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Biomedical subjects

T A Smith

Publications and source records attributed to T A Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

Health surveillance in milling, baking and other food manufacturing operations--five years' experience.

The objective of this study was to describe the incidence of allergic respiratory disease and its outcome in terms of symptoms and jobs, across different flour-using industries. It uses the findings of a health surveillance programme in a large food organization over a five-year period. The population under surveillance consisted of 3,450 employees with exposure to ingredient dusts, of whom 400 were in flour milling, 1,650 in bread baking, 550 in cake baking and 850 in other flour-using operations. A total of 66 employees with either asthma or rhinitis symptoms attributable to sensitization to allergens in the workplace were identified. The majority of these (48/66) had become symptomatic prior to the commencement of the health surveillance programme in 1993. The incidence rates (per million employees per year) for those who developed symptoms between 1993 and 1997 were 550 for flour milling, 1,940 for bread baking, 0 for cake baking and 235 for other flour-using operations. The agent believed to be responsible for symptoms was most commonly grain dust in flour millers and fungal amylase in bread bakers. Wheat flour appeared to have a weaker sensitizing potential than these other two substances. In terms of outcome, at follow-up 18% of symptomatically sensitized employees had left the company. Two of the ex-employees retired through ill health due to occupational asthma. Of those still in employment, 63% described an improvement in symptoms, 32% were unchanged and 4% were worse than when first diagnosed. Over half the cases still in employment were continuing to work in the same job as at the time of diagnosis.

Amylases↗
PubMed1999

Hydroxyurea treatment enhances metastatic cell adhesiveness: a possible chemotherapy-induced increase in metastatic potential?

Treatment of tumor cells with certain chemotherapeutic agents, including hydroxyurea, increases their metastatic potential. In the present study the adhesiveness of SW620 colonic metastasis cells treated with hydroxyurea was compared with untreated cells by measuring their ability to remain attached to tissue flask walls during gentle saline washes. Treatment of SW620 cells was found to significantly increase their adhesiveness, suggesting a mechanism by which hydroxyurea may enhance the metastatic potential of tumor cells.

Antineoplastic Agents↗
PubMed1999

RWMODEL II: computer simulation of the Rescorla-Wagner model of Pavlovian conditioning.

RWMODEL II simulates the Rescorla-Wagner model of Pavlovian conditioning. It is written in Delphi and runs under Windows 3.1 and Windows 95. The program was designed for novice and expert users and can be employed in teaching, as well as in research. It is user friendly and requires a minimal level of computer literacy but is sufficiently flexible to permit a wide range of simulations. It allows the display of empirical data, against which predictions from the model can be validated.

Animals↗
PubMed1999

Identification and quantification of somatic mosaicism for a point mutation in a Duchenne muscular dystrophy family.

Relatively few point mutations have been found in the dystrophin gene and of these only two have been associated with mosaicism. A single base insertion has been identified and quantified in a mother of two sons affected with Duchenne muscular dystrophy. It has been determined that she is a somatic mosaic with the mutation present in 25% of lymphocyte DNA. Further tissue lineages have been tested and the time at which the mutation arose was determined to be before the cellular differentiation into the bilaminar disc at approximately eight days after fertilisation. We suggest that the incidence of mosaicism for dystrophin point mutations may be higher than current data suggest.

Humans↗
PubMed1999

Dental students' sexual harassment experiences and attitudes.

The objective of this study was to describe the sexual harassment experiences and attitudes of students at the University of Kentucky College of Dentistry. A twenty-six-item questionnaire was developed and administered to 170 dental students in years one through four of the curriculum. Five questions explored students' personal experiences with sexual harassment--whether they had been harassed or had observed harassment; twenty-one questions addressed students' attitudes about sexual harassment. Computations of mean differences in Likert-type scale responses for the twenty-one attitude items were completed using independent t-tests for the following variables: gender, whether respondents had been sexually harassed or had observed harassment of others, and years in dental education. Almost 15 percent of the students reported being sexually harassed at least once in dental college. Females were sexually harassed more often than males (p < .01), and second, third, and fourth year students more often than first year students (p < .05). Additionally, 30 percent of the students reported witnessing sexual harassment in the college. Harassers included faculty (88 percent), dental students (8 percent), and others (4 percent). Differences (p < .05) in sexual harassment attitudes were found when responses were analyzed by gender, by whether students had been sexually harassed, by whether they had witnessed harassment, and by years in dental education. The data show that sexual harassment occurs in the college. Dental faculty and students could benefit from programs to educate them about sexual harassment, how to prevent it from occurring, and how to respond if they are sexually harassed.

