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Showing papers by "University of Colorado Denver published in 1992"


Journal ArticleDOI
TL;DR: This meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.
Abstract: This two-part meta-analysis combined data from eight prospective randomized trials designed to compare the nutritional efficacy of early enteral (TEN) and parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address whether route of substrate delivery affected septic complication incidence. Phase I (dropouts excluded) meta-analysis confirmed data homogeneity across study sites, that TEN and TPN groups were comparable, and that significantly fewer TEN patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that fewer TEN patients developed septic complications. Further breakdown by patient type showed that all trauma and blunt trauma subgroups had the most significant reduction in septic complications when fed enterally. In conclusion, this meta-analysis attests to the feasibility of early postoperative TEN in high-risk surgical patients and that these patients have reduced septic morbidity rates compared with those administered TPN.

1,310 citations


Journal ArticleDOI
TL;DR: In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen, which display the morphology of apoptosis.
Abstract: Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism of apoptosis is currently under active investigation.

1,148 citations


Journal Article
TL;DR: The data indicate that alpha 4 and beta 2 subunits are associated with each other in at least one neuronal nicotinic receptor subtype that has high affinity for agonists and is significantly increased in the cortex of rats chronically treated with nicotine.
Abstract: The subunit composition and pharmacological regulation of rat neuronal nicotinic cholinergic receptors were assessed. Specific immunoprecipitation was determined in solubilized rat brain homogenates using [3H]cytisine, a high affinity agonist at nicotinic receptors, in conjunction with polyclonal antisera generated against nonhomologous domains of the various subunits comprising this receptor class. In all brain regions tested, only antisera generated against the alpha 4 and beta 2 subunits were able to immunoprecipitate specifically receptors labeled by [3H]cytisine. Thus, these sera were further characterized in order to validate and optimize their use in the immunoprecipitation protocol. Preincubation of solubilized receptors from rat forebrain with antisera generated against the alpha 2, alpha 3, alpha 5, beta 3, or beta 4 subunits did not decrease the amount of precipitable alpha 4 or beta 2 subunit. On the other hand, when either anti-alpha 4 or anti-beta 2 serum was used to immunoprecipitate solubilized receptors from rat forebrain, the supernatants contained little if any remaining receptors that could be specifically precipitated by either antibody. Because these antisera do not cross-react, the data indicate that alpha 4 and beta 2 subunits are associated with each other in at least one neuronal nicotinic receptor subtype that has high affinity for agonists. Moreover, these results imply that all alpha 4 subunits that are labeled by [3H]cystisine are coupled to beta 2 subunits. We also present evidence that the alpha 4/beta 2 subtype characterized in this report is significantly increased in the cortex of rats chronically treated with nicotine.

892 citations


Journal ArticleDOI
TL;DR: Results support the hypothesis that premature birth results in part from infection caused by genital tract bacteria, and research efforts must be prioritized to determine the role of infection and the appropriate prevention of this cause of prematurity.

887 citations


Journal ArticleDOI
10 Jan 1992-Science
TL;DR: The fluorescent dyes FM1-43 and RH414 label motor nerve terminals in an activity-dependent fashion that involves dye uptake by synaptic vesicle that are recycling, suggesting that recycled vesicles mix with the pool morphologically and functionally.
Abstract: The fluorescent dyes FM1-43 and RH414 label motor nerve terminals in an activity-dependent fashion that involves dye uptake by synaptic vesicles that are recycling. This allows optical monitoring of vesicle recycling in living nerve terminals to determine how recycled vesicles reenter the vesicle pool. The results suggest that recycled vesicles mix with the pool morphologically and functionally. One complete cycle of release of transmitter, recycling of a vesicle, and rerelease of transmitter appears to take about 1 minute.

755 citations


Journal ArticleDOI
TL;DR: Nine newborn infants with severe persistent pulmonary hypertension who were candidates for extracorporeal membrane oxygenation treatment with low doses of NO showed rapid improvement in oxygenation without reduction of systemic blood pressure.

654 citations


Journal ArticleDOI
TL;DR: A multicenter, double-blind clinical trial compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparIn given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes.
Abstract: Background. Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. Methods. In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. Results. Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight h...

