Showing papers by "Emory University published in 1993"

A Clinically Based Classification System for Acute Pancreatitis: Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 Through 13, 1992

Abstract: • Acute pancreatitis is a protean disease capable of wide clinical variation, ranging from mild discomfort to apocalyptic prostration. Moreover, the inflammatory process may remain localized in the pancreas, spread to regional tissues, or even involve remote organ systems. This variability in presentation and clinical course has plagued the study and management of acute pancreatitis since its original clinical description. In the absence of accepted definitions for acute pancreatitis and its complications, it has not been possible to devise a clinical classification system useful for case management. Following 3 days of group meetings and open discussions, unanimous consensus on a series of definitions and a clinically based classification system for acute pancreatitis was achieved by a diverse group of 40 international authorities from six medical disciplines and 15 countries. The proposed classification system will be of value to practicing clinicians in the care of individual patients and to academicians seeking to compare interinstitutional data. (Arch Surg.1993;128:586-590)

Hypercholesterolemia increases endothelial superoxide anion production.

Abstract: Indirect evidence suggests accelerated degradation of endothelium-derived nitric oxide (ENDO) by superoxide anion (O2-) in hypercholesterolemic vessels (HV) To directly measure O2- production by normal vessels (NV) and HV, we used an assay for O2- based on the chemiluminescence (CL) of lucigenin (L) HV (1 mo cholesterol-fed rabbits) produced threefold more O2- than NV (147 +/- 020 nM/mg tissue/min, n = 7 vs 052 +/- 005 nmol/mg tissue/min, n = 8, P < 0001) Endothelial removal increased O2- production in NV (073 +/- 008, n = 6, P < 005), while decreasing it in HV (076 +/- 015, n = 5, P < 005) There was no difference between denuded HV and denuded NV Oxypurinol, a noncompetitive inhibitor of xanthine oxidase, normalized O2- production in HV, but had no effect in NV In separate isometric tension studies treatment with oxypurinol improved acetylcholine induced relaxations in HV, while having no effect on responses in normal vessels Oxypurinol did not alter relaxations to nitroprusside Thus, the endothelium is a source of O2- in hypercholesterolemia probably via xanthine oxidase activation Increased endothelial O2- production in HV may inactivate endothelium-derived nitric oxide and provide a source for other oxygen radicals, contributing to the early atherosclerotic process

Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells

Abstract: Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. Regulation of VCAM-1 gene expression may be coupled to oxidative stress through specific reduction-oxidation (redox) sensitive transcriptional or posttranscriptional regulatory factors. In cultured human umbilical vein endothelial (HUVE) cells, the cytokine interleukin 1 beta (IL-1 beta) activated VCAM-1 gene expression through a mechanism that was repressed approximately 90% by the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC). Furthermore, PDTC selectively inhibited the induction of VCAM-1, but not intercellular adhesion molecule-1 (ICAM-1), mRNA and protein accumulation by the cytokine tumor necrosis factor-alpha (TNF alpha) as well as the noncytokines bacterial endotoxin lipopolysaccharide (LPS) and double-stranded RNA, poly(I:C) (PIC). PDTC also markedly attenuated TNF alpha induction of VCAM-1-mediated cellular adhesion. In a distinct pattern, PDTC partially inhibited E-selectin gene expression in response to TNF alpha but not to LPS, IL-1 beta, or PIC. TNF alpha and LPS-mediated transcriptional activation of the human VCAM-1 promoter through NF-kappa B-like DNA enhancer elements and associated NF-kappa B-like DNA binding proteins was inhibited by PDTC. These studies suggest a molecular linkage between an antioxidant sensitive transcriptional regulatory mechanism and VCAM-1 gene expression that expands on the notion of oxidative stress as an important regulatory signal in the pathogenesis of atherosclerosis.

Cardiovascular Health and Disease in Women

Abstract: Each year approximately 2.5 million U.S. women are hospitalized for cardiovascular illness, which also claims the lives of 500,000 women annually; half these deaths are due to coronary heart disease1. Despite the magnitude of this problem and its adverse repercussions on the national public health, we have insufficient information about preventive strategies, diagnostic testing, responses to medical and surgical therapies, and other aspects of cardiovascular illness in women. This lack of information is compounded by the less frequent participation of women in research studies; the difference has been due in part to the exclusion of women of childbearing age . . .

Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain

Abstract: A major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age-related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/micrograms of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10-fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15-fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age-related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age-dependent increases in incidence of neurodegenerative diseases.

