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Biomedical subjects

E Smith

Publications and source records attributed to E Smith.

At least 19 recordsLinked to original sources

Mechanically loaded ex vivo bone culture system 'Zetos': systems and culture preparation.

This paper introduces the culture preparation of ovine, bovine and human cancellous bone cores to be used in an explants model Zetos. The three dimensional (3D) bone cores were prepared and evaluated for all three animals. Bone cells in vivo constantly interact with each other, migratory cells, surrounding extracellular matrix (ECM) and interstitial fluid in a microenvironment, which continuously responds to various endogenous and exogenous stimuli. The Zetos system was designed to culture and mechanically load viable cancellous bone explants in their near natural microenvironment. This 3D ex vivo system bridges the current gap between in vitro and in vivo methods. One aim of this work was to compare the macro and micro-architecture of ovine, bovine and human cancellous bone tissue in preparation for culture within the Zetos system in order to determine the optimal source of experimental material. A second aim was to optimise the preparations of the bone cores as well as develop techniques involved during tissue maintenance. Bone core response was visualised using histological and immunohistochemical methods. The results demonstrate that cancellous bone explants vary greatly in trabecular density and bone volume depending on species, age and location. Sheep and human samples displayed the greatest variation between bones cores when compared to bovine. Even cores taken from the same animal possessed very different characteristics. The histology demonstrated normal bone and cell structure after the core preparation. Immunohistochemistry results demonstrated antigen retention after preparation methods.

Aged↗

Comparison of plasma uric acid levels in five varieties of the domestic turkey, Meleagris gallopavo.

Plasma uric acid (PUA) is a consensus physiological biomarker for many phenotypes in vertebrates because it is a reliable indicator for processes such as oxidative stress and tubular function. In birds, it is considered a major antioxidant and is also the primary endproduct of nitrogen metabolism. Despite this importance, knowledge of baseline levels of PUA in physiologically normal birds, including the turkey, Meleagris gallopavo, is limited. Here, we compared PUA levels in a total of 106 apparently normal male and female birds at 8 and 32 wk of age from 5 strains of the domestic turkey, including Bourbon Red, Narragansett, Blue Slate, Royal Palm, and Spanish Black. Though differences in PUA were not significant at 8 and 32 wk of age, BW, variety, and sex effects were highly significant. When adjusted for BW, female birds had, on average, a higher PUA per kilogram of BW than male birds. When adjusted for both sex and BW, Royal Palm birds had the lowest average PUA, and Blue Slate had the highest PUA. Results of these investigations represent the first comparative analysis of PUA in physiologically normal turkey varieties. They suggest that differences in basal plasma levels of uric acid in physiologically normal turkeys are influenced by sex, weight, and genetic background but may be independent of age.

Aging↗

Mustard: a potential agent of chemical warfare and terrorism.

As one of the most important vesicant agents, the destructive properties of mustards on the skin, eyes and respiratory system, combined with a lack of antidote, makes them effective weapons. Such weapons are inexpensive, easily obtainable and frequently stockpiled. Sulphur mustard (mustard gas) has been used as a chemical warfare agent in at least 10 conflicts. In this article, the use of mustard as a potential agent of chemical warfare and terrorism is outlined. The dose-dependent effects of acute sulphur mustard exposure on the skin, eyes, and respiratory system are described, as well as the possible extents of injuries, the mechanisms of action and the long-term complications. Prevention and management of mustard exposure are briefly discussed. The need for awareness and preparedness in the dermatological community regarding mustard exposure is emphasized.

Adult↗

On the logical relationship between natural selection and self-organization.

Most evolutionary biologists cherish Darwin's theory of natural selection (NS) as the process of adaptive evolution more than 140 years after publication of his first book on the subject. However, in the past few decades the study of self-organization (SO) in complex dynamical systems has suggested that adaptation may occur through intrinsic reorganization without NS. In this study, we attempt to describe the logical framework that relates the general process of SO to the specific process of NS. We describe NS as a mechanism that coordinates the coevolution of species in an ecosystem to effectively capture, process and dissipate solar energy into the earth's shadow. Finally, we conclude that NS is an emergent process founded on the same thermodynamic imperatives that are thought to underlie all SO. This perspective suggests that the theory of self-organizing systems offers a broader physical context in which to understand the process of NS, rather than contesting it. It even suggests the possibility that there may be a physical basis for understanding the origin of the process of NS. Rather than being merely a fluke of nature, the origin of NS that may be driven by energy flows across gradients.

