Showing papers by "University of Utah published in 1993"

The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder.

Abstract: Objective In an attempt to surmount the problem of retrospectively establishing the childhood diagnosis of attention deficit hyperactivity disorder, the authors constructed the 61-item Wender Utah Rating Scale (WURS) for adults to use to describe their own childhood behavior. In this paper they present their initial data collection and evaluation of the instrument's validity. Method The scale was administered to 81 adult outpatients with attention deficit hyperactivity disorder, 100 "normal" adults, and 70 psychiatric adult outpatients with unipolar depression. The authors analyzed data from the 25 items of the scale that showed the greatest difference between the patients with attention deficit hyperactivity disorder and the normal comparison subjects and the relationship between the WURS and the patients' parents' judgment of childhood activity as measured by the Parents' Rating Scale. Results The patients with attention deficit hyperactivity disorder had significantly higher mean scores on all 25 items than did the two comparison groups. The difference between the mean total scores of the patients with attention deficit hyperactivity disorder and the normal subjects was also highly significant. A cutoff score of 46 or higher correctly identified 86% of the patients with attention deficit hyperactivity disorder, 99% of the normal subjects, and 81% of the depressed subjects. Correlations obtained between WURS scores and Parents' Rating Scale scores were moderate but impressive. The ability of WURS scores to predict response to methylphenidate replicated the authors' finding regarding the ability of Parents' Rating Scale scores to predict response to pemoline. Conclusions The WURS is sensitive in identifying childhood attention deficit hyperactivity disorder and may be useful in recognizing attention deficit hyperactivity disorder in patients with ambiguous adult psychopathology.

The Role of the Scale Parameter in the Estimation and Comparison of Multinomial Logit Models

Abstract: Multinomial logit (MNL) models are widely used in marketing research to analyze choice data, but it is not generally recognized that the unit of the utility scale in a MNL model is inversely relate...

Field-flow fractionation: analysis of macromolecular, colloidal, and particulate materials

Abstract: Field-flow fractionation (FFF) is a family of flexible elution techniques capable of simultaneous separation and measurement. Its sample domain extends across a broad macromolecular-colloidal-particulate continuum from about 1 nanometer to more than 100 micrometers and incorporates both simple and complex macromaterials of biological, biomedical, industrial, and environmental relevance. Complex materials are separated into components to simplify measurement. Component properties measurable by FFF include mass, size, density, charge, diffusivity, and thickness of adsorbed layers. When characterization by these properties is inadequate, other measurement tools can be readily coupled to FFF, either off-line or on-line, by virtue of its flow-elution operation. This article describes the principles and major subtechniques of the FFF family along with application of its measurement and separative capabilities.

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome

Abstract: Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

Parameterization of the Radiative Properties of Cirrus Clouds

Abstract: A new approach for parameterization of the broadband solar and infrared radiative properties of ice clouds has been developed. This parameterization scheme integrates in a coherent manner the δ-four-stream approximation for radiative transfer, the correlated k-distribution method for nongray gaseous absorption, and the scattering and absorption properties of hexagonal ice crystals. A mean effective size is used, representing an area-weighted mean crystal width, to account for the ice crystal size distribution with respect to radiative calculation. Based on physical principles, the basic single-scattering properties of ice crystals, including the extinction coefficient divided by ice water content single-scattering albedo, and expansion coefficients of the phase function, can be parameterized using third-degree polynomials in terms of the mean effective size. In the development of this parameterization the results computed from a light scattering program that includes a Geometric ray-tracing progr...

Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program

Abstract: Background and Methods Allogeneic bone marrow transplantation is curative in a substantial number of patients with hematologic cancers, marrow-failure disorders, immunodeficiency syndromes, and certain metabolic diseases. Unfortunately, only 25 to 30 percent of potential recipients have HLA-identical siblings who can act as donors. In 1986 the National Marrow Donor Program was created in the United States to facilitate the finding and procurement of suitable marrow from unrelated donors for patients lacking related donors. Results During the first four years of the program, 462 patients with acquired and congenital lymphohematopoietic disorders or metabolic diseases received marrow transplants from unrelated donors. The probability of engraftment by 100 days after transplantation was 94 percent, although 8 percent of patients later had secondary graft failure. The probability of grade II, III, or IV acute graft-versus-host disease was 64 percent, and the probability of chronic graft-versus-host disease at...

