bluuebunny/crossref_metadata_2025 huggingface dataset:
Tight Control of Exogenous SERCA Expression Is Required to Obtain Acceleration of Calcium Transients With Minimal Cytotoxic Effects in Cardiac Myocytes
Authors: O’Donnell J. Michael , Sumbilla Carlota M. , Ma Hailun , Farrance Iain K. G. , Cavagna Marco , Klein Michael G. , Inesi Giuseppe
Published: June 2012

Abstract
—Collateral effects of exogenous sarcoendoplasmic reticulum Ca
2+
ATPase (SERCA) expression were characterized in neonatal rat and chicken embryo cardiac myocytes, and the conditions required to produce acceleration of Ca
2+
transients with minimal toxicity were established. Cultured myocytes were infected with adenovirus vector carrying the cDNA of wild-type SERCA1, an inactive SERCA1 mutant, or enhanced green fluorescence protein under control of the cytomegalovirus promoter. Controls were exposed to empty virus vector. Each group was tested with and without phenylephrine (PHE) treatment. Under conditions of limited calf-serum exposure, the infected rat myocytes manifested a more rapid increase in size, protein content, and rate of protein synthesis relative to noninfected controls. These changes were not accompanied by reversal to fetal transcriptional pattern (as observed in hypertrophy triggered by PHE) and may be attributable to facilitated exchange with serum factors. SERCA virus titers >5 to 6 plaque-forming units per cell produced overcrowding of ATPase molecules on intracellular membranes, followed by apoptotic death of a significant number of rat but not chicken myocytes. Enhanced green fluorescence protein virus and empty virus also produced cytotoxic effects but at higher titers than SERCA. Expression of exogenous SERCA and enhancement of Ca
2+
transient kinetics could be obtained with minimal cell damage in rat myocytes if the SERCA virus titer were maintained within 1 to 4 plaque-forming units per cell. Expression of endogenous SERCA was unchanged, but expression of exogenous SERCA was higher in myocytes rendered hypertrophic by treatment with PHE than in nontreated controls.
Human Platelets Contain a Glycosylated Estrogen Receptor β
Authors: Nealen Michele L. , Vijayan K. Vinod , Bolton Everlie , Bray Paul F.
Published: June 2012

Abstract
—Platelets play an important role in the coronary thrombus formation that leads to myocardial ischemia and infarction. Gender differences in the development of coronary heart disease and its outcomes are partly regulated by estrogen and its receptors, but the roles of the latter in thrombogenicity are less well-defined. We previously demonstrated the presence of estrogen receptor (ER) β in cells of the megakaryocytic lineage. In this study, we characterize human platelet ERβ and its expression using biochemical and molecular biological techniques. Western immunoblotting showed that platelet ERβ migrated with an apparent molecular mass ≈3.7 kDa larger than ERβ in a variety of cell lines (including those of prostate and breast origin). A rigorous investigation of platelet ERβ mRNA by reverse transcriptase–polymerase chain reaction revealed normal transcripts and a single alternately spliced mRNA. However, this variant form was smaller, lacking exon 2, and could not account for the larger protein size seen in platelets. Treatment of ERβ with
N
-glycosidase F, which removes core carbohydrate residues, caused a more rapid migration through polyacrylamide gels but had no effect on ERβ from human cell lines. We conclude that the larger form of ERβ in human platelets is not attributable to alternate mRNA splicing but primarily to tissue-specific glycosylation.
Heme Oxygenase-1 Inhibits Atherosclerotic Lesion Formation in LDL-Receptor Knockout Mice
Authors: Ishikawa Kazunobu , Sugawara Daisuke , Wang Xu-ping , Suzuki Kazunori , Itabe Hiroyuki , Maruyama Yukio , Lusis Aldons J.
Published: June 2012

Abstract
—Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.
Autoimmunity Against the Second Extracellular Loop of β
1
-Adrenergic Receptors Induces β-Adrenergic Receptor Desensitization and Myocardial Hypertrophy In Vivo
Authors: Iwata Michikado , Yoshikawa Tsutomu , Baba Akiyasu , Anzai Toshihisa , Nakamura Iwao , Wainai Yumiko , Takahashi Toshiyuki , Ogawa Satoshi
Published: June 2012

