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Biomedical subjects

R J Turner

Publications and source records attributed to R J Turner.

At least 19 recordsLinked to original sources

Increased substance P immunoreactivity and edema formation following reversible ischemic stroke.

Previous results from our laboratory have shown that neurogenic inflammation is associated with edema formation after traumatic brain injury (TBI). This neurogenic inflammation was characterized by increased substance P (SP) immunoreactivity and could be attenuated with administration of SP antagonists with a resultant decrease in edema formation. Few studies have examined whether neurogenic inflammation, as identified by increased SP immunoreactivity, occurs after stroke and its potential role in edema formation. The present study examines SP immunoreactivity and edema formation following stroke. Experimental stroke was induced in halothane anaesthetized male Sprague-Dawley rats using a reversible thread model of middle cerebral artery occlusion. Increased SP immunoreactivity at 24 hours relative to the non-infarcted hemisphere was observed in perivascular, neuronal, and glial tissue, and within the penumbra of the infarcted hemisphere. It was not as apparent in the infarct core. This increased SP immunoreactivity was associated with edema formation. We conclude that neurogenic inflammation, as reflected by increased SP immunoreactivity, occurs following experimental stroke, and that this may be associated with edema formation. As such, inhibition of neurogenic inflammation may represent a novel therapeutic target for the treatment of edema following reversible, ischemic stroke.

Animals↗

p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma.

BACKGROUND: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour-associated antigens. OBJECTIVES: We tested the hypothesis that individuals with cutaneous SCC have functional circulating CD8+ T cells specific for p53. METHODS: Interferon-gamma immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53-derived HLA-A*0201-restricted epitopes from HLA-A*0201-positive patients and controls. RESULTS: We observed significantly elevated frequencies of p53-specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. CONCLUSIONS: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.

CD8-Positive T-Lymphocytes↗

Influence of fibrillin-1 genotype on the aortic stiffness in men.

Aortic stiffness is a predictor of cardiovascular mortality. The mechanical properties of the arterial wall depend on the connective tissue framework, with variation in fibrillin-1 and collagen I genes being associated with aortic stiffness and/or pulse pressure elevation. The aim of this study was to investigate whether variation in fibrillin-1 genotype was associated with aortic stiffness in men. The mechanical properties of the abdominal aorta of 79 healthy men (range 28-81 yr) were investigated by ultrasonographic phase-locked echo tracking. Fibrillin-1 genotype, characterized by the variable tandem repeat in intron 28, and collagen type I alpha 1 genotype characterized by the 2,064 G>T polymorphism, were determined by using DNA from peripheral blood cells. Three common fibrillin-1 genotypes, 2-2, 2-3, and 2-4, were observed in 50 (64%), 10 (13%), and 11 (14%) of the men, respectively. Those of 2-3 genotype had higher pressure strain elastic modulus and aortic stiffness compared with men of 2-2 or 2-4 genotype (P = 0.005). Pulse pressure also was increased in the 2-3 genotype (P = 0.04). There was no significant association between type 1 collagen genotype and aortic stiffness in this cohort. In conclusion, the fibrillin-1 2-3 genotype in men was associated with increased aortic stiffness and pulse pressure, indicative of an increased risk for cardiovascular disease.

Adult↗

Eu-estrogenemia.

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Adult↗

Spontaneous clinical improvement in HIV-associated follicular syndrome.

Since 1991 infrequent reports have described a distinctive triad of nodulocystic acne, striking follicular spines and an eruption resembling pityriasis rubra pilaris (PRP) in HIV-positive patients. It has been suggested that this may represent a subtype of PRP, or alternatively that it should be viewed as a unique HIV-associated follicular occlusion triad. Clinical manifestations may be severe, and in several cases have been ultimately fatal, with death occurring due to complications of cutaneous sepsis. We describe a case demonstrating severe conglobate acne, follicular keratotic spines and histologically confirmed PRP in association with HIV infection. Clinical features and treatment modalities of previously reported cases are reviewed. Despite refusing all topical and systemic treatment our patient showed spontaneous remission of skin signs after 2 years.

Acne Vulgaris↗

Multiple scrotal epidermolytic acanthomas; secondary to trauma?

Epidermolytic hyperkeratosis (EH) is an abnormality of epidermal maturation, most commonly due to mutations in keratins 1 and 10, which may be a congenital or an acquired defect. The term epidermolytic acanthoma was applied to a solitary discrete epidermal proliferation characterized by EH. Subsequently there have been several reports of disseminated epidermolytic acanthomas. We report a rare case of multiple epidermolytic acanthomas localized to the scrotum. With the aetiology of epidermolytic acanthoma unknown, trauma has been postulated as a possible cause. Our patient repetitively scratched his scrotum for 5 years and we believe that this action triggered his multiple scrotal epidermolytic acanthomas.

Acanthoma↗

The in-vitro effects of sevoflurane and desflurane on the contractility of pregnant human uterine muscle.

