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Biomedical subjects

K Reid

Publications and source records attributed to K Reid.

At least 19 recordsLinked to original sources
PubMed2000

10q23.3 loss of heterozygosity is higher in lymph node-positive (pT2-3,N+) versus lymph node-negative (pT2-3,N0) prostate cancer.

Loss of heterozygosity (LOH) in the region of 10q23.3 has been associated with multiple tumors, including glioblastoma multiforme, melanoma, endometrial carcinoma, and prostate carcinoma. The tumor suppressor gene, PTEN/MMAC1, is also located in this region, and, in addition to other tumor types (eg, glioblastoma multiforme, endometrial, and melanoma), PTEN/MMAC1 mutations have been found in prostate cancer cell lines, xenografts, and hormone refractory prostate cancer tissue specimens. The aim of this study was to evaluate LOH at 10q23.3 as a marker of cancer progression in node-positive prostate cancer. Genetic alterations in the region of 10q23.3 were assessed in 23 node-positive (pT2-3, N+) and 44 node-negative prostate (pT2-3, N0) cancers with D10S532, D10S1687, D10S541, and D10S583 flanking polymorphic genetic markers; PTENCA, a genetic marker within PTEN/MMAC1, was also tested. Using DNA from paired normal and microdissected tumor samples, LOH at microsatellite loci was determined after polymerase chain reaction amplification. LOH in at least 1 marker was identified in 14% (6 of 44) of lymph node-negative and 43% (10 of 23) of lymph node-positive prostate cancers (chi-square test, P = .007). This increase in genetic alterations in node-positive prostate cancer suggests that 10q23.3 is a marker for metastatic progression.

Adenocarcinoma↗
PubMed1999

Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt.

Extracellular signals often result in simultaneous activation of both the Raf-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kinase, MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is phosphatidylinositol 3-kinase). However, these two signaling pathways were shown to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI3K-Akt pathway was shown to inhibit the Raf-MEK-ERK pathway; this cross-regulation depended on the differentiation state of the cell: Akt activation inhibited the Raf-MEK-ERK pathway in differentiated myotubes, but not in their myoblast precursors. The stage-specific inhibitory action of Akt correlated with its stage-specific ability to form a complex with Raf, suggesting the existence of differentially expressed mediators of an inhibitory Akt-Raf complex.

Animals↗
PubMed1999

p75 neurotrophin receptor-mediated neuronal death is promoted by Bcl-2 and prevented by Bcl-xL.

The p75 neurotrophin receptor (p75NTR) has been shown to mediate neuronal death through an unknown pathway. We microinjected p75NTR expression plasmids into sensory neurons in the presence of growth factors and assessed the effect of the expressed proteins on cell survival. We show that, unlike other members of the TNFR family, p75NTR signals death through a unique caspase-dependent death pathway that does not involve the "death domain" and is differentially regulated by Bcl-2 family members: the anti-apoptotic molecule Bcl-2 both promoted, and was required for, p75NTR killing, whereas killing was inhibited by its homologue Bcl-xL. These results demonstrate that Bcl-2, through distinct molecular mechanisms, either promotes or inhibits neuronal death depending on the nature of the death stimulus.

Animals↗
PubMed1999

Correlation between wrist activity monitor and electrophysiological measures of sleep in a simulated shiftwork environment for younger and older subjects.

