PubMed Health⌕ Search

Biomedical subjects

H Stevenson

Publications and source records attributed to H Stevenson.

At least 19 recordsLinked to original sources
PubMed2001

Distinct functions of two isoforms of a homeobox gene, BP1 and DLX7, in the regulation of the beta-globin gene.

Homeotic proteins are transcription factors that regulate the expression of multiple genes involved in development and differentiation. We previously isolated a cDNA encoding such a protein from the human leukemia cell line K562, termed Beta Protein 1 (BP1), which is involved in negative regulation of the human beta-globin gene. Sequence comparison revealed that BP1 is a member of the distal-less (DLX) family of homeobox genes and that it shares its homeodomain and 3' sequences with another DLX cDNA, DLX7. BP1 and DLX7 exhibit unique 5' regions, diverging at nucleotide 565 of BP1. We mapped this new distal-less family member BP1 to chromosome 17q21-22 by FISH and PCR, which is the same locus to which DLX7 has been mapped. These results strongly suggest that BP1 and DLX7 are isoforms (derived from the same gene). Since our previous data demonstrated that BP1 and DLX7 are frequently co-expressed, we determined whether DLX7 is also involved in the negative regulation of the beta-globin gene. Mobility shift assays demonstrated that both BP1 and DLX7 proteins, synthesized in vitro, bind to the same BP1 binding site. However, using transient assays, we showed that although BP1 represses activity of a reporter gene through either of two silencer DNA sequences upstream of the beta-globin gene, DLX7 did not show repressor activity against the beta-globin promoter. Further characterization of these apparent isoforms is of significance since they are jointly expressed in acute myeloid leukemia and in many leukemia cell lines.

Base Sequence↗
PubMed2001

The benchmark approach applied to a 28-day toxicity study with Rhodorsil Silane in rats. the impact of increasing the number of dose groups.

The OECD study design, aimed at obtaining a no-observed-adverse-effect level (NOAEL), may be suboptimal for deriving a benchmark dose. Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design. Seven groups of 10 female rats each were intragastrically administered corn oil without (controls) or with 50, 150, 300, 450, 600 or 750 mg Rhodorsil Silane/kg body weight/day, once daily (7 days/week) for 4 weeks. From the complete dataset, two subsets were selected, one representing a study design with seven dose groups of five animals (7 x 5 design), the other representing a study design with four dose groups of 10 animals (4 x 10 design). Under the conditions of the present study, the NOAEL for Rhodorsil Silane 198 was assessed at 50 mg/kg body weight/day, based on the data of the 4 x 10 design. The benchmark approach resulted in a benchmark dose of 19 mg/kg body weight/day, based on the data of the 7 x 5 design. Comparison of the results demonstrated that the multiple dose (7 x 5) design led to a more reliable result than the OECD (4 x 10) design, despite the smaller total number of animals. The dose-response analysis showed that at "the NOAEL" the effect on relative spleen weight was larger than 10%, illustrating that at the NOAEL, adverse effects may occur.

Alanine Transaminase↗
PubMed2001

Basic science knowledge of dental students on conventional and problem-based learning (PBL) courses at Liverpool.

This cross-sectional study investigated performances of two consecutive cohorts of second year dental students on completion of a conventional didactic course and two succeeding cohorts of second year dental students on a recently introduced problem-based learning (PBL) course at The University of Liverpool School of Dentistry. A 40 part true/false questionnaire tested recall of factual knowledge in anatomy, biochemistry, oral biology and physiology. The results showed no significant difference in the total scores when negatively marked between the conventional and PBL course groups but higher total scores in the PBL groups when positively marked. Performances in anatomy, oral biology and physiology did not differ between the groups when negatively marked but the scores of the conventional course groups in biochemistry were significantly lower than the others. With positive marking biochemistry scores were not significantly different but all other subjects were significantly higher in the PBL course groups. The PBL course groups offered fewer blank responses than the conventional course groups but the ratio of correct to incorrect responses, for both definite and intelligent guess responses, were similar in these groups. The compositional profile of the study groups was similar with respect to educational background but the PBL course groups included more females and more older students. The results of this study show that the overall knowledge recall in the basic sciences by dental students on PBL or conventional didactic courses does not differ and may be helpful to those considering the introduction of PBL into the curriculum.

