Showing papers by "University of North Carolina at Chapel Hill published in 1994"

Nomenclature of systemic vasculitides. Proposal of an international consensus conference

Abstract: The following are some of the conclusions and proposals made at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. 1. Although not a prerequisite component of the definitions, patient age is recognized as a useful discriminator between Takayasu arteritis and giant cell (temporal) arteritis. 2. The name "polyarteritis nodosa," or alternatively, the name "classic polyarteritis nodosa," is restricted to disease in which there is arteritis in medium-sized and small arteries without involvement of smaller vessels. Therefore, patients with vasculitis affecting arterioles, venules, or capillaries, including glomerular capillaries (i.e., with glomerulonephritis), are excluded from this diagnostic category. 3. The name "Wegener's granulomatosis" is restricted to patients with granulomatous inflammation. Patients with exclusively nongranulomatous small vessel vasculitis involving the upper or lower respiratory tract (e.g., alveolar capillaritis) fall into the category of microscopic polyangiitis (microscopic polyarteritis). 4. The term "hypersensitivity vasculitis" is not used. Most patients who would have been given this diagnosis fall into the category of microscopic polyangiitis (microscopic polyarteritis) or cutaneous leukocytoclastic angiitis. 5. The name "microscopic polyangiitis," or alternatively, "microscopic polyarteritis," connotes pauci-immune (i.e., few or no immune deposits) necrotizing vasculitis affecting small vessels, with or without involvement of medium-sized arteries. Cryoglobulinemic vasculitis, Henoch-Schonlein purpura, and other forms of immune complex-mediated small vessel vasculitis must be ruled out to make this diagnosis. 6. The name "cutaneous leukocytoclastic angiitis" is restricted to vasculitis in the skin without involvement of vessels in any other organ. 7. Mucocutaneous lymph node syndrome must be present to make a diagnosis of Kawasaki disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Fools Rush in? The Institutional Context of Industry Creation

Abstract: Now organizations are always vulnerable to the liabilities of newness, but such pressures are especially severe when an industry is in its formative years. We focus on one set of constraints facing entrepreneurs in emerging industries-their relative lack of cognitive and sociopolitical legitimacy. We examine the strategies that founders can pursue, suggesting how their successful pursuit of legitimacy may evolve from innovative ventures to broader contexts, collectively reshaping industry and institutional environments.

Time, human agency, and social change: perspectives on the life course

Abstract: The life course has emerged over the past 30 years as a major research paradigm. Distinctive themes include the relation between human lives and a changing society, the timing of lives, linked or interdependent lives, and human agency. Two lines of research converged in the formation of this paradigm during the 1960s; one was associated with an older «social relationship» tradition that featured intergenerational studies, and the other with more contemporary thinking about age. The emergence of a life course paradigm has been coupled with a notable decline in socialization as a research framework and with its incorporation by other theories

Economic Stress, Coercive Family Process, and Developmental Problems of Adolescents

Abstract: We propose a model of family conflict and coercion that links economic stress in family life to adolescent symptoms of internalizing and externalizing emotions and behaviors. The 180 boys and 198 girls in the study were living in intact families in the rural Midwest, an area characterized by economic decline and uncertainty. Theoretical constructs in the model were measured using both trained observer and family member reports. These adolescents and their parents were interviewed each year for 3 years during the seventh, eighth, and ninth grades. Our theoretical model proposes that economic pressure experienced by parents increases parental dysphoria and marital conflict as well as conflicts between parents and children over money. High levels of spousal irritability, coupled with coercive exchanges over money matters, were expected to be associated with greater hostility in general by parents toward their children. These hostile/coercive exchanges were expected to increase the likelihood of adolescent emotional and behavioral problems. Overall, results were consistent with the proposed model. Moreover, the hypothesized processes applied equally well to the behavior of mothers and fathers, as well as sons and daughters.