650 citations


Journal ArticleDOI
TL;DR: This randomized trial compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices and determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival.
Abstract: Background. Endoscopic sclerotherapy is an accepted treatment for bleeding esophageal varices, but it is associated with substantial local and systemic complications. Endoscopic ligation, a new form of endoscopic treatment for bleeding varices, may be safer. We compared the effectiveness and safety of the two techniques. Methods. In this randomized trial we compared endoscopic sclerotherapy and endoscopic ligation in 129 patients with cirrhosis who had proved bleeding from esophageal varices. Sixty-five patients were treated with sclerotherapy, and 64 with ligation. Initial treatment for acute bleeding was followed by elective retreatment to eradicate varices. The patients were followed for a mean of 10 months, during which we determined the incidence of complications and recurrences of bleeding, the number of treatments needed to eradicate varices, and survival. Results. Active bleeding at the first treatment was controlled by sclerotherapy in 10 of 13 patients (77 percent) and by ligation in 12...

611 citations


Journal ArticleDOI
TL;DR: The dyes make it possible optically to study vesicle exocytosis and recycling in living nerve terminals in real time, and should be useful for marking terminals in a variety of preparations according to their level of activity.
Abstract: Living motor nerve terminals from several species can be stained in an activity-dependent fashion by certain styryl dyes, such as RH414, RH795, and a new dye, FM1–43, which can be imaged independently of the others. The dyes evidently become trapped within recycled synaptic vesicles. In frog cutaneus pectoris muscle, bright fluorescent spots spaced regularly along the length of the nerve terminals appear after stimulation in the presence of the dye. The spots align well with postsynaptic ACh receptors and are persistent for many hours, unless further stimulation is given, in which case the spots disappear. Destaining, like staining, requires transmitter release and proceeds gradually over several minutes at high stimulus frequencies (e.g., 30 Hz), and fluorescent spots in the same terminal disappear at about the same rate. We suggest that each spot is a cluster of hundred of synaptic vesicles and that the mechanism of staining involves the ability of the dyes to partition reversibly into the outer leaflet of surface membranes, without being able to penetrate the entire membrane thickness. Then, during endocytosis following transmitter release, dye molecules become trapped in recycled synaptic vesicle membranes. The dyes therefore make it possible optically to study vesicle exocytosis and recycling in living nerve terminals in real time, and should be useful for marking terminals in a variety of preparations according to their level of activity.

574 citations


Journal ArticleDOI
TL;DR: In this paper, the authors examine the roles that organization design and culture play in varying levels of success experienced by AMT-adopting organizations, and several hypotheses are presented on the relationships among culture, structure, and implementation outcomes based on the competing values model of organizational culture.
Abstract: The literature on advanced manufacturing technologies (AMTs) shows that a wide range of outcomes have been experienced by organizations that have adopted these technologies, ranging from implementation failure to increased productivity and enhanced organizational flexibility. This article examines the roles that organization design and culture play in the varying levels of success experienced by AMT-adopting organizations. Several hypotheses are presented on the relationships among culture, structure, and implementation outcomes based on the competing values model of organizational culture.

573 citations


Journal ArticleDOI
TL;DR: It is argued that the broad strategic concerns of managers require a portfolio of different kinds of cognitive maps, and the interactions among these maps are as important as the functions of each one separately.
Abstract: Research on managerial cognition in genetal, and on cognitive mapping in particular, is receving a great deal of attention in Europe and the US, but the work being done is currently disparate and loosely coupled. Furthermor, the development of maps as a decision aid has tended to focus on specific sub-areas of cognition. In this article we argue that the broad strategic concerns of managers require a portfolio of different kinds of cognitive maps. The interactions among these maps are as important as the functions of each one separately. We develop a framework for classifying cognitice maps and argue for the importance of managing multiple maps.

