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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 667 records · Page 37Linked to original sources
PubMed1993

Cross-sectional epidemiological study of respiratory disease in turkey farmers.

This study was a cross-sectional epidemiological investigation of respiratory disease in farmers involved in the turkey growing industry. Pulmonary function tests and health history questionnaires were administered to a total of 95 turkey farmers throughout Minnesota. Respiratory symptoms were greatest during the winter months when exposure to environmental agents was highest. Prevalence of symptoms was higher for smokers, personnel who worked in hen barns, and for persons who had worked in the turkey growing industry for more than 10 years. Pulmonary function was found to decrease during the work day. Also, pulmonary function was lowest for personnel working in hen bars, and for persons who had been employed in the industry for more than 10 years. These data support the association between respiratory disease and exposure to the environment in confinement farm buildings.

Adolescent↗
PubMed1993

Pharmacokinetics and bioavailability of medroxyprogesterone acetate in the dog and the rat.

Medroxyprogesterone acetate (MPA) has been administered to rats and dogs. Dogs received single oral doses of 2.5, 5, and 10 mg MPA and a single intravenous dose of 1 mg MPA. Rats received single oral doses of 0.2, 1, 5, and 20 mg kg-1 MPA and multiple oral doses (14 daily doses) of 0.2, 5, and 20 mg kg-1 MPA. Dog plasma MPA levels from the intravenous dose were characterized by a triexponential decay with disposition half-lives of 0.3, 1.8, and 21.6 h. A Loo-Riegelman analysis of the dog plasma MPA levels from oral doses indicated absorption was not a simple first-order process. The Weibull Function was used to characterize the absorption kinetics of MPA. The oral absorption of MPA in dogs appears to be dose-linear over the dosage range studied, and the absolute bioavailability was estimated at 27 per cent. Rat plasma MPA levels from single and multiple oral doses were analyzed by a non-compartmental approach. AUC and Cmax values were not dose-linear over the dosage range studied; indicative of the self-induced metabolism of MPA. Exposure of similar dosages of MPA to both the rat and the dog resulted in similar plasma profiles and pharmacokinetics.

Administration, Oral↗
PubMed1993

Transcriptional diversity at the duplicated human CD8 beta loci.

In order to understand the structural organization of the human CD8 beta locus, genomic clones containing CD8 beta sequences were isolated and analyzed. Physical linkage of these clones with the CD8 alpha locus using pulsed-field electrophoresis revealed a duplication of the CD8 beta locus. CD8B-1 lies 35 kb upstream from the CD8 alpha locus and contains eight exons, including four alternatively spliced cytoplasmic exons. The CD8B-2 gene contains six exons and is at present unlinked to CD8B-1. Analysis of sequences upstream to the leader exon of the CD8B-1 and CD8B-2 genes revealed a GC-rich promoter which lacks canonical "CCAAT" and "TATA" motifs, but which has sites for multiple transcriptional activators and three additional elements which are conserved in the murine CD8 beta promoter. Seven unique CD8 beta cDNA isoforms were isolated and characterized, which derive from alternative splicing of the transmembrane and/or cytoplasmic exons. Three cDNA are membrane spanning, while the remaining four isoforms lack a transmembrane region and are potentially secreted. These transcripts are differentially expressed in the thymus and in the periphery. Transfection experiments in murine fibroblasts confirmed that the membrane CD8 beta isoforms could be expressed as heterodimers with the CD8 alpha chain. The regulated expression of multiple CD8 beta cytoplasmic isoforms and their potential role in T lymphocyte signal transduction is discussed.

Alternative Splicing↗
PubMed1993

Approaches to disease cluster investigations in a state health department.

Classical tests for clustering rarely have a major role in the investigation of disease clusters at the neighbourhood level performed by a health department. When examining a single cluster, the boundaries are often ill-defined, and the dimension (geographic, occupational, iatrogenic) is rarely obvious. Furthermore, using cluster tests to routinely scan disease registries looking for clusters is undesirable for several reasons. A better approach is to be vigilant for unusual environmental exposures, and to evaluate the impact they may have. In this context, cluster techniques may serve as part of a larger investigation that includes other epidemiologic approaches.