FMR1 protein: conserved RNP family domains and selective RNA binding

Abstract: Fragile X syndrome is the result of transcriptional suppression of the gene FMR1 as a result of a trinucleotide repeat expansion mutation. The normal function of the FMR1 protein (FMRP) and the mechanism by which its absence leads to mental retardation are unknown. Ribonucleoprotein particle (RNP) domains were identified within FMRP, and RNA was shown to bind in stoichiometric ratios, which suggests that there are two RNA binding sites per FMRP molecule. FMRP was able to bind to its own message with high affinity (dissociation constant = 5.7 nM) and interacted with approximately 4 percent of human fetal brain messages. The absence of the normal interaction of FMRP with a subset of RNA molecules might result in the pleiotropic phenotype associated with fragile X syndrome.

Asian affinities and continental radiation of the four founding Native American mtDNAs.

Abstract: The mtDNA variation of 321 individuals from 17 Native American populations was examined by high-resolution restriction endonuclease analysis. All mtDNAs were amplified from a variety of sources by using PCR. The mtDNA of a subset of 38 of these individuals was also analyzed by D-loop sequencing. The resulting data were combined with previous mtDNA data from five other Native American tribes, as well as with data from a variety of Asian populations, and were used to deduce the phylogenetic relationships between mtDNAs and to estimate sequence divergences. This analysis revealed the presence of four haplotype groups (haplogroups A, B, C, and D) in the Amerind, but only one haplogroup (A) in the Na-Dene, and confirmed the independent origins of the Amerinds and the Na-Dene. Further, each haplogroup appeared to have been founded by a single mtDNA haplotype, a result which is consistent with a hypothesized founder effect. Most of the variation within haplogroups was tribal specific, that is, it occurred as tribal private polymorphisms. These observations suggest that the process of tribalization began early in the history of the Amerinds, with relatively little intertribal genetic exchange occurring subsequently. The sequencing of 341 nucleotides in the mtDNA D-loop revealed that the D-loop sequence variation correlated strongly with the four haplogroups defined by restriction analysis, and it indicated that the D-loop variation, like the haplotype variation, arose predominantly after the migration of the ancestral Amerinds across the Bering land bridge.

A Comparison of Directional Atherectomy with Coronary Angioplasty in Patients with Coronary Artery Disease

Abstract: Background Directional coronary atherectomy is a new technique of coronary revascularization by which atherosclerotic plaque is excised and retrieved from target lesions. With respect to the rate of restenosis and clinical outcomes, it is not known how this procedure compares with balloon angioplasty, which relies on dilation of the plaque and vessel wall. We compared the rate of restenosis after angioplasty with that after atherectomy. Methods At 35 sites in the United States and Europe, 1012 patients were randomly assigned to either atherectomy (512 patients) or angioplasty (500 patients). The patients underwent coronary angiography at base line and again after six months; the paired angiograms were quantitatively assessed at one laboratory by investigators unaware of the treatment assignments. Results Stenosis was reduced to 50 percent or less more often with atherectomy than with angioplasty (89 percent vs. 80 percent, P<0.001), and there was a greater immediate increase in vessel caliber (1.05 vs. 0....

Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies.

Abstract: Five or more dopamine receptor genes are expressed in brain However, the pharmacological similarities of the encoded D1-D5 receptors have hindered studies of the localization and functions of the subtypes To better understand the roles of the individual receptors, antibodies were raised against recombinant D1 and D2 proteins and were shown to bind to the receptor subtypes specifically in Western blot and immunoprecipitation studies Each antibody reacted selectively with the respective receptor protein expressed both in cells transfected with the cDNAs and in brain By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra Within each region, however, the precise distributions of each subtype were distinct and often complementary D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the olfactory bulb, and in either substantia nigra pars compacta or reticulata Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum Presynaptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release D1 was also present in axon terminals in the substantia nigra These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain

“Keyhole” method for accelerating imaging of contrast agent uptake

Abstract: Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeros for the missing data is followed, blurring results. Substitutinit instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be us~eiklly accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradientanld spin-echo images are shown. The method is believed to be coimpatible with other acceleration methods such as half-Fourier reconstruction and reading of mare than one line of k space per excitation.