Although several studies have examined the correlation between nocturnal PSG and activity measurement, validation studies of actigraphically measured sleep in shiftworking populations have not been reported. This study investigates the correlation between sleep recorded using EEG and actigraphic techniques during a simulated 12-hour shift rotation. Thirty-two subjects were allocated to groups according to age. Group (1) included sixteen subjects mean (+/- s.d.) age of 21.2 +/- 2.7 years, and Group (2) included sixteen subjects mean (+/- s.d.) age of 43.9 +/- 6.8 years. An adaptation night was followed by two 12-hour day shifts (7 am-7 pm), 24 hours off and then two 12-hour night shifts (7 pm-7 am). For the entire study subjects wore an activity monitor, and while in bed, sleep was recorded using polysomnography; both techniques were collected in 30-second epochs. A high epoch for epoch agreement between wrist activity monitoring and EEG measures of sleep was recorded for daytime and nighttime sleep periods (80-90%). There was a high correlation between EEG and actigraphically recorded sleep duration in young (0.98-0.77) and older (0.78-0.96) subjects for all sleep periods. Sleep efficiency correlations were extremely variable for both the young (0.72-0.15) and older (-0.18-0.58) subjects for daytime and nighttime sleep periods. Taken together these results suggest that wrist activity monitoring is a valid measure of sleep/wake activity and sleep duration, in a simulated shiftwork environment. However, some caution should be used for more specific measures, such as sleep efficiency particularly in older subjects.

Adult↗
PubMed1999

Signaling of neuronal cell death by the p75NTR neurotrophin receptor.

The neurotrophin receptor (p75NTR) is best known for mediating tropic support by participating in the formation of high-affinity nerve growth factor (NGF) receptor complexes with trkA, however, p75NTR more recently has been shown to act as a bona fide death-signaling receptor, which can signal independently of trkA. This article discusses the evidence for an active role of p75NTR in neuronal cell death and the mechanisms controlling this process, including roles for Bcl-2 family members, the c-jun stress kinase JNK, the transcription factor nuclear factor kappa B (NFkappaB), and caspases.

Animals↗
PubMed1999

Gap junctional communication in cultured human lung carcinoma cells.

Animal tumor models have demonstrated a close correlation between gap junctional, intercellular communication (GJIC) and tumor metastasis. To examine GJIC levels in human lung carcinoma cells, a novel technique was developed: cells were grown on a glass slide, half of which was coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse which opens transient pores on the plasma membrane was applied in the presence of the fluorescent dye, Lucifer yellow, causing the dye's penetration into the cells growing on the conductive part of the slide. The migration of the dye through gap junctions to the non-electroporated cells growing on the non-conductive area was then observed microscopically under fluorescence illumination. The results show that this is a rapid, precise and highly reproducible assay for GJIC assessment in lines established from lung carcinomas or freshly explanted lung tumor cells. Out of 17 established lines only two had extensive junctional communication, while out of 16 fresh tumor specimens none displayed GJIC. On the other hand, fibroblasts isolated from the same tumors had extensive junctional permeability. The examination of GJIC in a large number of samples could establish a correlation between GJIC and metastasis which might have prognostic value.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Three-dimensional motion analysis of upper limb movement in the bowing arm of string-playing musicians.

OBJECTIVES: To explore the role of three-dimensional movement analysis in defining patterns of joint movement while bowing on different stringed instruments, and its potential for future use by the clinician in the study of musculoskeletal problems in musicians. DESIGN AND METHODS: A protocol was developed for analysis of bowing arm movements using the MacReflex 3-D analysis system- including definition of marker sites, positioning of the musician within the calibrated area and standardised bowing sequences. This protocol was then used to determine whether the system was sensitive to differences between instrument types and to variation in bowing style and technique between individual players. The ranges of movement in the shoulder, elbow and wrist were compared between instrument groups in a cohort of 39 asymptomatic string players. RESULTS: The system gave reproducible results on repeated testing, and demonstrated clear differences between instruments, as well as stylistic differences between players. Range of shoulder movement increased progressively towards the upper register of the cello, while decreasing on the violin. Maximum elevation of the shoulder was significantly greater on the cello (P<0.001), while elbow flexion, and therefore range, was consistently greater on the violin. CONCLUSIONS: Clear and reproducible differences in style and technique were demonstrated between individuals. The increased range of shoulder movement in the upper register of the 'cello may contribute to the greater prevalence of neck and shoulder symptoms among 'cellists. Further study is required to establish whether different musculoskeletal symptoms produce characteristic patterns which could help in diagnosis and development is required to make the system feasible for routine use. RELEVANCE: Musculoskeletal problems are common among musicians. Different instruments and playing positions make different demands on joints and may contribute to the variance in reported incidence of musculoskeletal symptoms among violinists and cellists. Three-dimensional analysis may prove helpful in the future for the diagnosis of different musculoskeletal syndromes in string players, or for identifying movement patterns which could exacerbate repetitive strain injuries. However, as this is the first application of the technique in this complex area, preliminary work was required to establish feasibility and to obtain data on normal players.