Abstract
—Although immunoapheresis removing autoantibodies against the second extracellular domain of β
1
-adrenergic receptors (ARs) improves cardiac function in patients with cardiomyopathy, the underlying mechanisms have not been defined. We examined the role of autoimmunity against the domain in the development of cardiac dysfunction in vivo. Japanese white rabbits were immunized with a synthetic peptide corresponding to the second extracellular loop of β
1
-AR once a month with (β+biso rabbits, n=10) or without (β rabbits, n=13) bisoprolol treatment (2 mg/kg per day). Control rabbits received vehicle without bisoprolol treatment (n=13). Autoantibodies of IgG isotype against the domain were persistently detected in β and β+biso rabbits. Purified IgG from sera of β and β+biso rabbits increased cAMP production in a rabbit cardiac membrane preparation, which was blocked by bisoprolol. At 3 months, β-AR uncoupling with increased G protein–coupled receptor kinase 5 (GRK5) expression was found in β rabbits. At 6 months, left ventricular hypertrophy was noted with hemodynamic derangements in β rabbits. This was accompanied by decreased β
1
-AR density and increased inhibitory G protein and GRK5 expression, which were related to marked decrease in membrane cAMP production. These changes in β rabbits at 6 months were prevented in β+biso rabbits. There was no difference in the plasma norepinephrine concentration in the 3 groups over the observation period. Thus, autoimmunity against the second extracellular loop of β
1
-ARs induced profound β-AR desensitization and myocardial hypertrophy in vivo, associated with cardiac dysfunction. Sustained sympathomimetic-like actions of autoantibodies against the domain may be partly responsible for these changes.
Decreased Flow-Dependent Dilation in Carotid Arteries of Tissue Kallikrein–Knockout Mice
Authors: Bergaya Sonia , Meneton Pierre , Bloch-Faure May , Mathieu Eric , Alhenc-Gelas François , Lévy Bernard I. , Boulanger Chantal M.
Published: June 2012

Abstract
— Flow-dependent dilation is a fundamental mechanism by which large arteries ensure appropriate blood supply to tissues. We investigated whether or not the vascular kallikrein-kinin system, especially tissue kallikrein (TK), contributes to flow-dependent dilation by comparing wild-type and TK-knockout mice in which the presence or absence of TK expression was verified. We examined in vitro changes in the outer diameter of perfused carotid arteries from TK
+/+
and TK
−/−
mice. In both groups, exogenous bradykinin caused a similar dilation that was abolished by the B
2
receptor antagonist HOE-140, as well as by the NO synthase inhibitor
N
ω
-nitro-
l
-arginine methyl ester. However, purified kininogen dilated only TK
+/+
arteries, demonstrating the essential role of TK in the vascular formation of kinins. In TK
+/+
arteries, increasing intraluminal flow caused a larger endothelium-dependent dilation than that seen in TK
−/−
. In both strains the flow response was mediated by NO and by endothelium-derived hyperpolarizing factor, whereas in TK
−/−
vasoconstrictor prostanoids participated as well. HOE-140 impaired flow-dependent dilation in TK
+/+
arteries while showing no effect in TK
−/−
. This compound reduced the flow response in TK
+/+
arteries to a level similar to that in TK
−/−
. After NO synthase inhibition, HOE-140 no longer affected the response of TK
+/+
. Impaired flow-dependent dilation was also observed in arteries from knockout mice lacking bradykinin B
2
receptors as compared with wild-type animals. This study demonstrates the active contribution of the vascular kallikrein-kinin system to one-third of the flow-dependent dilation response via activation of B
2
receptors coupled to endothelial NO release.
Evaluation of Plasma, Metaraminol, and Hydrocortisone in Experimental Endotoxin Shock
Authors: SPINK WESLEY W. , VICK JAMES
Published: June 2012

An experimental model of canine endotoxin shock was employed for evaluating therapeutic agents that are used in the management of peripheral vascular collapse. An important feature of the present study was that an agent or agents were not administered until hypotension and oligulria were present. Progressive endotoxin shock was not reversed by the infusion of large amounts of canine plasma. Large doses of hydrocortisone did not prevent a lethal outcome. Even though the blood pressure was stabilized near normotensive levels with the vasopressor drug, metaraminol, progressive shock occurred. The most significant finding was that lethal endotoxin shock was prevented in six of the 10 animals studied by the simultaneous use of hydrocortisone and metaraminol. Only one-eighth the amount of metaraminol was necessary to maintain normotensive levels of blood pressure if a large dose of hydrocortisone was administered before the infusion of the pressor drug.
Effect of Heart Rate and Intracoronary Isoproterenol, Levarterenol, and Epinephrine on Coronary Flow and Resistance
Authors: LEWIS F. BRUCE , COFFMAN JAY D. , GREGG DONALD E.
Published: June 2012

The effect was determined of changes in heart rate and of intracoronary isoproterenol, levarterenol, and epinephrine on coronary flow in the stopped and beating heart. It was possible by this means to estimate the relative action of these variables on the extravascular and intravascular resistance of the coronary bed in a heart perfused at constant pressure. As heart rate was increased extravascular resistance rose, but intravascular resistance fell to a greater extent indicating a fall in net coronary resistance. Isoproterenol had the greatest and epinephrine the least effect in decreasing the total coronary resistance. The three drugs tested caused only a small fall in extravascular resistance. Since the effect was small, it was concluded that extravascular resistance can be ignored in determining the direct effect of these drugs upon the coronary vasculature.
Anatomy of the Ventricular Coronary Arteries in the Dog
Authors: BLAIR EMIL
Published: June 2012

The ventricular coronary arterial system of the dog displays preponderance of the left in 100 per cent of the animals studied. The single most important source of blood supply is the left circumflex artery, which supplies not only most of the left ventricle, but also significant portions of the right ventricle. Details of the septal branch are described. Morphological implications concerning death or survival in experimental coronary occlusive procedures are discussed. A simple nomenclature is offered.
Adrenal Medullary Secretion During Hypoxia, Bleeding, and Rapid Intravenous Infusion
Authors: FOWLER NOBLE O. , SHABETAI RALPH , HOLMES JOHN C.
Published: June 2012