Appealing Work: An Investigation of How Ethnographic Texts Convince

Abstract: This paper examines how written research accounts based on ethnography appeal to readers to find them convincing. In particular, it highlights the role of rhetoric in the readers' interaction with and interpretation of the accounts. Extending relevant work in the literatures of organization studies, anthropology and literary criticism, the paper develops three dimensions-authenticity, plausibility and criticality-central to the process of convincing. Further, through the analysis of a sample of ethnographic articles, it discloses the particular writing practices and more general strategies that make claims on readers to engage the texts and to accept that these three dimensions have been achieved. Through authenticity, ethnographic texts appeal to readers to accept that the researcher was indeed present in the field and grasped how the members understood their world. Strategies to achieve authenticity include: particularizing everyday life, delineating the relationship between the researcher and organization members, depicting the disciplined pursuit and analysis of data, and qualifying personal biases. Through plausibility, ethnographic texts make claims on readers to accept that the findings make a distinctive contribution to issues of common concern. Plausibility is accomplished by strategies that normalize unorthodox methodologies, recruit the reader, legitimate atypical situations, smooth contestable assertions, build dramatic anticipation, and differentiate the findings. Finally, through criticality, ethnographic texts endeavor to probe readers to re-examine the taken-for-granted assumptions that underly their work. Strategies to achieve criticality include: carving out room to reflect, provoking the recognition and examination of differences, and enabling readers to imagine new possibilities. The empirical analyses, which highlight both the rhetorical and substantive aspects of convincing, suggest that at a minimum ethnographic texts must achieve both authenticity and plausibility-that is, they must convey the vitality and uniqueness of the field situation and also build their case for the particular contribution of the findings to a disciplinary area of common interest. These analyses also suggest that the most provocative task and promising potential of ethnography is the use of richly-grounded data to not only reflect on the members' world, but more importantly to provoke an examination of the readers' prevailing assumptions and beliefs.

Mistyping ACE heterozygotes.

Abstract: Depar tment of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322 Human angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been proposed to be a significant predictor of risk for myocardial infarction (MI) among individuals otherwise at low risk for heart attack. (1~ The insertion sequence (288 bp) located within intron 16 of the h u m a n dipeptidyl carboxypeptidase 1 (DCP1) gene is a member of the Alu family. (2) Recently, Rigat et al. (3~ developed a rapid PCRbased assay for identifying the ACE genotypes. The procedure involves PCR amplification of genomic DNA utilizing a set of primers flanking the insertion sequence, which allows discrimination among the three ACE genotypes: II, DD, and ID. In genotyping a large pedigree in which one of the parents was an II homozygote, we were disturbed to encounter several DD genotypes among the offspring (Fig. 1, left). This was not a case of mistaken paternity as judged by several other criteria (not presented here). Furthermore, on repeating the PCR amplification under a slightly different condition, all of the DD genotypes amplified as ID (Fig. 1, right). However, on several other occasions, we observed that ID genotypes amplify as DDs. This led us to conclude that amplification of the I allele is sometimes suppressed in an ID heterozygote so that the latter can be mistyped as DD. This p h e n o m e n o n was also observed by Perna et al. (4) during amplification of an Alu I/D polymorphism within the h u m a n TPA gene. Although the mechan ism for this suppression is not currently understood, the mistyping is of u tmost concern because it is the ACE/DD genotype that has been shown to be significantly at a higher risk for MI when compared with the ID or the II genotype. (1) To resolve the mistyping of ID to DD, we examined several experimental parameters and found that inclusion of 5% dimethylsulfoxide (DMSO) in the reaction mixture greatly improved amplification of the I allele in an ID heterozygote (Fig. 2, left). In several trials with DMSO the ID heterozygotes amplified faithfully. However, to safeguard against any ID to DD mistyping we devised an additional PCR amplification protocol. This included utilization of a new sense primer (see legend to Fig. 2) from the 5' end of the insertion sequence, along with the standard antisense primer, (3~ re-

An Analysis of the Market Share-Profitability Relationship:

Abstract: A number of researchers in the marketing, management, and economics disciplines have expressed reservations regarding the validity and generalizability of the reported relationships between market ...

