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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 469 records · Page 26Linked to original sources
PubMed1998

The role of the monocyte in the generation and dissolution of arterial and venous thrombi.

Monocyte infiltration into forming thrombus has been demonstrated in experimental models of venous thrombosis developed in our laboratories. These cells produce and release plasminogen activators as the thrombus organises and resolves. Monocytes are also capable of assembling and releasing procoagulant factors and the evidence for their importance in thrombogenesis is reviewed. The ability of monocytes to maintain this fibrinolytic balance suggests that they may have a role in both thrombosis and thrombus resolution. Control of the mechanisms which regulate these activities may therefore be important in preventing thrombus formation or stimulating its resolution.

Animals↗
PubMed1998

Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.

To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.

Animals↗
PubMed1998

Vascular endothelial growth factor (VEGF) expression during arterial repair in the pig.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is reported to be a potent and specific mitogen for endothelial cells (EC) and an inducer of angiogenesis in vivo. Originally called vascular permeability factor (VPF), VEGF also increases permeability of microvessels to circulating macromolecules. The aim of this study was to examine whether the VEGF gene was expressed in porcine arteries following denudation of EC. DESIGN: Experimental animal model with mechanical injury to large arteries. METHODS: The right iliac artery of juvenile pigs was de-endothelialised using an inflated balloon catheter. At a number of time-points after injury, these arteries were harvested together with uninjured contralateral arteries. Sections of arteries were used for RNA analysis by Northern blots and for protein localisation studies by immunohistochemistry. RESULTS: Two VEGF transcripts (2.0 kb, 4.5 kb) were markedly elevated in pig arteries soon after injury. Newly synthesised VEGF protein was located in smooth muscle cells (SMC) throughout the media of injured arteries. CONCLUSIONS: The elevated expression of VEGF by SMC in denuded porcine arteries is evidence that this cytokine plays a role in the injury response of large arteries. Since several biological activities have been identified for VEGF, the function of this cytokine in the arterial repair process remains to be determined.

Animals↗
PubMed1998

Expression of a novel piscine growth hormone gene results in growth enhancement in transgenic tilapia (Oreochromis niloticus).

Several lines of transgenic G1 and G2 tilapia fish (Oreochromis niloticus) have been produced following egg injection with gene constructs carrying growth hormone coding sequences of fish origin. Using a construct in which an ocean pout antifreeze promoter drives a chinook salmon growth hormone gene, dramatic growth enhancement has been demonstrated, in which the mean weight of the 7 month old G2 transgenic fish is more than three fold that of their non transgenic siblings. Somewhat surprisingly G1 fish transgenic for a construct consisting of a sockeye salmon metallothionein promoter spliced to a sockeye salmon growth hormone gene exhibited no growth enhancement, although salmon transgenic for this construct do show greatly enhanced growth. The growth enhanced transgenic lines were also strongly positive in a radio-immuno assay for the specific hormone in their serum, whereas the non growth enhanced lines were negative. Attempts to induce expression from the metallothionein promoter by exposing fish to increased levels of zinc were also unsuccessful. Homozygous transgenic fish have been produced from the ocean pout antifreeze/chinook salmon GH construct and preliminary trials suggest that their growth performance is similar to that of the hemizygous transgenics. No abnormalities were apparent in the growth enhanced fish, although minor changes to skull shape and reduced fertility were noted in some fish. There is also preliminary evidence for improved food conversion ratios when growth enhanced transgenic tilapia are compared to their non-transgenic siblings. The long term objective of this study is to produce lines of tilapia which are both growth enhanced and sterile, so offering improved strains of this important food fish for aquaculture.

Animals↗
PubMed1998

Coordination of nitric oxide by heme-hemopexin.

Hemopexin, which acts as an antioxidant by binding heme (Kd < 1 pM), is synthesized by hepatic parenchymal cells, by neurons of the central and peripheral nervous systems, and by human retinal ganglia. Two key regulatory molecules, nitric oxide (.NO) and carbon monoxide (CO), both bind to heme proteins and since ferroheme-hemopexin binds CO, the possible role of heme-hemopexin in binding .NO was investigated. .NO binds rapidly to hemopexin-bound ferroheme as shown by characteristic changes in the Soret and visible-region absorbance spectra. Circular dichroism spectra of .NO-ferroheme-hemopexin in the Soret region exhibit an unusual bisignate feature with a zero crossover at the absorbance wavelength maximum, showing that exciton coupling is occurring. Notably, the .NO complex of ferroheme-hemopexin is sufficiently avid and stable to allow hemopexin to bind this molecule in vivo and, thus, hemopexin may protect against NO-mediated toxicity especially in conditions of trauma and hemolysis.

