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Showing papers by "Emory University published in 1996"


Journal ArticleDOI
12 Jul 1996-Cell
TL;DR: Cells undergoing apoptosis in vivo showed increased release of cy tochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c.

5,128 citations


Journal ArticleDOI
Frank Pajares1
TL;DR: In this article, the authors examined the contribution made by the self-efficacy component of Bandura's (1986) social cognitive theory to the study of self-regulation and motivation in academic settings.
Abstract: The purpose of this article is to examine the contribution made by the self-efficacy component of Bandura’s (1986) social cognitive theory to the study of self-regulation and motivation in academic settings. The difference between self-efficacy beliefs and other expectancy constructs is first explained, followed by a brief overview of problems in self-efficacy research. Findings on the relationship between self-efficacy, motivation constructs, and academic performances are then summarized. These findings demonstrate that particularized measures of self-efficacy that correspond to the criterial tasks with which they are compared surpass global measures in the explanation and prediction of related outcomes. The conceptual difference between the definition and use of expectancy beliefs in social cognitive theory and in expectancy value and self-concept theory is then clarified. Last, strategies to guide future research are offered.

4,166 citations


Journal ArticleDOI
TL;DR: In this paper, the authors compared two combinations, cisplatin and cyclophosphamide and paclitaxel, in women with ovarian cancer, and found that the alkylating agent and a platinum coordination complex have high response rates in advanced ovarian cancer.
Abstract: Background Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. Methods We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin (75 mg per square meter of body-surface area) with either cyclophosphamide (750 mg per square meter) or paclitaxel (135 mg per square meter over a period of 24 hours). Results Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin–paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin–pacli...

2,660 citations


Book
Cathy Caruth1
01 Jan 1996
TL;DR: In Unclaimed Experience as discussed by the authors, Caruth proposes that in the widespread and bewildering experience of trauma in our century, both in its occurrence and in our attempt to understand it, we can recognize the possibility of a history no longer based on simple models of straightforward experience and reference.
Abstract: "If Freud turns to literature to describe traumatic experience, it is because literature, like psychoanalysis, is interested in the complex relation between knowing and not knowing, and it is at this specific point at which knowing and not knowing intersect that the psychoanalytic theory of traumatic experience and the language of literature meet."-from the Introduction In Unclaimed Experience, Cathy Caruth proposes that in the "widespread and bewildering experience of trauma" in our century-both in its occurrence and in our attempt to understand it-we can recognize the possibility of a history no longer based on simple models of straightforward experience and reference. Through the notion of trauma, she contends, we come to a new understanding that permits history to arise where immediate understanding is impossible. In her wide-ranging discussion, Caruth engages Freud's theory of trauma as outlined in Moses and Monotheism and Beyond the Pleasure Principle; the notion of reference and the figure of the falling body in de Man, Kleist, and Kant; the narratives of personal catastrophe in Hiroshima mon amour; and the traumatic address in Lecompte's reinterpretation of Freud's narrative of the dream of the burning child.

2,641 citations


Journal ArticleDOI
TL;DR: Forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle .O2- production via NADH/NADPH oxidase activation.
Abstract: We tested the hypothesis that angiotensin II-induced hypertension is associated with an increase in vascular .O2- production, and characterized the oxidase involved in this process. Infusion of angiotensin II (0.7 mg/kg per d) increased systolic blood pressure and doubled vascular .O2- production (assessed by lucigenin chemiluminescence), predominantly from the vascular media. NE infusion (2.75 mg/kg per d) produced a similar degree of hypertension, but did not increase vascular .O2- production. Studies using various enzyme inhibitors and vascular homogenates suggested that the predominant source of .O2- activated by angiotensin II infusion is an NADH/NADPH-dependent, membrane-bound oxidase. Angiotensin II-, but not NE-, induced hypertension was associated with impaired relaxations to acetylcholine, the calcium ionophore A23187, and nitroglycerin. These relaxations were variably corrected by treatment of vessels with liposome-encapsulated superoxide dismutase. When Losartan was administered concomitantly with angiotensin II, vascular .O2- production and relaxations were normalized, demonstrating a role for the angiotensin type-1 receptor in these processes. We conclude that forms of hypertension associated with elevated circulating levels of angiotensin II may have unique vascular effects not shared by other forms of hypertension because they increase vascular smooth muscle .O2- production via NADH/NADPH oxidase activation.

