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Biomedical subjects

J C Nelson

Publications and source records attributed to J C Nelson.

At least 19 recordsLinked to original sources

Advanced backcross QTL analysis of a hard winter wheat x synthetic wheat population.

Advanced backcross quantitative trait locus (AB-QTL) analysis was used to identify QTLs for yield and yield components in a backcross population developed from a cross between hard red winter wheat (Triticum aestivum L.) variety Karl 92 and the synthetic wheat line TA 4152-4. Phenotypic data were collected for agronomic traits including heading date, plant height, kernels per spike, kernel weight, tiller number, biomass, harvest index, test weight, grain yield, protein content, and kernel hardness on 190 BC2F(2:4) lines grown in three replications in two Kansas environments. Severity of wheat soil-borne mosaic virus (WSBMV) reaction was evaluated at one location. The population was genotyped using 151 microsatellite markers. Of the ten putative QTLs identified, seven were located on homologous group 2 and group 3 chromosomes. The favorable allele was contributed by cultivated parent Karl 92 at seven QTLs including a major one for WSBMV resistance, and by the synthetic parent at three QTLs: for grain hardness, kernels per spike, and tiller number.

Chromosome Mapping↗

Mapping of a resistance gene effective against Karnal bunt pathogen of wheat.

A set of 130 wheat recombinant inbred lines (RILs) developed from a cross between parents susceptible (WL711) and resistant (HD29) to Karnal bunt (caused by Tilletia indica), were screened for 3 years with the pathogen populations prevalent in northern India. When 90 simple sequence repeats (SSRs) and 81 amplified fragment length polymorphism (AFLP) loci were mapped on the RILs, markers on chromosomes 2A, 4B and 7B accounted collectively for about one-third of the variation in the disease reaction. The genomic region of largest effect, identified on the long arm of chromosome 4B, reduced Karnal bunt disease by half in three different experiments and accounted for up to 25% of the phenotypic variation for KB reaction. A closely linked SSR marker, GWM538, may be useful in marker-assisted selection for Karnal bunt resistance in wheat.

Chromosome Mapping↗

Variable effects of nonsteroidal antiinflammatory agents on thyroid test results.

To investigate the effects of nonsteroidal antiinflammatory drugs (NSAIDs) on thyroid tests, 25 healthy subjects underwent a single-dose study and/or a 1-wk study. In the single-dose study, subjects received a single dose of one of six NSAIDs (aspirin, salsalate, meclofenamate, ibuprofen, naproxen, or indomethacin) at 0800 h. Total and free thyroid hormones and TSH were analyzed 0, 1, 2, 3, 4, and 8 h later. In the 1-wk study, subjects received one of six NSAIDs for 7 d. Thyroid hormones and TSH were analyzed at 0800 h each day. Total T(4) and total T(3) were measured by RIA, free T(4) and free T(3) were measured by equilibrium dialysis, and TSH was measured by immunometric assay. There were no changes in any hormones after a single dose or 1 wk of ibuprofen, naproxen, or indomethacin. Single-dose aspirin or salsalate decreased, whereas meclofenamate increased, various total and free thyroid hormone measurements. One week of aspirin or salsalate decreased total T(4), free T(4) (salsalate only), total T(3), free T(3), and TSH. These data confirm that aspirin, salsalate, and meclofenamate affect total and free thyroid hormone measurements and identify three NSAIDs that did not change thyroid tests. TSH remained within the normal range during acute or 1-wk administration of all of the NSAIDs.

Adult↗

Excitatory inputs to spiny cells in layers 4 and 6 of cat striate cortex.

