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Biomedical subjects

J Montgomery

Publications and source records attributed to J Montgomery.

At least 37 records · Page 2Linked to original sources

BDJ readership survey.

Over the summer, BDJ readers were surveyed about the BDJ as part of a series of BDJ surveys conducted since 1992. As well as assessing general views about the BDJ, the survey also aimed to discover how successful the 1998 BDJ redesign had been in incorporating reader's views from earlier surveys. The findings from the 1999 survey showed that the BDJ and BDA News continue to be the most read dental publications. Readers turn to the BDJ before any other UK dental journal for finding a job and reports on research. The full results of the survey are reported below.

Attitude of Health Personnel↗

Disaptation and recovery in the evolution of Antarctic fishes.

The radiation of notothenioid fishes provides an excellent system to explore issues of evolution and adaptation. Most studies emphasize adaptation to the extreme Antarctic environment; however, recent work provides cogent examples of disaptation or evolutionary loss of function. The nature and extent of regressive change is revealed by subsequent adaptive recovery. Ancestral notothenioids were benthic but some became secondarily pelagic through the retention of larval characters. Paedomorphosis has produced detrimental changes in lateral-line sensory systems that have been made good by compensatory adaptation. In the icefish family, compensatory adaptation has followed the loss of the oxygen-binding pigments haemoglobin and myoglobin.

Journal Article↗

Nickel-catalyzed cyclizations, couplings, and cycloadditions involving three reactive components.

Transition-metal-catalyzed processes that allow the efficient coupling of three reactive components in a chemoselective and stereoselective fashion are particularly useful in the synthesis of complex organic molecules from simple, readily available substrates. This account outlines work primarily from the author's laboratory on the development of nickel-catalyzed multicomponent coupling processes. An overview of new synthetic methods, a discussion of potential mechanisms, and a description of applications in complex-molecule synthesis are provided.

Aldehydes↗

A probable new Helicobacter species isolated from a patient with bacteremia.

A probable new Helicobacter species was isolated from the blood of a 14-month-old aboriginal child who presented with vomiting, diarrhea, fever, and dry cough. The most similar 16S rRNA gene sequence was that of Helicobacter fennelliae CCUG 18820(T) but the new sequence differed from it by at least 32 base substitutions and by the presence of a large (353-nucleotide) intervening sequence.

Australia↗

Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice.

Galpha15 activates phospholipase Cbeta in response to the greatest variety of agonist-stimulated heptahelical receptors among the four Gq class G-protein alpha subunits expressed in mammals. Galpha15 is primarily expressed in hematopoietic cells in fetal and adult mice. We disrupted the Galpha15 gene by homologous recombination in embryonic stem cells to identify its biological functions. Surprisingly, hematopoiesis was normal in Galpha15(-/-) mice, Galpha15(-/-) Galphaq(-/-) double-knockout mice (which express only Galpha11 in most hematopoietic cells), and Galpha11(-/-) mice, suggesting functional redundancy in Gq class signaling. Inflammatory challenges, including thioglycolate-induced peritonitis and infection with Trichinella spiralis, stimulated similar responses in Galpha15(-/-) adults and wild-type siblings. Agonist-stimulated Ca(2+) release from intracellular stores was assayed to identify signaling defects in primary cultures of thioglycolate-elicited macrophages isolated from Galpha15(-/-) mice. C5a-stimulated phosphoinositide accumulation and Ca(2+) release was significantly reduced in Galpha15(-/-) macrophages. Ca(2+) signaling was abolished only in mutant cells pretreated with pertussis toxin, suggesting that the C5a receptor couples to both Galpha15 and Galphai in vivo. Signaling evoked by other receptors coupled by Gq class alpha subunits appeared normal in Galpha15(-/-) macrophages. Despite discrete signaling defects, compensation by coexpressed Gq and/or Gi class alpha subunits may suppress abnormalities in Galpha15-deficient mice.

Animals↗

Hydroxyl radical production in the cortex and striatum in a rat model of focal cerebral ischemia.