2,435 citations


Journal ArticleDOI
TL;DR: Neisser as mentioned in this paper (Chair) Gwyneth Boodoo Thomas J. Bouchard, Jr. A. Wade Boykin Nathan Brody Stephen J. Loehlin Robert Perloff Robert J. Sternberg Susana Urbina
Abstract: Ulric Neisser (Chair) Gwyneth Boodoo Thomas J. Bouchard, Jr. A. Wade Boykin Nathan Brody Stephen J. Ceci Diane E Halpern John C. Loehlin Robert Perloff Robert J. Sternberg Susana Urbina Emory University Educational Testing Service, Princeton, New Jersey University of Minnesota, Minneapolis Howard University Wesleyan University Cornell University California State University, San Bernardino University of Texas, Austin University of Pittsburgh Yale University University of North Florida

2,389 citations


Journal ArticleDOI
05 Apr 1996-Science
TL;DR: The current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
Abstract: The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.

1,774 citations


Journal ArticleDOI
TL;DR: In this article, a three-layered integrated molecular orbital and molecular mechanics (ONIOM) approach has been proposed and shown to be successful in reproducing benchmark calculations and experimental results.
Abstract: The new ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) approach has been proposed and shown to be successful in reproducing benchmark calculations and experimental results. ONIOM3, a three-layered version, divides a system into an active part treated at a very high level of ab initio molecular orbital theory like CCSD(T), a semiactive part that includes important electronic contributions and is treated at the HF or MP2 level, and a nonactive part that is handled using force field approaches. The three-layered scheme allows us to study a larger system more accurately than the previously proposed two-layered schemes IMOMO, which can treat a medium size system very accurately, and IMOMM, which can handle a very large system with modest accuracy. This three-layered scheme has been applied to activation barriers for the Diels−Alder reaction of acrolein + isoprene, acrolein + 2-tert-butyl-1,3-butadiene, and ethylene + 1,4-di-tert-butyl-1,3-butadiene. In general, the results for b...

1,768 citations


Journal ArticleDOI
TL;DR: Elevations of blood pressure are a strong independent risk factor for end-stage renal disease; interventions to prevent the disease need to emphasize the prevention and control of both high-normal and high blood pressure.
Abstract: Background End-stage renal disease in the United States creates a large burden for both individuals and society as a whole. Efforts to prevent the condition require an understanding of modifiable risk factors. Methods We assessed the development of end-stage renal disease through 1990 in 332,544 men, 35 to 57 years of age, who were screened between 1973 and 1975 for entry into the Multiple Risk Factor Intervention Trial (MRFIT). We used data from the national registry for treated end-stage renal disease of the Health Care Financing Administration and from records on death from renal disease from the National Death Index and the Social Security Administration. Results During an average of 16 years of follow-up, 814 subjects either died of end-stage renal disease or were treated for that condition (15.6 cases per 100,000 person-years of observation). A strong, graded relation between both systolic and diastolic blood pressure and end-stage renal disease was identified, independent of associations between th...

1,592 citations


Journal ArticleDOI
01 Nov 1996-Neuron
TL;DR: These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.

1,552 citations


Journal ArticleDOI
30 May 1996-Nature
TL;DR: It is reported that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts.
Abstract: THE receptor–ligand pairs CD28–B7 and CD40–gp39 are essential for the initiation and amplification of T-cell-dependent immune responses1,2 CD28–B7 interactions provide 'second signals' necessary for optimal T-cell activation and IL-2 production3–5, whereas CD40–gp39 signals co-stimulate B-cell, macrophage, endothelial cell and T-cell activation6–12 Nonetheless, blockade of either of these pathways alone is not sufficient to permit engraftment of highly immunogenic allografts13–15 Here we report that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts The requirement for simultaneous blockade of these pathways for effective inhibition of alloimmunity indicates that, although they are interrelated, the CD28 and CD40 pathways are critical independent regulators of T-cell-dependent immune responses

