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Biomedical subjects

Linda Smith

Publications and source records attributed to Linda Smith.

18 recordsLinked to original sources
PubMed2006

Priming overgeneralizations in two- and four-year-old children.

Overgeneralization occurs when a child uses the wrong word to name an object and is often observed in the early stages of word learning. We develop a method to elicit overgeneralizations in the laboratory by priming children to say the names of objects perceptually similar to known and unknown target objects. Experiment 1 examined 18 two-year-old children's labelling of familiar and unfamiliar objects, using a name that was previously produced. Experiment 2 compared the labelling of 30 two-year-olds and 39 four-year-olds when presented with completely novel objects. The findings suggest that the retrieved word is a blend of previous activation from the prior retrieval and activation engendered by the similarity of the test object to instances of the target category. We put forward a theoretical account of overgeneralization based on current models of adult language processing. The account suggests a common mechanism of activation and retrieval, which may explain not only momentary lapses in the correct selection of words, but other types of naming errors traditionally thought to reflect differences in children's underlying category representations or, perhaps, gaps in their knowledge of words.

Child Language↗
PubMed2006

Attenuation of capillary leakage by hydroxyethyl starch (130/0.42) in a porcine model of septic shock.

OBJECTIVES: Capillary leakage, a frequent complication in septic shock, is characterized by loss of intravasal fluid resulting in generalized edema and hemodynamic instability despite massive fluid therapy. We have shown that administration of an established colloid 200/0.5 hydroxyethyl starch (HES) stabilized plasma volume in a porcine septic shock model. Recently, a new HES with a low molecular weight (130 kD) and lower molar substitution (0.42) has been developed. In this study, we compared effects of HES 130/0.42 and HES 200/0.5 on capillary leakage in porcine septic shock. DESIGN: Prospective randomized, controlled animal study. SETTING: University department of anesthesiology. SUBJECTS: Fourteen pigs (22.9 +/- 2.8 kg). INTERVENTIONS: Anesthetized and mechanically ventilated pigs were observed over 6 hrs. MEASUREMENT AND MAIN RESULTS: Septic shock was induced with fecal peritonitis (0.75 g.kg of body weight autologous feces). Animals were allocated to volume-replacement therapy with either HES 130/0.42 (n = 5) or HES 200/0.5 (n = 5) and compared with nonseptic controls receiving HES 130/0.42 (n = 4). Infusion rate was titrated to maintain a central venous pressure of 12 mm Hg. Albumin escape rate was calculated using iodine 125-labeled albumin. Plasma volume was determined using chromium-51-tagged erythrocytes. Albumin escape rate increased significantly in both groups in comparison to controls (HES 200/0.5, 45% +/- 3; HES 130/0.42, 38% +/- 5), but this increase was significantly smaller with HES 130/0.42. Both HES 200/0.5 (-14%, not significant) and HES 130/0.42 (-1%, not significant) stabilized plasma volume compared with controls. Systemic oxygenation was not significantly altered in either group. CONCLUSIONS: In this porcine septic shock model, HES 130/0.42 attenuated capillary leakage significantly more effectively than HES 200/0.5.

Animals↗
PubMed2005

Signalling DNA damage by regulating p53 co-factor activity.

In response to DNA damage the related phosphatidylinositol-3-OH-kinase-like-kinases ATM and ATR phosphorylate downstream protein targets which facilitate the DNA damage response. A new pathway in which ATM phosphorylates the transcriptional co-factor Strap has been elucidated. Phosphorylation causes the stabilization of nuclear Strap and favours the formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Most interestingly, in AT cells Strap remains cytoplasmic, and a mutant derivative that cannot be phosphorylated by ATM is similarly localised to the cytoplasm. These results argue that Strap is an important downstream effector in the DNA damage response.

Acetylation↗
PubMed2005

An evaluation of pulsed shortwave on knee osteoarthritis using radioleucoscintigraphy: a randomised, double blind, controlled trial.