The principal target of lateral geniculate nucleus in the cat visual cortex is the stellate neurons of layer 4. In previously reported work with intracellular recording and extracellular stimulation in slices of visual cortex, three general classes of fast excitatory synaptic potentials (EPSPs) in layer 4a spiny stellate neurons were identified. One of these classes, characterized by large and relatively invariant amplitudes (mean 1.7 mV, average coefficient of variation (CV) 0.083) were attributed to the action of geniculate axons because, unlike the other two classes, they could not be matched by intracortical inputs, using paired recording. We have examined in detail the properties of this synaptic input in twelve examples, selecting for study those EPSPs where there was secure extracellular stimulation of the single fibre input to a pair of stimuli 50 ms apart. In our analysis, we conclude that the depression that these inputs show to the second stimulus is entirely postsynaptic, since the evidence strongly suggests that the probability of transmitter release at the synaptic site(s) remains 1.0 for both stimuli. We argue that the most plausible explanation for this postsynaptic depression is a reduction in the average probability of opening the synaptic channels. Using a simple biochemical analysis (c.f. Sigworth plot), it is then possible to calculate the number of synaptic channels and their probability of opening, for each of the 12 connections. The EPSPs had a mean amplitude of 1.91 mV (+/- 1.3 mV SD) and a mean CV of 0.067 (+/- 0.022). The calculated number of channels ranged from 20 to 158 (59.4 +/- 48.7) and their probability of opening to the first EPSP had an average of 0.83 (+/- 0.09), with an average depression of the probability to 0.60 for the second EPSP. Geniculate afferents also terminate in layer 6. Intracellular recordings were also made in the upper part of this layer and a total of 51 EPSPs were recorded from pyramidal cells of three principal types. Amongst this dataset we sought EPSPs with similar properties to those characterized in layer 4a. Three examples were found, which is a much lower percentage (6%) than the incidence of putative geniculate EPSPs found in layer 4a (42%).

Action Potentials↗

Usefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (the Cardiovascular Health Study).

T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (> or =45 degrees ) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.

Aged↗

Reduction in levels of triiodothyronine following the first stage of the Norwood reconstruction for hypoplastic left heart syndrome.

OBJECTIVE: Thyroid hormone has important effects on cardiovascular performance. This study was performed to evaluate the changes in levels of triiodothyronine following the first stage of reconstruction for hypoplastic left heart syndrome. METHODS: We enrolled 14 newborns with hypoplastic left heart syndrome scheduled for first stage reconstruction. Blood samples were obtained pre-, intra-, and post-operatively. Levels of free and total triiodothyronine were determined by radioimmunoassay. Statistical comparison was performed using Wilcoxon's signed rank test. RESULTS: The levels of free triiodothyronine decreased from a baseline of 355+/-31 pg/dl to 205+/-21 pg/dl upon the institution of bypass, and declined to a level of 135+/-9 pg/dl at 24 hours postoperatively. Similarly, levels of total triiodothyronine decreased from 101+/-15 ng/dl to 65+/-4 ng/dl upon the institution of bypass, and continued to decline during the first 24 hours postoperatively. Levels of free and total triiodothyronine had returned to baseline by the fifth postoperative day. CONCLUSIONS: The data demonstrate significant decreases in levels of free and total triiodothyronine during the early postoperative period. These changes in levels of thyroid hormone may have adverse effects on cardiac function during this phase of recovery.

Adult↗

Reference ranges for thyroid function tests in premature infants beyond the first week of life.

