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Biomedical subjects

H F Thomas

Publications and source records attributed to H F Thomas.

At least 37 records · Page 2Linked to original sources

Collection and local use of accident and emergency hospital data in England.

OBJECTIVE: To obtain information on the collection and local use of accident and emergency data. METHODS: A postal questionnaire was sent to 248 English accident and emergency (A&E) departments. Responses were obtained from 217 (88%). RESULTS: Only 87 (40%) of departments were fully computerised, with 109 (50%) using manual systems, and 21 (10%) a mixture of both. Significantly more computerised departments reported that they undertook studies (epidemiological, accident prevention, and resource management) than non-computerised departments. Only limited information on the types of injury studied was provided. The most common topics were childhood accidents, road traffic accidents, and poisonings. Staff in 45 departments (21%) reported membership of safety organisations. Around 90% of departments reported that they notified general practitioners and health visitors of their patients' attendance, usually within 3 d of the event. CONCLUSIONS: Computerisation appears to help the collection of A&E data for public health research. There is scope to increase the involvement of public health and other workers in epidemiological studies using A&E data. A&E departments should themselves become more involved with local safety organisations.

Accident Prevention↗

Cancer mortality among local authority pest control officers in England and Wales.

OBJECTIVE: To examine cancer mortality by tumour site among local authority pest control officers. METHODS: Prospective mortality study, and follow up to the end of 1994, of 1485 male pest control officers aged between 17 and 69 and employed in 296 local authorities in England and Wales for at least six months between January 1980 and April 1984. Observed numbers of deaths were compared with those expected on the basis of the rates for relevant calendar year, cause, sex, and age specific groups for England and Wales. RESULTS: 200 deaths occurred during the follow up period of which 65 were certified as due to malignant neoplasms. No tumour type showed significantly more deaths than expected. Total all cause, lung cancer, and respiratory disease mortality were significantly lower than expected. CONCLUSIONS: 15 year follow up of a group of men handling a wide range of pesticides did not show any significant risk of cancer. This may be partially explained by the healthy worker effect and also the limited power of the study to detect significant increases in the less common tumours. Further long term follow up of this cohort will continue. Chemical control of pests that can cause human disease and can contaminate food and water has been, and will continue to be, a major public health measure. It is important to ensure that the health of those applying pesticides is not at excess risk. Negative results are important.

Adolescent↗

Regulation of bone sialoprotein and osteopontin mRNA expression by dexamethasone and 1,25-dihydroxyvitamin D3 in rat bone organ cultures.

Bone sialoprotein (BSP) and osteopontin (OPN) are prominent components of the extracellular matrix of mineralized connective tissues that have been implicated in the formation and remodelling of bone. Although these proteins have similar biochemical properties and are expressed by bone cells during bone formation it has been suggested that they have different functions and that their expression is regulated independently by hormones and cytokines. The precise role of these proteins has, however, yet to be firmly established. Since steroid hormones strongly influence the formation of bone we have analyzed the effects of glucocorticoids and 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) on the expression of BSP and OPN mRNAs in developing rat bone in vitro using in situ hybridization. In these studies it has been possible to identify the nature and spatial distribution of the cells that respond to these hormones by changes in sialoprotein expression. When cultured in the presence of the synthetic glucocorticoid, dexamethasone (dex), expression of BSP mRNA by hypertrophic cartilage cells in the tibiae and mandible was dramatically increased as were the number of responding cells indicating that glucocorticoids promote differentiation of hypertrophic cartilage cells as well as osteoblasts. Dexamethasone also stimulated a marked (> 5-fold) increase in OPN expression by osteoblasts and cells lining endosteal and periosteal bone surfaces. In contrast to dex, 1,25-(OH)2D3 suppressed BSP expression in osteoblastic cells whereas OPN expression was strongly (> 5-fold) stimulated in all three cultured bone tissues. Histological examination of the tissues showed that cell viability was retained over the culture period. However, in the presence of 1,25-(OH)2D3 considerable resorption of the tissue was evident, with cement and reversal lines being prominent. The increased expression of BSP and OPN by dex is consistent with the stimulation of bone formation by glucocorticoids, whereas the differential effects of 1,25-(OH)2D3 on BSP and OPN may reflect a stimulation of bone remodelling.

Animals↗

Dexamethasone stimulates luciferase gene expression through the rat bone sialoprotein gene promoter in transgenic mice.