Seismicity Remotely Triggered by the Magnitude 7.3 Landers, California, Earthquake

Abstract: The magnitude 7.3 Landers earthquake of 28 June 1992 triggered a remarkably sudden and widespread increase in earthquake activity across much of the western United States. The triggered earthquakes, which occurred at distances up to 1250 kilometers (17 source dimensions) from the Landers mainshock, were confined to areas of persistent seismicity and strike-slip to normal faulting. Many of the triggered areas also are sites of geothermal and recent volcanic activity. Static stress changes calculated for elastic models of the earthquake appear to be too small to have caused the triggering. The most promising explanations involve nonlinear interactions between large dynamic strains accompanying seismic waves from the mainshock and crustal fluids (perhaps including crustal magma).

Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy

Abstract: Diabetes is now the most common cause of progressive kidney failure leading to dialysis or transplantation. The central pathological feature of diabetic nephropathy is accumulation of extracellular matrix within the glomeruli. The factors in the diabetic milieu responsible for extracellular matrix accumulation are not understood. Here we report that in glomeruli of rats made diabetic there is a slow, progressive increase in the expression of transforming growth factor beta (TGF-beta) mRNA and TGF-beta protein. A key action of TGF-beta is induction of extracellular matrix production, and specific matrix proteins known to be induced by TGF-beta were increased in diabetic rat glomeruli. These proteins include an alternatively spliced form of fibronectin, tenascin, and the proteoglycan biglycan. TGF-beta has not previously been implicated in the matrix accumulation that occurs in the diabetic kidney. Glomeruli from humans with diabetic nephropathy also showed a striking increase in immunoreactive TGF-beta protein and deposition of the special form of fibronectin, whereas glomeruli from normal subjects or from individuals with other glomerular diseases (where extracellular matrix accumulation is not a feature) were negative or barely positive. These results implicate TGF-beta in the pathogenesis of diabetic nephropathy.

Evolutionary and Ecological Aspects of Photosynthetic Pathway Variation

Abstract: C4 and CAM photosynthesis are evolutionarily derived from C3 photosynthesis. The morphological and biochemical modifications necessary to achieve either C4 or CAM photosynthesis are thought to have independently arisen numerous times within different higher plant taxa. It is thought that C4 photosynthesis evolved in response to the low atmospheric CO2 concentrations that arose sometime after the end of the Cretaceous. Low CO2 concentrations result in significant increases in photorespiration of C3 plants, reducing productivity; both C3-C4 intermediate and C4 plants exhibit reduced photorespiration rates. In contrast, it may be argued that CAM arose either in response to selection of increased water-use efficiency or for increased carbon gain. Globally, all three pathways are widely distributed today, with a tendency toward ecological adaptation of C4 plants into warm, monsoonal climates and CAM plants into water-limited habitats. In an anthropogenically altered CQ2 environment, C4 plants may lose their competitive advantage over C3 plants. 411

Expansion of C4 ecosystems as an indicator of global ecological change in the late Miocene

Abstract: THE most common and the most primitive pathway of the three different photosynthetic pathways used by plants is the C3 pathway, or Calvin cycle, which is characterized by an initial CO2 carboxylation to form phosphoglyceric acid, a 3-carbon acid. The carbon isotope composition (δ13C) of C3 plants varies from about −23 to −35%l–3 and averages about −26%. Virtually all trees, most shrubs, herbs and forbs, and cool-season grasses and sedges use the C3 pathway. In the C4 pathway (Hatch–Slack cycle), CO2 initially combines with phosphoenol pyruvate to form the 4-carbon acids malate or aspartic acid, which are translocated to bundle sheath cells where CO2 is released and used in Calvin cycle reactions1–4. The carbon isotope composition of C4 plants ranges from about −10 to −14%, averaging about −13% for modern plants1–3. Warm-season grasses and sedges are the most abundant C4 plants, although C4 photosynthesis is found in about twenty families5. The third photosynthetic pathway, CAM, combines features of both C3 and C4 pathways. CAM plants, which include many succulents, have intermediate carbon isotope compositions and are also adapted to conditions of water and CO2 stress. The modern global ecosystem has a significant component of C4 plants, primarily in tropical savannas, temperate grasslands and semi-desert scrublands. Studies of palaeovegetation from palaeosols and palaeodiet from fossil tooth enamel indicate a rapid expansion of C4 biomass in both the Old World and the New World starting 7 to 5 million years ago. We propose that the global expansion of C4 biomass may be related to lower atmospheric carbon dioxide levels because C4 photosynthesis is favoured over C3 photosynthesis when there are low concentrations of carbon dioxide in the atmosphere.

Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative.