BACKGROUND: Increases in hydroxyl radical production have been used as evidence of oxidative stress in cerebral ischemia/ reperfusion. Ischemia can also induce increased dopamine release from the striatum that may contribute to hydroxyl radical formation. We have compared hydroxyl radical production in the cortex and striatum as an index of oxidative stress in a rat model of focal cerebral ischemia with cortical infarction. METHODS: Using a three vessel occlusion model of focal cerebral ischemia combined with bilateral microdialysis, hydroxylation of 4-hydroxybenzoate (4HB) was continuously monitored in both hemispheres in either the lateral striatum or frontoparietal cortex. The ischemia protocol consisted of one hour equilibration, 30 min of three vessel occlusion, then release of the contralateral common carotid artery (CCA) for 2.5 h. RESULTS: Induction of ischemia resulted in a 30-fold increase in dopamine release in the lateral striatum. Compared to the nonischemic striatum, the ratio of the hydroxylation product 3,4-dihydroxybenzoate (34DHB) to 4HB (trapping agent) in the ipsilateral striatum increased significantly 30 min after ischemia induction. In contrast, during the 30 min of three vessel occlusion there was no increase in the ratio in the cortex. Following the release of the contralateral CCA, the ratio from the ischemic cortex increased significantly compared to sham-operated animals. However, under all circumstances, the 34DHB/4HB ratio was greater in the striatum than in the cortex. CONCLUSION: The increase in the 34DHB/4HB ratio in the lateral striatum coincides with the increased dopamine release suggesting a role for dopamine oxidation in the increased production of hydroxyl radicals. The significant increase in the ratio from the ischemic cortex compared to that from the sham-operated animals is consistent with increased oxidative stress induced by ischemia. However, the lower 34DHB/4HB ratio in the cortex which does not receive dopaminergic innervation compared to the striatum suggests a different mechanism for hydroxyl radical production. Such an alternate mechanism may represent a more toxic oxidative insult that contributes to infarction.

3,4-Dihydroxyphenylacetic Acid↗

Molecular cloning and characterization of a novel repeat-containing Leishmania major gene, ppg1, that encodes a membrane-associated form of proteophosphoglycan with a putative glycosylphosphatidylinositol anchor.

Leishmania parasites secrete a variety of proteins that are modified by phosphoglycan chains structurally similar to those of the cell surface glycolipid lipophosphoglycan. These proteins are collectively called proteophosphoglycans. We report here the cloning and sequencing of a novel Leishmania major proteophosphoglycan gene, ppg1. It encodes a large polypeptide of approximately 2300 amino acids. The N-terminal domain of approximately 70 kDa exhibits 11 imperfect amino acid repeats that show some homology to promastigote surface glycoproteins of the psa2/gp46 complex. The large central domain apparently consists exclusively of approximately 100 repetitive peptides of the sequence APSASSSSA(P/S)SSSSS(+/-S). Gene fusion experiments demonstrate that these peptide repeats are the targets of phosphoglycosylation in Leishmania and that they form extended filamentous structures reminiscent of mammalian mucins. The C-terminal domain contains a functional glycosylphosphatidylinositol anchor addition signal sequence, which confers cell surface localization to a normally secreted Leishmania acid phosphatase, when fused to its C terminus. Antibody binding studies show that the ppg1 gene product is phosphoglycosylated by phosphoglycan repeats and cap oligosaccharides. In contrast to previously characterized proteophosphoglycans, the ppg1 gene product is predominantly membrane-associated and it is expressed on the promastigote cell surface. Therefore this membrane-bound proteophosphoglycan may be important for direct host-parasite interactions.

Amino Acid Sequence↗

Local striatal infusion of MPP+ does not result in increased hydroxylation after systemic administration of 4-hydroxybenzoate.

In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either 1-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resulted in a decrease in interstitial 4HBZ to < 50% of the non-MPP+ -treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+ infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.