The Lifetime Risk of Developing Breast Cancer

Abstract: Background The lifetime risk of developing breast cancer in U.S. women, often quoted as one in nine, is a commonly cited cancer statistic. However, many estimates have used cancer rates derived from total rather than the cancer-free population and have not properly accounted for multiple cancers in the same individual. Purpose Our purpose was to provide a revised method for calculating estimates of the lifetime risk of developing breast cancer and to aid in interpretation of the estimates. Methods A multiple decrement life table was derived by applying age-specific incidence and mortality rates from cross-sectional data to a hypothetical cohort of women. Incidence, mortality, and population data from 1975-1988 were used, representing the geographic areas of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The incidence rates reflected only the first breast primary cancer; mortality rates reflected causes other than breast cancer. The population denominator used in calculating incidence rates was adjusted to reflect only those women without previously diagnosed breast cancers in the hypothetical cohort. Results Our calculations showed an overall lifetime risk for developing invasive breast cancer of approximately one in eight with use of 1987-1988 SEER data, although up to age 85, it was still the commonly quoted one in nine. Conclusion Our estimate was calculated assuming constant age-specific rates derived from 1987-1988 SEER data. Because incidence and mortality rates change over time, conditional risk estimates over the short term (10 or 20 years) may be more reliable. A large portion of the rise in the lifetime risk of breast cancer estimated using 1975-1977 data (one in 10.6) to an estimate using 1987-1988 data (one in eight) may be attributed to 1) early detection of prevalent cases due to increased use of mammographic screening and 2) lower mortality due to causes other than breast cancer. A common misperception is that the lifetime risk estimate assumes that all women live to a particular age (e.g., 85 or 95). In fact, the calculation assumes that women can die from causes other than breast cancer at any possible age. Cutting off the lifetime risk calculation at age 85 assumes that no women develop breast cancer after that age. While the lifetime risk of developing breast cancer rose over the period 1976-1977 to 1987-1988, the lifetime risk of dying of breast cancer increased from one in 30 to one in 28, reflecting generally flat mortality trends.

Standardization versus Adaptation of International Marketing Strategy: An Empirical Investigation:

Abstract: An issue debated frequently in the international marketing literature centers on whether a business should pursue a strategy that is standardized across national markets or adapted to individual na...

A Population-Based Assessment of Invasive Disease Due to Group B Streptococcus in Nonpregnant Adults

Abstract: Background Group B streptococci (Streptococcus agalactiae) are a major cause of meningitis and septicemia in neonates and pregnant women, but the importance of group B streptococcal disease in nonpregnant adults has not been clearly defined. Methods We conducted a prospective surveillance of the pathogens responsible for meningitis for a period of 24 months in 35 hospitals and a referral laboratory in metropolitan Atlanta. We reviewed the clinical and laboratory records of all the nonpregnant adults identified as having invasive group B streptococcal disease during this period. Results During 1989 and 1990 there were 424 patients with invasive group B streptococcal disease (annual incidence, 9.2 cases per 100,000 population). Of these patients, 46 percent were 1 month of age or younger, 6 percent were older than 1 month but younger than 18 years of age, and 48 percent were 18 or older. Men and nonpregnant women accounted for 68 percent (n = 140) of all cases among adults (annual incidence, 4.4 per 100,000...

Molecular biology of the renin-angiotensin system

Abstract: T he renin-angiotensin system is one of the major regulators of blood pressure and fluid and electrolyte homeostasis. Its primary components are 1) angiotensinogen, a large globular protein that serves as the substrate for 2) renin, the enzyme that catalyzes the proteolytic conversion of angiotensinogen to the decapeptide angiotensin I; 3) angiotensin converting enzyme, a dipeptidyl carboxypeptidase that converts angiotensin I to the octapeptide angiotensin II; 4) angiotensin II itself; and 5) the angiotensin II receptor, responsible for transducing the cellular effects of angiotensin II (Figure 1). Binding of the final product of this enzymatic cascade (angiotensin II) to its receptor mediates vasoconstriction and aldosterone and catecholamine release, as well as drinking, secretion of prolactin and adrenocorticotrophic hormone, and glycogenolysis.' Historically, this hormonal system has been viewed as a systemic one, the various components of which were derived from different organs and were delivered to their site of action by the circulatory system. More recent evidence using molecular and biochemical approaches to angiotensin physiology raises the possibility that there are distinct, local renin-angiotensin systems with different mechanisms of regulation. Local reninangiotensin systems have been proposed in the vasculature,2 brain,3 heart,4 and kidney,5 but incontrovertible evidence for the existence of all components of the system in physiologically relevant amounts and relationships remains elusive. Although the role of these putative local systems is unknown, it is interesting to speculate that they may serve as a mechanism for limiting the actions of angiotensin II to a specific organ system or physiological event. Molecular biological and sophisticated biochemical measurements have opened a new era in our understanding of this important hormonal system. Not only have these techniques brought to the forefront the controversy surrounding the anatomic location of the individual components, but they also have provided insight into the regulation of the expression and formation of each protein or peptide and opened new strategies for therapeutic manipulation. The recent cloning of the AT, receptor6,7 and the development of pharmacological agents that distinguish this receptor from the closely related, but structurally distinct, AT2 binding site provide a fertile and relatively unexplored field for

Developmental Normative Data on The Test of Variables of Attention (T.O.V.A.

