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T Metcalfe

Publications and source records attributed to T Metcalfe.

15 recordsLinked to original sources
PubMed2003

Levels and patterns of persistent organochlorines in minke whale (Balaenoptera acutorostrata) stocks from the North Atlantic and European Arctic.

Regional variation in PCBs and organochlorine (OC) pesticide concentrations was examined using the blubber of 155 minke whales (Balaenoptera acutorostrata) sampled in seven regions in the North Atlantic and European Arctic, including western and southeastern Greenland, the Norwegian Sea, the North Sea and the Barents Sea. The levels and relative proportions of OCs were also used to examine the boundaries for North Atlantic minke whale stocks previously defined by the International Whaling Commission (IWC). Concentrations of major OC groups (sigmaPCB, 89.1-22 800 ng/g lipid; sigmaDDT, 65.3-6280 ng/g lipid; sigmaCHL, 33.3-2110 ng/g lipid) generally increased from west to east, while HCH concentrations (sigmaHCH, < 1-497 ng/g lipid) showed the opposite trend. Statistical comparison between six regions using sex-adjusted least squared mean concentrations showed that minke whales from the Barents Sea had significantly higher concentrations of EPCBs than those from the Vestfjorden/Lofoten, the North Sea, and west Svalbard, as well as significantly higher sigmaDDT concentrations compared to west Greenland animals. The differences in concentrations suggest that west and southeast Greenland minkes may represent one group of whales, which are distinct from both the Jan Mayen minkes and those from other IWC defined stocks in northern European waters. Principal components analysis using proportions of 71 PCB congeners and 20 OC pesticides (of total OCs) did not reveal any major differences among groups although minkes from the North Sea were distinguished from those from Greenland waters by higher loadings of more highly chlorinated PCBs and recalcitrant OC pesticides. The general similarity in mean levels of sigmaPCBs, sigmaDDT and sigmaCHL, as well as mean principal components analysis scores, among minkes sampled at Jan Mayen, Svalbard, Vestfjorden/Lofoten, the North Sea and the Barents Sea suggests that the whales are quite mobile and may feed in multiple areas within the northeastern Atlantic.

Analysis of Variance↗
PubMed2001

Apoptosis in normal and neoplastic mammary gland development.

Apoptosis plays important roles in mammary development from early embryonic formation of the mammary gland to the regression that follows cessation of cycling. The most dramatic occurrence of apoptosis is found during mammary involution. Most of the secretory epithelium in the lactating breast undergoes apoptosis as the mammary gland regresses and is reorganized for another cycle of lactation. We used the morphology, biochemical changes, and gene expression detected in apoptotic mammary epithelium during involution as a model for studying cell death during other stages of mammary development and for approaching the failure of apoptosis found in mammary hyperplasia. Morphological studies and gene expression have suggested that apoptosis during involution is comprised of two phases: an early limited apoptosis in response to hormone ablation and later protease promoted widespread apoptosis in response to altered cell-matrix interactions and loss of anchorage. We examined protein expression during involution for changes associated with loss of hormone stimulation and altered cell-matrix interactions. One of the proteins whose expression is able to inhibit apoptosis, and is altered during mammary epithelial cell was the serine-threonine protein kinase, Akt 1. Akt 1 activation is common to hormone, growth factor, and anchorage-mediated survival of epithelial cells. We found regulated expression of activated Akt 1 in the mammary gland during involution. Akt 1 activation peaked in pregnancy and lactation, and decreased significantly during apoptosis in mammary involution. Mechanisms of Akt 1 action include modulation of the ratio bcl-2 family members implicated in control of apoptosis. Bcl-2 family proteins were also expressed in pattern consistent with Akt 1 regulation. These observations led us to examine expression of activated Akt 1 and bcl-2 family proteins in premalignant hyperplasias. Akt 1 activation was increased; expression of anti-apoptotic proteins bcl-2 and bcl-x was strongly increased while pro-apoptotic bax was greatly diminished in three different lines of transplantable premalignant mammary hyperplasia. This data suggest that activation of Akt 1 by hormone- or anchorage-mediated pathways regulates survival of mammary epithelium and can contribute to initiation of neoplasia. These data suggest that perturbation of normal cell turnover can contribute to initiation of neoplasia.

Animals↗
PubMed1998

Agrobacterium VirD2 protein interacts with plant host cyclophilins.