Journal ArticleDOI
TL;DR: In this paper, the authors examined the role of personal achievement goals and feelings of school belonging in mediating the relation between perceptions of the school psychological environment and school-related beliefs, affect, and achievement.
Abstract: In a sample of 296 8th-grade middle school students, the authors examined the role of personal achievement goals and feelings of school belonging in mediating the relation between perceptions of the school psychological environment and school-related beliefs, affect, and achievement. Sequential regression analyses indicated that perceiving a task goal structure in middle school was positively related to academic self-efficacy and that this relation was mediated through personal task goals. Perceiving an ability goal structure was related to academic self-consciousness and this relation was mediated through personal relative ability goals. Perceiving positive teacher-student relationships predicted positive school-related affect and this relation was mediated through feelings of school belonging. Feelings of academic efficacy and school belonging in turn were positively related to final-semester academic grades. Results are discussed in relation to current middle school reform efforts. During the early adolescent years, middle schools play an important role in facilitating or inhibiting successful adolescent development (Carnegie Council on Adolescent Development, 1989). Schools potentially can provide early adolescents with opportunities to develop their intellectual capacities, to experience a sense of competence and belonging, and to interact with supportive, nonparental adults. Unfortunately, just when adolescents are particularly in need of these opportunities, the middle-school learning environment often fails to provide them (Carnegie Council on Adolescent Development, 1989; Eccles & Midgley, 1989). For instance, at a time when adolescents are known to be sensitive about how they appear to others, middle schools emphasize relative ability and social comparison in learning situations (Midgley, Anderman, & Hicks, 1995); and at a time when adolescents are particularly in need of supportive relationships with adults outside the home, the quality of relationships with teachers is less than optimal (Midgley, Feldlaufer, & Eccles, 1989). Understanding how particular

Journal ArticleDOI
TL;DR: The primary goals of this set of studies were to develop, and initiate the construct validation of, a self-report measure that assesses the major personality traits of psychopathy in noncriminal populations and clarify the nature of these traits via an exploratory approach to test construction.
Abstract: Research on psychopathology has been hindered by persisting difficulties and controversies regarding its assessment The primary goals of this set of studies were to (a) develop, and initiate the construct validation of, a self-report measure that assesses the major personality traits of psychopathy in noncriminal populations and (b) clarify the nature of these traits via an exploratory approach to test construction This measure, the Psychopathic Personality Inventory (PPI), was developed by writing items to assess a large number of personality domains relevant to psychopathy and performing successive item-level factor analyses and revisions on three undergraduate samples The PPI total score and its eight subscales were found to possess satisfactory internal consistency and test-retest reliability In four studies with undergraduates, the PPI and its subscales exhibited a promising pattern of convergent and discriminant validity with self-report, psychiatric interview, observer rating, and family history data In addition, the PPI total score demonstrated incremental validity relative to several commonly used self-report psychopathy-related measures Future construct validation studies, unresolved conceptual issues regarding the assessment of psychopathy, and potential research uses of the PPI are outlined

Journal ArticleDOI
TL;DR: Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53297 women with breast cancer and 100239 women without breast cancer from 54 epidemiological studies as mentioned in this paper.

Journal ArticleDOI
TL;DR: All proteins in mammalian cells are continually being degraded and replaced; in the cytosol, nucleus, and organelles, individual proteins are degraded at widely differing rates; some cytosolic enzymes have half-lives as short as 10 minutes, whereas others last for days.
Abstract: All proteins in mammalian cells are continually being degraded and replaced. In the cytosol, nucleus, and organelles, individual proteins are degraded at widely differing rates; some cytosolic enzymes have half-lives as short as 10 minutes, whereas others last for days. The average rate of protein turnover also varies among tissues; the majority of proteins in rat hepatocytes are replaced every few days, whereas those in muscle or brain cells are replaced every one to two weeks. The amount of intracellular protein turned over each day is quite large. In a normal 70-kg adult, about 280 g of protein is synthesized . . .

