bluuebunny/crossref_metadata_2025 huggingface dataset:
Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to
in vivo
function
Authors: Natarajan Paramasivam , Wang Jiyi , Hua Zhaolin , Graham Todd R.
Published: July 2004

Aminophospholipid translocases (APLTs) are defined primarily by their ability to flip fluorescent or spin-labeled derivatives of phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the external leaflet of a membrane bilayer to the cytosolic leaflet and are thought to establish phospholipid asymmetry in biological membranes. The identities of APLTs remain unknown, although candidate proteins include the Drs2p/ATPase II subfamily of P-type ATPases. Drs2p from budding yeast localizes to the trans-Golgi network (TGN), and here we show that this membrane contains an ATP-dependent APLT that flips 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD) PS and PE derivatives from the luminal to the cytosolic leaflet. To assess the contribution of Drs2p to this activity, TGN membranes were prepared from strains harboring WT or temperature-sensitive alleles of
DRS2
and null alleles of three other potential APLT genes (
DNF1
,
DNF2
, and
DNF3
). Assay of these membranes indicated that Drs2p was required for the ATP-dependent translocation of NBD-PS, whereas no active translocation of NBD-PE or NBD-phosphatidylcholine was detected. The specificity of Drs2p for NBD-PS suggested that translocation of PS would be required for the function of Drs2p in protein transport from the TGN. However,
cho1
yeast strains that are unable to synthesize PS do not phenocopy
drs2
but instead transport proteins normally via the secretory pathway. In addition, a
drs2 cho1
double mutant retains
drs2
transport defects. Therefore, whereas NBD-PS is a preferred substrate for Drs2p
in vitro
, endogenous PS is not an obligatory substrate
in vivo
for the role Drs2p plays in protein transport.
Heterodimeric complexes of Hop2 and Mnd1 function with Dmc1 to promote meiotic homolog juxtaposition and strand assimilation
Authors: Chen Yi-Kai , Leng Chih-Hsiang , Olivares Heidi , Lee Ming-Hui , Chang Yuan-Chih , Kung Wen-Mei , Ti Shih-Chieh , Lo Yu-Hui , Wang Andrew H.-J. , Chang Chia-Seng , Bishop Douglas K. , Hsueh Yi-Ping , Wang Ting-Fang
Published: July 2004

Saccharomyces cerevisiae
Hop2 and Mnd1 are abundant meiosisspecific chromosomal proteins, and mutations in the corresponding genes lead to defects in meiotic recombination and in homologous chromosome interactions during mid-prophase. Analysis of various double mutants suggests that
HOP2
,
MND1
, and
DMC1
act in the same genetic pathway for the establishment of close juxtaposition between homologous meiotic chromosomes. Biochemical studies indicate that Hop2 and Mnd1 proteins form a stable heterodimer with a higher affinity for double-stranded than single-stranded DNA, and that this heterodimer stimulates the strand assimilation activity of Dmc1
in vitro
. Together, the genetic and biochemical results suggest that Hop2, Mnd1, and Dmc1 are functionally interdependent during meiotic DNA recombination.
The TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins
Authors: Harrington Laura S. , Findlay Greg M. , Gray Alex , Tolkacheva Tatiana , Wigfield Simon , Rebholz Heike , Barnett Jill , Leslie Nick R. , Cheng Susan , Shepherd Peter R. , Gout Ivan , Downes C. Peter , Lamb Richard F.
Published: July 2004

Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K). The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation. Here, we show that TSC1-2 is required for insulin signaling to PI3K. TSC1-2 maintains insulin signaling to PI3K by restraining the activity of S6K, which when activated inactivates insulin receptor substrate (IRS) function, via repression of IRS-1 gene expression and via direct phosphorylation of IRS-1. Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors.
Closed chromatin loops at the ends of chromosomes
Authors: Nikitina Tatiana , Woodcock Christopher L.
Published: July 2004

The termini of eukaryotic chromosomes contain specialized protective structures, the telomeres, composed of TTAGGG repeats and associated proteins which, together with telomerase, control telomere length. Telomere shortening is associated with senescence and inappropriate telomerase activity may lead to cancer. Little is known about the chromatin context of telomeres, because, in most cells, telomere chromatin is tightly anchored within the nucleus. We now report the successful release of telomere chromatin from chicken erythrocyte and mouse lymphocyte nuclei, both of which have a reduced karyoskeleton. Electron microscopy reveals telomere chromatin fibers in the form of closed terminal loops, which correspond to the “t-loop” structures adopted by telomere DNA. The ability to recognize isolated telomeres in their native chromatin conformation opens the way for detailed structural and compositional studies.
Borealin
Authors: Gassmann Reto , Carvalho Ana , Henzing Alexander J. , Ruchaud Sandrine , Hudson Damien F. , Honda Reiko , Nigg Erich A. , Gerloff Dietlind L. , Earnshaw William C.
Published: July 2004