Agrobacterium tumefaciens induces crown gall tumors on plants by transferring a nucleoprotein complex, the T-complex, from the bacterium to the plant cell. The T-complex consists of T-DNA, a single-stranded DNA segment of the tumor-inducing plasmid, VirD2, an endonuclease covalently bound to the 5' end of the T-DNA, and perhaps VirE2, a single-stranded DNA binding protein. The yeast two-hybrid system was used to screen for proteins interacting with VirD2 and VirE2 to identify components in Arabidopsis thaliana that interact with the T-complex. Three VirD2- and two VirE2-interacting proteins were identified. Here we characterize the interactions of VirD2 with two isoforms of Arabidopsis cyclophilins identified by using this analysis. The VirD2 domain interacting with the cyclophilins is distinct from the endonuclease, omega, and the nuclear localization signal domains. The VirD2-cyclophilin interaction is disrupted in vitro by cyclosporin A, which also inhibits Agrobacterium-mediated transformation of Arabidopsis and tobacco. These data strongly suggest that host cyclophilins play a role in T-DNA transfer.

Bacterial Proteins↗
PubMed1998

Comparative levels of organochlorine compounds in flounders from the northeast coast of Newfoundland and an offshore site.

Muscle tissue of yellowtail flounder, Pleuronectes ferruginea (n = 6) and winter flounder, Pseudopleuronectes americanus (n = 9) collected from Bonavista Bay, Conception Bay and an offshore location off northeastern Newfoundland, Canada, were analyzed for PCBs and other organochlorine compounds to determine if there are geographical variations in the concentrations and patterns of these persistent contaminants. The concentrations of total PCB congeners on a wet weight basis were relatively homogeneous at low ng/g levels. DDE, HCH compounds, and components of technical chlordane were the dominant organochlorine contaminants. Lipid normalized data indicate that PCB concentrations were higher in both species collected in the moderately urbanized region of Conception Bay. Principal Component Analysis (PCA) of PCB congener patterns indicated that flounder collected in Conception Bay had greater proportions of highly chlorinated PCB congeners, which may indicate point-source contamination in this region. Concentrations and patterns of other organochlorine compounds were relatively consistent across all sampling locations.

Animals↗
PubMed1993

Control of imaginal cell development by the escargot gene of Drosophila.

Mutations in the escargot (esg) locus, which codes for a zinc-finger-containing protein with similarity to the product of the snail gene, cause a variety of defects in adult structures such as loss of abdominal cuticle and malformation of the wings and legs. esg RNA is expressed in wing, haltere, leg and genital imaginal discs and in abdominal histoblast nests in the embryo. Expression in imaginal tissues is also found in third instar larvae. In esg mutant larvae, normally diploid abdominal histoblasts replicate their DNA without cell division and become similar in appearance to the polytene larval epidermal cells. A similar phenotype was also found in imaginal discs of larvae mutant for both esg and the Drosophila raf gene. These results suggest that one of the normal functions of esg may be the maintenance of diploidy in imaginal cells.

Abdomen↗
PubMed1993

Sensing and controlling rotational orientation in normal subjects and patients with loss of labyrinthine function.

The disability resulting from uni-or bilateral loss of vestibular function was assessed by exposing subjects, in darkness, to random rotational displacements on a motorized chair away from a "center" position and requiring them to rotate themselves back to center using a "joystick" control. Normal subjects were accurate within 10 to 15 percent over 180-degree rotations. Alabyrinthine subjects failed to sense their rotation to any useful extent. Subjects with unilateral loss of function as a result of surgery produced hypometric responses to ipsilateral rotation and large amplitude, but inaccurate responses to contralateral rotation. This pattern became more symmetric and normometric with adaptation to loss of function. The procedure promises to be a more useful measure of adaptation than assessing vestibulo-ocular reflexes.

Adult↗
PubMed1992

Neurology of latent nystagmus.