Bone sialoprotein (BSP) is expressed by differentiated osteoblasts during the initial formation and mineralization of bone matrix. Studies using transgenic mice harboring 2.7 kb of the rat BSP promoter linked to a luciferase reporter gene have shown luciferase activity in bone and other mineralized tissues while most soft tissues tested expressed a much lower level of the reporter gene. To study regulation of the transgene, mice were administered dexamethasone (dex) by intramuscular injection. After 4 h and 24 h, various tissues were dissected from the treated mice as well as from untreated transgenic littermates. Luciferase assays showed that dex stimulated expression of the transgene significantly. In bone tissues, dex increased the average luciferase activity 1.6- to 11-fold compared with control tissues from untreated transgenic mice. The luciferase activity in lung, liver and kidney remained at a low level and showed no increase with dex treatment. In some animals, however, the luciferase activity in brain and skin was also increased after dex administration. These experiments indicate that a transgene comprising 2.7 kb of the rat BSP promoter linked to a luciferase reporter is regulated in a tissue and developmental stage-dependent manner and that glucocorticoid-induced stimulation of BSP gene expression may be mediated within this region of the promoter.

Animals↗

Identification of regulatory elements necessary for the expression of the COL1A1 promoter in murine odontoblasts.

Recent studies have indicated that odontoblasts and osteoblasts have unique regulatory mechanisms that control COL1A1 gene expression. We are currently examining the regulation of COL1A1 gene expression in odontoblasts and have produced transgenic mice containing various collagen promoter constructs fused to the indicator gene, chloramphenicol acetyl transferase (CAT). Mandibular first molars were removed from jaws of transgenic mice. Some teeth were assayed for CAT activity (CAT diffusion assays), others were fixed and prepared for immunohistochemistry (CAT antibodies). Our results indicate the CAT activity was present in tooth germs containing promoter constructs longer than 1.719 kb. Immunoreactivity to CAT was confined to the odontoblast cell layer. No CAT activity was present in tooth germs containing a 1.670 kb construct. These data suggest that there are important regulatory elements located between -1.719 kb and -1.670 kb on the collagen promoter in odontoblasts. Examination of sequences in this region of the promoter demonstrates consensus with those known to be involved with binding of translation products of homeobox genes.

Animals↗

Root formation.

This paper provides an overview of recent studies that have enhanced our understanding of the biological mechanisms that operate during root development. For the most part, these studies have been performed on rodents. As significant species differences have been shown to exist, this data cannot necessarily be extrapolated to the human model. The events associated with root odontoblast differentiation are reviewed in comparison to similar events in coronal odontoblast differentiation. Morphological as well as phenotypic differences are outlined and the inductive role of the epithelial root sheath is discussed. Both acellular and cellular cementum formation are reviewed highlighting morphological and phenotypic differences. The potential influence of the epithelial root sheath in the formation of both tissues is compared and contrasted. Finally, a discussion of the fate of the epithelial root sheath is presented with emphasis placed upon the possible roles of apoptosis and epithelium-mesenchymal transition.

Animals↗

Upstream regulatory elements necessary for expression of the rat COL1A1 promoter in transgenic mice.

The activity of fusion genes containing fragments of the COL1A1 promoter was measured in tissues from 6- to 8-day-old transgenic mice. ColCAT3.6 contains approximately 3.6 kb (-3521 to 115 bp) of the rat COL1A1 gene, the chloramphenicol acetyltransferase (CAT) reporter gene, and the SV40 splice and polyadenylation sequences. ColCAT2.3 and ColCAT1.7 are deletion constructs that contain 2296 and 1667 bp of COL1A1 upstream from the RNA start site, respectively. For each transgene, up to six lines of mice were characterized. Both ColCAT3.6 and ColCAT2.3 had similar activity in bone and tooth; ColCAT1.7 was inactive. In transgenic calvariae, levels of transgene mRNA paralleled levels of CAT activity. In tendon, the activity of ColCAT2.3 was 3- to 4-fold lower than that of ColCAT3.6, and the activity ColCAT1.7 was 16-fold lower than that of ColCAT2.3. There was little activity of the ColCAT constructs in liver and brain. These data show that DNA sequences between -2.3 and -1.7 kb are required for COL1A1 promoter expression in bone and tooth; sequences that control expression in tendon are distributed between -3.5 and -1.7 kb of the promoter, with sequences downstream of -1.7 kb still capable of directing expression to this tissue. The cis elements that govern basal expression of COL1A1 in transgenic calvariae appear to be different from those required for optimal expression of the COL1A1 promoter in stably transfected osteoblastic cells.

Animals↗

Development of the murine periodontium. I. Role of basement membrane in formation of a mineralized tissue on the developing root dentin surface.

The presence of basement membrane components on the forming root surface suggests a role for this structure during cementoblast differentiation. The purpose of this study was to investigate the role of root-associated basement membrane (RBM) in murine cementogenesis using tissue separation and recombination techniques. Root dentin specimens, with or without RBM, were combined with dental sac tissue, cultured for 2 weeks, harvested, and examined by light, immunofluorescence, and electron microscopy. Recombinations in which RBM was preserved on the root dentin surface were characterized by formation of an adherent mineralized tissue resembling acellular cementum; recombinations in which RBM was excluded were characterized by formation of mineralized tissue which did not adhere to the root dentin surface. These results suggest that formation of an adherent mineralized tissue on the developing root dentin surface is dependent upon the presence of indigenous basement membrane components.