Journal ArticleDOI
TL;DR: In this article, the relationship between organization science and managerial practice is examined and a reinterpretation of the role played by organizational scientists in relation to practitioners is presented. But organizational scientists should be viewed not as engineers offering technical advice to managers, but as providers of conceptual and symbolic language for use in organizational discourse.
Abstract: This paper examines the relationship between organization science and managerial practice. Science and practice are viewed as interdependent, yet semiautonomous, domains which engage in their own specialized forms of discourse or "language games." The paper examines both the internal dynamics of these language games and the relationship between them. The analysis suggests a reinterpretation of the role played by organizational scientists in relation to practitioners. Organizational scientists should be viewed not as engineers offering technical advice to managers but as providers of conceptual and symbolic language for use in organizational discourse. This view's implications for enhancing the relationship between organization science and managerial practice is discussed.

Journal ArticleDOI
TL;DR: It appears that providing cognitive therapy during acute treatment prevents relapse, and whether this preventive effect extends to recurrence remains to be determined.
Abstract: • Patients successfully treated during a 3-month period with either imipramine hydrochloride pharmacotherapy, cognitive therapy, or combined cognitive-pharmacotherapy were monitored during a 2-year posttreatment follow-up period. Half of the patients treated with pharmacotherapy alone continued to receive study medications for the first year of the follow-up. All other patients discontinued treatment at the end of the acute treatment phase. Patients treated with cognitive therapy (either alone or in combination with medication) evidenced less than half the rate of relapse shown by patients in the medication—on continuation condition, and their rate did not differ from that of patients provided with continuation medication. It appears that providing cognitive therapy during acute treatment prevents relapse. Whether this preventive effect extends to recurrence remains to be determined.

Book
01 Jan 1992

Journal ArticleDOI
TL;DR: The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants.
Abstract: Background. — A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. Methods. — Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-octalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. Results.— Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. Conclusions.— These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test—positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone. ( Arch Intern Med. 1992;152:1025-1032)

Journal ArticleDOI
TL;DR: The results demonstrate that the activity of the cdc25 phosphatase at the G2/M transition is directly regulated through changes in its phosphorylation state.
Abstract: The cdc25 tyrosine phosphatase is known to activate cdc2 kinase in the G2/M transition by dephosphorylation of tyrosine 15. To determine how entry into M-phase in eukaryotic cells is controlled, we have investigated the regulation of the cdc25 protein in Xenopus eggs and oocytes. Two closely related Xenopus cdc25 genes have been cloned and sequenced and specific antibodies generated. The cdc25 phosphatase activity oscillates in both meiotic and mitotic cell cycles, being low in interphase and high in M-phase. Increased activity of cdc25 at M-phase is accompanied by increased phosphorylation that retards electrophoretic mobility in gels from 76 to 92 kDa. Treatment of cdc25 with either phosphatase 1 or phosphatase 2A removes phosphate from cdc25, reverses the mobility shift, and decreases its ability to activate cdc2 kinase. Furthermore, the addition of okadaic acid to egg extracts arrested in S-phase by aphidicolin causes phosphorylation and activation of the cdc25 protein before cyclin B/cdc2 kinase activation. These results demonstrate that the activity of the cdc25 phosphatase at the G2/M transition is directly regulated through changes in its phosphorylation state.

Journal ArticleDOI
TL;DR: Asymptomatic intracranial aneurysms appear to be more frequent in people with polycystic kidney disease than in the general population, although the 95 percent confidence interval includes the possibility of no difference.
Abstract: Background and Methods. Intracranial aneurysms are a feature of autosomal dominant polycystic kidney disease, but their prevalence is uncertain. We studied 92 subjects with autosomal dominant polycystic kidney disease who had no symptoms or signs of any neurologic disorder. To determine the prevalence of intracranial aneurysms, we performed high-resolution computed tomography (CT) in 60 subjects, four-vessel cerebral angiography in 21, and both procedures in 11. Results. Four of the 88 subjects in whom the radiologic studies were successfully completed had intracranial aneurysms (4 percent; 95 percent confidence interval, 0.1 to 9 percent), as compared with the prevalence of 1 percent reported for an angiographic study of the general population. Three of the four subjects had multiple aneurysms. Seven subjects for whom the results of CT studies were suspicious underwent cerebral angiography: two had aneurysms, and five had normal vascular structures that accounted for the suspicious results of to...


Journal ArticleDOI
TL;DR: Recent studies have found, contrary to earlier assumptions, that ethanol has selective, dose-dependent effects on various neurotransmitter systems within the CNS, and these effects are observed at all levels of analysis, from molecular to behavioral.