The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Here, we describe Borealin, a novel member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin; and Borealin binds Survivin and INCENP in vitro. A second complex contains Aurora B and INCENP, but no Borealin or Survivin. Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore–spindle misattachments and an increase in bipolar spindles associated with ectopic asters. The extra poles, which apparently form after chromosomes achieve a bipolar orientation, severely disrupt the partitioning of chromosomes in anaphase. Borealin depletion has little effect on histone H3 serine10 phosphorylation. These results implicate the chromosomal passenger holocomplex in the maintenance of spindle integrity and suggest that histone H3 serine10 phosphorylation is performed by an Aurora B–INCENP subcomplex.
A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells
Authors: Stokes Alexander J. , Shimoda Lori M.N. , Koblan-Huberson Murielle , Adra Chaker N. , Turner Helen
Published: July 2004

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.
Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection
Authors: Warfield Kelly L. , Perkins Jeremy G. , Swenson Dana L. , Deal Emily M. , Bosio Catharine M. , Aman M. Javad , Yokoyama Wayne M. , Young Howard A. , Bavari Sina
Published: July 2004

Ebola virus is a highly lethal human pathogen and is rapidly driving many wild primate populations toward extinction. Several lines of evidence suggest that innate, nonspecific host factors are potentially critical for survival after Ebola virus infection. Here, we show that nonreplicating Ebola virus-like particles (VLPs), containing the glycoprotein (GP) and matrix protein virus protein (VP)40, administered 1–3 d before Ebola virus infection rapidly induced protective immunity. VLP injection enhanced the numbers of natural killer (NK) cells in lymphoid tissues. In contrast to live Ebola virus, VLP treatment of NK cells enhanced cytokine secretion and cytolytic activity against NK-sensitive targets. Unlike wild-type mice, treatment of NK-deficient or -depleted mice with VLPs had no protective effect against Ebola virus infection and NK cells treated with VLPs protected against Ebola virus infection when adoptively transferred to naive mice. The mechanism of NK cell–mediated protection clearly depended on perforin, but not interferon-γ secretion. Particles containing only VP40 were sufficient to induce NK cell responses and provide protection from infection in the absence of the viral GP. These findings revealed a decisive role for NK cells during lethal Ebola virus infection. This work should open new doors for better understanding of Ebola virus pathogenesis and direct the development of immunotherapeutics, which target the innate immune system, for treatment of Ebola virus infection.
In Heavy Drinkers Fatty Acid Ethyl Esters in the Serum Are Increased for 44 hr After Ethanol Consumption
Authors: Borucki Katrin , Kunstmann Steffen , Dierkes Jutta , Westphal Sabine , Diekmann Silvia , Bogerts Bernhard , Luley Claus
Published: July 2004

Background: Fatty acid ethyl esters (FAEEs) have been proposed as a marker of ethanol consumption because they can be detected for up to 24 hr after a moderate intake of ethanol, even though blood ethanol remains increased for only 8 hr. Therefore, this study investigated whether FAEEs can be found during a time period exceeding 24 hr in a group of patients who were hospitalized for ethanol detoxification. A second aim was to study the distribution of FAEEs between lipoproteins during that time.

Methods: Serum samples of 12 patients with acute ethanol intoxication were assayed for FAEEs. Blood samples were drawn 8.2, 20.2, 32.2, and 44.2 hr after hospitalization. FAEEs were quantified by gas chromatography‐mass spectrometry.

Results: Ethanol was no longer detectable after 20.2 hr from hospitalization, whereas FAEEs were still found after 32.2 and 44.2 hr. These late FAEEs were significantly higher than the FAEEs in 15 different healthy men who had abstained from ethanol for 4.5 days (p < 0.001 and p= 0.001). FAEEs were associated mainly with lipid‐free serum but tended to accumulate in very‐low‐density lipoprotein in patients with moderate hypertriglyceridemia.

Conclusions: In heavy drinkers, the FAEEs were increased after ethanol consumption for at least 44 hr. It remains to be studied whether they originate from a single ethanol intake or, in addition, from a slow release out of body storage compartments.
Alcohol Effects During Acamprosate Treatment: A Dose‐Response Study in Humans
Authors: Brasser Susan M. , McCaul Mary E. , Houtsmuller Elisabeth J.
Published: July 2004

Background: Acamprosate (calcium acetyl homotaurinate) reduces alcohol intake in animals and increases abstinence rates in alcohol‐dependent persons. Acamprosate's mechanism of action, however, remains poorly understood. In order to examine whether acamprosate/alcohol interactions contribute to acamprosate's efficacy, the present double‐blind, placebo‐controlled human laboratory study examined effects of acamprosate on the pharmacokinetics and subjective, psychomotor, and physiological effects of alcohol in heavy drinkers.

Methods: In a six‐week within‐subject design, participants were maintained on acamprosate (0, 2, and 4 g, p.o., double‐blind, in counterbalanced order) for 11 days at each dose. Physiological, subjective, and psychomotor measures were collected daily during each dosing cycle. During each acamprosate dose condition, subjects were challenged with 0, 0.5, and 1.0 g/kg ethanol (p.o., counterbalanced order) during three separate laboratory sessions. Subjective, physiological, and psychomotor effects of alcohol, and breath alcohol levels were collected at baseline and at 30‐min intervals for a 3‐hr post‐administration period.