Adaptation, Biological↗

Effects of selective attention on perceptual filling-in.

After few seconds, a figure steadily presented in peripheral vision becomes perceptually filled-in by its background, as if it "disappeared". We report that directing attention to the color, shape, or location of a figure increased the probability of perceiving filling-in compared to unattended figures, without modifying the time required for filling-in. This effect could be augmented by boosting attention. Furthermore, the frequency distribution of filling-in response times for attended figures could be predicted by multiplying the frequencies of response times for unattended figures with a constant. We propose that, after failure of figure-ground segregation, the neural interpolation processes that produce perceptual filling-in are enhanced in attended figure regions. As filling-in processes are involved in surface perception, the present study demonstrates that even very early visual processes are subject to modulation by cognitive factors.

Adult↗

Distribution and nature of arsenic along former railway corridors of South Australia.

Elevated concentrations of arsenic (As) have been detected in soils of former railway corridors in South Australia, Australia. Elevated As concentrations resulted from the long-term application of As-based herbicides to control grass growth along former railway corridors. A study of former railway corridors revealed considerable surface (0-10 cm) contamination with As (<20 to >1000 mg As kg-1). The distribution of As in soils was related with particle size fraction and iron (Fe) oxide content. Total As increased markedly with decreasing particle size; sand<<silt<clay, with increasing As concentration generally correlated with increasing Fe concentrations (R2=0.57). A sequential fractionation of soils collected from selected sites showed that As was primarily associated with the amorphous and crystalline Fe and Al oxide materials. Solid phase speciation of As-contaminated soil indicated that arsenate (AsV) was the dominant As species present in the soil. However, in some soils, arsenite (AsIII) composed up to 40% of the total As present. The reasons for the presence of AsIII under alkaline and aerobic conditions are unclear.

Journal Article↗

Developmental Vitamin D3 deficiency alters the adult rat brain.

There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention.

Aging↗

Increasing the diagnosis of multifocal primary breast cancer by the use of bilateral whole-breast ultrasound.

AIM: The aim of this study was to evaluate the contribution of bilateral whole-breast ultrasound (BBUS) to the diagnosis and management of women with newly diagnosed breast cancer. METHODS: Over a period of 6 months, 102 women presenting with breast cancer underwent BBUS. Data were collected on clinical findings, radiology, histology and surgical outcome. These women were compared with a control group of 124 women presenting over a similar 6-month period 1 year previously, who had undergone targeted breast ultrasound. RESULTS: Multicentric/multifocal tumours were demonstrated in 35 (34%) of the 102 participants and in 18 (15%) of the 124 controls, a statistically significant difference (Fisher's exact test, p = 0.001). Multiple tumours were diagnosed preoperatively in 18% of the study population compared with 8% of the controls, and BBUS identified invasive multifocal/multicentric tumours in significantly more women in the study population (11 versus 1 control) (Fisher's exact test, p = 0.019). Contralateral cancer was diagnosed in 4 women in the study population and none in the control population (Fisher's exact test, p = 0.040). Surgical review showed that the surgical management changed significantly in 8% (95% confidence interval 4 to 14%) of cases in the study population following BBUS. The increase in the number of women undergoing benign biopsies in the study population (10 versus 5 controls) was not statistically significant (Fisher's exact test, p = 0.11). CONCLUSION: BBUS increased the preoperative diagnosis of multiple tumours in women presenting with primary breast cancer, resulting in a management change in 8% of cases.

Adult↗

The separation of two hymenopteran parasitoids, Tersilochus obscurator and Tersilochus microgaster (Ichneumonidae), of stem-mining pests of winter oilseed rape using DNA, morphometric and ecological data.