Nutritional Regulation of the Insulin-Like Growth Factors*

Abstract: Nutrition is one of the main regulators of circulating IGF-I. In humans, serum IGF-I concentrations are markedly lowered by energy and/or protein deprivation. Both energy and proteins are critical in the regulation of serum IGF-I concentrations. Indeed, after fasting, optimal intake of both energy and protein is necessary for the rapid restoration of circulating IGF-I. We believe, however, that in adult humans energy may be somewhat more important than protein in this regard. While the lowest protein intake is able to increase IGF-I in the presence of adequate energy, there is a threshold energy requirement below which optimal protein intake fails to raise IGF-I after fasting. When energy intake is severely reduced, the carbohydrate content of the diet is a major determinant of responsiveness of IGF-I to GH. The essential amino acid content of the diet is also critical for the optimal restoration of IGF-I after fasting, when protein intake is reduced. The exquisite sensitivity of circulating IGF-I to nutrients, the nycthemeral stability of its concentrations and its relative short half-life constitute the basis for its use as a marker of both nutritional status and adequacy of nutritional rehabilitation. For these indications, IGF-I measurement is more sensitive and more specific than measurement of the other nutrient-related serum proteins (albumin, prealbumin, transferrin, retinol-binding protein). Animal models have been developed to investigate the mechanisms responsible for the nutritional regulation of IGF-I. There is no doubt that many mechanisms are involved (Fig. 12). Decline of serum IGF-I in dietary restriction is independent of the diet-induced alterations in pituitary GH secretion. The role of the liver GH receptors is dependent on the severity of the nutritional insult. In severe dietary restriction (fasting), a marked decrease of the number of somatogenic receptors supports the role of a receptor defect in the decline of circulating IGF-I. In contrast, in less severe forms of dietary restriction (protein restriction), the decline of IGF-I results from a postreceptor defect in the GH action at the hepatic level. Nutritional deprivation decreases hepatic IGF-I production by diminishing IGF-I gene expression. Decline in IGF-I gene expression is mainly caused by nutrient deficiency and less importantly by the nutritionally induced hormonal changes (insulin and T3). Diet restriction also increases the clearance and degradation of serum IGF-I through changes in the levels of circulating IGFBPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Physiological concentrations of purines and pyrimidines.

Abstract: The concentrations of bases, nucleosides, and nucleosides mono-, di- and tri-phosphate are compared for about 600 published values. The data are predominantly from mammalian cells and fluids. For the most important ribonucleotides average concentrations ±SD (μM) are: ATP, 3,152±1,698; GTP, 468±224; UTP, 567±460 and CTP, 278±242. For deoxynucleosidestriphosphate (dNTP), the concentrations in dividing cells are: dATP, 24±22; dGTP, 5.2±4.5; dCTP, 29±19 and dTTP 37±30. By comparison, dUTP is usually about 0.2 μM. For, the 4 dNTPs, tumor cells have concentrations of 6–11 fold over normal cells, and for the 4 NTPs, tumor cells also have concentrations 1.2–5 fold over the normal cells. By comparison, the concentrations of NTPs are significantly lower in various types of blood cells. The average concentration of bases and nucleosides in plasma and other extracellular fluids is generally in the range of 0.4–6 μM; these values are usually lower than corresponding intracellular concentrations. For phosphate compounds, average cellular concentrations are: Pi, 4400; ribose-1-P, 55; ribose-5-P, 70 and P-ribose-PP, 9.0. The metal ion magnesium, important for coordinating phosphates in nucleotides, has values (mM) of: free Mg2+, 1.1; complexed-Mg, 8.0. Consideration of experiments on the intracellular compartmentation of nucleotides shows support for this process between the cytoplasm and mitochondria, but not between the cytoplasm and the nucleus.

Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain

Abstract: Adeno-associated viral (AAV) vectors are non-pathogenic, integrating DNA vectors in which all viral genes are removed and helper virus is completely eliminated. To evaluate this system in the post-mitotic cells of the brain, we found that an AAV vector containing the lacZ gene (AAVlac) resulted in expression of beta-galactosidase up to three months post-injection in vivo. A second vector expressing human tyrosine hydroxylase (AAVth) was injected into the denervated striatum of unilateral 6-hydroxydopamine-lesioned rats. Tyrosine hydroxylase (TH) immunoreactivity was detectable in striatal neurons and glia for up to four months and we also found significant behavioural recovery in lesioned rats treated with AAVth versus AAVlac controls. Safe and stable TH gene transfer into the denervated striatum may have potential for the genetic therapy of Parkinson's disease.