Results: Acamprosate alone did not substantially affect subjective, physiological, or psychomotor performance measures. Acamprosate did not alter alcohol pharmacokinetics, or alcohol‐induced behavioral impairment or tachycardia, and most subjective alcohol effects were also unaltered by acamprosate as well. Although a trend appeared for acamprosate to increase subjective ratings of intoxication following the lower (0.5 g/kg) alcohol dose, adjustment for individual differences in blood alcohol level eliminated this effect, suggesting the trend was not due to a central effect of acamprosate.

Conclusions: Acamprosate does not alter alcohol pharmacokinetics, acute physiological or psychomotor alcohol effects, or most subjective alcohol effects.
Association of Functional Opioid Receptor Genotypes With Alcohol Dependence in Koreans
Authors: Kim Sung‐Gon , Kim Cheol‐Min , Kang Dong‐Ho , Kim Yun‐Jin , Byun Won‐Tan , Kim Seong‐Yeon , Park Je‐Min , Kim Myung‐Jung , Oslin David W.
Published: July 2004

Background: The functional polymorphism (A118G) of the μ‐opioid receptor gene (OPRM1) is thought to have clinical significance in the treatment of alcohol dependence. This study compared Koreans with one or two copies of the A118G polymorphism seeking treatment for alcohol dependence with a group of non–alcohol‐dependent controls.

Methods: Patients hospitalized for alcohol dependence (n= 112) and a group of non–alcohol‐dependent controls (n= 140) were interviewed on aspects of drinking history and psychiatric history. Patients and controls were excluded if they met criteria for any other major psychiatric disorder. Participants were genotyped at the OPRM1 locus.

Results: The allele frequency of the Asp40 allele was 0.397 in the alcohol‐dependent group, which is consistent with other literature demonstrating this polymorphism to be common in Asian populations. Within the alcohol‐dependent subjects, being homozygous for the Asp40 allele was associated with more days drinking than those heterozygous or homozygous for the Asn40 allele. Differences in the allele frequencies between alcohol‐dependent and non–alcohol‐dependent controls were not significant.

Conclusions: These results suggest that having one or two copies of the A118G allele is common among Koreans and may be an important genetic factor in the etiology of alcohol dependence and the frequency of alcohol consumption.
Developmental Alcohol Exposure Alters Light‐Induced Phase Shifts of the Circadian Activity Rhythm in Rats
Authors: Farnell Yuhua Z. , West James R. , Chen Wei‐Jung A. , Allen Gregg C. , Earnest David J.
Published: July 2004

Background: Developmental alcohol (EtOH) exposure produces long‐term changes in the photic regulation of rat circadian behavior. Because entrainment of circadian rhythms to 24‐hr light/dark cycles is mediated by phase shifting or resetting the clock mechanism, we examined whether developmental EtOH exposure also alters the phase‐shifting effects of light pulses on the rat activity rhythm.

Methods: Artificially reared Sprague‐Dawley rat pups were exposed to EtOH (4.5 g/kg/day) or an isocaloric milk formula (gastrostomy control; GC) on postnatal days 4 to 9. At 2 months of age, rats from the EtOH, GC, and suckle control groups were housed individually, and wheel‐running behavior was continuously recorded first in a 12‐hr light/12‐hr dark photoperiod for 10 to 14 days and thereafter in constant darkness (DD). Once the activity rhythm was observed to stably free‐run in DD for at least 14 days, animals were exposed to a 15‐min light pulse at either 2 or 10 hr after the onset of activity [i.e., circadian time (CT) 14 or 22, respectively], because light exposure at these times induces maximal phase delays or advances of the rat activity rhythm.

Results: EtOH‐treated rats were distinguished by robust increases in their phase‐shifting responses to light. In the suckle control and GC groups, light pulses shifted the activity rhythm as expected, inducing phase delays of approximately 2 hr at CT 14 and advances of similar amplitude at CT 22. In contrast, the same light stimulus produced phase delays at CT 14 and advances at CT 22 of longer than 3 hr in EtOH‐treated rats. The mean phase delay at CT 14 and advance at CT 22 in EtOH rats were significantly greater (p < 0.05) than the light‐induced shifts observed in control animals.

Conclusions: The data indicate that developmental EtOH exposure alters the phase‐shifting responses of the rat activity rhythm to light. This finding, coupled with changes in the circadian period and light/dark entrainment observed in EtOH‐treated rats, suggests that developmental EtOH exposure may permanently alter the clock mechanism in the suprachiasmatic nucleus and its regulation of circadian behavior.
Alcohol Intake, Type of Beverage, and Risk of Breast Cancer in Pre‐ and Postmenopausal Women
Authors: Petri Anette Lykke , Tjønneland Anne , Gamborg Michael , Johansen Ditte , Høidrup Susanne , Sørensen Thorkild I.A. , Grønbæk Morten
Published: July 2004

Background: Most studies of the relation between alcohol consumption and breast cancer have shown a modestly increased risk, although the results are still conflicting.

