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Biomedical subjects

S L Thompson

Publications and source records attributed to S L Thompson.

17 recordsLinked to original sources
PubMed2006

A novel mating system analysis for modes of self-oriented mating applied to diploid and polyploid arctic Easter daisies (Townsendia hookeri).

We have developed a new model for mating system analysis, which attempts to distinguish among alternative modes of self-oriented mating within populations. This model jointly estimates the rates of outcrossing, selfing, automixis and apomixis, through the use of information in the family structure given by dominant genetic marker data. The method is presented, its statistical properties evaluated, and is applied to three arctic Easter daisy populations, one consisting of diploids, the other two of tetraploids. The tetraploids are predominantly male sterile and reported to be apomictic while the diploids are male fertile. In each Easter daisy population, 10 maternal arrays of six progeny were assayed for amplified fragment length polymorphism markers. Estimates, confirmed with likelihood ratio tests of mating hypotheses, showed apomixis to be predominant in all populations (ca. 70%), but selfing or automixis was moderate (ca. 25%) in tetraploids. It was difficult to distinguish selfing from automixis, and simulations confirm that with even very large sample sizes, the estimates have a very strong negative statistical correlation, for example, they are not independent. No selfing or automixis was apparent in the diploid population, instead, moderate levels of outcrossing were detected (23%). Low but significant levels of outcrossing (2-4%) seemed to occur in the male-sterile tetraploid populations; this may be due to genotyping error of this level. Overall, this study shows apomixis can be partial, and provides evidence for higher levels of inbreeding in polyploids compared to diploids and for significant levels of apomixis in a diploid plant population.

Asteraceae↗
PubMed2003

Human utilization of subsurface extraterrestrial environments.

Caves have been used in the ancient past as shelter or habitat by many organisms (including humans). Since antiquity, humans have explored caves for the minerals they contain and sometimes for ceremonial purposes. Over the past century, caves have become the target of increasing exploration, scientific research, and recreation. The use of caves on extraterrestrial bodies for human habitation has been suggested by several investigators. Lunar lava tube bases received early attention because lava tubes were clearly visible in lunar images from the Apollo Era. More recently, Mars Observer Camera data has shown us clear evidence of large tubes visible in a number of volcanic regions on Mars. The budding field of cave geomicrobiology has direct application to questions about subsurface life on other planets. Caves contain many unusual organisms making their living from unlikely materials like manganese, iron, and sulfur. This makes caves and other subsurface habitats prime targets for astrobiological missions to Mars and possibly other bodies. We present the results of a completed Phase I and on-going Phase II NASA Institute for Advanced Concepts (NIAC) study that intensively examines the possibilities of using extraterrestrial caves as both a resource for human explorers and as a highly promising scientific target for both robotic and future human missions to Mars and beyond.

Exobiology↗
PubMed2001

Environmental effects on genomic imprinting in mammals.

Genomic imprinting is an epigenetic marking mechanism by which certain genes become repressed on one of the two parental alleles. Imprinting plays important roles in mammalian development, and in humans its deregulation may result in disease and carcinogenesis. During different medical, technological and scientific interventions, pre-implantation embryos and cells are taken from their natural environment and subjected to culture in artificial media. Studies in the mouse demonstrate that environmental stress, such as in vitro culture, can affect the somatic maintenance of epigenetic marks at imprinted loci. These effects are associated with aberrant growth and morphology at fetal and perinatal stages of development.

Animals↗
PubMed2001

Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.

AIMS: We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction. METHODS AND RESULTS: We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North America and Latin America (odds ratios (OR) [95% confidence intervals (CI)] compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2 [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10-fold but did not explain regional mortality differences. Germany and the U.K. had similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although invasive procedures were four- to 10-fold more common in Germany. Similarly the U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61-1.17]) despite three-fold higher use of invasive procedures in the U.S. CONCLUSIONS: Significant geographic variations in practice and adjusted mortality following fibrinolysis persist despite recent guidelines. These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations.

Adult↗
PubMed2000

Paediatric brain tumours: an embryological perspective.

Primitive neuroectodermal tumours are amongst the most common paediatric tumours of the central nervous system. These tumours are composed of undifferentiated cells and a variable component of more differentiated cell types. Most analysis of these tumours has focused on molecules normally found in the differentiated cells or those found in all primitive neuronal precursors. In this article we describe recent advances in understanding of the molecular processes involved in normal neurogenesis. We discuss the relevance of these data to the biology of neuronal tumours and describe strategies we and others have adopted to investigate the usefulness of molecules found in undifferentiated neuronal tissues in understanding the events which underlie oncogenesis in this tumour type.

Brain Neoplasms↗
PubMed1990

Rat liver peroxisomes catalyze the initial step in cholesterol synthesis. The condensation of acetyl-CoA units into acetoacetyl-CoA.