Assessment of risk for periodontal disease. I. Risk indicators for attachment loss.

Abstract: Specific risk indicators associated with either susceptibility or resistance to severe forms of periodontal disease were evaluated in a cross-section of 1,426 subjects, 25 to 74 years of age, mostly metropolitan dwellers, residing in Erie County, New York, and surrounding areas. The study sample exhibited a wide range of periodontal disease experience defined by different levels of attachment loss. Therefore, it was possible to accurately assess associations between the extent of periodontal disease and patient characteristics including age, smoking, systemic diseases, exposure to occupational hazards, and subgingival microbial flora. Age was the factor most strongly associated with attachment loss, with odds ratios for subjects 35 to 44 years old ranging from 1.72 (95% CI: 1.18 to 2.49) to 9.01 (5.86 to 13.89) for subjects 65 to 74 years old. Diabetes mellitus was the only systemic disease positively associated with attachment loss with an odds ratio of 2.32 (95% CI: 1.17–4.60). Smoking had relative risk...

The geography of innovation

Abstract: Preface. 1. Introduction. 2. Why Location Matters for Innovative Activity. 3. Spatial Patterns of Innovation. 4. Technological Infrastructure. 5. Regional Innovative Capacity. 6. Policy Implications. Appendix. Bibliography. Index.

An evaluation of the Kessner adequacy of prenatal care index and a proposed adequacy of prenatal care utilization index

Abstract: OBJECTIVES. The assessment of the adequacy of prenatal care utilization is heavily shaped by the way in which utilization is measured. Although it is widely used, the current major index of utilization, the Kessner/Institute of Medicine Index, has not been subjected to systematic examination. This paper provides such an examination. METHODS. Data from the 1980 National Natality Survey are used to disaggregate the components of the Kessner Index for detailed analysis. An alternative two-part index, the Adequacy of Prenatal Care Utilization Index, is proposed that combines independent assessments of the timing of prenatal care initiation and the frequency of visits received after initiation. RESULTS. The Kessner Index is seriously flawed. It is heavily weighted toward timing of prenatal care initiation does not distinguish timing of initiation from poor subsequent utilization, inaccurately measures utilization for full- or post-term pregnancies, and lacks sufficient documentation for consistent computer pro...

c-erbB-2 Expression and Response to Adjuvant Therapy in Women with Node-Positive Early Breast Cancer

Abstract: Background The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy. Methods Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation. Results Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if thei...

A Randomized Trial Comparing Fluconazole with Amphotericin B for the Treatment of Candidemia in Patients without Neutropenia

Abstract: Background Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. Methods To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count ≥ 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. Results Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. T...

Ryanodine Receptor/Ca2+ Release Channels and Their Regulation by Endogenous Effectors

Abstract: Current evidence suggests that excitable and nonexcitable cells may contain one or both of two intracellular Ca2+ release channels. Release of Ca2+ from intramembrane compartments can be triggered by the binding of the second messenger inositol I ,4,5-trisphosphate (lP3) to the IP3 receptor/Ca2+ release channel (for review, see 6). It also can be mediated by the ryanodine receptor (RyR)/Ca2+ release channel in response to a surface membrane action potential and/or a change in the concentration of a second messenger, by a mechanism referred to in musele as excitation-contraction (E-C) coupling. In striated muscle, rapid release of Ca2+ from the intracellular compart­ ment, sarcoplasmic reticulum (SR), is initiated by a surface membrane action potential that is communicated to the SR at specialized areas where the junctional SR comes in close contact with the surface membrane or tubular infoldings of the surface membrane (T-tubule); at these areas large protein structures are present that span the gap between the two membrane systems. These structures have been termed feet (see C rranzini-Armstrong & A Jorgensen, this volume) and are now commonly known as ryanodine receptor/Ca2+ release channels because of the presence of an intrinsic ci+ channel activity within the feet structures, and their ability to bind the plant