OBJECTIVE: To evaluate the effects of pulsed shortwave on osteoarthritis of the knee. METHODS: A double blinded, randomised, controlled trial. Thirteen female and 14 male patients with radiographic evidence of knee osteoarthritis were randomly allocated to either low dose (10 W), or high dose (20 W) or placebo high frequency pulsed shortwave. Knee radioleucoscintigraphy was performed pre and post treatment as well as objective functional and subjective evaluations. RESULTS: There were no significant differences between the groups in the pre and post treatment percentage change for radioleucoscintigraphy (P > 0.05). Functional and subjective measures also revealed no pre and post treatment differences between the groups (P > 0.05), except for improved knee range of motion in the placebo group (P < 0.05). CONCLUSION: Joint inflammation in knee osteoarthritis, measured using radioleucoscintigraphy, was not altered significantly by pulsed shortwave, therefore this therapeutic modality has little or no anti-inflammatory effect on conditions such as osteoarthritis of the knee.

Aged↗
PubMed2005

The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease.

BACKGROUND & AIMS: Recent data suggest that polymorphisms in the organic cation transporter (OCTN) genes OCTN1 (SLC22A4) and OCTN2 (SLC22A5) represent disease-causing mutations within the IBD5 locus (chromosome 5q31). We investigated associations with disease susceptibility, phenotype, and evidence for epistasis with CARD15 in 679 patients with Crohn's disease (CD) or ulcerative colitis (UC). METHODS: A total of 374 patients with CD, 305 patients with UC, and 294 healthy controls (HCs) were studied. Genotyping for single nucleotide polymorphisms IGR2096, IGR2198, and IGR2230, OCTN1 variant (SLC22A4 1672C-->T), and OCTN2 variant (SLC22A5 -207G-->C) was performed using the TaqMan system. RESULTS: The IBD5 OCTN1 and OCTN2 polymorphisms were in strong linkage disequilibrium (D', >0.959). IGR2198 variant allele frequency (49.1% vs 40.8%; P = .0046) and homozygosity (21% vs 14.8%; P = .044) were associated with CD versus HCs. Variant allelic frequency of OCTN1 (53.6% vs 43%; P = .0008) and OCTN2 (56.1% vs 48.4%; P = .0092) polymorphisms and homozygosity for the OCTN1/2-TC haplotype (28.4% vs 16%; P = .0042) were associated with CD versus HCs. IGR2198 homozygosity and TC homozygosity were associated with stricturing/penetrating disease at follow-up (P = .011 and P = .011, respectively) and disease progression (P = .038 and P = .049, respectively) on univariate analysis and with need for surgery on multivariate analysis (P = .016 and P = .004, respectively). In the absence of the IBD5 risk haplotype, no association of OCTN1/2 variants with CD was detected. No associations were seen with UC. CONCLUSIONS: The IBD5 locus influences susceptibility, progression, and need for surgery in CD. However, the contribution of OCTN1/2 variants is not independent of the IBD5 haplotype; a causative role for these genes remains plausible but is not yet proven. Further genetic, functional, and expression data are now required.

Adult↗
PubMed2005

Genotype-phenotype analysis in childhood-onset Crohn's disease: NOD2/CARD15 variants consistently predict phenotypic characteristics of severe disease.

INTRODUCTION: The incidence of early-onset CD in Scotland is among the highest worldwide. Three single nucleotide polymorphisms (SNPs) R702W, G908R and Leu1007finsC in the NOD2/CARD15 gene predispose to adult CD. We investigated the contribution of these variants to disease susceptibility and phenotype in the Scottish early-onset IBD population. PATIENTS AND METHODS: 906 individuals including 247 Scottish IBD patients aged <16 years at diagnosis, 414 parents and 245 controls were genotyped. Transmission disequilibrium testing (TDT), case-control analysis and detailed genotype-phenotype analysis were performed. RESULTS: The Leu1007finsC variant was associated with susceptibility to CD by case-control (4.2% versus. 1.4%, P = 0.01) and TDT analysis (P = 0.006). The Population Attributable Risk (PAR) for the 3 NOD2/CARD15 mutations was 7.9%. Carriage of NOD2/CARD15 variants was associated with, at diagnosis: decreased albumin (31.0% versus. 9.0%, P = 0.001) and raised CRP (25% versus. 9.5%, P = 0.04) and at follow up: need for surgery (39.5% versus. 12.8%, P = 0.0002) jejunal involvement (50% versus. 18.4%, P = 0.01) jejunal and ileal involvement (50% versus. 10.7%, P = 0.009), raised CRP (57.1% and 12.8%, P = 0.0009), lower weight/height centile (75.0% versus. 20.2%, P = 0.03, 50.0% versus. 16.0%, P = 0.001 respectively) and stricturing disease (45.5% versus. 19.4%, P < 0.05). Multifactorial analysis demonstrated carriage was associated with need for surgery (P = 0.004, OR 4.9 [1.5-14.7]). CONCLUSIONS: These NOD2/CARD 15 variants in the Scottish early onset CD population have a definite, albeit relatively small contribution to CD susceptibility (PAR 7.9%) but a major impact on phenotype. In particular NOD2/CARD15 variants are strongly associated with several markers of disease severity in pediatric CD, notably need for surgery.