Methods: The aim of this prospective population‐based cohort study was to assess the influence of alcohol intake and type of beverage (beer, wine, or spirits) on breast cancer risk in relation to menopausal status. Among 13,074 women aged 20 to 91 years, we examined the relationship between breast cancer risk, total alcohol intake, and type of alcohol in relation to menopausal status. The women were classified as premenopausal or as postmenopausal at younger than 70 years or 70 years or more.

Results: During follow‐up, 76 premenopausal and 397 postmenopausal women developed breast cancer. Premenopausal women who had an intake of more than 27 drinks per week had a relative risk of breast cancer of 3.49 (95% confidence limits, 1.36–8.99) compared with light drinkers (p= 0.011), whereas there were no differences in risk in the lower‐intake categories. The increased risk of breast cancer among premenopausal women was independent of the type of alcohol. Postmenopausal women older than 70 years of age who had an intake of more than six drinks per week of spirits had a relative risk of breast cancer of 2.43 (95% confidence limits, 1.41–4.20) compared with women who consumed less than one drink of spirits per week (p= 0.0014).

Conclusions: Total alcohol intake of more than 27 drinks per week increases breast cancer risk in premenopausal women independently of the type of alcohol. Among postmenopausal women, an intake of spirits of more than six drinks per week increases breast cancer risk.
Treatment Outcomes in Type A and B Alcohol Dependence 6 Months After Serotonergic Pharmacotherapy
Authors: Dundon William , Lynch Kevin G. , Pettinati Helen M. , Lipkin Craig
Published: July 2004

Background: Evidence supporting the use of serotonergic medications for the treatment of alcohol dependence is available from studies where pharmacotherapy targeted specific alcoholic subtypes. We previously established with Babor's alcohol typology that type A “lower risk/severity” alcoholics (n= 55) had better treatment response to 14 weeks of sertraline (200 mg/day) than placebo, and this was not found for type B “higher risk/severity” alcoholics (n= 45). The purpose of this study was to assess in this original study group whether treatment gains in the type A alcoholics were maintained or whether treatment outcomes changed for the type B alcoholics after discontinuing pharmacotherapy.

Methods: After the end of a 3‐month course of 200 mg/day sertraline, the subjects were interviewed at several time points about their alcohol drinking, if any, using the timeline follow‐back method. For 90% of the original study group, mixed effects and generalized estimating equation models were used to compare monthly drinking amounts over a 6‐month posttreatment period with drinking amounts in the last month of treatment.

Results: We found that type A alcoholics who had been treated with sertraline, in contrast to placebo, maintained the good outcomes they had achieved during treatment for at least 6 months after pharmacotherapy. We found that type B alcoholics who had been treated with sertraline, in contrast to placebo, continued to show no advantage for pharmacotherapy in the 6 months after completing treatment. In addition, heavy drinking in type B alcoholics increased over the 6 months postpharmacotherapy in those initially treated with sertraline compared with placebo.

Conclusions: These data support the importance of considering alcohol subtype when pharmacologically treating alcohol dependence.
Characterization of Acute Functional Tolerance to the Hypnotic Effects of Ethanol in Mice
Authors: Ponomarev Igor , Crabbe John C.
Published: July 2004

Background: Acute functional tolerance (AFT) to ethanol‐induced hypnosis is one of the main factors that affect the duration of ethanol‐induced loss of righting reflex (LRR: “sleep time”). Investigators who use duration of LRR as a measure of ethanol‐induced sedation should consider the potential magnitude and time course of this neuroadaptation when interpreting their results. However, AFT to the hypnotic effects of ethanol has not been well characterized. The present study explored this form of AFT using a novel method of monitoring LRR in mice.

Methods: Genetically heterogeneous mice were used to study effects of dose and time on the development of AFT. Mice were treated with different dose regimens and tested for LRR after hypnotic doses using a cylindrical restrainer. Measures of initial sensitivity and AFT to ethanol‐induced hypnosis were calculated and analyzed. Inbred strains of mice were then characterized for AFT magnitude after a single ethanol dose.

Results: Results showed that (a) AFT developed in a dose‐dependent fashion but attained an apparent maximum value; (b) AFT to ethanol‐induced hypnosis could develop partially after a small, subhypnotic dose; (c) AFT developed very rapidly and approached its maximum for a given dose by the 10th min after injection of ethanol; and (d) AFT has a strong genetic component.

Conclusion: Although specific for AFT to the hypnotic effects of ethanol, the present findings expand general knowledge about acute tolerance and should also be useful for investigators who use loss of righting reflex as a measure of ethanol sensitivity.
A Rat Model to Determine the Biomedical Consequences of Concurrent Ethanol Ingestion and Cigarette Smoke Exposure
Authors: Gentry‐Nielsen Martha J. , Top Elizabeth Vander , Snitily Mary U. , Casey Carol A. , Preheim Laurel C.
Published: July 2004

Background: Although scientists have used animal models for years to study the effects of ethanol (EtOH) ingestion on humans, the compounding effect of cigarette smoking has been virtually ignored. Because 80 to 95% of human alcoholics smoke, it is imperative to consider the added effects of smoking when trying to determine the consequences of excessive alcohol ingestion. We therefore have developed a rat model for studying the separate and combined results of smoking and drinking on human health.