The effect of desflurane and sevoflurane on the contractility of the uterus was examined in vitro on strips of human myometrium obtained at the time of elective cesarean section. Small strips (1 mm x 2 mm x 10 mm) of muscle were prepared and suspended in an organ bath containing oxygenated physiological saline. Force of contraction was recorded continuously using an isometric tension transducer. Following the onset of regular spontaneous contractions, baseline measurements were obtained and the strips were exposed to varying concentrations of sevoflurane or desflurane corresponding to 0.5, 1.0 and 1.5 minimum alveolar concentration (MAC). Sevoflurane depressed contractility to 72 +/- 18% of control at 0.5 MAC, 37 +/- 15% at 1.0 MAC and 27 +/- 16% at 1.5 MAC compared with 65 +/- 14 of control at 0.5 MAC, 43 +/- 18% at 1.0 MAC and 22 +/- 11% at 1.5 MAC for desflurane. The degree of depression of uterine muscle contractility produced by both these agents was significantly different from control at all concentrations. In conclusion, both sevoflurane and desflurane depress the contractility of isolated pregnant human myometrium at concentrations of 0.5, 1.0 and 1.5 MAC. These agents produce a similar degree of depression of uterine muscle contractility.

Journal Article↗

The effects of sevoflurane on isolated gravid human myometrium.

The volatile anaesthetic agents are known to influence uterine muscle tone. All of the agents studied to date have been found to produce uterine relaxation. This property has been used to produce therapeutic uterine relaxation for difficult obstetric deliveries and the Ex Utero Intrapartum Treatment (EXIT) procedure. This study describes the effects of sevoflurane on isolated human myometrium at concentrations of 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.5 and 3.5 MAC. Sevoflurane produces dose-dependent depression of uterine muscle contractility with an ED50 of 0.94 MAC. Frequency of contraction was increased at concentrations of 2.5 MAC and greater. At concentrations of 3.5 MAC and above, uterine activity was virtually abolished.

Analysis of Variance↗

Airway management on placental support (AMPS)--the anaesthetic perspective.

Neonatal airway obstruction has been reported to have a high mortality. Antenatal diagnosis of this condition is now possible. Anaesthetic and surgical techniques have been developed that allow neonatal airway obstruction to be managed at delivery, while the fetus remains oxygenated via the placental circulation. Three case studies are presented, and the anaesthetic issues for mother and fetus/neonate are discussed with reference to previously published cases of airway management on placental support. In particular, techniques for uterine relaxation and maintenance of placental circulation are explored. The history of these procedures and issues of planning and logistics are also discussed.

Adult↗

Imaging tip formation in single-mode optical fibres.

The formation of probe tips is a crucial step in all forms of scanning probe microscopy (SPM). In this work single-mode optical fibres are chemically etched in a variable temperature bath of etchant solution (HF acid buffered with ammonium fluoride) to produce tips for optical SPM. Tip evolution is monitored by prematurely truncating the etching process and imaging the tip end-structure using atomic force microscopy (AFM). In the case of a visible regime single-mode fibre the AFM images show a remarkable ring structure in the central cladding region and a tip structure in the core with a central depression; this serves to demonstrate the efficacy of chemical etching for converting compositional variation to three-dimensional topography. In the case of a standard, single-mode optical communications fibre the (projected) tip cone angle is assessed from AFM images in the early stages of tip formation. Values of the cone angle thus determined, for different etch conditions, are compared to those predicted by a model in which the independently determined core and cladding etch rates, and core diameter are the sole determinants of the final tip geometry. The model was devised in the context of etching multi-mode fibres and is shown to be valid here for single-mode fibres within the range of experimental accuracy and etch conditions examined.

Journal Article↗

Identification of a twin-arginine leader-binding protein.

The transport and targeting of a number of periplasmic proteins is carried out by the Sec-independent Mtt (also referred to as Tat) protein translocase. Proteins using this translocase have a distinct twin-arginine-containing leader. We hypothesized that specific leader-binding proteins exist to escort proteins to the translocase complex. A fusion was constructed with the twin-arginine leader from dimethyl sulphoxide (DMSO) reductase, subunit DmsA, to the N-terminus of glutathione-S-transferase. This leader fusion was bound to a glutathione affinity column through which an Escherichia coli anaerobic cell-free extract was passed. Proteins that bound to the leader were then separated and identified by N-terminal sequencing, which identified DnaK and a protein originating from the uncharacterized reading frame ynfI. This gene has been designated dmsD based on the findings presented in this paper. DmsD was purified as a His6 fusion and was shown to interact with preprotein forms of DmsA and TorA (trimethyl amine N-oxide reductase). A strain carrying a dmsD knock-out mutation showed a loss of anaerobic growth on glycerol-DMSO medium and reduced growth on glycerol-fumarate medium. This work suggests that DmsD is a twin-arginine leader-binding protein.