Journal ArticleDOI
TL;DR: The effects of two exercise approaches, Tai Chi and computerized balance training, on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls) are evaluated.
Abstract: OBJECTIVE: To evaluate the effects of two exercise approaches, Tai Chi (TC) and computerized balance training (BT), on specified primary outcomes (biomedical, functional, and psychosocial indicators of frailty) and secondary outcomes (occurrence of falls). DESIGN: The Atlanta FICSIT (Frailty and Injuries: Cooperative Studies of Intervention Techniques), a prospective, randomized, controlled clinical trial with three arms (TC, BT, and education [ED]). Intervention length was 15 weeks, with primary outcomes measured before and after intervention and at 4-month follow-up. Falls were monitored continuously throughout the study. SETTING: Persons aged 70 and older living in the community. PARTICIPANTS: A total of 200 participants, 162 women and 38 men; mean age was 76.2. MEASUREMENTS: Biomedical (strength, flexibility, cardiovascular endurance, body composition), functional (IADL), and psychosocial well-being (CES-D scale, fear of falling questionnaire, self-perception of present and future health, mastery index, perceived quality of sleep, and intrusiveness) variables. RESULTS: Grip strength declined in all groups, and lower extremity range of motion showed limited but statistically significant changes. Lowered blood pressure before and after a 12-minute walk was seen following TC participation. Fear of falling responses and intrusiveness responses were reduced after the TC intervention compared with the ED group (P = .046 and P = .058, respectively). After adjusting for fall risk factors, TC was found to reduce the risk of multiple falls by 47.5%. CONCLUSIONS: A moderate TC intervention can impact favorably on defined biomedical and psychosocial indices of frailty. This intervention can also have favorable effects upon the occurrence of falls. Tai Chi warrants further study as an exercise treatment to improve the health of older people.

Journal ArticleDOI
TL;DR: It is shown that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits and reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.
Abstract: Vulnerable areas of atherosclerotic plaques often contain lipid-laden macrophages and display matrix metalloproteinase activity. We hypothesized that reactive oxygen species released by macrophage-derived foam cells could trigger activation of latent proforms of metalloproteinases in the vascular interstitium. We showed that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits. Effects of these reactive oxygens and that of peroxynitrite, likely to result from simultaneous production of nitric oxide and superoxide, were tested in vitro using metalloproteinases secreted by cultured human vascular smooth muscle cells. Enzymes in culture media or affinity-purified (pro-MMP-2 and MMP-9) were examined by SDS-PAGE zymography, Western blotting, and enzymatic assays. Under the conditions used, incubation with xanthine/xanthine oxidase increased the amount of active gelatinases, while nitric oxide donors had no noticeable effect. Incubation with peroxynitrite resulted in nitration of MMP-2 and endowed it with collagenolytic activity. Hydrogen peroxide treatment showed a catalase-reversible biphasic effect (gelatinase activation at concentrations of 4 microM, inhibition at > or = 10-50 microM). Thus, reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques.

Journal ArticleDOI
TL;DR: Elsbach et al. as discussed by the authors investigated how organizational members respond to events that threaten their perceptions of their organization's identity and found that members made sense of these threats and affirmed positive perceptions of the school's identity by emphasizing and focusing on their school's membership in selective organizational categories that highlighted favorable identity dimensions and interorganizational comparisons.
Abstract: Author(s): Elsbach, KD; Kramer, RM | Abstract: This research investigates how organizational members respond to events that threaten their perceptions of their organization's identity. Using qualitative, interview, and records data, we describe how menebers from eight "top-20" business schools responded to the 1992 Business Week survey rankings of U.S. business schools. Our analysis suggests that the rankings posed a two-pronged threat to many members' perceptions of their schools' identities by (1) calling into question their perceptions of highly valued, core identity attributes of their schools, and (2) challenging their beliefs about their schools' standing relative to other schools. In response, members made sense of these threats and affirmed positive perceptions of their school's identity by emphasizing and focusing on their school's membership in selective organizational categories that highlighted favorable identity dimensions and interorganizational comparisons not recognized by the rankings. Data suggest that members' use of these categorization tactics depended on the level of identity dissonance they felt following the rankings. We integrate these findings with insights from social identity, self-affirmation, and impression management theories to develop a new framework of organizational identity management.