Methods: Male Sprague‐Dawley rats were exposed daily for 12 weeks in whole‐body chambers to cigarette smoke (smoke‐exposed) or room air (sham‐exposed). During the final 5 weeks of exposure, the rats were fed liquid diets that contained 0, 16, 26, or 36% EtOH calories. Smoke exposure was quantified by measurement of carboxyhemoglobin, nicotine, and cotinine levels. Body weights, food consumption, blood EtOH concentrations, and various assessments of liver damage and function also were followed.

Results: Smoke exposure in this rat model approximates that of a moderate to heavy human smoker. Smoke‐exposed rats weighed significantly less and ate less food than sham‐exposed controls, but both groups ingested equivalent amounts of EtOH for their body weights and had comparable blood EtOH levels. Liver aspartate and alanine aminotransferase levels remained normal. There was an EtOH‐induced decrease in asialoglycoprotein receptor binding, but it was not exacerbated by smoke exposure. Alterations in blood cholesterol levels reflected what has been reported for humans, rising with increasing EtOH ingestion and decreasing with smoke exposure.

Conclusion: Our rat model is relevant to what transpires in the vast majority of alcoholics. Both ethanol ingestion and smoke exposure can be manipulated to mimic light to moderate to heavy levels, making it appropriate for studying the separate and combined biomedical consequences of alcohol abuse and cigarette smoking.
Between the Ivory Tower and the Academic Assembly Line*
Authors: Barry Jim , Chandler John , Clark Heather
Published: July 2004

This paper considers the impact of managerialism and the reactions it has engendered in university life. It examines the degree to which institutions of higher education in the UK have in recent years been subjected to what some commentators have seen as a managerial assault, alongside economic pressures to restructure and reform, and explores the reactions of academic and administrative staff in middle and junior levels through a case study of two universities. Consideration is given to attempts to introduce managerial controls, including the setting of targets, appraisals and peer review, as well as to the resistances which followed. It is argued that the notion of resistance to domination and control has been underplayed in the literature of organization and management. In exploring its various manifestations it is shown that managerialism is not fully embedded in university life and that matters are far from settled. It is contended that those engaged in academe in middle and junior levels of the organizational hierarchy are actively seeking to keep alive the craft of scholarship by mediating and moderating the harsher effects of the changes through supportive or transformational styles of working.
Transition Trajectories for Market Structure and Firm Strategy in China
Authors: White Steven , Liu Xielin
Published: July 2004

Research in transition economies like China has sought and found explanations for strategic behaviour based on institutional and other social processes, leading to descriptions of China's emerging business system as ‘network capitalism’. This paper argues, however, that organizational capabilities and transaction costs are increasingly important influences on strategic choice as economic reforms proceed. An in‐depth case study of one firm's behaviour in two different asset markets – R&D and distribution in the Chinese pharmaceutical industry – illustrates fundamental differences in firm strategies for securing these assets. To account for this variety and move beyond the homogeneity implied by prior research, we propose a framework for differentiating the transition trajectories for different types of complementary assets. We propose conditions under which all three perspectives – institutional and social structure, organizational capabilities and transaction costs – predict similar trajectories and firm strategies, but different decision processes, and when their predictions differ.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Volume‐Independent Mechanisms of Hypertension in Hemodialysis Patients: Clinical Implications
Authors: Blankestijn Peter J. , Ligtenberg Gerry
Published: July 2004

The renin‐angiotensin and sympathetic nervous systems are often activated in hemodialysis (HD) patients; the pathogenesis of this condition is discussed. Medications aimed at reducing renin and sympathetic activity may improve the cardiovascular prognosis, independent of its effect on blood pressure. This knowledge has important implications for the choice of treatment in HD patients.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Dialysate Composition and Hemodialysis Hypertension
Authors: Flanigan Michael
Published: July 2004

Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High‐sodium bicarbonate‐based dialysate was first formulated in 1982 to enable short, safe, comfortable, high‐efficiency hemodialysis (HD). Near‐universal adaptation of these high‐sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patient's serum sodium activity. Then, rather than choosing between comfortable, safe, high‐efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low‐sodium, high‐efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low‐efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter‐ and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20–40% of patients. The application of even more severe salt loading through high‐salt sodium modeling only accentuates the long‐term problems of excessive thirst, weight gain, and hypertension.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Dietary Sodium Restriction for Hypertension in Dialysis Patients
Authors: Ahmad Suhail
Published: July 2004

