable permits, by combining the targets of regulation and the market flexibility of charges, would achieve control more efficiently than simple regulation or charges. In this paper the authors progress this proposed policy by considering various important issues which arise when designing such a tradable permit system for antimicrobials. The paper does not provide an exhaustive plan enabling a blueprint for such a market to be designed, but a proposal which may be used as platform for further specific development of such an initiative to deal with resistance.

Anti-Bacterial Agents↗

PubMed2000

Inability of cyclophosphamide-induced tolerance to permit engraftment of pluripotent stem cells contained in a moderate number of syngeneic bone marrow cells.

We have previously described cyclophosphamide (CP)-induced tolerance that comprises an intravenous (i.v.) injection of 1 x 10(8) allogeneic spleen cells (SC) followed, 2 days later, by an intraperitoneal (i.p.) administration of 200 mg/kg of CP. By using this method, we were able to readily induce both long-lasting mixed chimerism and skin allograft tolerance in most of H-2 matched combinations, but not in H-2 mismatched combinations. In the present study, we have investigated whether the treatment with SC followed by 200 mg/kg CP can permit engraftment of syngeneic pluripotent hematopoietic stem cells (HSC), and whether CP itself can permit the HSC engraftment. Recipient B6 (H-2b; Ly-5.2) mice received 1 x 10(7), 5 x 10(7) or 1 x 10(8) SC from syngeneic B6.Ly-5.1 (H-2b; Ly-5.1) mice and administered 2 day later 200 mg/kg CP. Using anti-Ly-5.1 and Ly-5.2 mAbs and a flow cytometry, the origins of lymphoid and myeloid cells injecting the recipients were observed over time. Chimerism was at least initially detectable in all groups treated with SC alone (without 200 mg/kg CP), but became undetectable by 32 weeks after the treatment with SC alone. In recipient B6 mice treated with B6.Ly-5.1 SC and 200 mg/kg CP, on the other hand, lymphoid-chimerism was detectable at 32 weeks in a transferred cell dose-dependent manner, but granulocyte-chimerism indicating pluripotent HSC engraftment disappeared earlier than 32 weeks after the treatment. In order to further evaluate the effect of CP itself on HSC engraftment, recipient B6 mice were given various doses of CP (50-400 mg/kg) and were injected with T cell-depleted 1 x 10(7) BMC from B6.Ly-5.1 mice. Multilineage mixed chimerism over 32 weeks was induced in only one of 11 B6 mice treated with 400 mg/kg CP followed by B6.Ly-5.1 BMC, although lymphoid chimerism was induced temporarily in recipient B6 mice treated with 200 mg/kg CP followed by B6.Ly-5.1 BMC and persistently in most of recipient B6 mice treated with 400 mg/kg CP followed by B6.Ly-5.1 BMC.

Animals↗

PubMed2000

Granulocyte colony stimulating factor permits dose intensification by interval compression in the treatment of Ewing's sarcomas and soft tissue sarcomas in children.

71 children with sarcomas were treated in a prospective pilot study to determine whether granulocyte colony stimulating factor (G-CSF) permits compression of the interval between chemotherapy cycles. Patients had Ewing's sarcoma/primitive neuroectodermal tumour (PNET), rhabdomyosarcoma, non-rhabdo soft tissue sarcomas or other advanced soft tissue tumours. The chemotherapy alternated vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, with G-CSF between courses. Therapy had two phases: induction (six cycles) and continuation (six cycles), which included primary tumour treatment with surgery and/or radiation. Chemotherapy cycles began every 14 days, or upon absolute neutrophil count (ANC) and platelet count recovery. The median chemotherapy cycle interval was 16 (11-48) days in the induction phase, with a median average relative dose intensification (ARDI) of 1.27 compared with every-21-day therapy. In the continuation phase, the median cycle interval was 21 days, with a median ARDI of 1.10. Radiation therapy prolonged chemotherapy intervals, whilst erythropoietin shortened them. Toxicity was modest for such chemotherapy. Event-free survival is comparable with or superior to that in recent large studies. G-CSF permits intensification of this regimen through interval compression. The impact of this approach on efficacy remains to be determined in a randomised trial.

Adolescent↗

PubMed2006

Verification of compliance with organic meat production standards by detection of permitted and nonpermitted uses of veterinary medicines (tetracycline antibiotics).

