Linkage analysis with adjustment for covariates: a method combining peeling with Gibbs sampling.
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Data Interpretation, Statistical↗
Biomedical subjects
A Kong
Publications and source records attributed to A Kong.
Importance sampling. I. Computing multimodel p values in linkage analysis.
In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of our method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation.
Diabetes Mellitus, Type 2↗
Efficient methods for computing linkage likelihoods of recessive diseases in inbred pedigrees.
Traditional methods for computing linkage likelihoods can be infeasible for data that involve considerable inbreeding and missing information, characteristics of large pedigrees affected by rare recessive diseases. For this type of data, we propose alternative procedures that can efficiently provide good approximates of linkage likelihoods. These approximation procedures are constructed based on a new mathematical representation of the multiloci inheritance model. Instead of representing each person by a single variable, the genotype, the disease gene alleles, and the marker alleles are taken as separate variables. This allows us to break down the computations into manageable pieces. This new representation is also potentially useful for multipoint mapping.
Algorithms↗
Prostatein C3-mRNA: a sensitive marker of androgen-responsiveness in prostate explant cultures.
Prostatein is an androgen-dependent protein which is secreted by the rat ventral prostate. To determine if prostatein or its mRNA were responsive to androgen in vitro, prostate explants were cultured in media containing 0 or 25 nM dihydrotestosterone (DHT), estradiol (E2), or cortisol (F). Prostatein concentrations in medium were measured by radioimmunoassay at 2 and 4 days and in homogenates at 4 days. They were not changed significantly by any of these steroids. The concentration of the mRNA for the C3-subunit of prostatein was determined by dot hybridization at 0, 2, 4, 6, and 8 days. It was decreased significantly by 2 days when compared with explants cultured in the presence of DHT and significant differences persisted through 8 days. In conclusion, quantitation of the mRNA for the C3-subunit of prostatein in short-term cultures of ventral prostate explants appears to be more sensitive to changes in androgen concentration than does measurement of prostatein, per se. Prostatein C3-mRNA may be a useful marker for in vitro studies of androgen agonists and antagonists.
Androgen-Binding Protein↗
Anaesthesia, movement and emesis.
One hundred and eighty-two women undergoing dilatation and curettage were allocated randomly to receive premedication comprising temazepam, papaveretum-hyoscine or placebo. The temazepam recipients reported significantly fewer episodes of postoperative nausea. Movement was blamed by 66% of patients who identified a cause for nausea. These patients had higher scores on a motion sickness susceptibility questionnaire and were more likely to have been treated previously for nausea or vomiting. It may be possible to identify susceptible patients before surgery.
Adult↗
Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.
We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.
Animals↗
A model for the study of the oral administration of peptide hormones.
The intragastric administration of lysine vasopressin (LVP) to rats is used as a model to study the biological activity of orally administered peptide hormones. Using a modification of the antidiuretic assay of Sawyer, LVP given by stomach tube caused a significant antidiuresis that was dose dependent in doses of 300 to 2000 mU. The simultaneous administration of the protease inhibitor, Trasylol, increased the antidiuretic effect of LVP. The synthetic peptide (1-deamino, 4 valine)-8-D-arginine-vasopressin also caused a dose-dependent prolonged and significant antidiuresis. No pressor effect was observed after intragastric administration of LVP in doses up to 40 U/rat. We are now using this model to test other procedures for enhancing the activity of lysine vasopressin administered in the gastrointestinal tract such as encapsulation into liposomes. The information gained with vasopressin will then be applied to insulin with the ultimate goal of making oral administration practical.
Administration, Oral↗