Journal ArticleDOI
01 Jul 1996-Neuron
TL;DR: It is concluded that PS1 is subject to endoproteolytic processing in vivo, and in brains of transgenic mice expressing human PS1, approximately 17 kDa and approximately 27 kDa PS1 derivatives accumulate to saturable levels, and at approximately 1:1 stoichiometry, independent of transgene-derived mRNA.

Journal ArticleDOI
TL;DR: The minimum clinically significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm, and studies of pain experience that report less than a 13-mm change in pain severity, although statistically significant, may have no clinical importance.

Journal ArticleDOI
TL;DR: Early-onset sepsis remains an important but uncommon problem among VLBW preterm infants and improved diagnostic strategies are needed to enable the clinician to distinguish between the infected and the uninfected V LBW neonate with symptoms and to target continued antibiotic therapy to those who are truly infected.

Journal ArticleDOI
TL;DR: It is shown that Felsenstein's method is not biased, but that it can be corrected to better agree with standard ideas of confidence levels and hypothesis testing, and can be made by using the more elaborate bootstrap method presented here, at the expense of considerably more computation.
Abstract: Evolutionary trees are often estimated from DNA or RNA sequence data. How much confidence should we have in the estimated trees? In 1985, Felsenstein [Felsenstein, J. (1985) Evolution 39, 783-791] suggested the use of the bootstrap to answer this question. Felsenstein's method, which in concept is a straightforward application of the bootstrap, is widely used, but has been criticized as biased in the genetics literature. This paper concerns the use of the bootstrap in the tree problem. We show that Felsenstein's method is not biased, but that it can be corrected to better agree with standard ideas of confidence levels and hypothesis testing. These corrections can be made by using the more elaborate bootstrap method presented here, at the expense of considerably more computation.

Journal ArticleDOI
TL;DR: The first evidence that p22phox is a critical component of superoxide-generating vascular NADH/NADPH oxidase is provided, suggesting a central role for this oxidase system in vascular hypertrophy is suggested.

Book
Bradd Shore1
28 Mar 1996
TL;DR: Drawing on recent developments in cognitive science as well as anthropology, Culture in Mind explores the cognitive world of culture in the ongoing production of meaning in everyday thinking and feeling.
Abstract: Culture in Mind is an ethnographic portrait of the human mind Using case studies from both western and nonwestern societies Shore argues that "cultural models" are necessary to the functioning of the human mind Drawing on recent developments in cognitive science as well as anthropology, Culture in Mind explores the cognitive world of culture in the ongoing production of meaning in everyday thinking and feeling

Journal ArticleDOI
Shehzad L. Mian1
TL;DR: In this paper, empirical evidence on the determinants of corporate hedging decisions is examined in light of currently mandated financial reporting requirements and, in particular, the constraints placed on anticipatory hedging.
Abstract: This paper provides empirical evidence on the determinants of corporate hedging decisions. The paper examines the evidence in light of currently mandated financial reporting requirements and, in particular, the constraints placed on anticipatory hedging. Data on hedging are obtained from 1992 annual reports for a sample of 3,022 firms. Out of the 771 firms classified as hedgers, 543 firms disclose information in their annual reports on their hedging activities; the remaining 228 firms report use of derivatives but no information on hedging activities. Based on the evidence, I draw the following conclusions with respect to the models of hedging: evidence is inconsistent with financial distress cost models; evidence is mixed with respect to contracting cost, capital market imperfections, and tax-based models; and evidence uniformly supports the hypothesis that hedging activities exhibit economies of scale.