In the production of "organic" meat, one of the controlled processes is the use of veterinary drugs. Strict standards are in place as to when and how such drugs may be used. Therefore, the aim of this project was to determine whether it was possible to distinguish between a single therapeutic dose of a tetracycline (permitted under the standards) and both multiple therapeutic dosing and prophylactic dosing (not permitted). This comprised an evaluation of (i) pigs that were treated with oxytetracycline and (ii) chickens dosed with two different tetracycline antibiotics (oxytetracycline and chlortetracycline). The methodology described, using bone sectioning and examination under ultraviolet illumination (either direct observation or fluorescent microscopy), allows samples from animals that have been treated with different dosing regimes (a single therapeutic dose, two successive therapeutic doses, and long-term, low-level "prophylactic" dosing) to be assessed for compliance with organic farming regulations. Validation of the methodology by blind checks of unknown samples by a second operator has been successfully performed, and validation results are presented. The developed methodology has been shown to be applicable to a variety of species and a selection of tetracycline drugs.

Animals↗

PubMed2000

Permitting jury discussions during trial: impact of the Arizona reform.

A field experiment tested the effect of an Arizona civil jury reform that allows jurors to discuss evidence among themselves during the trial. Judges, jurors, attorneys, and litigants completed questionnaires in trials randomly assigned to either a Trial Discussions condition, in which jurors were permitted to discuss the evidence during trial, or a No Discussions condition, in which jurors were prohibited from discussing the evidence during trial according to traditional admonitions. Judicial agreement with jury verdicts did not differ between conditions. Permitting jurors to discuss the evidence did affect the degree of certainty that jurors reported about their preferences at the start of jury deliberations, the level of conflict on the jury, and the likelihood of reaching unanimity.

Arizona↗

PubMedDate not supplied

A single genetic locus encoded by Yersinia pseudotuberculosis permits invasion of cultured animal cells by Escherichia coli K-12.

For many species of pathogenic bacteria, invasion and survival within animal cells is central to establishing a successful host-parasite relationship. Localization within host cells protects the microorganism from host defences, or permits it to cross epithelial barriers and subsequently become systemically distributed. The precise mechanisms that permit entry of bacteria into host tissues are unclear, therefore we have been studying the invasion of epithelial cells by Yersinia pseudotuberculosis. As a first step towards identifying the factors required for this process, we report here the identification of a single genetic locus from this organism that is sufficient to convert the innocuous Escherichia coli K-12 strain into an organism capable of invading cultured animal cells.

Carcinoma, Squamous Cell↗

PubMed2005

TMA-Combiner, a simple software tool to permit analysis of replicate cores on tissue microarrays.

We have previously published a suite of software tools that facilitates the reformulation of tissue microarray (TMA) data so that it may be analyzed using techniques originally devised for analysis of cDNA microarray data. However, current microarray data often feature multiple scores for a given tissue sample and antibody combination. Furthermore, an efficient and systematic method for combining scores that takes into account the differing staining properties of tissue epitopes has not been described. We thus present the TMA-Combiner, a new Microsoft Excel-based macro that permits analysis of data for which tissues may have two or more scores per antibody, and permits combination of data from multiple different tissue microarrays. It accomplishes this by rendering one score per tissue per antibody from two or more scores, using one of multiple user-selectable combination rules developed to account for the differing staining properties of tissue epitopes. This greatly facilitates analysis of tissue microarrays, particularly for users with large repositories of data, and may facilitate discovery of biological trends and help refine diagnostic accuracy of tissue markers in clinical samples.

Cluster Analysis↗

PubMed2000

A versatile system for receptor-mediated gene delivery permits increased entry of DNA into target cells, enhanced delivery to the nucleus and elevated rates of transgene expression.