This study reports the effect of hypoxia, of lowering blood pressure by bleeding, and of rapid infusion upon adrenal secretion in anesthetized dogs. Adrenal norepinephrine-like substances (NEL) were measured in adrenal venous blood by means of a bio-assay method, using the rabbit aortic strip. In 10 of 11 dogs breathing 7.1 per cent O
2
in N
2
, the left adrenal NEL output was augmented 1.5 to 6.6 times control levels. The increased adrenal medullary secretion during hypoxia was not dependent upon a fall in systemic arterial blood pressure and was not associated with an increase of 17-hydroxycorticosteroid output. In five dogs bled to a blood pressure of 80 to 90 mm. Hg, left adrenal NEL output was augmented 2.9 to 7.4 times control levels. In 11 animals in which the blood pressure was lowered to 40 to 50 mm. Hg by bleeding, left adrenal NEL output was augmented 1.8 to 17 times control levels. Seven dogs were made anemic and hypervolemic by rapid infusion of 1,125 to 1,900 ml. normal saline or Krebs' solution. Cardiac outputs were increased more than 200 per cent in six, and considerable dilution anemia was produced. However, left adrenal NEL outputs fell to values ranging from 14 to 50 per cent of control. During rapid infusions, output of adrenal 17-OHCS increased 18.5 to 92 per cent. It is concluded that increased adrenal medullary secretion did not participate in the increase of cardiac output observed in these seven animals.
Some Observations on the Role of the Lymphatics in Experimental Acute Pulmonary Edema
Authors: UHLEY HERMAN , LEEDS SANFORD E. , SAMPSON JOHN J. , FRIEDMAN MEYER
Published: June 2012

Lymph was collected from the right duct and thoracic duct of 13 dogs in which acute pulmonary edema was produced by partial obstruction of the left atrium by means of a balloon. Elevation of left atrial pressure to 30 mm. Hg resulted in an increase in thoracic duct flow within 30 minutes, followed by an increase in right duct flow within the next 15 minutes. Critical pulmonary edema became manifest approximately 30 minutes after the onset of increased right duct flow, and the dogs died in pulmonary edema approximately 90 minutes after inflation of the left atrial balloon, unless the left atrial pressure was reduced. The per cent of fluid in serial lung biopsies increased in the first biopsy taken 15 minutes after the elevation of left atrial pressure to 30 mm. Hg, and the increase was sustained, resulting in engorgement of the lungs unless the left atrial pressure was decreased. The small absolute increase in lymph from the right duct suggests that the lymphatics are unable to function significantly to relieve the pulmonary edema produced in the.se acute experiments, resulting in an overflow of fluid into the tracheobronchial tree. C41utamic oxalacetic transaminase showed marked increases in the lymph from the right duct but only modest increases in the lymph from the thoracic duct throughout the experiments. Pyruvic transaminase in lymph from the right and thoracic ducts was relatively unchanged.
Serial Hemodynamic Study of Cerebral Infarction in Man
Authors: KEMPINSKY WARREN H. , BONIFACE WILLIAM R. , KEATING, JOSE B. A. , MORGAN PETER P.
Published: June 2012

It has sometimes been proposed that the early period of resolution of neurologic deficit, which often follows acute cerebral infarction, is due to relaxation of a surrounding, second ary vasoconstriction. To investigate this as sumption, cerebral hemodynamics were studied by the inert gas method in 13 patients with re cent cerebral infarction. In 10 instances in the acute stage, there were no significant dif ferences between mean hemodynamic values based on jugular bulb blood samples from the side of the infarct and those from the contra- lateral side. Similarly, comparisons of mean values failed to disclose significant differences between studies performed shortly after the onset of the stroke and those done three weeks later, at a time when all patients investigated demonstrated clinical improvement. The inert gas method is not applicable to the study of the infarct itself, but it is considered valid for the demonstration of cerebral vasocon triction if the latter is sufficiently widespread. In the absence of hemodynamic change, it was concluded that this study does not support the vasoconstriction explanation. It was rec ognized, however, that vasoconstriction would need to be quite widespread to be detected by this method.
Effects of Atropine and Isoproterenol on Cardiac Output, Central Venous Pressure, and Mean Transit Time of Indicators Placed at Three Different Sites in the Venous System
Authors: GORTEX RALPH , GUNXELLS J. CAULIE , WEISSLER ARNOLD M. , STEAD EUGENE A.
Published: June 2012

Two milligrams of atropine given intravenously increased the cardiac output, the mean arterial pressure, and the heart rate and lowered the central venous pressure, stroke output, and peripheral resistance. Tsoproterenol given intravenously at the rate of 1 µg. per minute increased the cardiac output with only an average increase in pulse rate of nine beats per minute. The stroke volume was increased. The central venous pressure and the peripheral resistance were decreased. These observations on the circulation were made in the steady state. They demonstrate that the minute output of the heart can be increased by either a rise in rate or an increase in stroke volume in the presence of a fall in central venous pressure. They do not define the order of events leading to the steady state. When the indicator was placed in the superior vena cava, neither atropine nor isoproterenol changed the volume in which the indicator was diluted during its first circulation. Both atropine and isoproterenol decreased the volumes in which the indicators were diluted when they were injected into the antecubital or femoral veins.
Incidence of Infective Endocarditis Caused by Viridans Group Streptococci Before and After Publication of the 2007 American Heart Association's Endocarditis Prevention Guidelines
Authors: DeSimone Daniel C. , Tleyjeh Imad M. , Correa de Sa Daniel D. , Anavekar Nandan S. , Lahr Brian D. , Sohail Muhammad R. , Steckelberg James M. , Wilson Walter R. , Baddour Larry M.
Published: June 2012