Book ChapterDOI
TL;DR: The approach to OX-PHOS investigation combines the identification of patients with OX -PHOS defects using more sensitive muscle biopsy studies followed by further biochemical characterization of primary defects in Epstein–Barr virus-transformed lymphoblasts.
Abstract: Publisher Summary This chapter discusses the methods of assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines. Investigation of oxidative phosphorylation (OX-PHOS) in mitochondrial diseases has traditionally focused on the muscle biopsy. Skeletal muscle biopsy remains a valuable resource for biochemical studies as it is an easily accessed tissue and milligram quantities of mitochondria can be isolated for a wide range of OX-PHOS investigations. However, in mitochondrial diseases, the postmitotic muscle fibers commonly show secondary OX-PHOS defects that may hinder investigations of primary defects. Transformed cell lines expressing OX-PHOS defects provide a powerful model system for further genetic and biochemical characterization of nuclear and mitochondrial DNA (mtDNA) mutants and the design and testing of therapeutic approaches. The approach to OX-PHOS investigation combines the identification of patients with OX-PHOS defects using more sensitive muscle biopsy studies followed by further biochemical characterization of primary defects in Epstein–Barr virus-transformed lymphoblasts. The chapter presents novel methods for the production of transmitochondrial cybrids using lymphoblastoid and osteosarcoma ρO cells as recipients. Suspension enucleation of cells combined with electrofusion allows the use of any cell type, including lymphoblasts, as mitochondrial donors in fusions with either lymphoblastoid or osteosarcoma ρo cells.

Journal ArticleDOI
TL;DR: Because of new data, anatomical and functional models of the basal ganglia in normal and pathological conditions (e.g. Parkinson's and Huntington's diseases) have recently come under greater scrutiny and an update of these models is clearly timely.

Journal ArticleDOI
TL;DR: The found reduced levels of three dopamine nerve terminal markers in post–mortem striatum of chronic methamphetamine users suggest that chronic exposure to methamphetamine does not cause permanent degeneration of striatal dopamine nerve terminals at the doses used by the young subjects in this study.
Abstract: Methamphetamine is a drug that is significantly abused worldwide, Although long-lasting depletion of dopamine and other dopamine nerve terminal markers has been reported in striatum of nonhuman primates receiving very high doses of the psychostimulant, no information is available for humans. We found reduced levels of three dopamine nerve terminal markers (dopamine, tyrosine hydroxylase and the dopamine transporter) in post-mortem striatum (nucleus accumbens, caudate, putamen) of chronic methamphetamine users. However, levels of DOPA decarboxylase and the vesicular monoamine transporter, known to be reduced in Parkinson's disease, were normal. This suggests that chronic exposure to methamphetamine does not cause permanent degeneration of striatal dopamine nerve terminals at the doses used by the young subjects in our study. However, the dopamine reduction might explain some of the dysphoric effects of the drug, whereas the decreased dopamine transporter could provide the basis for dose escalation occurring in some methamphetamine users.


Journal ArticleDOI
TL;DR: Oxytocin plays an essential role only in milk ejection in the mouse, and females lacking oxytocin have no obvious deficits in fertility or reproduction, including gestation and parturition.
Abstract: Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential for mammalian reproduction. In addition to uterine contractions during labor and milk ejection during nursing, oxytocin has been implicated in anterior pituitary function, paracrine effects in the testis and ovary and the neural control of maternal and sexual behaviors. To determine the essential role(s) of oxytocin in mammalian reproductive function, mice deficient in oxytocin have been generated using embryonic stem cell technology. A deletion of exon 1 encoding the oxytocin peptide was generated in embryonic stem cells at a high frequency and was successfully transmitted in the germ line. Southern blot analysis of genomic DNA from homozygote offspring and in situ hybridization with an exonic probe 3' of the deletion failed to detect any oxytocin or neurophysin sequences, respectively, confirming that the mutation was a null mutation. Mice lacking oxytocin are both viable and fertile. Males do not have any reproductive behavioral or functional defects in the absence of oxytocin. Similarly, females lacking oxytocin have no obvious deficits in fertility or reproduction, including gestation and parturition. However, although oxytocin-deficient females demonstrate normal maternal behavior, all offspring die shortly after birth because of the dam's inability to nurse. Postpartum injections of oxytocin to the oxytocin deficient mothers restore milk ejection and rescue the offspring. Thus, despite the multiple reproductive activities that have been attributed to oxytocin, oxytocin plays an essential role only in milk ejection in the mouse.