Amino Acid Sequence↗

Low metabolic rate in scorpions: implications for population biomass and cannibalism.

Scorpions are abundant in arid areas, where their population biomass may exceed that of vertebrates. Since scorpions are predators of small arthropods and feed infrequently across multi-year lifespans, a parsimonious explanation for their observed, anomalously high biomass may be a depressed metabolic rate (MR). We tested the hypothesis that scorpion MR is significantly depressed compared with that of other arthropods, and we also measured the temperature-dependence of the MR of scorpions to quantify the interaction between large seasonal variations in desert temperatures and MR and, thus, long-term metabolic expenditure. Scorpion MR increased markedly with temperature (mean Q(10)=2.97) with considerable inter-individual variation. At 25 degrees C, the MRs of scorpions from two genera were less than 24 % of those of typical terrestrial arthropods (spiders, mites, solpugids and insects) of the same mass. It is likely, therefore, that the low MR of scorpions contributes to their high biomass in arid areas. The combination of high biomass and high production efficiency associated with low MR may also favor a density-dependent "transgenerational energy storage" strategy, whereby juveniles are harvested by cannibalistic adults that may be closely related to their juvenile prey.

Animals↗

A longitudinal study of the role and significance of mattering to others for depressive symptoms.

This paper addresses the hypothesis that the experience of mattering to others is inversely related to depressive symptomatology. We also assess the extent to which mattering overlaps or is redundant with other measures of personal and social resources. Based on multivariate analyses of two waves of data from a large urban community sample (n = 1,300), we identify three important findings. First, women experience substantially higher levels of mattering than do men. Therefore, if men and women had equal levels of mattering, women would report even higher depression scores relative to men. Second, it is clear that mattering and sub-dimensions of social support are substantially more confounded among men than among women. Finally, analyses confirm that mattering is conditionally predictive of depression by gender. Specifically, variations in mattering are predictive of depression for women, but not for men. This relationship is confirmed both cross-sectionally and over time.

Cross-Sectional Studies↗

Glutathione is a target in tellurite toxicity and is protected by tellurite resistance determinants in Escherichia coli.

Tellurite (TeO3(2-)) is highly toxic to most microorganisms. The mechanisms of toxicity or resistance are poorly understood. It has been shown that tellurite rapidly depletes the reduced thiol content within wild-type Escherichia coli. We have shown that the presence of plasmid-borne tellurite-resistance determinants protects against general thiol oxidation by tellurite. In the present study we observe that the tellurite-dependent depletion of cellular thiols in mutants of the glutathione and thioredoxin thiol:redox system was less than in wild-type cells. To identify the type of low-molecular-weight thiol compounds affected by tellurite exposure, the thiol-containing molecules were analyzed by reverse phase HPLC as their monobromobimane derivatives. Results indicated that reduced glutathione is a major initial target of tellurite reactivity within the cell. Other thiol species are also targeted by tellurite, including reduced coenzyme A. The presence of the tellurite resistance determinants kilA and ter protect against the loss of reduced glutathione by as much as 60% over a 2 h exposure. This protection of glutathione oxidation is likely key to the resistance mechanism of these determinants. Additionally, the thiol oxidation response curves were compared between selenite and tellurite. The loss of thiol compounds within the cell recovered from selenite but not to tellurite.

Bacterial Proteins↗

Transmembrane topology of the secretory Na+-K+-2Cl- cotransporter NKCC1 studied by in vitro translation.

The secretory Na(+)-K(+)-2Cl(-) cotransporter NKCC1 is a member of a small gene family of electroneutral salt transporters. Hydropathy analyses indicate that all of these transporters have a similar general structure consisting of large hydrophilic N and C termini on either side of a central, relatively well conserved, hydrophobic domain. Programs that predict the transmembrane topology of polytopic membrane proteins identify 10-12 putative membrane-spanning segments (MSSs) in this hydrophobic domain; but to date, there is little experimental data on the structure of this region for any of these transporters. In this report, we have studied the transmembrane topology of NKCC1 using an in vitro translation system designed to test the membrane insertion properties of putative MSSs (Bamberg, K., and Sachs, G. (1994) J. Biol. Chem. 269, 16909-16919). Fusion proteins consisting of putative NKCC1 MSSs inserted either (i) between an N-terminal cytosolic anchor sequence and a C-terminal reporter sequence containing multiple N-linked glycosidation sites or (ii) between an N-terminal signal anchor sequence and the same glycosidation flag were expressed in the presence of canine pancreatic microsomes. The glycosidation status of the reporter sequence, which indicated its luminal or extraluminal location in the microsomes, was then used to characterize the signal anchor or stop transfer activity of the inserted MSSs. The results of this experimental analysis yielded a topology scheme consisting of 12 membrane-spanning segments, two pairs of which apparently form rather tight hairpin-like structures within the membrane.

Amino Acid Sequence↗