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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 523 records · Page 29Linked to original sources

Increase of basic fibroblast growth factor (FGF) and FGF receptor messenger RNA during rat thyroid hyperplasia: temporal changes and cellular distribution.

Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. Involution of thyroid growth was then observed at 16 weeks, 4 weeks after withdrawal of goitrogens and reversion to a normal diet. Experimental animals quickly became hypothyroid compared with controls and exhibited thyroid hyperplasia (control (n = 10): total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight, means +/- S.D.; experimental (n = 10): T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment). Thyroid growth rate subsequently slowed between 2 and 10 weeks. Messenger RNA for basic fibroblast growth factor (basic FGF) and for the high-affinity FGF receptor, was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for basic FGF and its receptor were detectable in thyroids from control rats at all times, while none was detected in the livers from any animal. Basic FGF and receptor mRNAs increased, and were detected at greatest abundance in hyperplastic thyroids at 1 and 2 weeks respectively, during goitre formation, but subsequently declined in parallel with thyroid growth rate at 4 and 10 weeks. When quantified by radioimmunoassay, basic FGF extracted from thyroids was fivefold greater than in controls after 1 week of goitrogen treatment (control (n = 4): 24 +/- 9 pmol/micrograms DNA; goitre (n = 4): 100 +/- 16 pmol/micrograms DNA; P < 0.05). Basic FGF and FGF receptor mRNAs localized by in situ hybridization predominantly to the epithelial cell population within follicles. Localization by immunohistochemistry demonstrated that basic FGF was present in the thyroids of control rats, and was largely associated with the basement membrane of follicles. During thyroid hyperplasia, increased basic FGF immunoreactivity appeared over the cytoplasm of follicular epithelial cells and was lost from the extracellular matrix. Thyroid involution following removal of goitrogen/low iodine treatment was associated with a decrease in mRNA for basic FGF or its receptor, and a loss of immunoreactive basic FGF from the cytoplasm of follicular cells. These results suggest that autocrine expression of basic FGF and FGF receptor could contribute to thyroid hyperplasia in rats.

Animals↗

A bioeconomic model for comparing beef cattle genotypes at their optimal economic slaughter end point.

A bioeconomic model of a feedlot was developed for the comparison of beef cattle genotypes under specified management and marketing conditions. The optimization behavior of commercial feedlot managers is incorporated into the model using optimum economic rotation theory. The days spent in the feedlot (rotation) by a group of animals are derived using this theory so as to maximize an objective function. Differences among breeds in the present value of profits from a single rotation, expressed per animal, represent the expected price premium paid for a feeder animal of a particular breed. Feed requirements and growth rates for a genotype are predicted over time for a specified diet from estimated mature size. Estimates of carcass fatness over time as a function of the energy content of the diet and estimates of dressing percentage over time are used for each genotype. A base model is described that incorporates biological parameters estimated for 11 breeds from a major breed comparison experiment and uses prices of inputs and outputs for Ontario feedlots. Sensitivity of the model to these biological and economic assumptions is shown. When breeds are compared at constant days fed, weight, or fat depth slaughter points, rankings are inconsistent, relative to those when each breed is slaughtered at its optimal economic point. The model can be used to establish appropriate slaughter end points for comparing beef cattle breeds and crosses and to evaluate breeding objectives for feedlot traits in genetic improvement programs.

Agriculture↗

Altered expression of insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat thyroid hyperplasia and involution.