1-Methyl-4-phenylpyridinium↗

Improving communication among health professionals through education: a pilot study.

Communication can be thought of as a message that is sent, received, and understood. Each discipline of the health profession has its own jargon and means of expressing ideas in shorthand. These separate forms of communicating are effective among those of the same background but are often at the root of misunderstandings between professional groups. This article reviews communication theory and traces the difficulties created when inter-disciplinary teams of healthcare try to work together and communicate. As multi-disciplinary teams are increasingly dealing with the complex problems of today's healthcare system, clear communication and understanding has never been more important. If educators could assist in creating an understanding of vocabulary used for decision processes, communication could improve. The authors of this study performed a multi-stage Delphi survey that grouped terms used by administrators and clinicians and produced a lexicon of corresponding terms. An expert panel then reviewed and modified the list. The result is a lexicon that can be useful to assist clinicians and administrators to communicate with each other. By utilizing clinical terminology, or vice versa, instead of management or clinical jargon, some of the translation done by administration or clinicians could be reduced. Examples of how the lexicon can be utilized are provided in the article. This includes using it in health administration education to demonstrate the variances in clinical/managerial terms. It could also be provided as a primer to physicians, nurses, and other health professionals who assume administrative positions to enhance their communication with administrators.

Communication↗

The distribution of lead within ancient and modern human teeth: implications for long-term and historical exposure monitoring.

The preservation of lead within human tissue makes it possible to monitor long-term exposure to the element and to model changing sources of lead pollution throughout the lifetime of an individual. Dental tissues have recently been shown to be particularly useful for this purpose. Enamel, for instance, forms at known stages of life and is chemically stable in vivo whereas dentine is remodelled in a predictable fashion. The relative stability of enamel is reflected in its excellent post-mortem preservation. This raises the possibility of using historical or archaeological material to reconstruct long-term trends and establish baseline data relating to exposure among pre-industrial or even prehistoric populations. The use of archaeological material is currently problematic, however, because of the site-specific nature of diagenesis and incomplete understanding of its chemistry, particularly in respect of lead uptake into dental tissue from the burial environment. A detailed study of lead distribution within both ancient and modern human teeth is presented. Conclusions are drawn on the pattern of lead distribution resulting from tissue formation and the manner of its alteration in the burial environment. In particular, attention is drawn to a consistent enrichment of lead within the outer 30 microns of the enamel of both ancient and modern teeth which appears to be unrelated to diagenesis. The implications for current approaches to long-term monitoring and for the reconstruction of historical and archaeological exposure patterns are discussed.

Archaeology↗

Induction of antigen-specific T cell anergy: An early event in the course of tumor progression.

The priming of tumor-antigen-specific T cells is critical for the initiation of successful anti-tumor immune responses, yet the fate of such cells during tumor progression is unknown. Naive CD4(+) T cells specific for an antigen expressed by tumor cells were transferred into tumor-bearing mice. Transient clonal expansion occurred early after transfer, accompanied by phenotypic changes associated with antigen recognition. Nevertheless, these cells had a diminished response to peptide antigen in vitro and were unable to be primed in vivo. The development of antigen-specific T cell anergy is an early event in the tumor-bearing host, and it suggests that tolerance to tumor antigens may impose a significant barrier to therapeutic vaccination.

Animals↗

Ventilatory care in a selection of Ontario hospitals: bigger is not necessarily better! Critical Care Research Network (CCR-Net).