Journal ArticleDOI
TL;DR: The hair cell ACh receptor appears to be a nonspecific cation channel through which Ca2+ enters and triggers the opening of nearby Ca(2+)-activated K+ channels, however, the ACh-evoked K- channels are not the same as the “maxi” K+ channel activated by Ca2+, which could be prevented when the cell was dialyzed with the rapidCa2+ buffer BAPTA.
Abstract: Cochlear hair cells are thought to be inhibited by the release of ACh from efferent neurons. Several studies have implicated Ca2+ as a postsynaptic intermediary in hair cell inhibition, but its role remains unproven. We have made whole-cell, tight-seal recordings from single short hair cells (the avian analog of outer hair cells in the mammalian cochlea), isolated from the chick's cochlea, to determine the mechanism of cholinergic inhibition. These cells hyperpolarized upon exposure to ACh, although a brief depolarization preceded the much larger, longer- lasting hyperpolarization. In voltage clamp ACh evoked an outward current that reversed in sign near the K+ equilibrium potential. A small, transient inward current preceded the predominant outward current. The ACh-evoked K+ current depended on Ca2+ in the external saline, or could be prevented when the cell was dialyzed with the rapid Ca2+ buffer BAPTA. In BAPTA-loaded cells a residual inward current was seen. This activated with very little delay upon exposure of the cell to ACh and reversed near 0 mV membrane potential. Thus, the hair cell ACh receptor appears to be a nonspecific cation channel through which Ca2+ enters and triggers the opening of nearby Ca(2+)-activated K+ channels. However, the ACh-evoked K+ channels are not the same as the “maxi” K+ channels activated by Ca2+ influx through voltage-gated Ca2+ channels in these same cells.

Journal ArticleDOI
TL;DR: The empirical approach to exploratory data analysis should be viewed as complementary to the more robust treatments that statistical methodologies afford, and a single example of chemical compositions data obtained on environmental dust particles is illustrated.

Journal ArticleDOI
TL;DR: It is argued that inconsistencies between retail store image conceptualization and operationalization signal a critical separation between theory and measurement within the paradigm, and that the time has come for a new information processing theory—category-based information processing—to challenge piecemeal processing as the positive heuristic within the store image paradigm.
Abstract: This article presents the case that inconsistencies between retail store image conceptualization and operationalization signal a critical separation between theory and measurement within the paradigm. The authors attribute the separation to the influence of two rival, middle-level information processing theories. The first, piecemeal-based processing theory, has historically dominated retail store image operationalization and measurement within the area. The authors argue, however, that the time has come for a new information processing theory—category-based information processing—to challenge piecemeal processing as the positive heuristic within the store image paradigm. The advantages of adopting category-based processing over piecemeal processing are discussed both from a positive and normative perspective. Recommendations for managers and propositions for future research are offered.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate how individuals in cross-and same-sex friendships define and express intimacy, and reveal substantial similarities in the meanings of intimacy in both types of friendship, as well as some gender differences.
Abstract: The purpose of this study was to investigate how individuals in cross- and same-sex friendships define and express intimacy. In a self-report questionnaire 164 college students were asked what they meant by the term `intimacy' in the context of cross- and same-sex friendships. Individuals assigned an average number of two meanings to the term `intimacy', though the number of meanings ranged from one to five. Results revealed substantial similarities in the meanings of intimacy in both types of friendship, as well as some gender differences. For instance, five of the seven most frequently mentioned definitions of intimacy were specified by both cross- and same-sex friends: self-disclosures, emotional expressiveness, unconditional support, physical contact and trust. One of the remaining two meanings of intimacy, i.e. sexual contact, was mentioned by cross- but not same-sex friends. Sharing activities was given as a definition of intimacy by 9 percent of the males in same-sex friendships, and 4 percent of t...