Background—

The American Heart Association published updated guidelines for infective endocarditis (IE) prevention in 2007 that markedly restricted the use of antibiotic prophylaxis in certain at-risk patients undergoing dental and other invasive procedures. The incidence of IE caused by viridans group streptococci (VGS) in the United States after publication of the 2007 American Heart Association guidelines has not been reported.

Methods and Results—

We performed a population-based review of all definite or possible cases of VGS-IE using the Rochester Epidemiology Project of Olmsted County, Minnesota. Patient demographics and microbiological data were collected for all VGS-IE cases diagnosed from January 1, 1999, through December 31, 2010. We also examined the Nationwide Inpatient Sample hospital discharge database to determine the number of VGS-IE cases included between 1999 and 2009. We identified 22 cases with VGS-IE in Olmsted County over the 12-year study period. Rates of incidence (per 100 000 person-years) during time intervals of 1999–2002, 2003–2006, and 2007–2010 were 3.19 (95% confidence interval, 1.20–5.17), 2.48 (95% confidence interval, 0.85–4.10), and 0.77 (95% confidence interval, 0.00–1.64), respectively (
P
=0.061 from Poisson regression). The number of hospital discharges with a VGS-IE diagnosis in the Nationwide Inpatient Sample database during 1999–2002, 2003–2006, and 2007–2009 ranged between 15 318 to 15 938, 16 214 to 17 433, and 14 728 to 15 479, respectively.

Conclusions—

On the basis of data complete through 2010, there has been no perceivable increase in the incidence of VGS-IE in Olmsted County, Minnesota, since the publication of the 2007 American Heart Association endocarditis prevention guidelines.
Intrarenal Angiotensin III Is the Predominant Agonist for Proximal Tubule Angiotensin Type 2 Receptors
Authors: Kemp Brandon A. , Bell John F. , Rottkamp Daniele M. , Howell Nancy L. , Shao Weijian , Navar L. Gabriel , Padia Shetal H. , Carey Robert M.
Published: June 2012

In angiotensin type 1 receptor–blocked rats, renal interstitial (RI) administration of des-aspartyl
1
-angiotensin II (Ang III) but not angiotensin II induces natriuresis via activation of angiotensin type 2 receptors. In the present study, renal function was documented during systemic angiotensin type 1 receptor blockade with candesartan in Sprague-Dawley rats receiving unilateral RI infusion of Ang III. Ang III increased urine sodium excretion, fractional sodium, and lithium excretion. RI coinfusion of specific angiotensin type 2 receptor antagonist PD-123319 abolished Ang III–induced natriuresis. The natriuretic response observed with RI Ang III was not reproducible with RI angiotensin (1-7) alone or together with angiotensin-converting enzyme inhibition. Similarly, neither RI angiotensin II alone or in the presence of aminopeptidase A inhibitor increased urine sodium excretion. In the absence of systemic angiotensin type 1 receptor blockade, Ang III alone did not increase urine sodium excretion, but natriuresis was enabled by the coinfusion of aminopeptidase N inhibitor and subsequently blocked by PD-123319. In angiotensin type 1 receptor–blocked rats, RI administration of aminopeptidase N inhibitor alone also induced natriuresis that was abolished by PD-123319. Ang III–induced natriuresis was accompanied by increased RI cGMP levels and was abolished by inhibition of soluble guanylyl cyclase. RI and renal tissue Ang III levels increased in response to Ang III infusion and were augmented by aminopeptidase N inhibition. These data demonstrate that endogenous intrarenal Ang III but not angiotensin II or angiotensin (1-7) induces natriuresis via activation of angiotensin type 2 receptors in the proximal tubule via a cGMP–dependent mechanism and suggest aminopeptidase N inhibition as a potential therapeutic target in hypertension.
Multiple Endothelial Biomarkers and Noninvasive Vascular Function in the General Population
Authors: Schnabel Renate B. , Wild Philipp S. , Schulz Andreas , Zeller Tanja , Sinning Christoph R. , Wilde Sandra , Kunde Jan , Lubos Edith , Lackner Karl J. , Warnholtz Ascan , Gori Tommaso , Blankenberg Stefan , Munzel Thomas
Published: June 2012