We have investigated changes in the synthesis and localization of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in thyroid tissues during the induction of goitre in iodine-deficient rats, and during the subsequent involution of the gland following goitrogen withdrawal. Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. After twelve weeks the goitrogenic stimuli were removed and thyroids examined 4 weeks later. Circulating T4 levels became undetectable within two weeks of goitrogen administration while thyroid weight had increased five-fold. The thyroids continued to increase in size up to 10 weeks, but at a slower growth rate. IGF-I mRNA, detected by ribonuclease protection assay, was present in the control rat thyroid and increased in abundance after both 1 and 2 weeks of goitrogen administration. Levels of IGF-I mRNA showed a relative decline with prolonged goitrogen administration, and following thyroid involution the hybridization signal was similar to that seen in control glands. Northern blot hybridization showed that IGFBP-2, -3 and -5 mRNAs were all present in growth-quiescent, control thyroids and those encoding IGFBP-2 and -3 were elevated in the goitrous glands and remained so as long as goitrogen was administered, thereafter declining during thyroid involution. IGF-I and IGFBP-2 and -3 mRNAs and synthesized peptides, detected by in situ hybridization and immunohistochemistry respectively, were found to co-localize predominantly in follicular epithelial cells. IGFBP-5 mRNA abundance was unaltered during goitre formation, but was increased in the involuting thyroid. Both IGFBP-5 mRNA and peptide were localized to the parafollicular cells (C-cells) which were increased in number during involution. The results suggest that an increased expression of IGF-1 may contribute to early goitre formation, but that a relative increase in the abundance of IGFBP-2 and -3 may limit IGF availability at later times, and facilitate a slowing of thyroid growth rate. The discrete expression of IGFBP-5 by C-cells suggests that it could contribute indirectly to goitre formation or involution by acting in a paracrine fashion.

Animals↗

Genetic response and inbreeding with different selection methods and mating designs for nucleus breeding programs of dairy cattle.

Stochastic simulation was used to study the effect of selection and mating strategy on rates of genetic response and inbreeding with a closed nucleus breeding program for juvenile and adult schemes with 8 males and 64 females selected to produce 1024 progeny (512 females). Selection strategies considered using all available information or only individual and sibling records. Selection of sires was either unrestricted or restricted to between full-sib families. The effect of avoidance of mating of relatives to limit inbreeding was also evaluated. Four mating designs were examined: each dam was mated to 1, 2, 4, or all sires. Mating designs involving one sire per dam and more than one dam per sire were referred to as hierarchical. Use of several mates per dam resulted in a factorial mating design. Selected parents were mated either randomly, best to best, or best to worst. An index based on relative inbreeding to response ratio was used to describe the effectiveness of strategies for reducing inbreeding relative to changes in rates of genetic response. Strategies that lower index values were preferred and include selection on BLUP or approximations of BLUP and factorial mating designs that involve the random mating of dams to several sires. Factorial mating designs were effective for a range of heritabilities. Avoidance of matings of full sibs and restriction of selection of sires to between full-sib families enabled appreciable reductions in the index. Nucleus breeding programs based entirely on the selection of juveniles were not indicated because they had higher index values than adult schemes.

Animals↗

A community quality initiative for health care reform.

In 1989, the Madison Area Employers Health Care Coalition conducted a feasibility study for the purpose of finding solutions to common health care concerns. The study revealed three conclusions: (1) there was little or no price competition among providers; (2) employers lacked useful data and information regarding health care costs and outcomes; and (3) employers and employees lacked basic health care consumerism. These conclusions led to the development of a health care purchasing group in the spring of 1990 with the formation of the Employers Health Care Alliance Cooperative (The Alliance). The conclusions outlined above became the cornerstone of the services offered by The Alliance, which include provider contracting, data collection, and consumer education and advocacy. The Alliance also developed the community quality initiative, a partnership of employers, health care consumers, and providers committed to using continuous quality improvement methods.

Community Health Services↗

Health-related behaviour in Wales, 1985-1990.

This study looked at recent changes in Wales in four health-related behaviours: smoking, alcohol consumption, diet and physical activity. Data are drawn from three large-scale surveys conducted across Wales in 1985, 1988 and 1990. The results show a reduction in smoking prevalence between 1985 and 1990 among men and women, and a growing trend towards healthier eating, with reduced frequent consumption of salt and foods high in saturated fats. Encouraging progress towards healthier living has been made, but the results also indicate the extent of the remaining challenge: greater progress is particularly needed to encourage participation in exercise, and to reduce the numbers of people who drink alcohol in excess of recommended sensible limits.

Adult↗

Protein crystal growth in microgravity-temperature induced large scale crystallization of insulin.