A close relationship between sodium and hypertension exists and this relationship is even more pronounced in renal failure and dialysis patients. Hypertension is one of the strongest predictors of poor outcome in dialysis patients. Almost all end‐stage renal disease (ESRD) patients have hypertension and positive sodium balance, resulting in extracellular volume (ECV) expansion—the most important contributing factor to hypertension. Thus the effective management of hypertension requires normalization of the sodium balance and ECV. Two important methods to achieve this are limiting interdialytic weight gain (IDWG) and a dialysis process that is able to remove all IDWG and consistently attain dry weight. Since IDWG is directly dependent on sodium intake and the resulting thirst, sodium restriction is the most effective way to limit IDWG. Ultrafiltration and dialysate sodium concentration influence sodium removal, ECV control, and blood pressure (BP) control. Thus the dialysis session should be long enough to achieve dry weight and frequent enough to maintain appropriate BP.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Drug Therapy for Hypertension in Hemodialysis Patients
Authors: Hörl Matthias P. , Hörl Walter H.
Published: July 2004

The majority of end‐stage renal disease (ESRD) patients are hypertensive. Drug therapy for hypertension in hemodialysis (HD) patients includes all classes of antihypertensive drugs, with the sole exception of diuretics. Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may decrease morbidity and mortality by reducing the mean arterial pressure (MAP), aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as left ventricular hypertrophy (LVH) and probably reduction of C‐reactive protein (CRP) and oxidant stress. Potential risk factors include hyperkalemia, anaphylactoid reaction with AN69 membranes (particularly ACE inhibitors), and aggravation of renal anemia. β‐blockers decrease not only mortality, blood pressure (BP), and ventricular arrhythmias, but also improve left ventricular function in ESRD patients. Nonselective β‐blockers can cause an increase in serum potassium (particularly during fasting or exercise). Lisinopril and atenolol have a predominant renal excretion and therefore a prolonged half life in ESRD patients. Thus thrice‐weekly supervised administration of these drugs after HD can enhance BP control. The use of calcium channel blockers is also associated with lower total and cardiovascular‐specific mortality in HD patients. Minoxidil is a very potent vasodilator that is generally reserved for dialysis patients with severe hypertension. Hypertensive dialysis patients who are noncompliant with their medications may benefit from transdermal clonidine therapy once a week. The majority of dialysis patients need a combination of several antihypertensive drugs for adequate BP control.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Hypertension Control with Daily Dialysis
Authors: Saad Ehab , Charra Bernard , Raj Dominic S. C.
Published: July 2004

Hypertension is present in 60–90% of patients on maintenance hemodialysis (HD) and it is an important cause of cardiovascular (CV) mortality and morbidity. Frequent and prolonged HD has been uniformly shown to control hypertension in end‐stage renal disease (ESRD) patients more effectively than conventional HD. The etiology of hypertension is predominantly volume dependent, but in a subset of patients increased renin, sympathetic overactivity, and endothelial dysfunction may play a role. Intradialytic hypotension precludes attainment of dry weight and hence optimal control of hypertension in conventional HD is challenging. Frequent and prolonged dialysis with gentle and persistent ultrafiltration allows time for refilling of the intravascular compartment and permits normalization of extracellular volume. It is also possible that intensive dialysis enables removal of pressor molecules and improves endothelial function. Improved blood pressure control translates into regression of left ventricular hypertrophy in patients on daily HD. Thus prolonged and frequent dialysis permits better control of hypertension via volume and volume‐independent mechanisms and also improves cardiac geometry.
American Society of Diagnostic and Interventional Nephrology Section Editor: Stephen Ash: An Alternative Approach to the Central Circulation from Above the Diaphragm
Authors: Ross Jamie
Published: July 2004

This is a review of a new fluoroscopically guided safe technique to place tunneled cuffed hemodialysis (HD) catheters via the supraclavicular location. Right supraclavicular catheters were placed in 12 patients who had no patent internal jugular veins. The placements were all successful and without serious complications. Over the 2 years of follow‐up, two episodes of thrombosis/stenosis (16.7%) resulted in catheter removal. The rate of infection was 8%, or one episode in 1204 patient‐days. The average length of use was 111 days. The average rate of blood flow was 354 cc/min. The right supraclavicular approach for tunneled HD catheters is safe and compares favorably to the internal jugular approach for patients with limited access options.
Special Article: National Surveillance of Dialysis‐Associated Diseases in the United States, 2001
Authors: Tokars Jerome I. , Finelli Lyn , Alter Miriam J. , Arduino Matthew J.
Published: July 2004

In December 2001, all U.S. chronic hemodialysis (HD) centers were surveyed regarding selected patient care practices and dialysis‐associated diseases. The results were compared with similar surveys conducted in previous years. During 1997–2001, the percentage of patients vaccinated against hepatitis B virus (HBV) infection increased from 47% to 60% and the percentage of staff vaccinated increased from 87% to 89%. In 2001, an estimated 65% of patients had been vaccinated for influenza and 26% for pneumococcal pneumonia. In 2001, routine testing for antibody to hepatitis C virus (anti‐HCV) was performed on staff at 42% of centers and on patients at 62% of centers; anti‐HCV was found in 1.5% of staff and 8.6% of patients. In 2001, the incidence of HBV infection was higher among patients in centers where injectable medications were prepared at the dialysis station, and both HCV prevalence and incidence were higher among patients in centers where injectable medications were prepared at the dialysis station compared to a dedicated medication room. During 1995–2001, the percentage of patients who received dialysis through central catheters increased from 13% to 25%; this trend is worrisome, as infections and antimicrobial use are higher among patients receiving dialysis through catheters. However, during the same period, the percentage of patients receiving dialysis through fistulas increased from 22% to 30%. In 2001, 25% of catheters were used for new patients awaiting an arteriovenous (AV) access, 28% for established patients with a failed access awaiting new AV access, 40% as an access of last resort, and 6% for other reasons, including patient preference. The percentage of centers reporting one or more patients infected or colonized with vancomycin‐resistant enterococcus (VRE) increased from 12% in 1995 to 31% in 2001.
Psychiatric morbidity in psoriasis: A review
Authors: Russo Paul AJ , Ilchef Ralf , Cooper Alan J
Published: July 2004