Vascular reactivity is reflected by blood biomarkers and noninvasive vascular function measurement. The relation of biomarkers to flow-mediated dilation and peripheral arterial tonometry in the general population is little understood. In 5000 individuals (mean age, 56±11 years; age range, 35–74 years; 49% women) of the population-based Gutenberg Health Study we simultaneously assessed 6 biomarkers of cardiovascular function (midregional proadrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro B-type natriuretic peptide, copeptin, C-terminal proendothelin 1, and neopterin) in relation to flow-mediated dilation and peripheral arterial tonometry. Strongest partial correlations (adjusted for age and sex) were observed for baseline pulse amplitude with MR-proADM (
r
=0.13) and MR-proANP (
r
=−0.13); hyperemic response variables showed the highest correlation for MR-proADM and peripheral arterial tonometry ratio (
r
=−0.14). In multivariable linear regression models, strongest associations with baseline vascular function were observed for MR-proANP with baseline pulse amplitude (β per SD increase [99.17%], −0.080 [−0.115 to −0.044];
P
<0.0001 after Bonferroni correction for multiple testing) and MR-proADM (−0.044 [−0.070 to −0.017];
P
<0.0001), as well as MR-proANP (−0.033 [−0.057 to −0.009];
P
=0.0017) and N-terminal pro B-type natriuretic peptide (−0.027 [−0.051 to −0.003];
P
=0.015) with brachial artery diameter. For hyperemic response variables, highest associations were seen for peripheral arterial tonometry ratio with MR-proADM (−0.022 [−0.043 to −0.004];
P
=0.043), MR-proANP (0.016 [−0.0034 to 0.035];
P
=0.18), and C-terminal proendothelin 1 (−0.025 [−0.043 to −0.008];
P
=0.00094]. In our large, population-based study, we identified MR-proADM and MR-proANP as circulating biomarkers of vascular function most strongly related to noninvasive measures of conduit artery and peripheral arterial performance. Whether determination of blood biomarkers helps to better understand vascular pathology and may provide prognostic information needs to be investigated in future studies.
An Essential Role for ΔFosB in the Median Preoptic Nucleus in the Sustained Hypertensive Effects of Chronic Intermittent Hypoxia
Authors: Cunningham J. Thomas , Knight W. David , Mifflin Steven W. , Nestler Eric J.
Published: June 2012

One of the main clinical features of obstructive sleep apnea is sustained hypertension and elevated sympathetic activity during waking hours. Chronic intermittent hypoxia (CIH), animal model of the hypoxemia associated with obstructive sleep apnea, produces a similar sustained increase in blood pressure. This study determined the role of ΔFosB in the median preoptic nucleus (MnPO) in the sustained increase in mean arterial pressure associated with CIH. Rats were injected in the MnPO with viral vectors that expressed green fluorescent protein alone or green fluorescent protein plus a dominant-negative construct that inhibits the transcriptional effects of ΔFosB. In green fluorescent protein–injected rats and uninjected controls, 7-day exposure to CIH increased mean arterial pressure by 7 to 10 mm Hg during both intermittent hypoxia exposure and normoxia. Dominant-negative inhibition of MnPO ΔFosB did not affect changes in mean arterial pressure during intermittent hypoxia exposure but significantly reduced the sustained component of the blood pressure response to CIH during the normoxic dark phase. Inhibition of MnPO ΔFosB reduced the FosB/ΔFosB staining in the paraventricular nucleus and rostral ventrolateral medulla but not the nucleus of the solitary tract. PCR array analysis identified 6 activator protein 1–regulated genes expressed in the MnPO that were increased by CIH exposure,
ace
,
ace2
,
nos1
,
nos3
,
prdx2
, and
map3k3
. Dominant-negative inhibition of ΔFosB in the MnPO blocked increased expression of each of these genes in rats exposed to CIH except for Prdx2. ΔFosB may mediate transcriptional activity in MnPO necessary for sustained CIH hypertension, suggesting that neural adaptations may contribute to diurnal hypertension in obstructive sleep apnea.
Obsessive–compulsive personality disorder co-occurring with obsessive-compulsive disorder: Conceptual and clinical implications
Authors: Starcevic Vladan , Berle David , Brakoulias Vlasios , Sammut Peter , Moses Karen , Milicevic Denise , Hannan Anthony
Published: June 2012

Objectives:

There are ongoing uncertainties in the relationship between obsessive–compulsive disorder (OCD) and obsessive–compulsive personality disorder (OCPD). This study aimed to test the proposition that OCPD may be a marker of severity of OCD by comparing groups of OCD individuals with and without OCPD on a number of variables.

Method:

A total of 148 adults with a principal diagnosis of OCD were administered the Mini International Neuropsychiatric Interview, Yale–Brown Obsessive–Compulsive Scale, Sheehan Disability Scale, Vancouver Obsessional Compulsive Inventory and Symptom Checklist 90-Revised. Participants with a DSM-IV diagnosis of OCPD were compared with those without OCPD.

Results:

Some 70 (47.3%) participants were diagnosed with OCPD. The groups of participants with and without OCPD did not differ significantly with respect to any of the demographic variables, clinician-rated severity of OCD, levels of disability and mean age of onset of OCD. All self-rated OCD symptom dimensions except for contamination and checking were significantly more prominent in participants with OCPD, as were all self-rated dimensions of psychopathology. Participants with OCPD had significantly more frequent hoarding compulsions and obsessions involving a need to collect and keep objects. Of Axis I disorders, only panic disorder was significantly more frequent in participants with OCPD than in those without OCPD.