We report eye movement findings in 30 patients with latent nystagmus and who were found to have a variety of associated oculomotor disorders. Latent nystagmus is defined clinically as nystagmus which appears on covering one eye and beats towards the uncovered eye. Recordings showed that the latent nystagmus in 28 patients had slow phases with linear or exponentially decreasing velocity. This nystagmus is termed 'LN'. In 13 of these patients certain manoeuvres (e.g. pursuit) provoked nystagmus with exponentially increasing slow phase velocities characteristic of the congenital form of nystagmus termed 'CN' and we propose that this is a forme fruste of CN. In two patients the nystagmus provoked by cover was latent CN. Twenty-nine patients had a history of strabismus and one had a marked phoria. Some patients had amblyopia whilst others had normal vision in each eye. Although binocular vision was usually absent, six patients had varying degrees of stereopsis. A temporonasal predominance of monocularly elicited optokinetic response previously associated with LN, was present only in a minority of patients. Some responses were bidirectionally absent or of low velocity, possibly the result of a cortical impairment of visual motion detection. The most deranged responses had slow phases which were in the opposite direction to the stimulus as described in CN. The presence of 'forme fruste' CN in many of these patients suggests that some of the derangements of optokinetic responses are due to CN. The findings indicate a greater overlap between the incidences of LN and CN than previously estimated. Thirty percent of patients had large saccadic 'square wave' intrusions. These were not present when there was marked amblyopia. They are attributed to a competitive incongruence of visual fields and eye positions. Dissociations found between the presence and severity of strabismus, stereopsis, amblyopia and optokinetic abnormalities point to these features being relatively independent although associated in typical clusterings. This is evidence against the theory that strabismus and LN are directly caused by nasotemporal optokinetic imbalance which persists because of failure to develop binocular vision. The variability of findings favours the view that LN and CN arise from a genetic or acquired embryological disorder with various degrees and directions of expression.

Adolescent↗
PubMed1992

Clinical and vestibulometric status following labyrinthectomy or vestibular nerve section for Menière's disease.

A clinical and vestibulometric comparison of 10 patients following labyrinthectomy, 5 following vestibular nerve section, and 10 control subjects was undertaken in order to evaluate the long-term effectiveness of these procedures. Testing was performed a mean of 8.5 years after surgery. Vestibulometry assessed time constants, gain, and phase advance of the vestibulo-ocular reflex (VOR) in both horizontal and vertical planes of head movement. Loss of the anticipated increase in phase advance in the vertical VOR of the labyrinthectomy group, significantly different from the vestibular nerve section group (P less than 0.05 and P less than 0.01 for each direction of rotation), suggests that posterior and superior semicircular canal function remains intact following per-meatal labyrinthectomy. Although stabilometry suggested that balance in the labyrinthectomy group was poorer than in the two other groups (P less than 0.025 without optic fixation), clinical assessment demonstrated excellent functional results. Per-meatal labyrinthectomy remains a safe and effective procedure for the relief of vestibular symptoms, although vestibular nerve section may provide more complete removal of contributory end-organ function.

Aged↗
PubMed1992

Chronic microsporidian infection of the nasal mucosae, sinuses and conjunctivae in HIV disease.

A case of chronic infection of the nasal mucosae, sinuses and conjunctivae with a microsporidian parasite in association with HIV infection and immune deficiency is reported. This microsporidian resembles both Encephalitozoon cuniculi and the newly described Encephalitozoon hellem by electron microscopy. This occurred in an adult male resident in the UK with no history of foreign travel. Although there are previous descriptions of conjunctival infections from the USA, this is the first description of infection of the nasal epithelium. Further studies are underway to classify this protozoan.

Adult↗
PubMed1991

Cervico-ocular function in patients with spasmodic torticollis.

The cervico-ocular (COR) and active and passive vestibulo-ocular reflexes (VOR) were measured in seven patients with spasmodic torticollis (ST) and six normal controls. The COR was found to be weak or absent in both groups. The VOR gain was similar in the two groups but five patients had a significant asymmetry of the response. There was no evidence of abnormal cervico-vestibular interaction during active head rotation. The study suggests that the VOR asymmetry frequently found in ST cannot be explained on the basis of an abnormal cervical input.

Adult↗
PubMed1989

Vitamin E concentrations in human brain of patients with Alzheimer's disease, fetuses with Down's syndrome, centenarians, and controls.

The concentration of vitamin E (alpha-tocopherol) was measured in samples of cortex from patients with Alzheimer's disease (AD), fetuses with Down's syndrome (DS), and also in a group of centenarians. The mean tocopherol concentrations in the two patient groups did not differ significantly from appropriate controls. When expressed per lipid the mean tocopherol concentration of the centenarians was greater than that of the controls but this reflected a significant decrease in the lipid concentration of the former group. These results indicate that neither the normal aging processes, Alzheimer's disease, nor the increased in vitro lipid peroxidation reported in fetuses with Down's syndrome result from a gross lack of alpha-tocopherol, or cause a significant depletion of the vitamin.

Adult↗