Journal ArticleDOI
TL;DR: The risk of SUDS may be reduced by encouraging patients to be compliant with medications, especially in times of unusual life stress, as well as investigation of the circumstances at the time of death suggested two possible modes of death.
Abstract: Sudden unexplained death syndrome (SUDS) accounts for about 10% of deaths in patients with epilepsy. It is associated with subtherapeutic postmortem serum antiepileptic drug (AED) levels but no anatomic cause of death on autopsy. The mechanisms of death are not known. We investigated 44 cases of SUDS for details of seizure history, treatment, medical and psychological history, events at the time of death, and postmortem findings. Cases of status epilepticus, drowning or other identifiable causes of death were excluded. Two groups emerged: five children with uncontrolled seizures receiving multiple AEDs and good compliance with medications, and 39 adults with less frequent seizures, often receiving monotherapy, but noncompliant with medications. Four children (80%) but only one adult (3%) had fully therapeutic postmortem AED levels. Sixty-three percent of adults recently had experienced an unusually stressful life event. Investigation of the circumstances at the time of death suggested two possible modes of death: (a) a seizure with an immediately fatal arrhythmia, or, (b) a seizure, recovery, then delayed secondary respiratory arrest or arrhythmia. Even though the mechanisms of death are unknown, the risk of SUDS may be reduced by encouraging patients to be compliant with medications, especially in times of unusual life stress.

Journal ArticleDOI
TL;DR: It is concluded that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.
Abstract: Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and xanthine oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases in XD and XO activity in EC induced by hypoxia were associated upon reoxygenation with increased (P less than 0.05) extracellular superoxide anion (O2-.) levels that were inhibited by treatment with XO inhibitors (tungsten, allopurinol) or an anion-channel blocker (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid). EC monolayers subjected to hypoxia/reoxygenation also leaked more preloaded 51Cr, were more adherent to neutrophils, and permitted greater albumin transit than control monolayers. Treatment with tungsten, allopurinol, and/or superoxide dismutase decreased (P less than 0.05) 51Cr release, neutrophil adherence, and albumin transit in EC monolayers exposed to hypoxia/reoxygenation. We conclude that prolonged hypoxia increases both XO and XD activity in EC and may predispose the endothelium to oxidative and inflammatory damage.

Journal ArticleDOI
10 Dec 1992-Nature
TL;DR: In this article, the authors assess the contribution of sea-salt aerosol particles to the cycling of sulphur in (and particularly its removal from) the marine boundary layer (MBL).
Abstract: THE oxidation of sulphur dioxide to sulphate in the marine boundary layer (MBL) is an important pathway in the global sulphur cycle. Oxidation by ozone in the aqueous phase is an important process in cloud droplets but has not generally been thought to be significant in the clear air of the MBL. Yet the lower part of the MBL contains abundant sea-salt aerosol particles, which are largely water of sufficiently high pH (ref. 2) to support ozone oxidation of SO2 to sulphate. We have argued previously that 5–25% of the total non-sea-salt sulphate (n.s.s. SO^(2−)_4) observed in the MBL may be formed by this mechanism; here we assess its contribution to the cycling of sulphur in (and particularly its removal from) the MBL. We show that, owing to the effects of mass transfer, the n.s.s. SO^(2−)_4 so generated will be predominantly associated with particles of 2–9 μm diameter, and will accordingly dry-deposit at a rapid rate. Because part of the dimethyl sulphide (DMS) emitted by marine organisms is converted to SO_2 in the MBL, this additional removal pathway for sulphur may markedly reduce the proposed feedback between greenhouse warming, oceanic DMS emissions and sulphate haze albedo.