Arm↗
PubMed1999

Assessment of the antioxidant potential of scotch whiskeys by electron spin resonance spectroscopy: relationship to hydroxyl-containing aromatic components.

Electron spin resonance (ESR) spectroscopy has been used to assess the antioxidant capacity of eight Scotch whiskeys by measuring the extent by which the original spirits, or pyridine solutions of their residues, reduced Fremy's radical or galvinoxyl radical. All whiskeys displayed antioxidant activity greater than that of a 0.2 mM solution of Trolox in the Fremy's assay and of a 0.1 mM solution of quercetin in the galvinoxyl assay. The relative antioxidant capacities determined according to the two assays were highly correlated and strongly related to the total phenol content as determined by using the Folin-Ciocalteu method. Activity was a consequence of maturation in oak casks with the "newmake" spirit showing no effect. Of 10 aromatic constituents analyzed, activity was most strongly correlated with ellagic acid and gallic acid in both assays. The reductive capacities of four major phenolics were determined, which, in summation, accounted for 31-53% of the total antioxidant activity of the whiskeys. There was no evidence for synergistic interaction between the phenols investigated.

Alcoholic Beverages↗
PubMed1999

Chromosome painting in marsupials: genome conservation in the kangaroo family.

In order to deduce the ancestral genome arrangement in the karyotypically diverse marsupial family Macropodidae, and to assess chromosome change in this family, chromosome-specific paints from the tammar wallaby (2n = 16) were hybridized to metaphase spreads from the two species proposed to represent the 2n = 22 ancestral karyotype, as well as species with derived 2n = 20 and 2n = 14 karyotypes. Identical patterns were observed in the two 2n = 22 species, from which the rearrangements to form the three derived karyotypes may be easily deduced to be 1, 3 and 4 different fusions, respectively. The identical Thylogale and Dorcopsis genomes may both be used to represent the pleisiomorphic macropodid chromosome complement. Variation in the X chromosome was also investigated by hybridizing an X-Y shared tammar wallaby 12-kb repeat element to chromosomes from the other four macropodid species, finding that it hybridized only to the most closely related species, and therefore is of recent origin.

Animals↗
PubMed1999

Cytochrome P-450-dependent bioactivation of 1,1-dichloroethylene to a reactive epoxide in human lung and liver microsomes.

We investigated the cytochrome P-450-dependent metabolism of 1, 1-dichloroethylene (DCE) by human lung and liver microsomes and compared the results from analogous experiments in mice. Metabolites were identified by HPLC analysis of their glutathione conjugates and/or hydrolyzed products and were detected by using [14C]DCE. The role of human CYP2E1 in the metabolic reactions was examined by comparing p-nitrophenol hydroxylase activities with levels of metabolites formed and by using the CYP2E1-selective inhibitor diallyl sulfone. The major products formed in microsomal incubations containing NADPH were the DCE-epoxide-derived glutathione conjugates 2-(S-glutathionyl)acetyl glutathione and 2-S-glutathionyl acetate. Lower levels of the acetal of 2,2-dichloroacetaldehyde were also detected. In lung samples from eight patients, the amounts of epoxide-derived conjugates formed ranged from 15.6 +/- 4.23 to 34.9 +/- 12.75 pmol/mg protein/min. The levels in murine lung were higher at 40.0 +/- 3.8 pmol/mg protein/min. In liver samples from five patients, conjugate levels ranged from 46.5 +/- 8.3 to 240.0 +/- 10. 5 pmol/mg protein/min, whereas levels in murine liver were 83.0 +/- 6.2 pmol/mg protein/min. Conjugate levels formed in human liver correlated with the relative levels of p-nitrophenol hydroxylase activity present, but this relationship was equivocal in human lung. Diallyl sulfone inhibited the formation of the glutathione conjugates (20-65%) in liver samples from all four patients, whereas only one of five human lung samples exhibited this inhibition (27%). These results demonstrated that the DCE-epoxide is a major metabolite formed by human microsomes and is mediated by CYP2E1 in liver and in some individuals in lung.