Animals↗

Development of the murine periodontium. II. Role of the epithelial root sheath in formation of the periodontal attachment.

Experimental manipulation of the developing murine tooth germ has provided evidence that basement membrane components on the forming root surface are involved in early periodontal attachment formation. The purpose of this investigation was to determine the role of epithelial root sheath (ERS) cells in murine cementogenesis and periodontal ligament formation using tissue separation and recombination techniques. Root dentin specimens, with and without root-associated basement membrane components (D + RBM or D - RBM), were recombined with dental sac in the presence or absence of ERS. Recombinations were cultured for 2 weeks, harvested, and examined by light, electron, and immunofluorescence microscopy. Mineralized tissue formed in all tissue recombinations. However, when ERS was included in recombinations between D + RBM and dental sac, 25% of recombinations formed a periodontal ligament with fibrous attachment of the root specimen to adjacent bone. These results support the hypothesis that root and periodontal ligament formation is influenced by epithelio-mesenchymal interactions and further support a key role for ERS in these processes.

Alveolar Process↗

Dogs that bite.

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Animals↗

Acute pesticide poisoning in the UK and information and training needs of general practitioners: recording a conundrum.

A postal questionnaire of all general practitioners (n = 68) in a District Health Authority was undertaken to identify the information and training they had received on acute pesticide poisoning. Fifty-six (82%) replies were received. The responses showed that 33 (59%) had not seen the standard Department of Health Guide to acute pesticide poisoning and only 20 (36%) of the respondents thought that their practice had a copy of this publication. None of those surveyed had ever used Health and Safety Executive Guidance Notes on pesticides. Ten practitioners (18%) reported that they had at some time diagnosed a case of acute pesticide poisoning and three (5%) had done so in the last two years. Only three respondents (5%) considered they had sufficient information to diagnose all the main pesticides listed in the Department of Health Guide but 24 (43%) considered they had sufficient information to diagnose rodenticide poisoning. Twenty-three (41%) considered they had insufficient information to diagnose any acute pesticide poisoning category. The sources of information used in cases of suspected acute pesticide poisoning were the National Poisons Information Services (e.g., Guy's Hospital) for 30 (54%); Accident and Emergency Departments for 19 (34%); and industry for nine (16%). Four (7%) considered they had sufficient training as a medical student to diagnose cases of acute pesticide poisoning and four (7%) considered they had sufficient training since graduating to diagnose such cases. Some of the problems related to the identification and diagnosis of acute pesticide poisoning are discussed and a number of specific recommendations are made to improve the information and training available to general practitioners.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Differential utilization of regulatory domains within the alpha 1(I) collagen promoter in osseous and fibroblastic cells.

Type I collagen is expressed in a variety of connective tissue cells and its transcriptional regulation is highly complex because of the influence of numerous developmental, environmental, and hormonal factors. To investigate the molecular basis for one aspect of this complex regulation, the expression of alpha 1(I) collagen (COL1A1) gene in osseous tissues, we fused a 3.6-kb DNA fragment between bases -3,521 and +115 of the rat COL1A1 promoter, and three deletion mutants, to the chloramphenicol acetyltransferase (CAT) marker gene. The expression of these ColCAT transgenes was measured in stably transfected osteoblastic cell lines ROS 17/2.8, Py-la, and MC3T3-E1 and three fibroblastic lines NIH-3T3, Rat-1, and EL2. Deletion of the distal 1.2-kb fragment of the full-length ColCAT 3.6 construct reduced the promoter activity 7- to 30-fold in the osteoblastic cell lines, twofold in EL2 and had no effect in NIH-3T3 and Rat-1 cells. To begin to assess the function of COL1A1 upstream regulatory elements in intact animals, we established transgenic mouse lines and examined the activity of the ColCAT3.6 construct in various tissues of newborn animals. The expression of this construct followed the expected distribution between the high and low collagen-producing tissues: high levels of CAT activity in calvarial bone, tooth, and tendon, a low level in skin, and no detectable activity in liver and brain. Furthermore, CAT activity in calvarial bone was three- to fourfold higher than that in the adjacent periosteal layer. Immunostaining for CAT protein in calvaria and developing tooth germ of ColCAT3.6 mice also confirmed the preferred expression of the transgene in differentiated osteoblasts and odontoblasts compared to fibroblast-like cells of periosteum and dental papilla. This study suggests that the 3.6-kb DNA fragment confers the strong expression of COL1A1 gene in high collagen producing tissues of intact animals and that the 5' flanking promoter sequence between -3,521 and -2,295 bp contains one or more stimulatory elements which are preferentially active in osteoblastic cells.

3T3 Cells↗