Book
05 Aug 1992
TL;DR: This chapter discusses Iron, Aging, and Human Disease: Historical Background and New Hypotheses, and Implications for Prevention and Therapy: Preventive Measures for the Maintenance of Low But Adequate Iron Stores.
Abstract: Introduction. Iron, Aging, and Human Disease: Historical Background and New Hypotheses (R.B. Lauffer). Chemistry and Molecular Biology of Iron and Iron-Binding Proteins: Structure and Molecular Biology of Iron-Binding Proteins and the Regulation of 'Free' Iron Pools (R.R. Crichton and R.J. Ward). Genetic Control of the Genes for Iron Storage and Transport: Links with the Acute Phase Response (J.T. Rogers). Iron Accumulation and METABOLISM in Humans: Iron Balance in Western Societies as Measured by Serum Ferritin (J.W. Halliday and B.A. Leggett). Hereditary Hemochromatosis and Other Diseases Associated with Iron Overload (J.W. Halliday and L.W. Powell). Iron and the Immune System (J.H. Brock). Cellular Acquisition of Iron and the Iron withholding Defense Against Microbial and Neoplastic Invasion (E.D. Weinberg). Iron and Oxidative Stress: Iron and Damage to Biomolecules (B. Halliwell). Lipofuscin, Lysosomes, and Iron (U.T. Brunk, M.R. Marzabadi, and C.B. Jones). Roles for Iron in Cardiovascular Diseases: Role of Iron in the Oxidative Modification of Low Density Lipoprotein (S. Parthasarathy). Iron and Myocardial Reperfusion Injury (J.L. Zweier). Stored Iron as a Risk Factor for Ischemic Heart Disease (J. Sullivan). Iron and Stroke (L.S. Terada, I.R. Willingham, and J.E. Repine). Roles for Iron in Other COmmon Diseases: Iron and Cancer (R.G. Stevens). Brain Iron and Nigra-Striatal Dopamine Neurons in Parkinson's Disease (D. Ben-Shachar, and M. Youdim). Proteins of Iron Regulation in Alzheimer's Disease (J.R. Connor). Iron-Promoted Oxidative Damage in Rheumatic Diseases (C.W. Trenam, P.G. Winyard, C.J. Morris, and D.R. Blake). Iron and Ethanol-Induced Tissue Damage (A.I. Cederbaum). Iron Metabolism and Oxygen Radical Injury in Premature Infants (J. Sullivan). Implications for Prevention and Therapy: Preventive Measures for the Maintenance of Low But Adequate Iron Stores (R.B. Lauffer). Therapeutic Strategies to Inhibit Iron-Catalyzed Tissue Damage (B. Hed lund and P.E. Hallaway) Iron and Oxidative Balance (J. McCord).

Journal ArticleDOI
TL;DR: In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity, thus indicating a reduced placental glucose transportcapacity.
Abstract: In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity.

Journal ArticleDOI
TL;DR: It is found that there is no increase in lung preproET-1 mRNA or ET-1 levels in adult SDR with an equivalent degree of pulmonary hypertension due to chronic hypoxia, implying that the increases in ET- 1 production in FHR were not a common consequence of all pulmonary hypertensive states.
Abstract: The role of endogenous circulating or locally produced endothelin-1 (ET-1) in pulmonary hypertensive states is unknown. To investigate this we measured ET-1 levels and preproendothelin-1 (prepro-ET-1) mRNA expression at various ages in control Sprague-Dawley (SDR) rats and in fawn-hooded rats (FHR), a strain which develops idiopathic pulmonary hypertension. Although serum ET-1 levels were similar in SDR and FHR, we found twofold increases in FHR whole lung homogenate ET-1 levels by radioimmunoassay. Coexisting threefold increases in preproET-1 mRNA expression were found in FHR lungs by densitometric analysis of Northern blots and by filter hybridization, suggesting the increase in lung ET-1 was due to enhanced intrapulmonary production of the peptide. To test whether the increase in lung preproET-1 mRNA was primary or secondary to established pulmonary hypertension, we compared preproET-1 mRNA expression prior to development of pulmonary hypertension in fetal (19 day gestation) and neonatal (5 day old) FHR and SDR. Despite similar right ventricular size in SDR and FHR, preproET-1 mRNA was already elevated in neonatal FHR lungs. Furthermore, we found no increase in lung preproET-1 mRNA or ET-1 levels in adult SDR with an equivalent degree of pulmonary hypertension due to chronic hypoxia, implying that the increases in ET-1 production in FHR were not a common consequence of all pulmonary hypertensive states. The functional significance of these observations remains unclear but raises the possibility of a role for ET-1 in the pathophysiology of pulmonary hypertension in the FHR.

Journal Article
TL;DR: A case is made for the death of unselected thymocytes in vivo being regulated by endogenous glucocorticoids, as characterized by cell shrinkage, membrane alterations, nuclear collapse and chromatin fragmentation into oligonucleosomes.