We have developed a method for stabilisation of polyelectrolyte gene delivery vectors by crosslinking their surfaces with biodegradable multivalent copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA). The resulting nanoparticulate vectors resist attack by serum proteins and can be modified for cell-specific delivery by incorporation of targeting ligands onto the polymer coating. Here we show that vascular endothelial growth factor (VEGF), transferrin and basic fibroblast growth factor (bFGF) can each be linked to polyHPMA-coated poly(L-lysine)/DNA complexes. All ligand-targeted complexes demonstrated increased uptake into receptor-positive cells (measured using plasmids containing 32P-dCTP), that could be antagonised with excess free ligand. Targeted complexes also showed increased transfection, resistant to inhibition by serum, suggesting the possibility of effective application in vivo. Analysis using fluorescence microscopy confirmed enhanced uptake of ligand-targeted complexes (using Texas Red-labelled plasmid DNA), although VEGF- and transferrin-targeted complexes were restricted to cytoplasmic or perinuclear distributions. In contrast, bFGF-targeted complexes showed efficient delivery into the nucleus, with accumulation of more than 100000 plasmids per cell within distinct intranuclear compartments. This method permits versatile targeting of genes to selected cells and may also permit manipulation of intracellular trafficking. It should find several important applications in gene delivery systems both in vitro and in vivo.

Cell Nucleus↗

PubMed1980

Large evoked potentials to dynamic random-dot correlograms and stereograms permit quick determination of stereopsis.

The combination of three technological innovations permits the fast and objective determination of stereopsis in nonverbal subjects: (i) It is shown that dynamic random-dot correlograms (RDC) are as effective as dynamic random-dot stereograms (RDS) in eliciting large evoked potentials (EP), and that the generation of RDC is simpler than that of RDS. (ii) The presentation of RDC in the form of red-green anaglyphs is insensitive to subjects' head tilt, because alternation of correlation (binocular fusion) with uncorrelation (binocular rivalry) does not depend on the direction of binocular disparity, whereas perception of depth in RDS does. (iii) Projection TV techniques, using backprojected large screens viewed from near distances, permit noncooperative subjects (e.g., human infants or monkeys) to be surrounded with the stimulus, so they cannot look away.

Animals↗

PubMed1999

A large non-immunized human Fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies.

We report the design, construction, and use of the first very large non-immunized phage antibody library in Fab format, which allows the rapid isolation and affinity analysis of antigen-specific human antibody fragments. Individually cloned heavy and light chain variable region libraries were combined in an efficient two-step cloning procedure, permitting the cloning of a total of 3.7 x 10(10) independent Fab clones. The performance of the library was determined by the successful selection of on average 14 different Fabs against 6 antigens tested. These include tetanus toxoid, the hapten phenyl-oxazolone, the breast cancer-associated MUC1 antigen, and three highly related glycoprotein hormones: human chorionic gonadotropin, human luteinizing hormone, and human follicle-stimulating hormone. In the latter category, a panel of either homone-specific or cross-reactive antibodies were identified. The design of the library permits the monitoring of selections with polyclonal phage preparations and to carry out large scale screening of antibody off-rates with unpurified Fab fragments on BIAcore. Antibodies with off-rates in the order of 10(-2) to 10(-4) s-1 and affinities up to 2.7 nM were recovered. The kinetics of these phage antibodies are of the same order of magnitude as antibodies associated with a secondary immune response. This new phage antibody library is set to become a valuable source of antibodies to many different targets, and to play a vital role in target discovery and validation in the area of functional genomics.

Amino Acid Sequence↗

PubMed2000

Inducible NF-kappaB activation is permitted by simultaneous degradation of nuclear IkappaBalpha.

Signal-induced phosphorylation and ubiquitination of IkappaBalpha targets this inhibitor of NF-kappaB for proteasome-mediated degradation, thus permitting the release of active NF-kappaB. Upon cell stimulation, NF-kappaB activation results in neotranscription and neosynthesis of its own inhibitor, IkappaBalpha. As reported earlier, the neosynthesized inhibitor is then accumulated in the nucleus, where it rapidly binds to and terminates the function of nuclear NF-kappaB upon withdrawal of the stimulus. The present work was aimed at understanding how NF-kappaB activity is preserved while stimuli persist, despite intense, simultaneous IkappaBalpha neosynthesis, which would be expected to end NF-kappaB activity. We here show that incoming IkappaBalpha in the nucleus represents a target for resident nuclear proteasome complexes. Signal-induced, proteasome-dependent degradation of phosphorylated and ubiquitinated IkappaBalpha occurs in the nucleus, thus permitting the onset and persistence of NF-kappaB activity as long as stimulation is maintained. Our results suggest that intranuclear proteolysis of IkappaBalpha is necessarily required to avoid self-termination of NF-kappaB activity during cell activation.