Age Factors↗
PubMed2000

The value of a questionnaire in assessing the acquisition and retention of basic science knowledge by dental students.

This cross-sectional study aimed to assess and compare, by performances in a questionnaire, the level of knowledge of basic medical sciences in 6th-form school pupils studying science subjects as entrance requirements to University and in 2nd, 3rd and 4th-year undergraduate dental students. A 40-part multiple response, true/false questionnaire, testing recall of factual knowledge in anatomy, biochemistry, physiology and oral biology, was used as the method of assessment. The results suggested that this simple format was an acceptable and useful method of assessment of the knowledge level of the study groups. The difference in scores of knowledge, expected to be higher in 2nd-year students compared to 6th form groups, was greatest in anatomy and oral biology, less in biochemistry and, unexpectedly, was not apparent in physiology. A difference in performance on the knowledge questionnaire was observed between 4th and 2nd year dental students, attributable primarily to decreased scores for 4th year dental students in biochemistry and, to a lesser extent, anatomy. The results obtained with this standardised test of factual knowledge recall may be of value to teachers compiling medical sciences courses for dental undergraduates and to those planning and evaluating new curricula with a less didactic approach.

Cross-Sectional Studies↗
PubMed2000

Exhaled nitric oxide during incremental and constant workload exercise in chronic cardiac failure.

BACKGROUND: Nitric oxide (NO) is present in exhaled breath and produced by the pulmonary vascular endothelium as a potent vasodilator. Exercise is normally associated with pulmonary vasodilatation and a decrease in pulmonary vascular resistance to accommodate the increase in cardiac output. If production of NO is impaired in patients with chronic congestive cardiac failure (CCF), this might contribute to their exercise intolerance. PATIENTS AND METHODS: We quantified NO production (V NO) in 12 patients with chronic stable CCF and 12 controls, at rest and during incremental cardiopulmonary exercise on a treadmill, and at a later date during constant workload exercise. RESULTS: Patients had reduced V NO compared with controls during incremental exercise [381 (180) vs. 777 (275) nL min-1; mean (SD); P < 0.0001] but at constant workload V NO was similar between the two groups [353 (124) vs. 389 (189) nL min-1; P = 0.25]. Plasma levels of nitrate, the stable end-product of NO production, were significantly higher in patients [resting value 46.1 (21.6) vs. 23.0 (10.0) microM; P = 0.004] and were not influenced by exercise. CONCLUSION: Impaired NO-mediated pulmonary vasodilatation does not appear to contribute to exercise limitation in CCF. Alternatively, the lower NO production observed during maximal exercise in the patient group compared with controls may reflect a reduced incremental response of a system that is already abnormally activated in heart failure.

Aged↗
PubMed1999

Assessment factors for human health risk assessment: a discussion paper.

The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factors to be identified, the range of values assigned, as well as the presence or absence of a scientific basis for these values. Options are presented for a set of default values and probabilistic distributions for assessment factors based on the state of the art. Methods of combining default values or probabilistic distributions of assessment factors are also described. Second, the effect parameter, the no-observed-adverse-effect level (NOAEL), is discussed. This NOAEL as selected from the toxicological database may be a poor substitute for the unknown, true no-adverse-effect level (NAEL). New developments are presented with respect to the estimation of the NAEL. The already widely discussed Benchmark Dose concept can be extended to obtain an uncertainty distribution of the Critical Effect Dose (CED). This CED distribution can be combined with estimated uncertainty distributions for assessment factors. In this way the full distribution of the Human Limit Value will be derived and not only a point estimate, whereas information on dose-response relations is taken into account. Finally, a strategy is proposed for implementation of the new developments into human health risk assessments.

Animals↗
PubMed1998

Exposure and risk estimation for pesticides in high-volume spraying.