Air Pollutants↗
PubMed1993

Competitive as well as uncompetitive N-methyl-D-aspartate receptor antagonists affect cortical neuronal morphology and cerebral glucose metabolism.

The studies examined the effects of three antagonists (CPP, CGS 19755, and CGP 37849) that act competitively at the glutamate recognition site of the NMDA receptor complex on cortical neuronal morphology and cerebral limbic glucose metabolism. Responses were compared to the effects of dizocilpine, an uncompetitive NMDA receptor ion channel antagonist as a positive control. CGS 19755 and CGP 37849 (100 mg kg-1 i.p.) caused vacuolation in cortical pyramidal neurons in the posterior cingulate cortex four hours after dosing and this dose of CGP 37849 caused a pattern of limbic glucose metabolism activation similar to that seen after dizocilpine. CPP was without effect at 100 mg/kg i.p. probably due to poor brain penetration. The data indicates that the functional consequences (structural and metabolic) of NMDA receptor blockade with NMDA antagonists acting competitively at the glutamate recognition site and uncompetitively in the receptor ion channel are ultimately the same. Comparisons of the potential therapeutic window for CGS 19755 and CGP 37849 with dizocilpine (neuroprotection versus vacuolation) suggests that the window for the competitive antagonists is greater. This indicates that the potential therapeutic window for the different classes of NMDA antagonists may vary with the site in the receptor complex at which they interact.

2-Amino-5-phosphonovalerate↗
PubMed1993

Cathepsin-D expression in cervical carcinoma and its prognostic significance.

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean -3.709, p = 0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.

Adenocarcinoma↗
PubMed1993

Thalamic infarction secondary to cervical manipulation.

Vertebrobasilar infarction is a well documented complication of cervical manipulation. A commonly proposed pathogenesis is an intimal tear of the vertebral artery leading to cerebellar and other posterior fossa lesions. However, there have been no cases of thalamic infarct reported. This case demonstrates a thalamic infarction concurrent with brainstem and cerebellar infarction secondary to cervical manipulation and intimal tearing of the vertebral artery. Immediately following manipulation, the patient developed nystagmus, quadriparesis, and a speech deficit. After an aggressive course of in-patient rehabilitation, the patient progressed to a community ambulator with deficits in speech and perception. This case demonstrates one of the inherent risks associated with repetitive forceful cervical manipulation.

Adult↗
PubMed1993

A mathematical model of the right ventricular muscle geometry and mass.

An understanding of the geometry of the right ventricular (RV) free wall is imperative for both modelling its mechanics and assessing its mass by imaging techniques such as echocardiography. In this paper, a new model of the RV free wall geometry is discussed in which the wall is assumed to have a parabolic long-axis and a circular short-axis curvature respectively. By use of analytic geometry, mathematical expressions for RV surface area, volume and mass were derived. In vitro model validation was carried out in the following manner: (1) echocardiographic images of 16 isolated calf hearts were obtained; (2) measurements were made from the images to determine the parameters required by the model; (3) wall mass was determined by use of these parameters; and (4) the calculated wall mass was then compared with actual RV wall mass (determined by weighting). The model was found to be very accurate for determination of RV free wall mass (R = 0.92); it should prove useful in the study of the stress-strain relationships for the RV and for precise quantitative assessment of RV free wall mass.

Animals↗
PubMed1993

A revised HindIII map and sequence analysis of a large 'left-hand' non-essential region of the rabbit poxvirus genome.

Sequence analysis of a 21.5 kb region of the left-hand non-essential region of rabbit poxvirus (RPV) was performed to analyze the structure and gene organization of this region. Initial mapping and cloning studies revealed that the early published HindIII maps are incorrect in that the location of the terminal HindIII B and C fragments, as previously published, are reversed. The sequence of this region was compared to similar regions of several strains of vaccinia virus. The results indicate that this region of RPV has a high degree of homology with a similar region of vaccinia. Analysis of the translated open reading frames (ORFs) has facilitated the detection of several previously unreported ORFs related to human complement proteins. In addition, two defective copies of a homologue of the 77 kDa cowpox virus (CPV) host range gene which allows CPV to grow on Chinese hamster ovary cells have been detected, suggesting a gene duplication has occurred. However, one copy of this gene is segmented into three separate ORFs. Analysis has also identified a large number of indirect repeat elements. A possible role of these repeats in the generation of deletions and gene duplications is suggested.