Abstract: Normal aging in humans has been recently shown to be accompanied by reduced control over production of the multifunctional cytokine IL-6. This cytokine was reported to be quantitatively elevated in most serum samples obtained from "normal" elderly humans. In the present investigation, we report that IL-6 levels are elevated in serum samples obtained from aged mice, and its spontaneous production could also be easily detected in culture supernatants of unstimulated lymphoid cells obtained from aged, but not mature, adult donors. Spontaneous production of IL-6 was consistently observed in culture supernatants of lymphoid cells from both the spleen and mesenteric lymph nodes from aged donors, but was absent from supernatants derived from their peripheral lymph nodes. In aged mice, the reduced regulation of IL-6 production could be effectively prevented and/or reversed by supplementing aging animals with dehydroepiandrosterone sulfate, a steroid hormone whose endogenous production is known to decline with advancing age in all species tested. It was also established that serum obtained from old dehydroepiandrosterone sulfate-treated mice contained lower (normal) levels of serum amyloid P substance (an acute phase reactant), reduced levels of serum Ig (all classes and isotypes) and lower titers of tissue-specific autoantibodies than untreated aged controls. Therefore, a number of well described, age-related conditions, some of which could be contributing to the pathologic phenotype of old age, may actually represent secondary effects to this age-associated change in IL-6 production.

The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers.

Abstract: Background: Remifentanil (G187084B) is a new short-acting opioid with a unique ester structure. Metabolism of remifentanil by ester hydrolysis results in very rapid elimination. The aim of this study was to characterize in detail the pharmacokinetic profile of remifentanil in healthy male volunteers. Methods: Ten healthy adult male volunteers received a zero-order infusion of remifentanil at doses ranging from 1 to 8 μg-kg -1 -min -1 for 20 min. Frequent arterial blood samples were drawn and analyzed by gas chromatographic mass spectroscopy to determine the remifentanil blood concentrations. The raw pharmacokinetic data were analyzed using three different parametric compartmental modeling methods (traditional two-stage, naive pooled data, and NONMEM)

Auctions of Divisible Goods: On the Rationale for the Treasury Experiment

Abstract: We compare a sealed-bid uniform-price auction (the Treasury's experimentalformat) with a sealedbid discriminatory auction (tbe Treasury'sformat beretofore), assuming the good is perfectly divisible. We show that the auction theory thatprompted the experiment, which assumes single-unit demands, does not adequately describe the bidding game for Treasury securities. Collusive strategies are self-enforcing in uniform-price divisible-good auctions. In these equilibria, the sellers expected revenue is lower than in equilibria of discriminatory auctions.

Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics

Abstract: Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women Treatment with multiple medications and diet can normalize cholesterol levels in many persons with FH and prevent or delay the development of coronary atherosclerosis Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH Previously published blood cholesterol criteria greatly underdiagnosed new cases of FH among members of known families with FH in Utah and overdiagnosed FH among participants of general population screening, revealing the need for different cholesterol screening criteria in persons from these 2 different settings The statistical concept of a priori probabilities was applied to derive 2 sets of practical screening criteria: one for persons participating in general population screening studies and another for close relatives of confirmed FH cases, showing dramatic differences At a cholesterol level of 310 mg/dl, only 4% of persons in the general population would have FH but 95% of persons who were first-degree relatives of known cases would have FH Detailed tables were derived to provide practical total and low-density lipoprotein blood cholesterol screening criteria for diagnosing FH in different screening settings and specific age groups In population screening the new FH criteria require a total cholesterol > 360 mg/dl for age 40+ (or 270 mg/dl in youth) Among first-degree relatives of confirmed cases in families with FH, the new total cholesterol criteria are much lower (> 290 mg/dl for age 40+, > 220 mg/dl for youth)(ABSTRACT TRUNCATED AT 250 WORDS)

A molecular variant of angiotensinogen associated with preeclampsia

Abstract: Pregnancy–induced hypertension (PIH) is a heterogeneous disorder which complicates 5–7% of all pregnancies and remains a leading cause of maternal, fetal and neonatal morbidity and mortality. Severe preeclampsia is the most distinctive and life–threatening form; a multi–system disorder more common in first pregnancies, it is characterized by high blood pressure and proteinuria. In a series of Caucasian women with pregnancy–induced hypertension, we have observed a significant association of preeclampsia with a molecular variant of angiotensinogen, T235, found previously to be associated with essential hypertension. This finding is corroborated in a sample ascertained in Japan. Together, these observations support a new pathophysiological interpretation of preeclampsia and of its relation to some forms of essential hypertension.