During twenty applications with a spray pistol of methomyl to chrysanthemums, inhalation exposure as well as potential and actual dermal exposure were monitored using the 'whole-body'-method. On the basis of the exposure data, in terms of exposure to the liquid formulation and the spray liquid, the possible health risk for methomyl and thirteen other pesticides, frequently used in ornamentals, was indicatively assessed. From the No-Observed-Adverse-Effect-Level (NOAEL) in animal experiments an Indicative Limit Value (ILV) was derived. The ILV is considered indicative for the limit of daily exposure for a worker which probably gives no rise to adverse health effects. This value is a rough approximation since the database for a proper assessment of such a value is generally incomplete. Assuming that exposure is independent of the pesticide, using a suitable format, the actual observed exposure can be compared with the ILV. To reduce the dermal exposure levels below the ILV the exposure of especially the hands has to be reduced e.g. by using impermeable gloves.

Agriculture↗
PubMed1998

Assessment of vascularity in histological sections: effects of methodology and value as an index of angiogenesis in breast tumours.

The aims of this study were to (a) determine how the quantification of blood vessels in histological sections (vascularity) is affected by the methodology used and (b) assess the value of vascularity as an index of angiogenesis by comparing tumour and normal breast tissue. Archival specimens of breast, lung and oral carcinoma, oral dysplasia and normal breast tissue were used to test the effects of the following experimental variables on vascularity: pretreatment of the sections (enzymatic digestion, heating), endothelial markers (von Willebrand factor and CD31 antibodies), method of quantification (highest microvascular density, average microvascular density and microvascular volume) and interobserver variations. All the variables examined significantly affected the estimated vascularity; this depended on the type of tissue and method used. The pretreatment of the sections before staining was the most important variable, altering the vascularity ranking of the tumours. Vascularity in breast tumours was similar to that of the normal breast intralobular stroma, suggesting that an area of high microvascular density in the tumour does not necessarily represent tumour-induced angiogenesis. Contradictory results have been published regarding the value of vascularity as a tumour prognostic factor. Our results suggest that statistically significant differences in vascularity values are most likely to arise from failure to optimize the staining protocol and from the method used to assess vascularity.

Blood Vessels↗
PubMed1998

Proposal for the assessment of quantitative dermal exposure limits in occupational environments: Part 1. Development of a concept to derive a quantitative dermal occupational exposure limit.

Dermal uptake of chemicals at the workplace may contribute considerably to the total internal exposure and so needs to be regulated. At present only qualitative warning signs--the "skin notations"--are available as instruments. An attempt was made to develop a quantitative dermal occupational exposure limit (DOEL) complementary to respiratory occupational exposure limits (OELs). The DOEL refers to the total dose deposited on the skin during a working shift. Based on available data and experience a theoretical procedure for the assessment of a DOEL was developed. A DOEL was derived for cyclophosphamide and 4,4-methylene dianiline (MDA) according to this procedure. The DOEL for MDA was tested for applicability in an actual occupational exposure scenario. An integrated approach is recommended for situations in which both dermal and respiratory exposures contribute considerably to the internal exposure of the worker. The starting point should be an internal health based occupational exposure limit--that is, the maximum dose to be absorbed without leading to adverse systemic effects. The proposed assessment of an external DOEL is then either based on absorption rate or absorption percentage. The estimation of skin penetration seems to be of crucial importance in this concept. If for a specific substance a maximal absorption rate can be estimated a maximal skin surface area to be exposed can be assessed which may then serve the purpose of a DOEL. As long as the actual skin surface exposed is smaller than this maximal skin surface area the internal OEL will not be exceeded, and therefore, no systemic health problems would be expected, independent of the dermal dose/unit area. If not, the DOEL may be interpreted as the product of dermal dose/unit area (mg/cm2) and exposed skin surface area (cm2). The proposed concept for a DOEL is relevant and can be made applicable for health surveillance in the occupational situation where dermal exposure contributes notably to the systemic exposure. Further research should show whether this concept is more generally applicable.

Humans↗
PubMed1998

Gender differences in knee injury epidemiology among competitive alpine ski racers.