Carbon Monoxide↗
PubMed1998

A comparative study on the efficacy of CD8-positive cells in enhancing allogeneic bone marrow engraftment: cell sorting vs microbead selection.

We have used a superparamagnetic microbead selection system to positively select a murine bone marrow CD8+ cell population. The functional ability of these cells to enhance allogeneic bone marrow engraftment was compared with that of fluorescence activated cell sorter purified CD8+ cells. The CD8+ cell population prepared by the microbead selection procedure was as effective as cell sorter purified CD8+ cells in enhancing T cell-depleted allogeneic bone marrow engraftment in lethally irradiated mice. Phenotypic characterization of these cells shows that most of these CD8+ cells express CD3 and the T cell antigen receptor complex.

Animals↗
PubMed1998

Stability and patterning of speech movement sequences in children and adults.

Children (aged 4 and 7 years) and young adults produced a six-syllable utterance 15 times. The displacement of the lower lip was recorded with an Optotrak system and analyzed in a number of ways. First, using a procedure recently developed in our laboratory, displacement records from the 15 repetitions were amplitude- and time-normalized, and the spatiotemporal index (the STI) was computed. The STI reflects the degree to which repeated performance of a task produces movement trajectories that converge on a single pattern. Children produced less stable movement trajectories, as reflected in higher values on the STI. In a second analysis, standard measurements of amplitude and peak velocity were made for two opening and two closing lip movements. These measures suggested that, relative to the size of their oral structures, children have large movement ranges in speech. Also, children tend to move with a lower peak velocity. This large-amplitude, low-velocity movement style may reflect different underlying control processes. Finally, another analysis focused on open-close movement sequences associated with two words of the utterance. A pattern-recognition algorithm applied to the normalized waveforms from the open-close sequences revealed that children and adults produced equally distinctive movement trajectories for the two syllables. Taken together, these preliminary results suggest that nonlinear and nonuniform changes occur in components of the speech motor system during development.

Adult↗
PubMed1998

Spatiotemporal stability of lip movements in older adult speakers.

Although the intelligibility of healthy older adults normally seems unimpaired, age-related changes occur in sensorimotor components of the speech system and in such global parameters as speech rate. In order to clarify the effect of these changes on the variability of speech movements, we examined oral peripheral abilities, speech rate, and speech kinematics in a group of 10 adults age 76-83, compared to a group of 10 young adults. Participants repeated a short phrase 15 times at habitual, fast, and slow rates. The resulting lip displacement signals were time- and amplitude-normalized, and successive standard deviations along the movement waveforms were summed to produce a spatiotemporal index (STI) representing individual variability in movement pattern. Participants tended to show greatest variability at slow rate, less variability at fast rate, and least variability at habitual rate. For the older adults, STI at habitual rate was significantly higher (more variable) and speech durations were longer than those of young adults. Perioral strength and tactile acuity were poorer in these older adults than in young adults. We conclude that as sensorimotor abilities change in old age, speakers are less consistent in the spatiotemporal organization of speech movements, reflecting decreased stability of speech motor control.

Adult↗
PubMed1998

Domestic allergens in public places III: house dust mite, cat, dog and cockroach allergens in British hospitals.