Conclusions:

A high frequency of OCPD among individuals with OCD suggests a strong, although not necessarily a unique, relationship between the two conditions. This finding may also be a consequence of the blurring of the boundary between OCD and OCPD by postulating that hoarding and hoarding-like behaviours characterise both disorders. Results of this study do not support the notion that OCD with OCPD is a marker of clinician-rated severity of OCD. However, individuals with OCPD had more prominent OCD symptoms, they were more distressed and exhibited various other psychopathological phenomena more intensely, which is likely to complicate their treatment.
Stimulant side effects and inverted-U: Implications for ADHD guidelines
Authors: Levy Florence
Published: June 2012

Objective:

To review literature relevant to a possible prediction of stimulant side effects in attention deficit hyperactivity disorder (ADHD), with implications for guidelines.

Method:

Recent literature on inverted-U effects of dopamine in the prefrontal cortex (PFC), default mode processing, and motor circuits relevant to stimulant side effects is reviewed.

Results:

The literature on inverted-U effects in the PFC suggests that catechol-O-methyltransferase (COMT) Met versus Val polymorphisms may predict excess dopaminergic effects, including headache and introversion in Met/Met subjects, but therapeutic effects in Val/Val subjects, while dopamine transporter polymorphisms may predict motor side effects. In particular, an understanding of ‘inverted-U’ effects helps to explain why some children may experience side effects while others show improvements at similar dose ranges.

Conclusion:

Genetic prediction of stimulant side effects should be investigated, particularly given recent controversies in relation to National Health and Medical Research Council guidelines for stimulant use. A better understanding of treatment-emergent effects will also provide a better understanding of therapeutic effects.
Democratic governance at times of crisis: rebuilding our communities and building on our citizens
Authors: Fraser-Moleketi Geraldine J.
Published: June 2012

Crises have opened avenues to change and have often shown the way to progress and reform. Examples abound world-wide. Crises have proved beneficial when citizens and governments have taken pains to explore the lessons they may yield and listen to the messages that they contain. The goal in this article is to open a debate which sheds some light on the sources of our current deep malaise and tries to make some sense of the direction which international agencies, and governments at large, would be advised to follow. This article represents the outgrowth of the experience of years of public service on both the national level and, since January 2009, at the United Nations Development Programme (UNDP). Though it does not pretend and should not be construed to represent the views of the UNDP on major global issues, it inevitably reflects the fruit of long hours of work on its behalf, in several parts of the world. Unlike some other inter-regional organizations, the UNDP encompasses all Member States in its remit. For obvious reasons, however, its workaday operations are more directly related to the concerns of developing countries. In democratic governance, which is a major area of UNDP activity, the countries and the regions that are currently undergoing a rapid course of change stand out for consideration. The author of this article has been intensely involved in consultations over this process. Accordingly, what follows reflects, to some extent, the sum of this experience. It happens that my watch has seen years of deep crises, both natural and man-made. Indeed, some of these crises have also demonstrated the measure and the progress of globalization. Events in one part of the world were soon replicated in others. Thus, the uprising in Tunisia soon spread to Libya and Egypt. The financial meltdown, which began in the US, in September 2008, has already migrated to Europe and has not stopped there. In the words of Timothy Geithner, the American Treasury Secretary, addressing the Asia-Pacific Economic Cooperation Forum in Hawaii, in November 2011, ‘We are all directly affected by the crisis in Europe’ ( New York Times, 2011c: A7). Though so far its effects have not been evenly felt across the board, this and other crises have shown that the countries that fared better and have been better able to weather the storm but also reap the benefits that come with globalization, were those whose state authorities and local government structures displayed a higher degree of competence, preparedness, commitment and professionalism.
Domestic reform and global integration: public administration reform in China over the last 30 years
Authors: Xue Lan , Zhong Kaibin
Published: June 2012

This article tries to depict China’s public administration reform as an interactive process between two major themes, domestic reform and global integration. The development and implementation of public administration reforms in China from 1978 to 2008 are reviewed. The driving forces shaping the process of public administration reform in China are analyzed, using a territorial locus (domestic/international) – policy dimension (supply-side/demand-side) analytical framework. Our analysis suggests that the public administration reforms over the past few decades have demonstrated the Chinese government’s intention to advance the government’s transition from an economic-centered state to a people-oriented one. While much progress has been made, there are many issues that remain to be resolved by the new generation of leadership in China.

Points for practitioners

This article aims to contribute to the discussion about the process of China’s public administration reform over the past three decades since late 1978 – the reform-and-open up years. In China’s public administration reform, the transition of the economic system from a planned economy to a socialist market economy has become the most important driving force, which is coupled with the transformation from a public administration system based on personal will and charisma to one that is increasingly based on rule of law. At the same time, the influence of other countries has also played an important role in today’s globalized environment. China has learned a great deal from international experiences in public administration reform. The entry into the WTO has also provided a strong impetus for China to integrate with global public administrative practice. So, China’s public administration system has always actively engaged in a transformative process characterized by domestic reform and global integration.
Asian model of government re-examined in the aftermath of the global economic crunch: a Japanese perspective from the experience of the triple disasters in March 2011
Authors: Nakamura Akira
Published: June 2012

This article addresses three related issues about the role and functions of government in East Asia in general and Japan in particular. First, it tries to describe the important function of national bureaucracy in Japan’s economic growth, a development mode that has often been labelled ‘statism’ or ‘administrative centred government’. The first section delineates how this model became entrenched in the country. Second, the article highlights several reform attempts to alter this basic configuration of Japanese government power, through efforts to dilute the control of bureaucracy and replace it with an ‘executive centred government’. The second section dwells on this transition and evaluates the results of different reform efforts. Finally, the article examines the effect of the disasters in March 2011 on these aspects of the country’s leadership, noting that the incumbent party leaders had little faith in the wisdom of mandarins, and planned to resolve the ongoing crises by themselves. The final section of the article deals with the schisms and fissures of the interface between electived members and non-elected administrators within the context of Japan’s crises.