Attitude↗
PubMed1999

Facilitative glucose transporter expression in human cancer tissue.

Glucose utilisation by cancer cells is greatly enhanced when compared with that by normal tissue. Glucose is taken up by cells and then phosphorylated to glucose-6-phosphate. Facilitative hexose uptake is achieved by five transmembrane transporters, termed glut1-5, which are protein products of their respective GLUT genes. Glut types differ in their kinetics, which are tailored to the requirements of the cell type they serve, although more than one glut may be expressed by a particular cell type. Herein are reviewed the results from approximately 30 studies which examined glut expression in human cancer tissue. These studies measured GLUT messenger RNA (mRNA) either using the reverse-transcriptase polymerase chain reaction or by Northern blot analysis, or detected glut proteins using the appropriate antibodies. Tumour tissue is frequently associated with the abnormal and/or over-expression of gluts, especially glut1. Some tumour cells express specific GLUT mRNA but not the respective protein. Some studies have reported associations between glut expression and proliferative indices, whilst others suggest that glut may be of prognostic significance, especially in lung cancer.

Female↗
PubMed1999

Retroperitoneal leiomyosarcomas unassociated with the gastrointestinal tract: a clinicopathologic analysis of 17 cases.

Data are limited on leiomyosarcomas within the abdomen and retroperitoneum, particularly if one discounts those associated with the gastrointestinal (GI) tract. Recently, some authors proposed that certain tumors in this location are more appropriately termed extra-GI stromal tumors, given their histologic resemblance to GI stromal tumors as opposed to conventional soft tissue leiomyosarcomas. We evaluated the clinical and pathologic features of 17 cases of leiomyosarcoma (16 retroperitoneal, one intra-abdominal) and recorded the tumor size, predominant cell type, tumor cellularity, nuclear pleomorphism, extent of tumor cell necrosis, and number of mitotic figures per 10 high power fields (MFs/10HPFs). Cases were only included for study if the excised tumor did not arise from abdominal or pelvic viscera or major blood vessels, if adequate clinical follow-up was available, and if the tumor unequivocally resembled conventional soft tissue leiomyosarcoma, both by light microscopic and immunohistochemical examination. The cohort included 16 women and 1 man, and ages ranged from 44 to 72 years (median, 60 yr). Tumors ranged in size from 6.5 to 29.5 cm (median, 13.5 cm). Fifteen tumors were composed predominantly of spindled cells, one tumor was composed predominantly of epithelioid cells, and one tumor was composed of an admixture of spindled and epithelioid cells. Follow-up intervals ranged from 4 to 169 months (median, 47 mo). Fifteen (88%) of seventeen patients developed an adverse outcome, defined as the development of metastatic disease or death due to tumor. Patients whose tumors had greater than 10 MFs/10HPFs had significantly shorter intervals to either metastasis or death than did those whose tumors had 10 or fewer MFs/10HPFs (8.4 mo vs. 42 mo; P = .003). No other features correlated with time to adverse outcome. In conclusion, the majority of patients with leiomyosarcomas located within the abdomen or retroperitoneum progress to metastatic disease or die from their tumor. The only feature that is significantly associated with a shorter interval to either metastasis or death is more than 10 MFs/10HPFs.

Adult↗
PubMed1998

Measurements of human breast cancer using magnetic resonance spectroscopy: a review of clinical measurements and a report of localized 31P measurements of response to treatment.