Adolescent↗
PubMed2005

Arsenic and selenium in human hair: a comparison of five countries with and without arsenicosis.

The selenium (Se) content of the diet and/or selenium supplements might have an ameliorating effect on arsenic (As) toxicity as recently shown by Wang et al., Yang et al., and as reviewed by Spallholz et al.. The underlying principles of the ameliorating effect is the complexation of Se with As forming the seleno-bis (S-glutathionyl) arsinium ion excreted in bile and the complexation of Se with As in tissues forming nontoxic insoluble selenides. Additional protection afforded by Se supplementation from arsenicosis could be the elevation of glutathione peroxidase activity reducing the oxidative stress induced by As. The present study assessed the status of Se and As in hair by neutron activation analysis (NAA). Human hair samples were collected from the United States, Canada, The People's Republic of China (PRC), Bangladesh, and Nepal, the latter two countries now engaged in a struggle to find relief from human arsenicosis resulting from extensive domestic groundwater contamination by As. No statistically significant differences were observed in the samples between the Se and As content of hair from, Lubbock, Texas (USA) or Winnipeg, Canada. The concentration of As in all hair samples analyzed correlated (r = 0.960, p < 0.001) with the amount of As in the drinking water. Selenium levels in hair were highest from Nepal. The results demonstrate the viability of hair as a noninvasive biomonitor in assessing aspects of dietary Se and environmental As exposure. The hair data confirmed the known low intake of Se in the Keshan disease area of the PRC, the very high accumulation in hair of As from subjects consuming contaminated groundwaters, and an adequate Se status in subjects from North America consuming municipal water of low As content. The high As content of hair from people in Bangladesh is the result of a high As consumption from contaminated water compounded by a less than desirable intake of Se. From Nepal, the As content of hair corresponded to the known low and high intake of As from contaminated groundwater. The very high Se content found in all hair samples from Nepal might be the result of the use of henna.

Arsenic↗
PubMed2004

A new effector pathway links ATM kinase with the DNA damage response.

The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap.

Antibodies, Monoclonal↗
PubMed2004

Effect of testosterone on T cell-mediated immunity in two species of Mediterranean lacertid lizards.

One of the primary assumptions of the immunocompetence handicap hypothesis is that testosterone has an immunosuppressive effect, but conflicting results have been reported in a variety of bird species concerning the effect of testosterone on the humoral and the T cell-mediated components of the immune system. The T cell-mediated component of the immune system is particularly important during the breeding season, because the likelihood of injury during sexual competition is high and T cell-mediated immunity is essential for healing wounds and resisting infection. In this study we examined the effect of experimentally increased levels of testosterone during breeding season on T cell-mediated immunity in male lizards of two Mediterranean lacertid species, Psammodromus algirus and Acanthodactylus erythrurus. The hormonal treatment significantly increased testosterone of the experimental individuals. T cell-mediated responses to phytohemagglutinin stimulation were significantly suppressed in testosterone-treated males of both species. Furthermore, there was a significant negative relationship between individual variability in T cell-mediated responsiveness and plasma testosterone concentration. The present study is the first to demonstrate testosterone-induced suppression of T cell-mediated immunity in lizards.

Analysis of Variance↗
PubMed2004

Resuscitation from septic shock with capillary leakage: hydroxyethyl starch (130 kd), but not Ringer's solution maintains plasma volume and systemic oxygenation.