Points for practitioners

The article first describes the ‘statism’ traditional in Japan. How Japanese bureaucrats devised a method to foster rapid development of the country during the 1960s and the early 1970s is the central focus of this section. Subsequently, this article examines the Hashimoto and Koizumi administrations and discusses to what extent they succeeded in entrenching ‘an executive centred government’ to replace the traditional statism mode of management. Later, the article touches on the mammoth earthquake that struck northern Japan on 11 March 2011. The Democratic Party of Japan had to deal with the crises within the confines of the statism legacy.
Developmental social work in South Africa: Translating policy into practice
Authors: Patel Leila , Hochfeld Tessa
Published: June 2012

Developmental social work is receiving increasing international recognition and much may be learnt from its application in different societal contexts. The article draws on empirical data from a South African study and provides valuable insight into how social workers conceptualize and translate developmental social work into practice.
Fewer Answers and Further Questions: Jews and Gentiles in Acts
Authors: Hedrick Pamela
Published: June 2012

The author of the Acts of the Apostles uses criteria commonly employed in his cultural context to legitimate the Jesus movement and the extension of the mission to the Gentiles as the divine plan. While these literary strategies result in material that can be employed uncritically and tragically to serve a bias against the Jewish people, a far more fruitful transposition of the Lukan strategies would raise intelligent questions about the ways of God in the world and the cooperation of humans with those ways.
Interpreting Acts
Authors: Holladay Carl R.
Published: June 2012

Interpreters of Acts face three recurrent questions: 1) What is its genre? 2) Why was it written? and 3) How is Scripture used? In deciding genre, readers must decide if Acts is history, and, if so, in what sense. Determining its literary or theological purpose can be done in terms of asking what Acts accomplishes.
The Ecclesiology of Acts
Authors: Rowe C. Kavin
Published: June 2012

This article examines the ecclesiology of Acts by considering the political shape of Acts vis-à-vis the wider Roman world. The discussion of three scenes in Acts shows that there is a profound and productive tension at the heart of Acts’ theological vision. This tension generates the distinctive Christian politics that is Acts’ ecclesiology: a public witness to Jesus Christ in a world that did not know him.
Suicide and the morality of kinship in Sri Lanka
Authors: Widger Tom
Published: June 2012

Ethnographic research amongst Sinhala Buddhists in community and clinical settings in the Madampe Division, northwest Sri Lanka, suggests that local understandings and practices of suicidal behaviour reflect the kinship structure. In particular, acts of self-harm and self-inflicted death arise in response to the breaking of core kinship rights, duties and obligations, or as a challenge to inflexibility or contradictions within the system. In either case, the morality of kinship is closely associated with the causes of suicidal behaviour, as the ‘inevitability’ or ‘evitability’ of kin relationships is negotiated and lived in practice. This article analyses how local political economies give rise to particular kinship and moral conditions, with special attention paid to those between household (gē) members and brothers-in-law (massinā).
Suicide in a central Indian steel town
Authors: Parry Jonathan
Published: June 2012

Over the past 15 years ‘farmer suicides’ have occasioned grave public concern; and it has recently been claimed that Chhattisgarh has the highest incidence in the country. This article suggests that the representation of such cases as the major public policy problem to do with self-inflicted death is politically inflected and that there are good grounds for supposing that—at least in certain pockets—the urban suicide rate is as high, if not higher. In the industrial area around steel town of Bhilai, this has risen dramatically over the last 20 years and it is the aristocracy of public sector labour that is significantly most susceptible. This is ultimately attributable to the liberalisation of the economy and the consequent downsizing of this workforce, which has led to a crisis in the reproduction of class status. Such workers are privileged; think of themselves as different from the informal sector ‘labour class’ and fear sinking into it. Suicides are significantly under-reported and the official statistics are systematically inflected by fear of the police and the law, which encourage both concealment and the deliberate obfuscation of likely motives, and almost certainly increase the ‘lethal probabilities’ of suicide attempts.
The heat-resistant and tribological mechanism of nano-Fe3O4–reinforced nitrile butadiene rubber
Authors: Wang Qilei
Published: June 2012