OBJECTIVE: To determine whether there is variability in the structure and process of ventilatory care in intensive care units (ICUs) of the hospitals of Southwestern Ontario. DESIGN: Self-administered questionnaire-based survey. SETTING: ICUs of selected community and teaching hospitals of Southwestern Ontario. PARTICIPANTS: Head of respiratory therapy service of respective hospitals; in those hospitals without respiratory therapists, the ICU nurse manager. INTERVENTION: Self-administered questionnaire. OUTCOME MEASURE(S): The availability of different models of ventilators and respiratory therapist and physician coverage were assessed. In addition, the use of clinical practice guidelines, respiratory therapists, and the nursing role in ventilatory care were determined. RESULTS: In general, the structure of ventilatory care, including availability of different modes of ventilation, and coverage by respiratory therapists and physicians was more comprehensive in larger hospitals. However, the availability of some modes of ventilation varied more than expected among hospitals of comparable size. Similarly, variability in the process of ventilatory care, defined by the availability of clinical practice guidelines and the roles of respiratory therapists varied both within and among hospitals of different size. CONCLUSIONS: The structure and process of ventilatory care in this sample of Southwestern Ontario ICUs was found to be variable. Not all this variability could be accounted for by hospital size, suggesting a potential for improvement in overall ventilatory care. Further study is required before any specific recommendations can be considered.

Critical Care↗

Transformation of peripheral inputs by the first-order lateral line brainstem nucleus.

Extracellular recording techniques were used to record the responses of medial nucleus cells and posterior lateral line nerve fibers in mottled sculpin, Cottus bairdi, and goldfish, Carassius auratus, to a 50-Hz dipole source (vibrating sphere). Responses were characterized in terms of (1) receptive fields that relate responsiveness (spike rate and phase-locking) to the location of the source along the length of the fish, (2) input-output functions that relate responsiveness to vibration amplitude for a fixed source location, and (3) peri-stimulus time histograms that relate responsiveness to time during a sustained period of vibration. Relative to posterior lateral line nerve fibers, medial nucleus cells in both species were similar in showing (1) lower spontaneous and evoked rates of spike activity, (2) greater degrees of adaptation, (3) greater heterogeneity in all response characteristics, and (4) evidence for inhibitory/excitatory interactions. Whereas receptive fields of nerve fibers in both species faithfully reflect both pressure gradient amplitudes (with rate changes) and directions (with phase-angle changes) in the stimulus field, receptive fields of medial nucleus were more difficult to relate to the stimulus field, Some, but not all, receptive fields could be modeled with excitatory center/inhibitory surround and inhibitory center/excitatory surround organizations.

Animals↗

Instantaneous analysis of aldehydes in biological fluids using a spray interface coupled to a mass spectrometer.

A new interface coupled to a mass spectrometer was developed for the direct analysis of volatile organic compounds from small volumes of aqueous samples, including blood or tissue homogenates (St-Germain et al. 1995, Anal. Chem. 67:4536-4541). The greatest advantages of our system are minimal sample treatment, an instantaneous response time coupled with detection limits in the range of < 1 ppb for most compounds. For the analysis of low-molecular weight aldehydes, such as formaldehyde, acetaldehyde, propanal, and hexanal, lower detection limits were obtained when samples were converted to methoxime derivatives prior to injection. The detection limit for hexanal in water or Krebs-Ringer solution was 0.01 microM (10 pmol injected). The reproducibility of replicate injections was 4.4%. The usefulness of our system was illustrated by measuring aldehyde accumulation in peroxidized solutions of polyunsaturated fatty acids and rat tissue homogenates. Data confirmed that peroxidation of omega-3 fatty acids produces propanal, whereas omega-6 fatty acids form hexanal. Peroxidation of heart and brain homogenates formed predominantly propanal. However, the recovery of hexanal after sample treatment with methoxylamine depended on the derivatization time and temperature, suggesting that this aldehyde may form Schiff base linkages. These results show that spray extraction coupled to mass spectrometry provides a quick (< 1 min), clean and reproducible way to detect aldehydes produced from lipid peroxidation in aqueous samples.

Aldehydes↗

Susceptibility of pneumococcal carriage isolates to penicillin provides a conservative estimate of susceptibility of invasive pneumococci.