SUMMARY Psoriasis is a common condition, affecting 1.5–2% of the population of industrialized countries. It is important for clinicians to be aware that psoriasis can have a substantial emotional impact on an individual, which is not necessarily related to the extent of skin disease. This review examines current literature addressing the psychological and emotional aspects of psoriasis. A literature search of the MEDLINE (1966–2002) and PsycINFO (1984–2002) computer databases and bibliographies was carried out. Papers selected for the review included English language reviews and all original research relevant to the topic, in the form of randomized controlled trials, cohort studies, case–control studies, cross‐over and uncontrolled clinical trials, patient surveys, quality‐of‐life studies, case series and case reports. Despite significant shortcomings, the available prevalence studies showed uniformly high rates of psychopathology among psoriasis sufferers. The few intervention studies available are summarized and critically discussed. Psoriasis is associated with a variety of psychological problems, including poor self esteem, sexual dysfunction, anxiety, depression and suicidal ideation. The clinical severity of the psoriasis may not reflect the degree of emotional impact of the disease. A number of psychological interventions have shown promise in recent trials. It is important that clinicians consider the psychosocial aspects of this illness.
Guttate psoriasis following Ecstasy ingestion
Authors: Tan Boon , Foley Peter
Published: July 2004

SUMMARY A 23‐year‐old man presented with the onset of a widespread pruritic eruption 4 days after ingestion of an Ecstasy tablet for the first time. The rash was characterized by small papules up to 10 mm in diameter distributed in a guttate pattern over most of his body and displaying the Köbner phenomena. Histology diagnosed a psoriasiform drug eruption. The eruption was not responsive to the initial treatment of topical betamethasone dipropionate 0.1% ointment and oral prednisolone. Prompt resolution was achieved with narrowband UVB treatment and avoidance of rechallenge.
Scarring of the eyelids from Coblation™ treatment
Authors: Bellaney Grant John
Published: July 2004

SUMMARY Coblation™ therapy has been recently proposed as a new bipolar electrosurgical method for facial resurfacing. Initial reports suggested this therapy to be very safe with a minimal amount of training required. To date there have be no reports of scarring with its use. Scarring of the lower eyelids is reported in a 50‐year‐old woman who underwent Coblation™ to improve the skin texture and fine lines of her lower eyelids. It is concluded that Coblation™ can cause scarring.
Atrophic dermatofibrosarcoma protuberans: An uncommon and misleading variant
Authors: Wu Jason K , Malik Mohsin M , Egan Conleth Anthony
Published: July 2004

SUMMARY A 23‐year‐old man presented with an atrophic lesion on his left anterior shoulder that had been present for at least 10 years. A previous biopsy had suggested a fibrohistiocytic origin; however, clinically it resembled morphoea or atrophoderma, and the lesion was observed. Fifteen months later, the lesion was noted to have grown slightly. A repeat biopsy showed dermatofibrosarcoma protuberans, with a storiform spindle cell proliferation with positive CD34 staining. The lesion was excised with a 3‐cm margin. Awareness of this rare presentation may assist in earlier diagnosis.
Multiple eccrine hidrocystomas
Authors: Lee Michael R , Ryman William
Published: July 2004

SUMMARY The clinical and pathological features and treatment of two patients with multiple eccrine hidrocystomas are presented. The first case is characterized by multiple pearly papules with a bluish hue located in the periorbital region and the bridge of the nose. The second case is characterized by multiple, skin‐coloured papules located in the periorbital area, forehead, chin and nose. Both were exacerbated by a hot and humid environment. Histopathologically, both demonstrated a unilocular cyst located in the dermis, with a 2–3‐layer wall composed of cuboidal epithelium that was non‐keratinizing. Treatment with topical atropine sulphate 1% in aqueous solution three times a day was instituted in the first case; however, this was poorly tolerated because of blurred vision and nausea. The lesions were subsequently hyfrecated with a good response. The second case was treated with topical atropine sulphate 1% in aqueous solution three times a day with a good response.
Weathering of hair in trichoteiromania
Authors: Banky Jeremy P , Sheridan Adam T , Dawber Rodney PR
Published: July 2004