Adolescent↗
PubMed1998

Are cholinergic pathways involved in the anesthetic response to alpha2 agonists.

1. We investigated whether change in neuronal activity in cholinergic pathways mediates the anesthetic effect of the alpha2 agonist, dexmedetomidine, by determining whether physostigmine, a cholinesterase inhibitor, could antagonize the hypnotic response to dexmedetomidine in the rat and whether dexmedetomidine decreases the release of acetylcholine (ACh) in the thalamus in vivo. 2. Physostigmine did not significantly change the duration of the hypnotic response to dexmedetomidine. There was no significant change in thalamic ACh release after administration of dexmedetomidine. Therefore, alpha2-adrenergic agonists produce their anesthetic effect through mechanisms which do not involve alteration of the activity of the brainstem cholinergic nuclei.

Acetylcholine↗
PubMed1998

Rescue of dorsal root sensory neurons by nerve growth factor and neurotrophin-3, but not brain-derived neurotrophic factor or neurotrophin-4, is dependent on the level of the p75 neurotrophin receptor.

Sensory neurons isolated from dorsal root ganglia of postnatal mice were analysed for cell surface p75, using fluorescent antibody staining with flow cytometry. They were found to follow a single bell-shaped distribution of p75 level, with no discrete group of p75-negative neurons. Sensory neurons were then separated by fluorescence-activated cell sorting into high- and low-p75 populations, consisting of cells within the highest and lowest 15th percentiles, respectively, of p75 expression levels. The sorted neurons were tested for trkA staining. All high-p75 neurons were positive for trkA, while many low-p75 cells were negative for trkA. The sorted neurons were placed in culture, and their survival in the absence and presence of various neurotrophins was measured. Low-p75 cells were found to have enhanced survival in the absence of neurotrophins, while cells with high p75 levels had reduced survival, compared to the overall population. Almost all high-p75 neurons were rescued with nerve growth factor, whereas less than half of the low-p75 cells were rescued. The slope of the dose response to nerve growth factor did not differ markedly between high- and low-p75 cells. High-p75, but not low-p75, neurons were responsive to neurotrophin-3. There was only a small response to either brain-derived neurotrophic factor or neurotrophin-4 in both high- and low-p75 neurons. All low-p75 neurons, and 68% of high-p75 neurons, survived in the presence of ciliary neurotrophic factor. These results, while consistent with our hypothesis that p75 may act as a death factor in postnatal sensory neurons, also imply a role for p75 in the modulation of trk responsiveness to neurotrophins. They also indicate overlapping neurotrophin responses in sensory neurons, especially in those with high p75 levels. A large proportion of low-p75 cells were not responsive to any of the nerve growth factor-related neurotrophins, suggesting an important role for cytokines such as ciliary neurotrophic factor and leukaemia inhibitor factor in the survival of sensory neurons.

Animals↗
PubMed1998

Chronic desipramine treatment desensitizes the rat to anesthetic and antinociceptive effects of the alpha2-adrenergic agonist dexmedetomidine.