In the last few years, it has been demonstrated by this group and others that rat liver peroxisomes participate in cholesterol synthesis. It has been shown that the key regulatory enzyme of isoprenoid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, is present in liver cells not only in the endoplasmic reticulum but also within peroxisomes. It has been also demonstrated that rat liver peroxisomes in the presence of cytosolic proteins in vitro are able to convert [14C]mevalonic acid to [14C]cholesterol. In addition, a recent study demonstrated that the largest cellular concentration of sterol carrier protein-2 is inside peroxisomes. It is of interest, therefore, to inquire whether other proteins known to be involved in cholesterol biogenesis are also present in peroxisomes. In this study we investigated the first step in cholesterol synthesis, the condensation of two acetyl-CoA units to acetoacetyl-CoA. It was demonstrated that peroxisomal thiolase, purified by DEAE-phosphocellulose chromatography from gemfibrozil-treated rats, is active not only toward acetoacetyl-CoA and 3-ketoacyl-CoA, consistent with literature reports, but is also capable of converting acetyl-CoA units to acetoacetyl-CoA. This is the first demonstration of condensation activity in rat liver peroxisomes.

Acetyl Coenzyme A↗
PubMed1987

Cholesterol synthesis in rat liver peroxisomes. Conversion of mevalonic acid to cholesterol.

The key regulatory enzyme of cholesterol, dolichol, and isopentenyl adenosine biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) is a 97-kilodalton transmembrane glycoprotein which was believed until recently to reside exclusively in the endoplasmic reticulum of mammalian cells. However, several recent publications have shown that the enzyme in liver cells is present not only in the endoplasmic reticulum but also within peroxisomes. In an effort to clarify the role of peroxisomal HMG-CoA reductase, highly purified (95%) rat liver peroxisomes from cholestyramine-treated rats were incubated with RS-[2-14C]mevalonic acid plus cytosolic proteins and then tested for the presence of newly synthesized cholesterol. For comparison, highly purified microsomes from the same liver preparation were incubated at several protein concentrations under the same conditions. A three-step procedure was employed to resolve the newly synthesized cholesterol from the complex mixture of sterol intermediates in cholesterol biosynthesis. After termination of the reaction and addition of a [3H]cholesterol standard, the incubation products were extracted and separated by thin layer chromatography into a number of fractions. The fraction containing C-27 sterols was further resolved by reverse-phase high pressure liquid chromatography. After acetylation, the products were then separated by silicic acid high pressure liquid chromatography. Confirmation of the identity of newly synthesized cholesterol was obtained by recrystallization with added non-radioactive cholestenyl acetate standard. The results indicate that highly purified rat liver peroxisomes are able to convert mevalonic acid to cholesterol in the presence of cytosolic fraction in vitro. An abstract of these results has been published (Krisans, S. K., Thompson, S. L., Burrows, R., and Laub, R. J. (1986) J. Cell Biol. 103, 525 (abstr.).

Animals↗
PubMed1987

Correlation between intracavernous papaverine injection and Doppler analysis in impotent men.

One hundred impotent men were evaluated with Doppler pulse-wave analysis and intracavernous papaverine. Fifty-four men with normal Doppler study response had abnormal responses to papaverine. A normal Doppler study response failed to predict the inability of papaverine to induce an erection in 54 per cent of cases. Twenty-seven patients had abnormal Doppler study responses, and only 2 of these men had a normal response to papaverine. An abnormal Doppler study response was highly predictive of a vascular abnormality.

Erectile Dysfunction↗
PubMed1985

Evidence for peroxisomal hydroxylase activity in rat liver.

This study presents evidence for the first time that rat liver peroxisomes contain a hydroxylase capable of converting 3 alpha, 7 alpha, 12 alpha,- trihydroxy-5 beta-cholestane to a cholestanetetrol. Furthermore, this hydroxylase differs from both the mitochondrial and microsomal enzymes in its response to various co-factors. Highly purified peroxisomal, mitochondrial, and microsomal fractions from cholestryamine-treated rats were incubated with [22(23)-3H]3 alpha,7 alpha,12 alpha,-trihydroxy-5 beta-cholestane under a variety of conditions. The products were acidified, extracted, and subjected to thin-layer chromatography to determine the amount of cholestanetetrol produced. The identification of the 25- and 26-hydroxylated products from the incubations with the microsomes was confirmed by gas chromatography-mass spectrometry. Peroxisomal fractions incubated with a NADPH-generating system, Mg2+, and ATP showed a rate of 40 pmol/min/mg conversion of 3 alpha,7 alpha,12 alpha,-trihydroxy-5 beta-cholestane to a cholestanetetrol. Co-factor studies indicated that both the peroxisomal and mitochondrial hydroxylase activities were dependent on NADPH, Mg2+, and ATP (with different concentration requirements) whereas the microsomal hydroxylase(s) required only NADPH. An abstract of this work has been published (1).