BACKGROUND: Exposure and sensitization to indoor allergens is a major cause of asthma. OBJECTIVES: This study investigated the levels of house dust mite, cat, dog and cockroach allergens in the dust and air in hospitals and the effects of regular vacuum cleaning on allergen levels in hospital chairs. METHODS: Der p 1, Fel d 1, Can f 1 and Bla g 2 were measured in the dust collected by vacuuming upholstered chairs and a 1 m2 area of carpet and mattress in 14 hospitals. Air samples were collected using an air sampler (flow rate 60 L/min) on 10 separate days for 4 h in the outpatient department in one of the hospitals during busy clinics when patients were waiting for their appointments. In addition, dust samples were collected on four occasions, at 4-weekly intervals, from 36 fabric covered chairs in the outpatient area of a busy chest clinic by vacuuming each chair for 2 min. During the intervening weeks, 18 of the chairs (active group) were each cleaned by vacuuming for 1 min, three times per week. Der p 1, Fel d 1, Can f 1 and Bla g 2 were assayed using monoclonal antibody-based ELISA. RESULTS: In total, 83 carpets, 69 mattresses and 42 upholstered chairs were sampled. The levels of dust mite allergen Der p 1 and cockroach allergen Bla g 2 found in the hospital setting were low. High levels of Fel d 1 (GM 22.9 microg/g, range 4.5-58) and Can f 1 (GM 21.6 microg/g, range 4-63) were found in upholstered chairs. Airborne Can f 1 was detected on every occasion (range 0.12-0.56 ng/m3), whilst detectable airborne Fel d 1 was found on 7 out of the 10 sampling days (range 0.09-0.22 ng/m3). Der p 1 and Bla g 2 were below the detection limit in all airborne samples. Following repeated vacuuming the mean cat and dog allergen levels decreased significantly (P<0.001) and were almost fivefold lower in the vacuumed chairs compared with the control group. CONCLUSIONS: Low levels of mite allergen are unlikely to be of any clinical significance to mite-sensitive asthmatic patients. However, upholstered chairs in hospitals constitute a significant reservoir of cat and dog allergen. Inhalation of airborne allergen in patients attending their hospital appointment may exacerbate asthma in those highly allergic to cats or dogs. These results question the wisdom of introducing soft furnishings and carpets into hospitals. Three-times weekly vacuuming significantly reduces allergen levels in upholstered chairs.

Air Pollution, Indoor↗
PubMed1998

The systemic stress response to thermal injury in children.

OBJECTIVE: Thermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them. PATIENTS: Twenty-three children, 13 girls and 10 boys aged between 5 months and 12 years 3 months (mean, 2 years 11 months), with burns covering 10-61% of their body surface (mean, 20.5%) were studied during the first 5 days following injury. MEASUREMENTS: The levels of arginine vasopressin, angiotensin II, cortisol, adrenaline, noradrenaline and dopamine were measured in sequential blood samples obtained from thermally injured children on admission and at specified time intervals during the 5 days of the investigation. RESULTS: At admission the concentrations of all the hormones were high, and varied widely between individual patients. The geometric mean and 95% confidence intervals of admission hormone levels were as follows: arginine vasopressin 18.3 (8.3-40.7) pmol/l; angiotensin II 122.0 (56.0-266.2) pmol/l; cortisol 650.6 (473.0-895.0) nmol/l; dopamine 1.0 (0.1-8.0) nmol/l; adrenaline 6.4 (3.2-12.5) nmol/l and noradrenaline 2.3 (1.3-4.3) nmol/l. Although the concentrations of arginine vasopressin and cortisol returned to normal 24 to 36 h after admission, the levels of angiotensin II, adrenaline and dopamine fluctuated and remained higher than normal throughout the study (108 h). CONCLUSIONS: Thermal injury results in the release of abnormally high levels of stress hormones in children. Although there are similarities between some of the data reported here and those reported in adults, higher levels of adrenaline and lower levels of noradrenaline than reported in adults suggest important differences too. These differences may need to be taken into account in the management of burn-injured children.

Angiotensin II↗
PubMed1998

Learning about reflection.

An understanding of the nature and function of reflection in recognizing and developing nursing knowledge is a key concern. This paper describes a longitudinal study investigating the ways in which undergraduate student nurses reflected about practice as they progressed through a 3-year programme in adult nursing. The method was qualitative, with data gained from written critical incidents based on practice experiences and classroom discussions, and analysed using the constant comparative method. Findings revealed the range of issues students perceived as most important, and to some extent, changes in levels of thinking. A strong theme occurring throughout related to the complexity of learning what it means to be a professional and, in consequence, what they learn about themselves. Students' preoccupation with emotional aspects of learning and nursing care was evident. They had difficulty in disentangling 'personal' and 'professional' involvement but later data indicates that they had begun to learn to differentiate between involvement as a general characteristic of nursing practice and a overwhelming personal attachment. They generally use their own and each others' experiences to examine meaning, in preference to formal theoretical explanations although there is evidence students moved from acceptance of information to the questioning and critiquing of arguments and professional assumptions, particularly concerning their relevance and appropriateness for practice.

Adolescent↗
PubMed1998

A case of monosomy 21 found to be an unbalanced de novo t(5p;21q) by fluorescence in situ hybridization.

A case is presented in which monosomy 21 was detected by routine cytogenetics and fluorescence in situ hybridization (FISH) studies demonstrated an unbalanced translocation t(5;21). The patient was partially monosomic for both 5p and 21q. The phenotype of the infant showed some features of the 5p- (cri-du-chat) syndrome, but there were also features present which were uncharacteristic of this syndrome. The present findings, combined with similar cases reported in the literature, provide further support for a proximal monosomy 21q syndrome.