Tersilochus obscurator Aubert and Tersilochus microgaster (Szépligeti) are larval endoparasitoids of economically-important stem-mining pests of winter oilseed rape (Brassica napus L.) in Europe. They are difficult to separate morphologically. Their hosts are Ceutorhynchus pallidactylus (Marsham) and Psylliodes chrysocephala Linnaeus, respectively. The parasitoids' taxonomic status, identification, host range and phenology were studied using genetic, morphometric and ecological data. The study used 527 female parasitoids from the UK and Germany, either field-collected in emergence traps or reared from field-collected host larvae. Two morphometric characters, the ovipositor sheath to first metasomal tergite ratio and the percentage of the mesopleuron spanned by the sternaulus, were measured. A 440 bp section of mitochondrial DNA cytochrome oxidase subunit I (COI) gene was sequenced from 35 parasitoids reared from C. pallidactylus, 20 reared from P. chrysocephala and individuals from two outgroups, Tersilochus heterocerus Thomson and Phradis interstitialis Thomson. Distinct and invariable COI sequences corresponded exclusively to each parasitoid group, confirming that T. obscurator and T. microgaster are discrete species. Measurements of host-reared and COI-sequenced specimens indicated that the ranges of both morphometric characters overlapped between species. Using these ranges as criteria, all but 3.6% of UK specimens and 2% of German specimens were identifiable to species without reference to host or phenology. There were differences in emergence phenology in the UK, adult T. microgaster emerging from winter diapause by 29 March 2000, T. obscurator emerging between 12 April and 24 May 2000. The value of molecular techniques in the identification of closely-related parasitoid species is discussed.

Animals↗

HPV and other risk factors of oral cavity/oropharyngeal cancer in the Czech Republic.

OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of development of a subgroup of head and neck cancers has been proposed recently. The main risk factors of oral and oropharyngal cancer observed in our population are smoking and alcohol consumption. The incidence of oral/oropharyngeal tumours in the Czech Republic is relatively high and there are no data available about the prevalence of HPV DNA presence in these tumours. MATERIALS AND METHODS: Eighty patients with a primary oropharyngeal cancer were enrolled. The presence of HPV DNA has been evaluated by polymerase chain reaction in 68 cases from which the tumour tissue and demographical and clinical data were available. The typing of HPV was performed by nucleotide DNA sequencing. RESULTS: The HPV DNA was detected in 51.5% of samples tested. Among the HPV DNA positive tumours, 80% contained HPV16. In the analysed group there were 54 men and 14 women. The prevalence of HPV DNA was lower in oral (25%) than in oropharyngeal (57%) tumours, and higher in never smokers (100%) and never drinkers (68.8%). HPV DNA presence was not related to gender, age, number of lifetime sexual partners or practice of oral-genital sex, size of tumour or presence of regional metastases. CONCLUSIONS: The difference in the prevalence of HPV DNA positive tumours between cases of oral cavity and oropharyngeal carcinoma exposed and not exposed to tobacco or alcohol support the theory that HPV DNA positive tumours form an aetiologically distinct subgroup of head and neck tumours.

Adult↗

Antitumour antibiotics with potent activity against multidrug resistant (MDR) Staphylococcus aureus: a new approach to targeting resistant bacteria.

As hospital reports of strains of resistant bacteria are continuing to increase, a new approach is required for the identification of small molecules with antibacterial activity. Natural products that bind covalently to their biological target have been largely unexplored, although in the field of cancer chemotherapy, such molecules have been shown to counter resistance developed through efflux mechanisms. The azinomycins are potent antitumour agents that alkylate DNA and one of the natural products, compound 1, is a mono-alkylator that has been reported to retain potent antitumour activity. All four diastereomers of 1 were synthesized via a route involving late stage introduction of the epoxide stereocentre and separation of the resulting compounds. A non-alkylating analogue and a potential alkylator that cannot intercalate were also made. All four diastereomers are potent antibacterial agents in cell lines containing efflux-based resistance mechanisms. MIC values in the range of 0.25-1.0 microg/ml were observed. Comparison with the antitumour activity of the compounds suggests that the antibacterial activity stems from a similar mechanism of action involving DNA alkylation. As the ultimate molecular target of the azinomycins is unknown, bacterial strains may represent an interesting route for the discovery of the downstream mechanisms affected by DNA alkylation.

Alkylation↗

Aspirin and indomethacin for the prevention of experimental port-site metastases.

BACKGROUND: Nonsteroidal antiinflammatory drugs have been shown to have antitumor and chemopreventative effects. We investigated the potential of these drugs to inhibit port-site and intraperitoneal metastases. METHODS: The antiproliferative effect of aspirin and indomethacin on tumor cells was measured in vitro and in vivo. The in vivo experiments used DA rats to measure the effects of aspirin and indomethacin on the development of port-site metastases and the proliferation of intraperitoneal tumor cells after laparoscopy. RESULTS: In vitro, aspirin and indomethacin had an antiproliferative effect on tumor cells, inhibiting cell division and killing cells in a concentration and time-dependent manner. Orally administered aspirin and indomethacin, at the maximum tolerated dose, did not reduce the rate of intraperitoneal tumor cell division and had no effect on peritoneal metastases, or the number or size of port-site metastases. CONCLUSIONS: Despite promising in vitro studies, this study does not suggest there will be any clinical therapeutic value associated the use of aspirin or indomethacin for the prevention of the spread of tumor following the spillage of cells into the peritoneal cavity at laparoscopic surgery.