Adenosine Triphosphate↗
PubMed1985

Bile acid synthesis in rat liver peroxisomes: metabolism of 26-hydroxycholesterol to 3 beta-hydroxy-5-cholenoic acid.

Rat liver peroxisomes have been found to oxidize 26-hydroxycholesterol, the product of cholesterol C-26 hydroxylation to 3 beta-hydroxy-5-cholenoic acid. Peroxisomes were purified by differential and equilibrium density centrifugation in a steep linear metrizamide gradient to greater than 95% purity. Purity of peroxisomes was determined by measurement of specific marker enzymes. The activities of cytochrome oxidase (a mitochondrial marker) and acid phosphatase (a lysosomal marker) in the purified peroxisome fractions were below the level of detection. Esterase activity indicated a 2-4% microsomal contamination. Subsequent to incubation of peroxisomes with [16,22-3H]-26-hydroxycholesterol, the reaction products were extracted, methylated, acetylated, and subjected to thin-layer, high pressure liquid, and gas-liquid chromatographic analyses. 3 beta-Hydroxy-5-cholenoic acid was the major identifiable metabolite of 26-hydroxycholesterol. Incubations of pure microsomal fractions (greater than 99%) with 26-hydroxycholesterol under the same conditions demonstrated that the production of 3 beta-hydroxy-5-cholenoic acid by peroxisomes was not attributable to microsomal contamination. This study demonstrates that peroxisomes participate in the side-chain oxidation of intermediates in bile acid synthesis.

Adenosine Triphosphate↗
PubMed1981

Comparative right and left ventricular volumes and pump function in the newborn lamb.

A quantitative cineangiographic method is presented for studying neonatal lamb ventricular volumes and pump function without thoracotomy or surgical instrumentation of the heart. When this method was employed in lambs with a mean age of 24.4 hours it was found that the right and left ventricular end-diastolic volumes, ejection fractions and systolic outputs did not differ significantly at this early postnatal time. Restudy of these lambs at a mean age of 15.6 days showed that right and left ventricular end-diastolic volumes, normalized for body weight, and ejection fractions had not changed significantly. Although systolic outputs decreased, the difference was not significant. Thus there is early postnatal equalization of left and right heart volumes, and deviations from this relation should suggest abnormal hemodynamic function.

Animals↗
PubMed1978

Measurement of atrial septal defect during cardiac catheterization. Experimental and clinical results.

The size of experimental and clinical secundum atrial septal defects may be accurately measured during cardiac catheterization. The position of the defects in the septum and their distance from the aortic and mitral valves may also be ascertained. A balloon catheter inflated with radiopaque dye is used for the measurement. The volume of dye in the balloon has been correlated with its maximal diameter. Thus, a no. 8-10 French catheter filled with 10 ml of diatrizoate (50 percent) has a diameter of approximately 25 mm and a no. 8-22 French catheter filled with 40 ml of diatrizoate a diameter of approximately 43 mm. Persistent arrhythmias or other adverse effects of the procedure were not observed. There was a high correlation between balloon-measured atrial septal defects and those measured at necropsy in the animals or at operation in the patients. These measurements aid in determining whether an ostium secundum defect is of proper size and location to be closed transvenously and may also prove valuable in physiologic studies of atrial septal defects or other cardiac anomalies.

Adolescent↗
PubMedDate not supplied

Production of experimental atrial septal defects.

Atrial septal defects (ASDs) were successfully created by punch biopsy technique in 67 dogs. The technique is simple, effective and provides an ideal model for the study of ASDs, either for testing closure devices or physiological experiments. The position and size of the defects may be varied according to preference. Of 45 animals subjected to cardiac catheterization, 39 (87 percent) has a patent atrial septal defect.

Animals↗
PubMedDate not supplied

Umbrella catheter for nonoperative closure of atrial septal defects.

Since a 1974 report of nonoperative closure of atrial septal defects (ASDs) using an umbrella catheter device, an additional 25 dogs have undergone creation of atrial septal defects, 12 of which have subsequently had successful transvenous closure. An improved model of the closure device has been developed, still using a pair of interlocking umbrella-like components made of stainless steel and Dacron. The umbrellas are smaller, lighter, and have an automatic opening ring. They are loaded simultaneously into a single capsule on the distal end of the outer catheter and are passed into the heart on a single passage, thus eliminating several steps of the original technique. Closure time has diminished from an average of 30 minutes to 5-10 minutes. The completeness of closure was documented in 12 animals by repeat cardiac catheterization which included hydrogen electrode studies. Autopsies on 10 sacrificed dogs revealed no adverse effects or migration of the device; two dogs are living and healthy. In the one clinical application, the patient has done well, remaining afebrile with an increased activity tolerance and resumption of normal activities. The umbrella has remained in position and appears to be functioning well.

Animals↗