OBJECTIVE: Because of its practical importance for public health monitoring in developing countries, we aimed to determine whether susceptibility to penicillin of pneumococci isolated from the upper respiratory tract (URT) is representative of the susceptibility of pneumococci causing pneumonia in children. METHOD: The serogroup distribution and minimum inhibitory concentration of penicillin for 56 and 90 isolates from blood and cerebrospinal fluid, respectively, were compared with those of 833 pneumococcal carriage isolates from Papua New Guinean children. These included 154 and 98 strains from bacteremic and nonbacteremic hospitalized patients with pneumonia, respectively, 350 from outpatients with respiratory infections and 176 and 55, respectively, from children in a community-based study who were healthy or sick with pneumonia. RESULTS: Proportions of pneumococci intermediately resistant to penicillin were comparable in the URT and blood (60%) in 1985 through 1987 when serogroup distributions in the two sites were similar. However, penicillin resistance was higher in the URT (75%) than blood (44%) in 1980 through 1984 when the less frequently carried, less resistant serogroups (1 to 5, 7 to 12, 45 and 46) accounted for a high proportion of bacteremic strains. CONCLUSIONS: URT isolates from any group of sick or healthy children could provide a conservative estimate of antimicrobial susceptibility of invasive strains and is a practical way of monitoring susceptibility as well as evaluating the continued effectiveness of standard antibiotic therapy. If there was cause for concern, it would then be necessary to examine invasive isolates.

Carrier State↗

The generation and subtraction of sensory expectations within cerebellum-like structures.

The generation of expectations about sensory input and the subtraction of such expectations from actual input appear to be important features of sensory processing. This paper describes the generation of sensory expectations within cerebellum-like structures of four distinct groups of fishes: Mormyridae; Rajidae; Scorpaenidae; and Apteronotidae. These structures consist of a sheet-like array of principal cells. Apical dendrites of the principal cells extend out into a molecular layer where they are contacted by parallel fibers. The basilar regions of the arrays receive primary afferent input from octavolateral endorgans, i.e., electroreceptors, mechanical lateral line neuromasts, or eighth nerve endorgans. The parallel fibers in the molecular layer convey various types of information, including corollary discharge signals associated with motor commands, sensory information from other modalities such as proprioception, and descending input from higher stages of the sensory modality that is processed by the structure. Associations between the signals conveyed by the parallel fibers and particular patterns of sensory input to the basal layers lead to the generation of a negative image of expected sensory input within the principal cell array. Addition of this negative image to actual sensory input results in the subtraction of expected from actual input, allowing the unexpected or novel input to stand out more clearly. Intracellular recording indicates that the negative image is probably generated by means of anti-Hebbian synaptic plasticity at the parallel fiber to principal cell synapse. The results are remarkably similar in the different fishes and may generalize to cerebellum-like structures in other sensory systems and taxa.

Afferent Pathways↗

Evaluation of sodium 4-hydroxybenzoate as an hydroxyl radical trap using gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection.

Molecular and tissue damage induced by reactive oxygen species is a serious consequence of the production of free radicals in biological systems. Biological markers produced by reactions with hydroxyl radicals are useful indices of free radical processes in vivo. In this respect, hydroxylation of aromatic compounds such as salicylate (2-hydroxybenzoate) has been used extensively as a measure of hydroxyl radical formation. 4-Hydroxybenzoate will also trap hydroxyl radicals with fewer of the complications for which salicylate has been criticized. We describe two sensitive and specific methods using gas chromatography-ion trap mass spectrometry and high-performance liquid chromatography with electrochemical detection for a number of these aromatic marker compounds in biological fluids. The use of an ion trap mass spectrometer provides enhanced sensitivity along with full mass spectral identification of the compounds of interest. 4-Hydroxybenzoate and salicylate were compared as hydroxyl radical traps (i) by determining relative hydroxyl radical trapping efficiencies in vitro, (ii) by measuring individual dihydroxybenzoate isomers in rat serum following intraperitoneal injection of either 2- or 4-hydroxybenzoate, and (iii) by comparing in vivo hydroxyl radical trapping using intrastriatal microdialysis in the rat. The techniques described have broad applications in the area of free radical biomedical research.

Animals↗