To improve the tribological properties of nitrile butadiene rubber (NBR), nano-Fe3O4 particles with good lubricity were added into the NBR to prepare NBR/nano-Fe3O4 composites. In our experiment, surface microstructure of the composites was observed by JSM-5600LV low-vacuum scanning electron microscope; disposition of nano-Fe3O4 was measured by an energy dispersive x-ray spectrometer; friction and wear condition of the composites were tested by UMT-2MT friction testing machine, and friction condition of the composites were tested for different temperatures by SRV high temperature friction testing machine. The results showed that after adding nano-Fe3O4 particles in NBR, surface of the composites was smoother than NBR due to less defects and the tribological properties were significantly improved. Friction and wear rate of the composites were 300% lower than NBR, and we owe this to the nano-Fe3O4 particles that played a role as solid lubricant on the surface of the composites. Meanwhile, friction coefficient was greatly affected by friction time; when the friction time was more than 10 min, the friction coefficient would become larger and there would be more abrasion; the friction coefficient of the composites was less affected by the temperature with the additional increase in nano-Fe3O4 particles.
Circulatory Diseases in the U.S. Elderly in the Linked National Long-Term Care Survey-Medicare Database
Authors: Akushevich Igor , Kravchenko Julia , Ukraintseva Svetlana , Arbeev Konstantin , Yashin Anatoli I.
Published: June 2012

Incidence rates of acute coronary heart disease (ACHD; including myocardial infarction and angina pectoris), stroke, and heart failure (HF) were studied for their age, disability, and comorbidity patterns in the U.S. elderly population using the National Long Term Care Survey (NLTCS) data linked to Medicare records for 1991–2005. Incidence rates increased with age with a decrease in the oldest old (stroke and HF) or were stable at all ages (ACHD). For all diseases, incidence rates were lower among institutionalized individuals and higher in individuals with higher comorbidity indices. The results could be used for understanding currently debated effects of biomedical research, screening, and therapeutic innovations on changes in disease incidence with advancing age as well as for projecting future Medicare costs.
Differential Transcriptomic Analysis of Spontaneous Lung Tumors in B6C3F1 Mice: Comparison to Human Non–Small Cell Lung Cancer
Authors: Pandiri Arun R. , Sills Robert C. , Ziglioli Vincent , Ton Thai-Vu T , Hong Hue–Hua L. , Lahousse Stephanie A. , Gerrish Kevin E. , Auerbach Scott S. , Shockley Keith R. , Bushel Pierre R. , Peddada Shyamal D. , Hoenerhoff Mark J.
Published: June 2012

Lung cancer is the leading cause of cancer-related death in people and is mainly due to environmental factors such as smoking and radon. The National Toxicology Program (NTP) tests various chemicals and mixtures for their carcinogenic hazard potential. In the NTP chronic bioassay using B6C3F1 mice, the incidence of lung tumors in treated and control animals is second only to the liver tumors. In order to study the molecular mechanisms of chemically induced lung tumors, an understanding of the genetic changes that occur in spontaneous lung (SL) tumors from untreated control animals is needed. The authors have evaluated the differential transcriptomic changes within SL tumors compared to normal lungs from untreated age-matched animals. Within SL tumors, several canonical pathways associated with cancer (eukaryotic initiation factor 2 signaling, RhoA signaling, PTEN signaling, and mammalian target of rapamycin signaling), metabolism (Inositol phosphate metabolism, mitochondrial dysfunction, and purine and pyramidine metabolism), and immune responses (FcγR-mediated phagocytosis, clathrin-mediated endocytosis, interleukin 8 signaling, and CXCR4 signaling) were altered. Meta-analysis of murine SL tumors and human non–small cell lung cancer transcriptomic data sets revealed a high concordance. These data provide important information on the differential transcriptomic changes in murine SL tumors that will be critical to our understanding of chemically induced lung tumors and will aid in hazard analysis in the NTP 2-year carcinogenicity bioassays.
Evaluating palliative care ward staffing using bed occupancy, patient dependency, staff activity, service quality and cost data
Authors: Roberts Dai , Hurst Keith
Published: June 2012

Background:

Palliative care staffing has remained unchallenged for decades while service provision has changed markedly, bringing new workforce demands. There is little evidence to inform hospice workforce structures, which strive to deliver the highest-quality holistic care.

Aim:

The study had three main aims, to: (i) adapt the acuity-quality workforce planning method used extensively in the UK National Health Service (NHS) for use in hospices; (ii) compare hospice and NHS palliative care staffing establishments and their implications; and (iii) create ward staffing benchmarks and formulae for hospice managers.

Design:

A method adapted from a widely used nursing workforce planning and development (WP&D) study was used to collect data in hospice and palliative care wards.

Setting:

Twenty-three palliative care and hospice wards, geographically representing England, were studied.

Results:

A dataset, which profiles and benchmarks hospice and NHS palliative care ward occupancy, patient dependency, staff activity, ward establishments, quality and costs in 23 palliative care and hospice wards has been created. The database reveals large differences between hospice and palliative care wards. For example, hospice wards are better staffed and more expensive to run but staff deliver higher-quality care (measured using an established service quality audit) despite facing heavier workloads. Consequently, staffing multipliers are created to help managers estimate workload-based ward staffing.

Conclusions:

This dataset provides evidence-based recommendations to inform palliative care nursing workforce modelling, including deciding future nursing workforce size and mix based on rising workloads. The new dataset is suitable for use in UK hospice wards and may be appropriate for future international use.