Animals↗

Barriers to accessing safe motherhood and reproductive health services: the situation of women with disabilities in Lusaka, Zambia.

PURPOSE: To ascertain how well health services in Lusaka, Zambia currently meet the safe motherhood and reproductive health care needs of women who have physical impairment leading to disability. METHODS: A qualitative study was conducted in Lusaka, Zambia. In-depth tape-recorded interviews were conducted with 24 purposively selected women with disabilities and with 25 safe motherhood/reproductive public sector health service providers. Qualitative analysis was conducted using NVivo software. RESULTS: Women with disabilities encounter various social, attitudinal and physical barriers to accessing safe motherhood and reproductive health (RH) services in this particular setting. The strong desire for children and affection can increase vulnerability to sexual exploitation. At the same time, a generalized assumption among reproductive health service providers that women with disabilities will not be sexually active, and not require RH services, leads to increased vulnerability to sexually transmitted infection including HIV. Once pregnant, traditional beliefs about transmission of disabilities can create barriers to integration in ante-natal clinics. Nurse-midwives' fear of delivery complications in women with physical impairments can also result in routine over-referral to a tertiary maternity facility which is outside the locality and harder for women with mobility limitations to get to. CONCLUSION: Greater understanding of the influences underpinning societal attitudes towards sexuality and disability in this setting, and more extensive communication between health care staff and women with disabilities would facilitate positive action towards improving safe motherhood and reproductive health services for women with disabilities.

Adult↗

[HPV-associated tonsillar cancer. An update].

The major risk factors for head and neck squamous cell carcinomas (HNSCC) are considered to be tobacco and alcohol. A link between oncogenic types of the human papilloma virus (HPV) and the risk of HNSCC has been suggested in the literature. However, the causal link is now becoming more firmly established on the basis of recent analyses. About 20% of all HNSCC and more than 50% of tonsillar cancers contain HR-HPV. The causal role of HPV-infection in carcinogenesis and the molecular mechanisms involved could thus far be best elucidated in the case of cervical carcinomas. New insights and increasing evidence for the analogy of HPV-positive HNSCC with cervical cancer are discussed. The definition of HPV-positive HNSCC has become more important due to the implications for risk factors and prognosis.

Alcohol Drinking↗

An evaluation of the use of tooth temperature to assess human pulp vitality.

AIM: To evaluate change in tooth surface temperature following a thermal stimulus as a simple and reliable method to assess the presence and the extent of blood flow through teeth. METHODOLOGY: Miniature thermometers were used to measure the relationship between surface temperature of teeth and internal flow of 37 degrees C water (in vitro) or blood (in vivo). In addition, thermal stimuli were applied to the external surface of the teeth, and the rate of temperature recovery was related to internal flow. RESULTS: Under in vitro conditions, the surface temperature of teeth and rate of temperature recovery were related to the rate of internal water flow. However, in vivo neither standing surface temperature (P = 0.47) nor rate of temperature recovery (P = 0.19) were significantly related to evidential pulp vitality. CONCLUSION: Change in the surface temperature of teeth is not suitable as a simple clinical means to assess pulp vitality.

Adult↗

A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome.

The prognosis of patients with primary refractory acute myelogenous leukemia (AML) is poor. Our initial report suggested that some patients could achieve durable remission after allogeneic stem cell transplantation (SCT). Herein, we update our initial experience and report further analysis of this group of patients to determine whether there are pre-SCT prognostic factors predictive of posttransplantation relapse and survival. We reviewed the records of 68 patients who consecutively underwent transplantation at the City of Hope Cancer Center with allogeneic SCT for primary refractory AML between July 1978 and August 2000. Potential factors associated with overall survival and disease-free survival were examined. With a median follow-up of 3 years, the 3-year cumulative probabilities of disease-free survival (DFS), overall survival (OS), and relapse rate for all 68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%-41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only variables associated with shortened OS and DFS included the use of an unrelated donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005 and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk: 1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can cure approximately one third of patients with primary refractory AML. Cytogenetic characteristics before SCT correlate with transplantation outcome and posttransplantation relapse.

Adolescent↗