Abstract: Developmental normative data for 775 children aged 6-16 are presented for the Test of Variables of Attention (T.O.V.A.), a 23-minute fixed-interval visual Continuous Performance Test with minimal language demands and no left-right discrimination. The target is presented on 22.5% and 77.5% of the trials during the first and second halves, respectively, T.O.V.A. indices include omission and commission errors, response time means and standard deviations, and anticipatory responses. Attention and impulse control developed in a non-linear manner, changing rapidly in early childhood and leveling off during later childhood and adolescence.

Imitative Learning of Actions on Objects by Children, Chimpanzees, and Enculturated Chimpanzees

Abstract: In this study we compared the abilities of chimpanzees and human children to imitatively learn novel actions on objects. Of particular interest were possible differences between chimpanzees raised mostly with conspecifics (mother-reared) and chimpanzees raised in a human-like cultural environment (enculturated). Subjects were thus 3 enculturated and 3 mother-reared chimpanzees, along with 8 18-month-old and 8 30-month-old human children. Each subject was tested over a 2-day period with 16 novel objects. The introduction of each object was preceded by a baseline period in which the subject's natural proclivities toward the object were determined. For 12 objects, a human experimenter demonstrated first a simple and then a complex novel action, instructing the subject in each case to "Do what I do" (chimpanzees were prepared for the task behaviorally as well). For the other 4 objects, demonstration of a single action took place on the first day and the subject's opportunity to imitate was delayed until the second day, 48 hours later. Actions that a subject produced in baseline were excluded from further analysis. For each analyzed action, the subject's behavior was scored as to whether it successfully reproduced (1) the end result of the demonstrated action, and (2) the behavioral means used by the demonstrator. Results showed that in immediate imitation the mother-reared chimpanzees were much poorer imitators than the enculturated chimpanzees and the human children, who did not differ from one another. Surprisingly, on the delay trials, the enculturated chimpanzees significantly outperformed the other 3 groups. We conclude from these results that a human-like sociocultural environment is an essential component in the development of human-like social-cognitive and imitative learning skills for chimpanzees, and perhaps for human beings as well.

Pharmacokinetics of remifentanil (GI87084B) and its major metabolite (GI90291) in patients undergoing elective inpatient surgery.

Abstract: BackgroundRemifentanil is a highly potent opioid with a rapid onset and a short duration of action due to its rapid hydrolysis by esterases in blood and tissues. The major metabolite of remifentanil, GI90291, is much less potent than remifentanil.MethodsThe pharmacokinetics of remifentanil and its m

Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels.

Abstract: BACKGROUNDPatients with hypertension and myocardial hypertrophy may have signs and symptoms of myocardial ischemia in the absence of obstructive coronary disease. Prior investigations have demonstrated impaired coronary flow reserve and have led to speculation that microvascular dysfunction might contribute to ischemia in these patients. Experimental studies have shown that the endothelium, an important regulator of microvascular tone, can be damaged by hypertension and is dysfunctional in cardiomyopathy. We hypothesized that endothelium-dependent vasodilation is impaired in the coronary microvasculature of patients with hypertension and ventricular hypertrophy.METHODS AND RESULTSWe studied coronary microvascular responses in 10 patients with left ventricular hypertrophy secondary to essential hypertension (HTN) (mean arterial pressure at catheterization, 151/94 mm Hg; mean posterior wall thickness, 1.4 +/- 0.1 cm) and nine normal control subjects with no history of hypertension (mean arterial pressure at...

Processes of social learning in the tool use of chimpanzees (Pan troglodytes) and human children (Homo sapiens).

Abstract: Common chimpanzees (Pan troglodytes) and 2-year-old human children (Homo sapiens) were presented with a rakelike tool and a desirable but out-of-reach object. One group of subjects observed a human demonstrator use the tool in one way, and another group observed a demonstrator use the tool in another way. Children in both cases did what the model did. Chimpanzee subjects, however, behaved identically in the 2 model conditions. Both groups performed better than subjects who saw no demonstration. This pattern of results suggest that the chimpanzees were paying attention to the general functional relations in the task and to the results obtained by the demonstrator but not to the actual methods of tool use demonstrated. Human children were focused on the demonstrator's actual methods of tool use (her behavior). The different social learning processes used by the 2 species have implications for their different forms of social organization.