A review of the literature has shown that in human breast tumours, large signals from phosphomonoesters (PME) and phosphodiesters (PDE) are evident. In serial measurements in 19 patients with breast cancer, a decrease in PME was significantly associated with a stable or responding disease (p = 0.017), and an increase in PME was associated with disease progression. Extract studies have shown PME to comprise of phosphoethanolamine (PEth) and phosphocholine (PCho), with the PEth to PCho ratio ranging from 1.3 to 12. The PCho content of high grade tumours was found to be higher than low grade tumours. In some animal models, changes in PCho have been shown to correlate with indices of cellular proliferation, and spheroid studies have shown a decrease in PCho content in spheroids with smaller growth fractions. A serial study of 25 patients with advanced primary breast tumours undergoing hormone, chemotherapy or radiotherapy treatments, showed that in this heterogenous group there were significant changes in metabolites that were seen during the first 3 weeks (range 2-4 weeks) of treatment, that correlated with volume change over this period, employed here as a measure of response. Changes in PME (p = 0.003), total phosphate (TP) (p = 0.008) and total nucleoside tri-phosphate (TNTP) (p = 0.02) over 3 (+/-1) weeks were significantly associated with response, as were the levels of PME (p<0.001), PDE (p = 0.01), TP (p = 0.001) and TNTP (p = 0.007) at week 3 (+/-1). PME at week 3 (+/-1) was also significantly associated with the best volume response to treatment (p = 0.03). A reproducibility analysis of results from the observation of normal breast metabolism in four volunteers showed a mean coefficient of variation of 25%, after correcting for changes resulting from the menstrual cycle. Reproducibility studies in four patients with breast cancer showed a mean coefficient of variation of 33%, with the reproducibility being better in patients measured on different days (difference in TP was -6%) compared with those measured on the same day (difference in TP was -29%).

Adult↗
PubMed1998

Herpes simplex virus type 1 ICP-0 induces reactivation of pseudorabies virus from latently infected trigeminal ganglia explant cultures.

Pseudorabies virus (PrV), like other alphaherpesviruses, is a neurotropic virus that can establish a latent infection in swine. Reactivation of PrV from latency may occur spontaneously or after induction with corticosteroids. The mechanisms involved in the establishment of latency and reactivation are currently unknown. Here, we examined gene-specific reactivation of PrV by herpes simplex virus type 1 (HSV-1) immediate early protein, ICP-0. Primary neuronal cell cultures established from the trigeminal ganglia of latently infected swine were superinfected with recombinant adenoviruses expressing ICP-0. Reactivation of PrV occurred in cultures that were superinfected with two different ICP-0-expressing adenovirus recombinants, but not in cultures that were either mock-infected, or superinfected with wild-type adenovirus, or recombinant adenoviruses not expressing ICP-0. Infectious PrV was detected between 4 and 7 days postinfection, regardless of the promoter driving expression of ICP-0. Results from these experiments show that HSV-1 ICP-0, a homologue of PrV EP0, can induce PrV reactivation from explanted trigeminal ganglia of latently infected swine.

Animals↗
PubMed1998

Proliferation is associated with 2-deoxy-D-[1-3H]glucose uptake by T47D breast tumour and SW480 and SW620 colonic tumour cells.

The interpretation of therapy-induced changes in the uptake of fluorodeoxyglucose by tumours, detected using PET, is dependent on which tumour characteristics are associated with its uptake. In this study the relationship between proliferation (S-phase fraction) and the uptake of 2-deoxy-D-[1-3H]glucose by T47D breast tumour and SW480 and SW620 colonic tumour cells was measured between 2 and 12 days after seeding. Strong correlations (p < 0.001) were observed between viable cell number and the uptake of 2-deoxy-D-[1-3H]glucose/flask by each of the cell lines. Uptake of this compound was also found to correlate with S phase fraction in the T47D line (p < 0.05) and the SW480 (p < 0.01) and the SW620 (p < 0.001) colonic tumour lines. The findings of the present study suggest that therapy-induced changes in the uptake of this compound may at least partially reflect changes in proliferative fraction.

Antimetabolites↗
PubMed1998

Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian children.

Among Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas.

Animals↗
PubMed1998

An investigation into the dosimetry of a nine-field tomotherapy irradiation using BANG-gel dosimetry.