OBJECTIVES: To establish reference ranges for the more sensitive assays of thyrotropin and the best available assays of free thyroxine in premature infants after the first week of life. STUDY DESIGN: Free thyroxine measurements by direct equilibrium dialysis and thyrotropin measurements by third generation immunometric assay were measured in 120 healthy premature infants 25 to 36 weeks' gestation at birth and every 3 weeks until hospital discharge. Infants were stratified by postconceptional age. Differences in free thyroxine and thyrotropin levels among groups were determined by ANOVA. Correlations between hormone measurements and gestational and postnatal ages were sought by linear regression analysis. Reference ranges were determined as arithmetic (free thyroxine) and geometric (thyrotropin) mean+/-2 SD ranges. RESULTS: From 120 infants, 164 samples were obtained and grouped by postconceptional age at sampling. Free thyroxine was not different among postconceptional age groups and did not correlate with gestational or postnatal age. The free thyroxine reference range based on these data was 10 to 33 pmol/l (0.8 to 2.6 ng/dl). Thyrotropin did not correlate with gestational age. There was a clinically trivial but statistically significant (r(2)=0.03, p<0.05) correlation of thyrotropin with postnatal age. The thyrotropin reference based on these data was 0.8 to 12 mU/l. CONCLUSIONS: Free thyroxine was closely regulated in these premature infants and levels were similar to those in older children and adults, once the natal surge in thyrotropin has subsided. After the first week of life a single range for each hormone appeared appropriate for all premature infants until 40 weeks postconceptional age.

Female↗

Improving performance at the local level: implementing a public health learning workforce intervention.

In an effort to continually improve performance of the essential public health services with community partners, the diverse public health workforce in a major metropolitan area engaged in an organizational learning process. Core public health organizational competencies, identified in a multi-year collaborative applied research initiative, provided the curricula content for the public health learning experience. All members (about 600) of the Columbus and Franklin County (Ohio) Health Departments participated in four one-half day small group, highly interactive modules conducted during a 2-year period. The purpose of this article is to describe the design and implementation of this workforce intervention, the lessons learned, and implications for developing organizational capacity and improved performance.

Competency-Based Education↗

Diagnosing and treating depression in the elderly.

As the population of people over 65 years of age increases, clinicians will see more cases of late-life depression. Currently, the rates of depression in the elderly are higher for nursing home patients and other medical inpatients and outpatients than for the noninstitutionalized, non-medically ill elderly. Depression in the elderly may be difficult to diagnose because of factors such as late onset, comorbid medical illness, dementia, and bereavement, but depression is not a natural part of aging. People who are depressed have increased suffering, impaired functioning, and increased mortality. Fortunately, antidepressants have been shown to effectively treat late-life depression. While monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) are efficacious for treating depression in the elderly, their side effect profiles may be difficult and even dangerous for some older patients. However, serotonin selective reuptake inhibitors (SSRIs) and other second generation antidepressants appear to be both effective and better tolerated in the elderly. Since elderly patients may be more sensitive to drugs, clinicians may need to closely monitor these patients for dosing, side effects, and drug-drug interactions.

Age Factors↗

Pharmacokinetic evaluation of triiodothyronine supplementation in children after modified Fontan procedure.

BACKGROUND: Triiodothyronine (T(3)) supplementation may be a useful adjunct in the management of patients after cardiopulmonary bypass. Limited data are available regarding the use and pharmacokinetics of T(3) in children. The present study was performed to evaluate T(3) pharmacokinetics in a cohort of children undergoing the modified Fontan procedure. METHODS AND RESULTS: A total of 28 patients were enrolled in this randomized, prospective study. The patients were divided into 4 groups: 1 group received a placebo and 3 groups received intravenous T(3) at dosages of 0.4, 0.6, and 0.8 microg/kg, respectively. All 28 patients survived their operative procedures. Two patients developed low cardiac output, and 3 patients had pleural effusions. The median length of hospital stay was 7 days. The mean free T(3) level was 316+/-67 pg/dL after then administration of a placebo. Patients who received T(3) had mean peak free T(3) levels of 972+/-88, 1351+/-299, and 1869+/-281 pg/dL for the dosages of 0.4, 0.6, and 0.8 microg/kg, respectively. The calculated half-life of T(3) was 7 hours. CONCLUSIONS: The half-life of intravenous T(3) in children is approximately one-third of that reported for adults. These results provide a framework for studying the efficacy of T(3) supplementation in children undergoing open-heart surgery.

Cardiac Output↗

Mapping of quantitative trait loci for ethanol preference in quasi-congenic strains.