Chromosome Aberrations↗
PubMed1998

Prenatal screening and women's perception of infant disability: a Sophie's Choice for every mother.

Prenatal screening can significantly benefit parents and the community. However, it has created a dilemma for women as it requires them to quickly decide whether to continue a pregnancy or terminate it should the test indicate a foetal abnormality. This can be psychologically traumatic for women torn between their connection to an unborn child with all its possible imperfections, and a desire to prevent its suffering as a disabled child in later life. A woman must also consider her own and her family's future welfare. Extensive research into the physical aspects of prenatal screening has not explored the meaning of the experience for women or whether termination is the most appropriate option. This article examines recent qualitative studies, concluding that women who terminate a pregnancy following prenatal screening may experience an acute grief reaction or be plagued by guilt and fear that can precipitate marital breakdown. Additionally, there is a risk that through striving to eradicate congenital disability, a community risks promoting a cult of perfectionism that may have discriminatory effects on disabled people.

Abortion, Induced↗
PubMed1998

Rat and mouse epiblasts differ in their capacity to generate extraembryonic endoderm.

In this study we have compared the in vitro differentiation potential of epiblast tissue from mouse and rat embryos. Epiblasts were isolated from egg cylinder stage embryos by microdissection and placed in culture. Rat cultures were distinguished by the copious production of parietal endoderm cells. Mouse epiblasts, in contrast, did not produce parietal endoderm. This difference in capacity to regenerate extraembryonic endoderm marks a surprising distinction in development of the pluripotential lineage between these two closely related rodents.

Animals↗
PubMed1998

Maintenance of pluripotential embryonic stem cells by stem cell selection.

As gastrulation proceeds, pluripotential stem cells with the capacity to contribute to all primary germ layers disappear from the mammalian embryo. The extinction of pluripotency also occurs during the formation of embryoid bodies from embryonic stem (ES) cells. In this report we show that if the initial differentiated progeny are removed from ES cell aggregates, further differentiation does not proceed and the stem cell population persists and expands. Significantly, the presence of even minor populations of differentiated cells lead to the complete loss of stem cells from the cultures. This finding implies that the normal elimination of pluripotent cells is dictated by inductive signals provided by differentiated progeny. We have exploited this observation to develop a strategy for the isolation of pluripotential cells. This approach, termed stem cell selection, may have widespread applicability to the derivation and propagation of stem cells.

Animals↗
PubMed1998

Modulation of tubulin polypeptide ratios by the yeast protein Pac10p.

Normal assembly and function of microtubules require maintenance of the proper levels of several proteins, including the tubulin polypeptides themselves. For example, in yeast a significant excess of beta-tubulin causes rapid microtubule disassembly and subsequent cell death. Even the modest excess of beta-tubulin produced by genetic alterations such as deletion of the minor alpha-tubulin gene TUB3 affects cell growth and can confer microtubule phenotypes. We show here that the levels of the yeast protein Pac10p affect the relative levels of the tubulin polypeptides. Cells deleted for PAC10 have the same phenotypes as do cells that express reduced levels of alpha-tubulin or Rbl2p, two proteins that bind beta-tubulin. Conversely, overexpression of Pac10p enhances the ability of alpha-tubulin or Rbl2p to suppress the lethality associated with excess beta-tubulin. However, Pac10p is itself not a beta-tubulin binding protein. Pac10 null cells show a 30% decrease in the ratio of alpha-tubulin to beta-tubulin. The results suggest that Pac10p modulates the level of alpha-tubulin in the cell, and so influences microtubule morphogenesis and tubulin metabolism.

Cloning, Molecular↗
PubMed1998

The human FXY gene is located within Xp22.3: implications for evolution of the mammalian X chromosome.

It has been proposed that the pseudoautosomal region of mammals has evolved by sequential addition of autosomal material onto the X and Y chromosomes followed by movement of the pseudoautosomal boundary to create X-unique regions. We have previously described a gene, Fxy , that spans the pseudoautosomal boundary in mice such that the first three exons of the gene are located on the X chromosome, but the remainder of the gene is located on both X and Y chromosomes. Therefore, this gene might be in a state of transition between pseudoautosomal and X-unique locations. In support of this theory we show here that the human FXY gene is located in Xp22.3 in humans, proximal to the pseudoautosomal boundary.

Amino Acid Sequence↗