BANG-gel dosimetry offers the potential for measuring the dose delivered by a radiotherapy treatment technique, in three dimensions, with high spatial resolution and good accuracy. The ability to measure comprehensively a 3D dose distribution is a major advantage of the gel dosimeter over conventional planar and point-based dosimeter devices, particularly when applied to the verification of complex dose distributions characteristic of intensity-modulated radiotherapy (IMRT). In this paper an in-house manufactured BANG-gel dosimeter was applied to study the dose distributions of two irradiation experiments for which the distributions were known: (i) a dosimetrically simple parallel-opposed irradiation, and (ii) a more complex nine-field 'static tomotherapy' intensity-modulated irradiation delivered with the Nomos MIMiC. The uniform distribution in (i) allowed a study of the magnetic resonance (MR) imaging parameters to achieve an optimal trade-off between noise and image resolution (optimum image resolution for the Siemens 1.5T Vision system was determined to be approximately 0.8 mm2 with a slice thickness of 2 mm). The spatial uniformity of gel sensitivity to radiation was found to depend strongly on the presence of oxygen, which must be eliminated for the gel dosimeter to be of use. The gel dosimeter was found to agree well with predicted dose distributions and accurately measured the steep penumbral fall-off of dose, even after many days, proving its potential for the verification of IMRT distributions. In the nine-field IMRT delivery (ii) the predicted dose was computed by both an in-house 'component-delivery' dose algorithm and the Peacock planning-system dose algorithm. Good agreement was found between the two algorithms despite the latter's omission of the change in penumbral characteristics with aperture-size during delivery, lack of inhomogeneity correction and approximate modelling of leaf leakage. These effects were found to be small for the problem studied. The predicted distribution agreed well with the gel-measured distribution at medium and high doses (50-90% isodose lines) although differences of up to 10% were observed at lower doses (30% isodose line). The gel dosimeter was found to have the potential to verify IMRT distributions but required considerable care to achieve accurate results. Attention was required to achieve uniformity of gel sensitivity (to prevent oxygen contamination), and in the calibration process.

Acrylamide↗
PubMed1998

DNA template amplification genetic studies on archival human preimplantation biopsied microtubed cell samples.

Biopsied cell samples can remain in storage following an initial, unequivocally successful preimplantation genetic diagnosis (PGD). The fidelity of the DNA template for polymerase chain reaction (PCR) amplification of microtubed human preimplantation embryonic cells stored at -70 degrees C for extended periods of time (6 months to 4 years) has been assessed. PCR protocols and specific nested primer sets for the beta-globin, ZP3 and CA repeat motif successfully used for previous human embryo PGD research were employed for these studies. The results show that the DNA template of microtubed biopsied blastomere and mural trophectoderm cell samples stored for periods of up to 4 years may be successfully amplified by PCR. Specific gene sequences were able to be analysed at the 1-2 or 3-5 biopsied cell level with a 71-100% success rate. Analysis of DNA fragments amplified from the CA dinucleotide repeat locus showed that in 8/9 samples both alleles were amplified at the cellular level. No DNA contamination was detected in the stored microtubed samples, or in the experimental controls.

Actins↗
PubMed1998

Respiratory symptoms and sensitization in bread and cake bakers.

This purpose of this study was to examine the relationship between exposure to wheat flour, soya flour and fungal amylase and the development of work-related symptoms and sensitization in bread and cake bakery employees who have regular exposure to these substances. The study populations consisted of 394 bread bakery workers and 77 cake bakery workers whose normal jobs involved the sieving, weighing and mixing of ingredients. The groups were interviewed with the aim of identifying the prevalence, nature and pattern of any work-related respiratory symptoms. They were also skin-prick tested against the common bakery sensitizing agents, i.e., wheat flour, soya flour, rice flour and fungal amylase. The results of personal sampling for sieving, weighing and mixing operations at the bakeries from which the study groups were taken were collated in order to determine typical exposures to total inhalable dust from the ingredients, expressed as 8 hour time-weighted average exposures. Data from the health surveillance and collated dust measurements were compared with the aim of establishing an exposure-response relationship for sensitization. The prevalence of work-related symptoms in bread bakery and cake bakery ingredient handlers was 20.4% and 10.4% respectively. However, in a large proportion of those reporting symptoms in connection with work, the symptoms were intermittent and of short duration. It is considered that the aetiology of such symptoms is likely to be due to a non-specific irritant effect of high total dust levels, rather than allergy. None of the cake bakers and only 3.1% of the bread bakers had symptoms which were thought to be due to allergy to baking ingredients. Using skin-prick testing as a marker of sensitization, the prevalence of positive tests to wheat flour was 6% for the bread bakers and 3% for the cake bakers. Comparable prevalences for soya flour were 7% and 1% respectively. However, the prevalence of positive skin-prick tests to fungal amylase was 16% amongst the bread baking group with only a single employee (1%) in the cake baking group having a positive test. Furthermore, this employee had previously worked in a bread bakery. The difference in rates of sensitization to wheat flour between the bread and cake bakers is not statistically significant, whereas the difference for soya flour is at the borderline of statistical significance (p = 0.045). In contrast, the difference in fungal amylase sensitization is significant at the 0.1% level. For both bread and cake bakers, the 8 hour time-weighted average exposures for each of the activities showed a wide variation with mixing having the lowest average exposure and sieving the highest. Out of the allergens studied in this investigation, fungal amylase is the principal sensitizer in large scale bread bakeries, with the main source of exposure being the handling of bread improvers. In contrast, the risk of sensitization to wheat flour is low in both bread and cake bakeries. The absence of positive skin-prick tests in the subgroup of cake bakery employees who regularly handle fungal-amylase-containing flour suggests that their levels of exposure are below the threshold for sensitization to amylase.