Effects of Early Intervention on Intellectual and Academic Achievement: A Follow‐up Study of Children from Low‐Income Families

Abstract: Follow-up data, obtained 4-7 years after intervention ended, are presented for the Carolina Abecedarian Project, an experimental study of early childhood educational intervention for children from poverty families. Subjects were randomly assigned to 1 of 4 intervention conditions: educational treatment from infancy through 3 years in public school (up to age 8); preschool treatment only (infancy to age 5); primary school treatment only (age 5-8 years), or an untreated control group. Positive effects of preschool treatment on intellectual development and academic achievement were maintained through age 12. School-age treatment alone was less effective. Results generally supported an intensity hypothesis in that scores on cognitive and academic achievement measures increased as duration of treatment increased.

Probability Inequalities for Sums of Bounded Random Variables

Abstract: If S is a random variable with finite rnean and variance, the Bienayme-Chebyshev inequality states that for x > 0, $$\Pr \left[ {\left| {S - ES} \right| \geqslant x{{{(\operatorname{var} S)}}^{{1/2}}}} \right] \leqslant {{x}^{{ - 2}}}$$ (1) If S is the surn of n independent, identically distributed random variables, then, by the central limit theorem*, as n → ∞, the probability on the left approaehes 2Ф( - x), where Ф(x) is the standard normal distribution function. For x large, Ф( - x) behaves as const. x -1 exp( - x2/2).

Potential Role of Human Cytomegalovirus and p53 Interaction in Coronary Restenosis

Abstract: A subset of patients who have undergone coronary angioplasty develop restenosis, a vessel renarrowing characterized by excessive proliferation of smooth muscle cells (SMCs). Of 60 human restenosis lesions examined, 23 (38 percent) were found to have accumulated high amounts of the tumor suppressor protein p53, and this correlated with the presence of human cytomegalovirus (HCMV) in the lesions. SMCs grown from the lesions expressed HCMV protein IE84 and high amounts of p53. HCMV infection of cultured SMCs enhanced p53 accumulation, which correlated temporally with IE84 expression. IE84 also bound to p53 and abolished its ability to transcriptionally activate a reporter gene. Thus, HCMV, and IE84-mediated inhibition of p53 function, may contribute to the development of restenosis.

Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function.

Abstract: The D-type cyclin-dependent kinases CDK4 and CDK6 are complexed with many small cellular proteins (p14, p15, p16, p18, and p20). We have isolated cDNA sequences corresponding to the MTS2 genomic fragment that encodes the CDK4- and CDK6-associated p14 protein. By use of a yeast interaction screen to search for CDK6-interacting proteins, we have also identified an 18-kD human protein, p18, that is a homolog of the cyclin D-CDK4 inhibitors p16 (INK4A/MTS1) and p14 (MTS2/INK4B). Both in vivo and in vitro, p18 interacts strongly with CDK6, weakly with CDK4, and exhibits no detectable interaction with the other known CDKs. Recombinant p18 inhibits the kinase activity of cyclin D-CDK6. Distinct from the p21/p27 family of CDK inhibitors that form ternary complexes with cyclin-CDKs, only binary complexes of p14, p16, and p18 were found in association with CDK4 and/or CDK6. Ectopic expression of p18 or p16 suppresses cell growth with a correlated dependence on endogenous wild-type pRb.

The Health Belief Model and HIV Risk Behavior Change

Abstract: The Health Belief Model (HBM) was initially developed in the 1950s by a group of social psychologists in the U.S. Public Health Service in an effort to explain the widespread failure of people to participate in programs to prevent or to detect disease (Hochbaum, 1958; Rosenstock, 1960, 1966, 1974). Later, the model was extended to apply to people’s responses to symptoms (Kirscht, 1974) and to their behavior in response to diagnosed illness, particularly compliance with medical regimens (Becker, 1974). Over three decades, the model has been one of the most widely used psychosocial approaches to explaining health-related behavior.