INTRODUCTION: The effects of long-term administration of the tricyclic antidepressant agent desipramine on the hypnotic, antinociceptive, anesthetic-sparing, and central norepinephrine turnover suppressant action of short-term dexmedetomidine, a highly selective alpha2-adrenergic agonist, were studied in rats. METHODS: Rats were given a 3- or 4-week course of twice daily administration of desipramine, 10 mg/kg, or saline. The effect of a hypnotic dose of dexmedetomidine, 250 microg/kg given intraperitoneally, on the duration of loss of righting reflex was determined. The tail flick latency response was determined before and after 50 microg/kg dexmedetomidine. The minimum anesthetic concentration of halothane and the central norepinephrine turnover rate were determined before and after administration of 30 microg/kg dexmedetomidine. Changes in the affinity and density of the alpha2-adrenergic receptor in locus coeruleus and spinal cord also were determined. RESULTS: Treatment with desipramine decreased dexmedetomidine-induced loss of righting reflex duration by 67% and eliminated the antinociceptive effect of dexmedetomidine. Dexmedetomidine produced a 55% decrease in minimum anesthetic concentration in the control group but no reduction in desipramine-treated rats. Desipramine did not change the receptor density or binding affinity of alpha2 receptors at the site for hypnotic (locus coeruleus) or antinociceptive (spinal cord) responses. No decrement in the central norepinephrine turnover rate was noted in the locus coeruleus of dexmedetomidine after 3 weeks of treatment with desipramine. The alpha1-adrenergic antagonist prazosin at 1 or 5 mg/kg completely (minimum anesthetic concentration reduction), almost completely (antinociceptive), or partially (hypnotic) restored responsiveness to normal. CONCLUSIONS: These data indicate that treatment with desipramine induces hyporesponsiveness to the hypnotic, analgesic, and minimum anesthetic concentration-reducing, but not to the suppression of central norepinephrine turnover, properties of dexmedetomidine. The hyporesponsiveness appears to involve an alpha1-adrenergic mechanism.

Adrenergic alpha-Agonists↗
PubMed1997

Effect of a covalently attached synergistic anion on chelator-mediated iron-release from ovotransferrin: additional evidence for two concurrent pathways.

The mechanism by which the iron-transport protein transferrin releases its iron in vivo is presently unclear. In vitro studies have implicated two concurrent chelator-mediated iron-release pathways: one which is hyperbolic in nature, involving a conformational change in the protein as a rate limiting step, and a second which has been proposed to be first-order in nature and to involve initial release of a synergistic anion. We have examined the effect that an affinity-label analog of the synergistic anion has on chelator-mediated iron-release from this protein. A covalently attached anion would inhibit iron-release via any pathway in which anion release is a prerequisite to iron release. The present investigation examined the effect that the covalently attached anion had on iron-release to pyrophosphate (PPi) and N, N-bis(phosphonomethyl)glycine (DPG), two chelators which are believed to utilize both pathways concurrently. Results show that when the affinity-label anion is utilized, strictly hyperbolic data are obtained, with similar observed kmax values. This is strong support for the hypothesis of a common, chelator-independent rate-limiting step for the one available pathway. These results also support strongly the hypothesis that synergistic anion removal is a prerequisite step to iron-release via the second pathway.

Anions↗
PubMed1997

Neural stem cells.

This article is concerned with the idea that neural precursor cells in vertebrates can self-renew and give rise to all cell types within the nervous system. Supportive evidence for this notion of neural stem cells comes from clonal analyses undertaken both in vivo and in vitro. Neural stem cells also give rise to other cells in the body, including skin melanocytes and a range of mesenchymal cells in the head and neck. What determines the fate of these stem cells is their initial location within the developing neural tube and their final location post migration from the proliferative zone of the neural tube. A population of cells in the adult brain also have the characteristics of classical stem cells, a finding that opens the way for potential replacement therapy in nervous system-degenerative diseases. Much of the work in our laboratory has been concerned with the regulation of expansion and differentiation of these cells into their myriad progeny and the role of a series of various growth factors in this process. Different factors, such as members of the fibroblast growth factor family, act at different times to regulate stem cell proliferation and differentiation. Some factors, including members of the TGF beta superfamily, appear to be directly involved in the specification of cell fate. Finally, we are beginning to be able to determine the steps in the development of some lineages from multipotential stem cell to fully functional differentiated cell.

Animals↗