SUMMARY A 74‐year‐old woman presented with an 18‐month history of broken vertex scalp hairs as a consequence of chronic rubbing. Light microscopy of the 1–2 cm hairs demonstrated distal brush‐like splitting. Education and behavioural therapy were instituted. After 4 months of reduced rubbing of the vertex scalp hairs, the hairs re‐grew with no evidence of persistent hair shaft abnormality.
The Transmission of Monetary Policy in the Euro Area: Are the Effects Different Across Countries?*
Authors: Peersman Gert
Published: July 2004

This paper analyses whether the effects of the monetary policy of the European Central Bank (ECB) may be different across Euro area countries. First, the limitations in the current empirical literature are highlighted. The paper then suggests how to deal with these limitations and provides new empirical evidence on the effects of a common monetary policy shock across individual member countries. Surprisingly, very similar output effects are found across countries.
From R&D to Productivity Growth: Do the Institutional Settings and the Source of Funds of R&D Matter?
Authors: Guellec Dominique , Van Pottelsberghe de la Potterie Bruno
Published: July 2004

This paper presents estimates of the long‐term impact of various sources of knowledge (R&D performed by the business sector, the public sector and foreign firms) on multifactor productivity growth of 16 countries from 1980 to 1998. The main results show that the three sources of knowledge are significant determinants of long‐term productivity growth. Further evidence suggests that several factors determine the extent to which each source of knowledge contributes to productivity growth. These factors are the absorptive capability, the origin of funding, the socioeconomic objectives of government support, and the type of public institutions that perform R&D.
Analysing I(2) Systems by Transformed Vector Autoregressions*
Authors: Kongsted Hans Christian , Nielsen Heino Bohn
Published: July 2004

We characterize the restrictions imposed by the minimal I(2)‐to‐I(1) transformation that underlies much applied work, e.g. on money demand relationships or open‐economy pricing relationships. The relationship between the parameters of the original I(2) vector autoregression, including the coefficients of polynomially cointegrating relationships, and the transformed I(1) model is characterized. We discuss estimation of the transformed model subject to restrictions as well as the more commonly used approach of unrestricted reduced rank regression. Only a minor loss of efficiency is incurred by ignoring the restrictions in the empirical example and a simulation study. A properly transformed vector autoregression thus provides a practical and effective means for inference on the parameters of the I(2) model.
A Comparison of Johansen's, Bierens’ and the Subspace Algorithm Method for Cointegration Analysis*
Authors: Wagner Martin
Published: July 2004

The methods listed in the title are compared by means of a simulation study and a real world application. The aspects compared via simulations are the performance of the tests for the cointegrating rank and thequalityof the estimated cointegrating space. The subspace algorithm method, formulated in the state space framework and thus applicable for vector autoregressive moving average (VARMA) processes, performs at least comparably to the Johansen method. Both the Johansen procedure and the subspace algorithm cointegration analysis perform significantly better than Bierens’ method. The real‐world application is an investigation of the long‐run properties of the one‐sector neoclassical growth model for Austria. The results do not fully support the implications of the model with respect to cointegration. Furthermore, the results differ greatly between the different methods. The amount of variability depends strongly upon the number of variables considered and huge differences occur for the full system with six variables. Therefore we conclude that the results of such applications with about five or six variables and 100 observations, which are typical in the applied literature, should possibly be interpreted with more caution than is commonly done.
Pacinian corpuscle in the juxtaoral organ of Chievitz
Authors: Ide Fumio , Mishima Kenji , Saito Ichiro
Published: July 2004

The juxtaoral organ of Chievitz (JOOC) is a normal permanent anatomical structure located within the soft tissue overlying the angle of the mandible in the buccotemporal space. Although the sensory organ nature of JOOC, repeatedly mentioned in German publications, has been neglected in the last decade by the American anatomists and pathologists, we incidentally found JOOC‐type squamous epithelium accompanied by Pacinian corpuscles. This fortuitous finding appears to be the first report of the authentic Paciniform nerve endings within JOOC, supporting its mechanosensory function.
Maspin expression in normal and neoplastic salivary gland
Authors: De Lima Navarro Ricardo , Trierveiler Martins Marília , De Araújo Vera Cavalcanti
Published: July 2004

Background:  Maspin inhibits cell motility, invasion and metastasis. Loss or reduction in maspin expression has been associated with tumoral progression.

Methods:  The presence of maspin was studied immunohistochemically in salivary gland tumours presenting cells with myoepithelial differentiation in their composition, and in normal salivary gland.

Results:  Pleomorphic adenoma (PA) presented high expression of maspin, except in the spindle cells and occasional luminal cells. Epithelial–myoepithelial carcinoma and tubular adenoid cystic carcinoma (ACC) showed intense expression in all cells. Cribriform ACC evidenced only few positive cells of the luminal type, while solid subtype showed rare positive cells. Normal salivary gland tissue has shown low levels of maspin positivity.

Conclusions:  Maspin has small participation in normal salivary gland, is increased in PA, and decreases as the histological malignancy raises. Hence, in salivary gland, its expression is not exclusive of myoepithelial cells; thus, it should not be used as a marker for this cell. Nevertheless, we believe it is an important marker of biological behaviour in these tumours.