Structure and Function of DNA Photolyase

Abstract: Cyclobutane pyrimidine dimers (Pyr Pyr) are the major DNA photoproducts induced by the UV component of solar radiation. Photoreactivating enzyme (DNA photolyase) repairs DNA by utilizing the energy of visible light to break the cyclobutane ring of the dimer. Photolyases are monomeric proteins of 50-60 kDa with stoichiometric amounts of two noncovalent chromophore/cofactors. One of these cofactors is FADH-, and the second chromophore is either methenyltetrahydrofolate (MTHF) or 8-hydroxy-5-deazariboflavin (8-HDF). The enzyme binds the DNA substrate in a light-independent reaction, the second chromophore of the bound enzyme absorbs a visible photon and, by dipole-dipole interaction, transfers energy to FADH- which, in turn, transfers an electron to Pyr Pyr in DNA; the Pyr Pyr- splits and back electron transfer restores the dipyrimidine and the functional form of flavin ready for a new cycle of catalysis.

Choline and Human Nutrition

Abstract: Choline is crucial for sustaining life. It modulates the basic signaling processes within cells, is a structural element in membranes, and is vital during critical periods in brain development. Choline metabolism is closely interrelated with the metabolism of methionine and folate. We believe that the normal human diet provides sufficient choline to sustain healthy organ function. However, vulnerable populations may become choline deficient, including the growing infant, the pregnant or lactating woman, the cirrhotic, and the patient fed intravenously. Further studies of choline requirements in these groups are required.

Improving dietary behavior: the effectiveness of tailored messages in primary care settings.

Abstract: OBJECTIVES. To achieve the Healthy People 2000 objectives, public health professionals must develop effective dietary interventions that address psychosocial and behavioral components of change. This study tested the effect of individually computer-tailored messages designed to decrease fat intake and increase fruit and vegetable intake. METHODS. Adult patients from four North Carolina family practices were surveyed at baseline and then randomly assigned to one of two interventions or to a control group. The first intervention consisted of individually computer-tailored nutrition messages; the second consisted of nontailored nutrition information based on the 1990 Dietary Guidelines for Americans. Patients were resurveyed 4 months postintervention. RESULTS. The tailored intervention produced significant decreases in total fat and saturated fat scores compared with those of the control group (P < .05). Total fat was decreased in the tailored group by 23%, in the nontailored group by 9%, and in the control ...

Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression.

Abstract: Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.

Dispersion Polymerizations in Supercritical Carbon Dioxide

Abstract: Conventional heterogeneous dispersion polymerizations of unsaturated monomers are performed in either aqueous or organic dispersing media with the addition of interfacially active agents to stabilize the colloidal dispersion that forms. Successful stabilization of the polymer colloid during polymerization results in the formation of high molar mass polymers with high rates of polymerization. An environmentally responsible alternative to aqueous and organic dispersing media for heterogeneous dispersion polymerizations is described in which supercritical carbon dioxide (CO2) is used in conjunction with molecularly engineered free radical initiators and amphipathic molecules that are specifically designed to be interfacially active in CO2. Conventional lipophilic monomers, exemplified by methyl methacrylate, can be quantitatively (>90 percent) polymerized heterogeneously to very high degrees of polymerization (>3000) in supercritical CO2 in the presence of an added stabilizer to form kinetically stable dispersions that result in micrometer-sized particles with a narrow size distribution.

A sorting classification of parallel rendering

Abstract: We describe a classification scheme that we believe provides a more structured framework for reasoning about parallel rendering. The scheme is based on where the sort from object coordinates to screen coordinates occurs, which we believe is fundamental whenever both geometry processing and rasterization are performed in parallel. This classification scheme supports the analysis of computational and communication costs, and encompasses the bulk of current and proposed highly parallel renderers - both hardware and software. We begin by reviewing the standard feed-forward rendering pipeline, showing how different ways of parallelizing it lead to three classes of rendering algorithms. Next, we consider each of these classes in detail, analyzing their aggregate processing and communication costs, possible variations, and constraints they may impose on rendering applications. Finally, we use these analyses to compare the classes and identify when each is likely to be preferable. >