Amylases↗
PubMed1998

FDG uptake, tumour characteristics and response to therapy: a review.

The use of FDG-PET imaging in tumour detection is now well established. Many studies have suggested that changes in the uptake of FDG predict tumour response to therapy and that further clinical information regarding tumour grade and proliferative status may also be derived from FDG-uptake scans. More studies are required to verify the role of FDG-PET in patient management. Upregulation of hexokinase and glucose transporters, especially Glut-1, and downregulation of glucose-6-phosphatase are frequently associated with transformation. The extent of these changes has been related to both differentiation and proliferation largely corresponding with FDG-uptake studies.

Animals↗
PubMed1998

Endotoxin treatment of equine infectious anaemia virus-infected horse macrophage cultures decreases production of infectious virus.

Lentiviruses replicate in cells of the immune system, and activation of immune cells has been shown to modulate virus replication. To determine the effects of macrophage activation on replication of equine infectious anaemia virus (EIAV), primary horse macrophage cultures (HMCs) were established from 20 different horses, infected with an avirulent strain of EIAV, and stimulated with 5 microg/ml of bacterial endotoxin. Supernatants collected from HMCs were assayed for the presence of tumour necrosis factor (TNF-alpha) and for production of infectious virus. Results indicated that EIAV replication in vitro varied significantly (P < or = 0.0001) from horse to horse, regardless of the treatment of HMCs. Also, EIAV replication was significantly (P < or = 0.0001) decreased in HMCs stimulated with bacterial endotoxin as compared to untreated HMCs. No significant correlation was found between virus replication and production of TNF-alpha following treatment of virus-infected cells with bacterial endotoxin. However, when HMCs were treated with endotoxin prior to virus infection, inhibition of EIAV replication was proportional to increasing levels of endotoxin. PCR and RT-PCR were used to amplify EIAV proviral DNA and mRNA sequences, respectively, at various time-points following infection. The results indicated that the early events of EIAV replication, up to and including transcription of multiple-spliced mRNAs, were not inhibited by treatment of EIAV-infected macrophages with bacterial endotoxin. This suggests that endotoxin treatment inhibits a posttranscriptional step in the virus replication cycle.

Animals↗
PubMed1998

Carotenoids and cancer: prevention and potential therapy.

Epidemiological studies suggest that cancer risk is related to dietary intake of carotenoid-rich fruit and vegetables. Whether or not carotenoids are the active component has yet to be definitively proven, although some of these studies have shown that after elimination of obvious factors, such as fibre content, these foods still possess anticancer properties. On the other hand, two large intervention studies have shown that beta-carotene supplementation increases the risk of lung cancer in smokers. However, high doses of beta-carotene were used in these studies. Experimental work on animals and cells has shown that treatment with carotenoids can inhibit the development of cancer. Such studies have revealed a variety of mechanisms, in addition to antioxidant and conversion to vitamin A, including up-regulation of gap junctional communication, induction of detoxifying enzymes and inhibition of proliferation. Studies on tumour cells indicate that carotenoids can interfere with the growth of transformed cells, suggesting that they may be effective in the treatment of some cancers.

Carotenoids↗