Cell Nucleus↗

PubMedDate not supplied

Identification of Albizia gum exudates which are not permitted food additives.

Trees of the genus Albizia have frequently been confused with Acacia species. The genus Albizia has been recommended for more extensive arid zone development; its species are sources of tannins and gum exudates, which are not included in any of the regulatory lists of permitted food additives. Analytical data permitting their identification are therefore required to allow food law compliance to be monitored. This paper presents data which serve to characterize the gums from seven Albizia species, making a total of eleven Albizia species for which data are available. The presence of tannins, and high proportions of aluminium and heavy metals, indicates that gum importers and food processors must be vigilant to ensure that Albizia gums do not enter human food chains as adulterants or contaminants.

Amino Acids↗

PubMed1992

Prevention of immunologic stress contributes to the growth-permitting ability of dietary antibiotics in chicks.

The growth-permitting ability of antibiotics fed to broiler chicks was studied as it relates to the state of activation of the immune system. In Experiment 1, chicks were fed two levels of antibiotics (0 or 100 mg streptomycin + 100 mg penicillin/kg diet) and were raised either in an environment with poor sanitation to create a chronic immune stress or in a clean environment. Chicks raised in the unsanitary environment and not fed antibiotics had significantly lower (P < 0.05) rates of weight gain and efficiencies of feed utilization, and higher levels of plasma interleukin-1, compared with chicks raised in the clean environment or chicks raised in the unsanitary environment and fed antibiotics. Adding antibiotics to the diet of birds in the clean environment did not affect any variable. In Experiment 2, chicks were raised in a conventional environment and fed two levels of an antibiotic (0 or 100 mg tetracycline/kg diet). After a 15-d feeding period, half of the chicks were injected with Salmonella typhimurium lipopolysaccharide to create an acute immunologic stress. Feeding antibiotic resulted in improved weight gain, feed consumption and efficiency of feed utilization. Lipopolysaccharide-injected birds developed heavier livers, spleens and intestines relative to body weights and higher rectal temperatures and hepatic metallothionein concentrations, presumably due to an immunologic stress. Omitting antibiotic from the diet resulted in similar changes. These results indicate that feeding antibiotics may permit growth by preventing immunologic stress and associated metabolic changes brought about by monokines including interleukin-1.

Animals↗

PubMed1995

Decreases in anesthesia-controlled time cannot permit one additional surgical operation to be reliably scheduled during the workday.

We tested whether anesthesiologists can decrease operating room (OR) costs by working more quickly. Anesthesia-controlled time (ACT) was defined as the sum of 1) the time starting when the patient enters an OR until preparation or surgical positioning can begin plus 2) the time starting when the dressing is finished and ending when the patient leaves the OR. Case time was defined as the time starting when one patient undergoing an operation leaves an OR and ending when the next patient undergoing the same operation leaves the OR. An actual case series was constructed of 709 consecutive patients who underwent one of 11 elective operations at a tertiary care center. Statistical analysis of measured OR times showed that ACt would have to be decreased by more than 100% to permit one additional scheduled, short (30-min) operation to be performed in an OR during an 8-h workday after a prior series of cases, each lasting more than 45 min. Anesthesiologists alone cannot reasonably decrease case times sufficiently to permit one extra case to be reliably scheduled during a workday. Methods to decrease ACT (e.g., using preoperative intravenous catheter teams, procedure rooms, and/or shorter acting drugs) may simply increase costs.

Ambulatory Surgical Procedures↗

PubMed1998

Notochord repression of endodermal Sonic hedgehog permits pancreas development.

Notochord signals to the endoderm are required for development of the chick dorsal pancreas. Sonic hedgehog (SHH) is normally absent from pancreatic endoderm, and we provide evidence that notochord, in contrast to its effects on adjacent neuroectoderm where SHH expression is induced, represses SHH expression in adjacent nascent pancreatic endoderm. We identify activin-betaB and FGF2 as notochord factors that can repress endodermal SHH and thereby permit expression of pancreas genes including Pdx1 and insulin. Endoderm treatment with antibodies that block hedgehog activity also results in pancreatic gene expression. Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development.

Activins↗