One of the major stumbling blocks that prevents rapid structure determination using x-ray crystallography is macromolecular crystal growth. There are many examples where crystallization takes longer than structure determination. In some cases, it is impossible to grow useful crystals on earth. Recent experiments conducted in conjunction with NASA on various Space Shuttle missions have demonstrated that protein crystals often grow larger and display better internal molecular order than their earth-grown counterparts. This paper reports results from three Shuttle flights using the Protein Crystallization Facility (PCF). The PCF hardware produced large, high-quality insulin crystals by using a temperature change as the sole means to affect protein solubility and thus, crystallization. The facility consists of cylinders/containers with volumes of 500, 200, 100, and 50 ml. Data from the three Shuttle flights demonstrated that larger, higher resolution crystals (as evidenced by x-ray diffraction data) were obtained from the microgravity experiments when compared to earth-grown crystals.

Animals↗

Enrichment of peripheral blood stem cells in a primate model following administration of a single dose of rh-IL-1 beta.

In a pre-clinical primate model, the effect of a single intravenous injection of rh-GM-CSF (50 micrograms/kg), rh-IL3 (20 micrograms/kg), rh-IL-1 beta (1 micrograms/kg), rh-G-CSF (50 micrograms/kg) and rh-pIXY 321 (50 micrograms/kg) on peripheral blood mononuclear cell and hematopoietic stem cell concentration was determined. The results indicated that administration of a single dose of rh-IL-1 beta increased the concentrations of hematopoietic stem cells, including CFU-GM progenitors and precursors to CFU-GM. No toxicity was noted with this procedure. None of the remaining cytokines tested caused a significant increase in the peripheral blood hematopoietic stem cell concentration when administered in this manner and only G-CSF caused an increase in peripheral blood mononuclear cell concentrations. Autologous transplantation with limiting numbers of peripheral blood mononuclear cells (1 x 10(7) cells/kg) collected either 24 or 72 h following injection of 1 microgram/kg rh-IL-1 beta conferred a survival advantage to recipients compared with controls. These results imply that a single intravenous administration of rh-IL-1 beta may increase the concentration of peripheral blood stem cells to levels sufficient for transplantation.

Animals↗

Molding our image: the media and dentistry.

Dentistry has had a few nasty media shocks in the past year. Part of the problem is that dentists who are willing to talk to the press in good times, shy away from the media when the questions get tough. And if you won't answer the question, what's a journalist--and the public--to think?

American Dental Association↗

"Checkerboard" DNA-DNA hybridization.

A method is introduced for hybridizing large numbers of DNA samples against large numbers of DNA probes on a single support membrane. Denatured DNA from up to 43 samples was fixed in separate lanes on a single membrane mounted in a Miniblotter 45. The membrane was then rotated 90 degrees in the same device, which enabled simultaneous hybridization with 43 different DNA probes. Hybridizations were also performed on lysates of bacterial cells blotted to membranes. A MiniSlot device allowed lysates loaded in parallel channels to be aspirated through the membrane, depositing horizontal lanes on the membrane surface. Hybridizations were performed in vertical lanes with either digoxigenin-labeled whole genomic probes or 16S rRNA-based oligonucleotide probes directly conjugated to alkaline phosphatase. The method permits the simultaneous determination of the presence of multiple bacterial species in single or multiple dental plaque samples, thus suggesting its usefulness for a range of clinical or environmental samples.

Base Sequence↗

A multidisciplinary approach to neonatal ambulance design.

The transport of a critically ill neonate from a community hospital to a regional intensive care unit requires the expertise of a specially trained team and a transport environment that addresses the unique needs of critically ill neonates. Utilization of ground vehicles for the transportation of neonates as compared to air transport seems to be increasing on a national basis. Traditional ambulance design falls short of meeting the distinctive needs of a neonatal transport service. The purpose of this article is to describe the process used by one facility to design a neonatal-specific ambulance. Use of a multidisciplinary team in developing this vehicle helped address the identified needs of this midwestern transport service.

Ambulances↗

Low density lipoprotein cholesterol/apolipoprotein B-100 ratio: interaction of family history of premature atherosclerotic coronary artery disease with race and gender in 7 to 11 year olds.