Amino Acid Sequence↗
PubMed1993

Measuring the impact of epilepsy: the development of a novel scale.

The impact of a chronic illness is experienced not only through its physical symptoms, but also as a result of its effect on psychosocial functioning. In the case of an illness such as epilepsy, where the physical manifestations are transient, the psychosocial consequences may, with time, come to be of greater concern. We have been involved in developing a quality of life model for epilepsy. As part of the refinement of the initial model, we have devised a novel scale to measure the impact of the condition on a number of different aspects of daily life. The scale was administered to 75 patients attending an epilepsy out-patient clinic. Initial analysis of its psychometric properties is encouraging, although the inclusion of an item relating to employment reduced the scale's reliability. As a result, the wording of the existing item has been amended and an additional item has been incorporated. We hope the scale will be useful in investigations of treatment for epilepsy and of its psychosocial aspects.

Adolescent↗
PubMed1993

The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures.

The dissolution and bioavailability of etodolac from capsules exposed to high relative humidity and temperature were compared to those from capsules stored at room temperature (RT). Dissolution of stressed and control capsules was evaluated using a USP basket apparatus at 100 rpm with 900 mL pH 7.5 phosphate buffer (0.05 M) at 37 degrees C. The dissolution of etodolac from capsules exposed to stressed conditions was also evaluated with enzymes (pancreatin, 1%, w/v) added to the dissolution medium. The bioavailability of etodolac from capsules exposed to stressed conditions was compared in both dogs and humans to capsules stored at RT conditions. Capsules, 200 and 300 mg, exposed to stressed conditions failed the dissolution (without enzymes) specification [not less than 85% released (80% Q) in 30 min]. However, upon enzyme addition, all capsules met the specification. The rate and extent of absorption from these 200 and 300 mg etodolac capsules in dogs were equivalent to those from capsules stored at RT conditions that passed the dissolution specification. Similarly, the bioavailability of etodolac from 300 mg capsules that failed the dissolution specification upon exposure to stressed conditions was equivalent to that of control capsules in 24 adult male volunteers. Thus, an in vitro dissolution test with enzymes provides a better indication of stressed capsule performance in vivo.

Animals↗
PubMed1993

Impact of parental separation and divorce on adopted and nonadopted children.

The impact of parental separation and divorce on adopted and nonadopted children was examined. Although children from nonintact homes showed poorer adjustment than did children from intact homes, the results were comparable for adoptees and nonadoptees. In addition, life stress associated with marital disruption was found to account for the majority of children's adjustment problems.

Adaptation, Psychological↗
PubMed1993

TnpA trans-activates methylated maize Suppressor-mutator transposable elements in transgenic tobacco.

The maize Suppressor-mutator (Spm) transposable element is subject to epigenetic inactivation in transgenic tobacco, as it is in maize. Spm inactivation in tobacco is correlated with increased methylation of sequences near the element's transcription start site. To determine whether element-encoded gene products can promote the reactivation of an inactive element, we investigated the effects of introducing individual CaMV 35S promoter-driven cDNAs for tnpA, tnpB, tnpC and tnpD, the element's four known protein-coding sequences. Introduction of the tnpA cDNA promoted the reactivation of the inactive resident Spm element, as judged by the appearance of regenerants with very early excision events and transposed elements. By contrast, the tnpB, tnpC and tnpD cDNAs had no affect on the activity of the resident Spm element. Similar results were obtained when the element-encoded cDNAs were introduced either by Agrobacterium-mediated retransformation or by a genetic cross. Reactivation of an inactive Spm by the tnpA cDNA is accompanied by reduced methylation of several methylation-sensitive restriction sites near the element's transcription start site. Maintenance of the reactivated Spm element in an active state requires the continued presence of the tnpA cDNA. Elimination of the tnpA cDNA locus by genetic segregation generally results in decreased element activity, as judged by a low frequency of excision events, and is accompanied by increased methylation of the element's 5'-end. Exceptions resembling the phenomenon of "presetting" are also observed in which progeny plants that did not receive the tnpA cDNA locus after meiotic segregation maintain high excision activity and exhibit low methylation levels.

Crosses, Genetic↗