Ethanol preference, a component of alcoholism, has been known for four decades to differ greatly between C57BL/6 and BALB/c inbred mouse strains. For mapping quantitative trait loci (QTLs) that affect ethanol preference, we used a set of B6.C Recombinant QTL Introgression (RQI) strains, which carry about 5% of the donor BALB/cJ (C) genome on a C57BL/6ByJ (B6) background. After characterizing males of the progenitor and RQI strains for variations in ethanol preference, we scanned their genome for polymorphisms at 244 dinucleotide-repeat marker loci known to differ between B6 and C. Because of the introgression of BALB/c-type QTLs onto the B6 background, some strains showed ethanol preference significantly lower or higher than that of the background strain, suggesting that genetic interaction between ethanol preference QTLs and the background can be operative. The genomic region showing the strongest influence on ethanol preference was on mouse chromosome 15, and corresponds to human chr.12q11-q13.

Alcohol Drinking↗

Stress, depressive symptoms, and smoking cessation among pregnant women.

Perceived stress and depressive symptoms were examined as correlates and predictors of smoking cessation during pregnancy in a sample of 819 pregnant smokers (454 baseline smokers and 365 baseline quitters). Women who quit early in pregnancy had lower levels of stress and depressive symptoms than baseline smokers. Adjusting for level of addiction and other demographic factors related to stress and depressive symptoms eliminated the significant association between depressive symptoms and smoking cessation. Lower levels of stress and depressive symptoms were not predictive of cessation in later pregnancy. Prenatal healthcare providers should continue to assess level of addiction and provide targeted intensive cessation interventions. Interventions that reduce stress and depression may also be of benefit to women who are continuing smokers in early pregnancy.

Adult↗

Maturation of human hypothalamic-pituitary-thyroid function and control.

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Adolescent↗

Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins.

Systemic inaccuracies, proportional to the concentrations of serum proteins and the thyroxine (T4) they carry, have been reported in direct free T4 immunoassays. However, analytical recoveries of free T4 have not been carefully examined in most current methods, and they have not previously been examined across the pathophysiological range of serum T4 binding. In the present study we investigated ranges of serum T4 binding using free and total T4 measurements from 1359 individuals. Carefully characterized, gravimetrically calibrated, serum-based free T4 test solutions were then prepared with a constant normal free T4 concentration (12 ng/L) and varied serum T4 binding (approximately 300:1 to 24,000:1, ng protein bound T4: ng free T4). These standardized test solutions were analyzed using five T4 analog based free T4 methods. Analytical recoveries were calculated as ratios of actual free T4 measurements to the target value, and expressed as a percent of the target. Analytical recoveries were directly proportional to the extent of serum T4 binding and ranged 2% to 155%, 25% to 131%, 53% to 106%, 37% to 93%, and 37% to 73%, lowest to highest, in different methods. These systemic inaccuracies will confound interpretations of free T4 test results in clinical conditions with altered T4 binding. Future investigations into free T4 status must examine the analytical recovery of the free T4 method(s) used, as they relate to the extent of serum T4 binding in the clinical condition(s) studied.

Adolescent↗

Autonomic and neurohumoral control of postprandial blood pressure in healthy aging.