A questionnaire was sent in 1995 to all members of the Vermont Alpine Racing Association and several New England NCAA Division I ski racing programs. A total of 1010 surveys were sent and 404 responses were received. The survey included questions regarding the racer's age, gender, number of years spent ski racing, injury to knee(s), surgery to knee(s), and reinjury to a surgically reconstructed anterior cruciate ligament (ACL) requiring subsequent surgery. Only injuries that occurred during alpine skiing were included. One-quarter of respondents (27%) reported a history of a knee injury. Female racers were 2.3 times more likely to have sustained a knee injury than male racers. More impressively, one in five female alpine racers (22%) reported an ACL disruption, and females were 3.1 times more likely to sustain an ACL injury in comparison to their male counterparts. Of the athletes who had surgery to reconstruct their ACL, approximately one-third (36%) required subsequent surgery to the same knee. One in five (22%) ACL reconstructions failed, requiring additional surgery to the same ACL. Females reported a higher rate of reinjury to an ACL graft than males (27% vs. 13%), but this was not statistically significant.

Adult↗
PubMed1996

Community-based resilient peer treatment of withdrawn maltreated preschool children.

The purpose of the present study was to evaluate differences in the social play of maltreated and nonmaltreated preschool children and the effectiveness of a resilient peer treatment (RPT) for socially withdrawn victims of physical abuse and neglect. RPT is a peer-mediated classroom intervention based on a developmental-ecological model. It involves pairing withdrawn children with resilient peers in the natural classroom under the supervision of a parent assistant. Forty-six Head Start children, of whom 22 were maltreated, were randomly assigned to RPT and control conditions. Outcome variables were observational categories of social play and standardized teacher ratings. Before treatment, maltreated children were significantly more isolated and less interactive in peer play than nonmaltreated children. RPT resulted in a significant increase in positive interactive peer play and a decrease in solitary play for maltreated and nonmaltreated, socially withdrawn children. Moreover, treatment gains in social interactions were validated 2 months following treatment. Findings are discussed in terms of a developmental-ecological model.

Child Abuse↗
PubMed1993

Tumor immunology.

Explore the source record for details and available documents.

Adjuvants, Immunologic↗
PubMed1990

Tumor cell lines established in vitro: an independent prognostic factor for survival in non-small-cell lung cancer.

OBJECTIVE: To determine the relation between in-vitro establishment of tumor cell lines and survival in patients with non-small-cell lung cancer. DESIGN: Cohort study. SETTING: Single-institution tertiary care center. PATIENTS: One hundred twenty-three consecutive patients with non-small-cell lung cancer from whom a viable tumor specimen could be obtained. INTERVENTION: Tumor tissue was removed at the time of entry into a therapeutic protocol. The tumor tissue was processed in the laboratory for attempted cell-line establishment. Patients classified as potentially curable (stages I, II, and IIIA) were treated with surgical resection, radiation therapy, or a combination. Patients suitable for palliative therapy only (stages IIIB and IV) were treated with radiation therapy with or without chemotherapy. Chemotherapy was based on in-vitro drug sensitivity when available. Cell-line establishment was correlated to clinical outcome. MEASUREMENTS AND MAIN RESULTS: Univariate analysis of survival was done using the log-rank test; multivariate analysis was done by Cox modeling step-up and step-down techniques. Cell lines were established from the tumor specimens of 25 patients (20%). Those patients experienced a median survival of 7 months compared with 18 months in patients from whom cell lines could not be established (P less than 0.001). In the 61 patients with potentially curable disease, 8 patients (13%) with cell lines established had a median survival of 8 months compared with 32 months for those without cell lines established (P = 0.001). In the 62 palliative group patients, the median survival of the 17 patients (27%) from whom tumor cell lines were established was 5 months compared with 7 months for those without cell lines (P = 0.15). Multivariate analysis in both groups showed cell-line establishment to be a significant indicator of prognosis (P less than 0.0001 for curable group; P less than 0.01 for palliative group). CONCLUSION: In-vitro tumor growth is related to decreased patient survival, which in turn reflects the biologic aggressiveness of cancers giving rise to these tumor cell lines.

Analysis of Variance↗
PubMed1987

If the model fits....

Explore the source record for details and available documents.

Decision Making, Organizational↗