BACKGROUND: In adults, a low density lipoprotein cholesterol (LDL-C)/apolipoprotein B-100 (ApoB) ratio is an indicator of ApoB-enriched small dense LDL, which is associated with premature coronary artery disease (CAD). Since this LDL subclass may be inherited, we investigated whether a low LDL-C/ApoB ratio was associated with a positive family history of premature CAD in young children. METHODS: Subjects were 66 children aged 7 to 11 years who were recruited through a school-based family history survey, flyers, and hospital newspaper advertisements. They were divided according to family history and assessed for fatness, blood pressure, lipids, lipoproteins, and apoproteins. RESULTS: Family history interacted with gender such that girls with a positive family history had a lower LDL-C/ApoB ratio than girls with a negative family history, while the opposite was true in boys; ie, family history-positive boys had a higher ratio than family history-negative boys. The association of a low ratio with a positive family history was seen most clearly in white girls. Family history-positive whites had higher ApoB than family history-negative whites, whereas the pattern was reversed in the blacks. The LDL-C/ApoB ratio and ApoB were not related to other CAD risk factors such as fatness, blood pressure, or other lipids and lipoproteins. CONCLUSION: In young children, a low LDL-C/ApoB ratio and high ApoB levels were associated with a positive family history of CAD only in the white girls, suggesting that this group is at increased risk of genetically mediated CAD.

Apolipoprotein B-100↗

The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision.

BACKGROUND: We have previously demonstrated that the minimum alveolar concentration of isoflurane at 1 atm that is required to prevent movement in 50% of patients or animals exposed to a maximal noxious stimulus is markedly reduced by increasing fentanyl concentrations. Total intravenous anesthesia with propofol is increasing in popularity, yet the propofol concentrations required for total intravenous anesthesia or the interaction between propofol and fentanyl have not yet been defined. METHODS: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide pseudo-steady-state concentrations and allow equilibration between plasma-blood concentration and their biophase concentration. For the induction of anesthesia patients were randomly allocated to receive propofol only or propofol plus fentanyl 0.2, 0.8, 1.5, 3.0, and 4.5 ng/ml. In each group patients were randomized to target propofol concentrations of 1.5-10 micrograms/ml. At 7 and 10 min arterial blood samples were taken for subsequent measurement of propofol and fentanyl concentrations. At 10 min loss of consciousness was assessed by the patients' ability to respond to a simple verbal command. Thereafter a new target concentration of propofol was entered to ensure loss of consciousness, and succinylcholine was administered to facilitate tracheal intubation. Patients were rerandomized to a new target concentration of propofol (1-19 micrograms/ml) until skin incision. Before skin incision and 1 min after skin incision, arterial blood samples were again obtained for subsequent measurement of fentanyl and propofol concentrations. At skin incision and for 1 min the patient was observed for purposeful movement. Only samples in which the pre- and poststimulus drug concentrations were within 35% of each other were included. The propofol blood concentration at which 50% or 95% of patients did not respond to verbal command (Cp50s and Cp95s, respectively) and to skin incision (Cp50i and Cp95i, respectively), were calculated by logistic regression. RESULTS: There were 56 evaluable patients for calculating the propofol Cp50s and 53 patients for calculating the propofol Cp50i. For propofol alone the Cp50s was 3.3 micrograms/ml and the Cp95s 5.4 microgram/ml. Increasing fentanyl concentrations reduced the Cp50s (P = 0.03), and increasing age decreased the Cp50s (P = 0.04). For propofol alone the Cp50i was 15.2 (95% confidence interval 7.6-22.8) micrograms/ml and the Cp95i 27.4 micrograms/ml. Increasing fentanyl concentrations markedly reduced the Cp50i (P < 0.01), with a 50% reduction in Cp50i produced by 0.63 ng/ml fentanyl. The propofol Cp50i was decreased by 63% with 1 ng/ml fentanyl and 89% by 3 ng/ml fentanyl. At higher fentanyl concentrations the decrease in Cp50i was proportionally less, demonstrating a ceiling effect. CONCLUSIONS: We defined the propofol concentration required for loss of consciousness and showed that it is reduced by increasing fentanyl concentration and by increasing age. The propofol concentration (alone) adequate for skin incision is high but is markedly reduced by fentanyl. A ceiling effect in the Cp50i for propofol is seen with fentanyl concentrations greater than 3 ng/ml.

Adult↗