BACKGROUND: Postprandial hypotension (PPH) is a common and morbid problem in elderly people that is associated with an impaired vascular response to meal digestion. Healthy aging in the absence of blood pressure elevation is associated with autonomic and neurohumoral changes that may influence the vascular response to meal ingestion. However, it is not known whether these age-related changes are associated with the development of PPH. METHODS: We measured hemodynamic (blood pressure, heart rate, and forearm vascular resistance), autonomic (power spectral analysis of heart rate and blood pressure variability), and neurohumoral (plasma norepinephrine, renin, aldosterone, and endothelin) responses to a mixed 425 kilocalorie (kcal) meal in 89 rigorously screened healthy subjects aged 20-39, 40-59, and 60-83 years. RESULTS: After the meal, supine mean arterial blood pressure fell significantly only in the middle-aged group by 5.4 +/- 7.9 mm Hg at 30 minutes (p = .02). Forearm vascular resistance fell after the meal in all age groups ( p = .0001). Older groups had higher plasma norepinephrine (p = .02), lower heart rate (p = .03), lower cardiovagal activity (p = .0001), and lower sympathetic vasomotor (p = .000) activity, but there was no difference in the response of these variables to a meal. CONCLUSION: Healthy aging, in the absence of blood pressure elevation, alters the level of autonomic activity without further impairing the ability to maintain blood pressure during meal digestion. Hemodynamic, autonomic, and neurohumoral responses to meal ingestion remain unchanged in very healthy, normotensive elderly adults.

Adult↗

Statistical description of interrater variability in ordinal ratings.

Ordinal categorical assessments are common in medical practice and in research. Variability in such measurements amongst raters making the assessments can be problematic. In this paper we consider how such variability can be described statistically. We review three current approaches, including kappa-type statistics, loglinear models for agreement, and latent class agreement models, and discuss their limitations. We present a new graphical approach to describing interrater variability that involves a simple frequency distribution display of the category probabilities. The method enables description of interrater variability when raters are a random sample from some population as opposed to the traditional setting in which only a few selected raters provide assessments. Advantages of this approach relative to current approaches include the following: (1) it provides a simple visual summary of the rating data, (2) description is closely linked to familiar methods for describing variability in continuous measurements, (3) interpretation is straightforward, and (4) a large sample of raters can be accommodated with ease. We illustrate the method on simulated ordinal data representing radiologists' ratings of mammography images and on rating data from a national image reading study of mammography screening.

Data Interpretation, Statistical↗

The hypothalamic-pituitary-thyroid negative feedback control axis in children with treated congenital hypothyroidism.

Measurements of serum concentrations of free T4, T3, TSH, and thyroglobulin (Tg) were conducted in 42 infants (2-9 months of age) detected and treated through the Northwest Newborn Regional Screening Program and 63 children and adolescents (1-18 yr of age) with congenital hypothyroidism (CH) detected and managed in the Northern California Kaiser Permanente Medical Care Program. Normal feedback control axis data were developed by Quest Diagnostics, Inc. - Nichols Institute Diagnostics and Loma Linda University, from free T4 and TSH measurements in 589 healthy subjects, 2 months to 54 yr of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Twenty-four of the 42 CH infants and 57 of the 63 CH children manifested serum TSH concentrations appropriate for the measured free T4 level. In the remaining 18 infants and 6 children, serum free T4 values were increased 0.2-1.4 ng/dL (2.6-18.0 pmol/L) for the prevailing TSH level, suggesting a state of mild to moderate pituitary-thyroid hormone resistance. In the treated children, the mean T3 concentration was lower (by 32%, 102 vs. 150 ng/dL; 1.57 vs. 2.31 nmol/L) than in normal children, in agreement with earlier data in hypothyroid adults treated with exogenous T4. Serum Tg concentrations were normal or elevated in 90% of the 19 children with ectopic glands and 93% of 27 children with eutopic glands in whom measurements were available. There was a positive correlation between serum TSH and Tg concentrations (P < 0.001), suggesting significant endogenous thyroid hormone production in these children. Our results suggest that the majority of infants and children with CH have a normal hypothalamic-pituitary-thyroid negative feedback control axis during treatment and that the measurement of serum TSH is a useful marker complementing the free T4 measurement in the management of children with CH. A minority have variable pituitary-thyroid hormone resistance, with relatively elevated serum TSH levels for their prevailing serum free T4 concentration. The prevalence of resistance is greater (43%) in young infants (< 1 yr of age) than in older children (10%), indicating that, in most children, the resistance improves with age.

Adolescent↗