There is evidence suggesting that early fluid resuscitation is beneficial in the treatment of septic shock. The question as to which solution should be used remains controversial. Using a porcine septic shock model, we tested the effects of a new synthetic colloid hydroxyethyl starch (HES 130 kD) and a crystalloid regimen with Ringer's solution (RS) on plasma volume (PV) maintenance as well as on systemic and regional hemodynamics. Fourteen anaesthetized mechanically ventilated pigs received 0.75 g kg body weight of feces into the abdominal cavity to induce sepsis. They were randomly allocated to receive 6% HES 130 kD (n = 5) or RS (n = 5) and were compared with nonseptic controls receiving 6% HES 130 kD (n = 4). The infusion rate was titrated to maintain a central venous pressure of 12 mmHg. PV was determined by chromium-51-tagged erythrocytes and hematocrit. Albumin escape rate (AER) was calculated using iodine-125-labeled albumin. Arterio-intramucosal pCO2 gap, systemic hemodynamics, and oxygenation were obtained before and 6 h after induction of sepsis. AER increased in the HES (+38%) and RS groups (+38%) compared with control. PV was reduced in the RS group (-39%), but was maintained in the HES group (-1%). After 6 h of sepsis, HES 130 kD-treated animals had a significantly higher cardiac output (166 +/- 28 mL min kg vs. 90 +/- 18 mL min kg, P < 0.05), and a significantly higher mixed-venous oxygen saturation (65% +/- 8% vs. 40% +/- 14%, P < 0.05) than RS animals. In this porcine septic shock model with concomitant capillary leakage syndrome, resuscitation with HES 130 kD but not RS could maintain PV and preserve systemic hemodynamics and oxygenation.

Animals↗
PubMed2004

No ladies allowed.

Explore the source record for details and available documents.

Decision Making, Organizational↗
PubMed2003

Mapping the themes of Maori talk about health.

AIM: This paper reports the findings of a qualitative research project that investigated: how Maori talk about health; Maori health; and Maori experiences of interacting with both mainstream and Maori providers of healthcare. METHODS: Twenty eight self-identified Maori were recruited from urban, marae-based healthcare services. Rich descriptions of commonly occurring themes were used to examine participants' experiences, explanations and ideas. RESULTS: Twelve themes provide an overview of how Maori health is conceptualised, the importance of 'traditional' concepts, the experiences of Maori within mainstream healthcare, and Maori health promotion mechanisms. CONCLUSIONS: Providing holistic healthcare to Maori in a respectful and collaborative way will provide opportunities for health professionals to have a positive impact on the health of individuals, their whanau and, in turn, their communities, hapu and Iwi.

Attitude to Health↗
PubMed2003

Chk2 activates E2F-1 in response to DNA damage.

The E2F-1 transcription factor is regulated during cell cycle progression and induced by cellular stress, such as DNA damage. We report that checkpoint kinase 2 (Chk2) regulates E2F-1 activity in response to the DNA-damaging agent etoposide. A Chk2 consensus phosphorylation site in E2F-1 is phosphorylated in response to DNA damage, resulting in protein stabilization, increased half-life, transcriptional activation and localization of phosphorylated E2F-1 to discrete nuclear structures. Expression of a dominant-negative Chk2 mutant blocks induction of E2F-1 and prevents E2F-1-dependent apoptosis. Moreover, E2F-1 is resistant to induction by etoposide in tumour cells expressing mutant chk2. Therefore, Chk2 phosphorylates and activates E2F-1 in response to DNA damage, resulting in apoptosis. These results suggest a role for E2F-1 in checkpoint control and provide a plausible explanation for the tumour suppressor activity of E2F-1.

Apoptosis↗
PubMedDate not supplied

The development of embodied cognition: six lessons from babies.

The embodiment hypothesis is the idea that intelligence emerges in the interaction of an agent with an environment and as a result of sensorimotor activity. We offer six lessons for developing embodied intelligent agents suggested by research in developmental psychology. We argue that starting as a baby grounded in a physical, social, and linguistic world is crucial to the development of the flexible and inventive intelligence that characterizes humankind.

Artificial Intelligence↗
PubMedDate not supplied

Guidelines for the management of head injuries in remote and rural Alaska.

Numerous recommendations on the initial evaluation and treatment of the head injured patient have been proposed over the last several years. Most assume there is readily available access to computed tomography and neurosurgical specialists. Many clinicians in Alaska must evaluate and begin treatment of head injured patients in circumstances quite different from this. Vast distances, severe weather and limited medical evacuation capability are factors that come into play while caring for these patients. The current medicolegal climate also contributes to clinician anxiety over missing rare but potentially serious injuries. These guidelines developed by Alaska clinicians from multiple specialties are meant to assist clinicians dealing with this very common problem and represent a reasonable approach to these patients in remote and rural Alaska.

Alaska↗