Positive-negative selection methods and vectors

Abstract: Positive-negative selector (PNS) vectors are provided for modifying a target DNA sequence contained in the genome of a target cell capable of homologous recombination. The vector comprises a first DNA sequence which contains at least one sequence portion which is substantially homologous to a portion of a first region of a target DNA sequence. The vector also includes a second DNA sequence containing at least one sequence portion which is substantially homologous to another portion of a second region of a target DNA sequence. A third DNA sequence is positioned between the first and second DNA sequences and encodes a positive selection marker which when expressed is functional in the target cell in which the vector is used. A fourth DNA sequence encoding a negative selection marker, also functional in the target cell, is positioned 5' to the first or 3' to the second DNA sequence and is substantially incapable of homologous recombination with the target DNA sequence. The invention also includes transformed cells containing at least one predetermined modification of a target DNA sequence contained in the genome of the cell. In addition, the invention includes organisms such as non-human transgenic animals and plants which contain cells having predetermined modifications of a target DNA sequence in the genome of the organism.

Lithium perturbation and goosecoid expression identify a dorsal specification pathway in the pregastrula zebrafish

Abstract: The zebrafish dorsoventral axis can first be distinguished at gastrulation, upon formation of the embryonic shield, the site of the organizer. We have asked whether the shield is specified before gastrulation. First, we show that brief exposure of premidblastula embryos to lithium, which is known to shut down the phospho-inositol signaling pathway, produces excessive shield formation and extreme hyper-dorsal development. Second, we show that the zebrafish goosecoid homeobox gene is activated at or just after the midblastula in a localized domain of cells that subsequently populate the most anterior region of the incipient shield and axial hypoblast, goosecoid expression is elevated and radialized by early lithium treatment, suggesting that goosecoid plays a role in establishing the organizer and shield. Our results demonstrate that the zebrafish dorsal axis is signaled by a pathway initiated in the cleavage-stage embryo. Furthermore, they provide novel insights into anterior morphogenesis.

Non-Hodgkin's Lymphomas

Abstract: Part 1 Lymphomagenesis: Lymphocyte differentiation Adult T-cell leukaemia/Lymphoma - a model of retrovirus-induced lymphomagenesis Burkitt's lymphoma and Epstein-Barr virus-associated lymphoid malignancies - models for lymphomagenesis T(14 18) translocation. Part 2 Methods: Histological and immunohistochemical methods Genotype. Part 3 Nodal Non-Hodgkin's Lymphomas: The normal lymph node - structure and function Histological classification Staging of NHLs Analytical study of the different subtypes of NHLs - clinical, histological and immunohistochemical aspects NHLs in childhood NHLs associated with HIV infection. Part 4 Extra-Nodal Non-Hodgkin's lymphomas: Malignant lymphomas of mucosa-associated lymphoid tissues Primary gastrointestinal NHLs Pathology of gastro-intestinal NHLs Cutaneous lymphomas NHLs of the Mediastinum NHLs of the lung Bone marrow involvement Blood involvement in chronic (mature) B & T lymphoproliferative syndromes Liver involvement Spleen involvement Extra-cranial head-and-neck NHLs Central nervous system involvement NHLs of bone Urogenital localizations. Part 5 Treatment of Non-Hodgkin's Lymphomas: Methodology and problems in the comparison of results Treatment of lowgrade NHLs The role of radiation therapy Treatment of aggressive lymphomas (intermediate and highgrade) Intensive chemoradiotherapy and bone-marrow transplantation Salvage therapy after failure Treatment of NHLs in childhood.

Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear

Abstract: We derived mice that carry a targeted insertion of a neor gene in the int-2 (Fgf-3) proto-oncogene coding sequences. The mutation was found to be recessive and mice that were homozygous for the insertion did not often survive to adulthood. The mutant mice had defects in the development of the tail and inner ear that could be correlated with disruption of int-2 expression in the posterior primitive streak and hindbrain or otic vesicle. While the tail phenotype was 100% penetrant, we found that the inner ear phenotype had reduced penetrance and variable expressivity. The variable expressivity could not be attributed to variability in the genetic background of the mutant allele or to leaky expression from the mutant allele. Thus, we conclude that even in a uniform genetic background, stochastic variation in the expression of a developmental circuit can result in dramatic differences in phenotypic consequences.

A Comparison of Seven Antiarrhythmic Drugs in Patients with Ventricular Tachyarrhythmias

Abstract: Background The relative efficacies of various antiarrhythmic drugs in the treatment of ventricular tachyarrhythmias are not well known. This study examined the effectiveness of imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial. Methods Patients were randomly assigned to undergo serial testing of the efficacy of the seven antiarrhythmic drugs by one of two strategies: electrophysiologic study or Holter monitoring together with exercise testing. The seven drugs were then tested for efficacy in random order in patients who were eligible to receive them. The frequencies of predictions of drug efficacy and of adverse drug effects during the initial drug titration were tabulated for all 486 randomized subjects. Patients received long-term treatment with the first antiarrhythmic drug that was predicted to be effective on the basis of drug t...