bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines
Authors: Yacoby Iftach , Bar Hagit , Benhar Itai
Published: April 2007

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of
Staphylococcus aureus
bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens
Staphylococcus aureus
,
Streptococcus pyogenes
, and
Escherichia coli
with an improvement in potency by a factor of ∼20,000 compared to the free drug.
Dissemination of
Acinetobacter baumannii
Clones with OXA-23 Carbapenemase in Colombian Hospitals
Authors: Villegas Maria Virginia , Kattan Juan Nicolas , Correa Adriana , Lolans Karen , Guzman Ana Maria , Woodford Neil , Livermore David , Quinn John P.
Published: April 2007

During 2005, 66 carbapenem-resistant isolates of
Acinetobacter baumannii
were collected from seven tertiary-care hospitals participating in a nationwide surveillance network in Colombia. The isolates were multidrug resistant and produced the carbapenemases OXA-23 and OXA-51. Forty-five belonged to four clones while 21 were unique pulsotypes. One clone was present in two hospitals within one city, while another had spread between two hospitals in different cities. Blood, secretions, and abdominal fluids were the most frequent sites of isolation. This is the first description of widespread dissemination of OXA-23 in South America.
Efficacy of Tachyplesin III, Colistin, and Imipenem against a Multiresistant
Pseudomonas aeruginosa
Strain
Authors: Cirioni Oscar , Ghiselli Roberto , Silvestri Carmela , Kamysz Wojciech , Orlando Fiorenza , Mocchegiani Federico , Di Matteo Fabio , Riva Alessandra , Łukasiak Jerzy , Scalise Giorgio , Saba Vittorio , Giacometti Andrea
Published: April 2007

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant
Pseudomonas aeruginosa
strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.
Differential Interaction of Dendritic Cells withRickettsia conorii: Impact on Host Susceptibility to Murine Spotted Fever Rickettsiosis
Authors: Fang Rong , Ismail Nahed , Soong Lynn , Popov Vsevolod L. , Whitworth Ted , Bouyer Donald H. , Walker David H.
Published: April 2007

Spotted fever group rickettsioses are emerging and reemerging infectious diseases, some of which are life-threatening. In order to understand how dendritic cells (DCs) contribute to the host resistance or susceptibility to rickettsial diseases, we first characterized the in vitro interaction of rickettsiae with bone marrow-derived DCs (BMDCs) from resistant C57BL/6 (B6) and susceptible C3H/HeN (C3H) mice. In contrast to the exclusively cytosolic localization within endothelial cells, rickettsiae efficiently entered and localized in both phagosomes and cytosol of BMDCs from both mouse strains.Rickettsia conorii-infected BMDCs from resistant mice harbored higher bacterial loads compared to C3H mice.R. conoriiinfection induced maturation of BMDCs from both mouse strains as judged by upregulated expression of classical major histocompatibility complex (MHC) and costimulatory molecules. Compared to C3H counterparts, B6 BMDCs exhibited higher expression levels of MHC class II and higher interleukin-12 (IL-12) p40 production upon rickettsial infection and were more potent in priming naïve CD4+T cells to produce gamma interferon. In vitro DC infection and T-cell priming studies suggested a delayed CD4+T-cell activation and suppressed Th1/Th2 cell development in C3H mice. The suppressive CD4+T-cell responses seen in C3H mice were associated with a high frequency of Foxp3+T regulatory cells promoted by syngeneicR. conorii-infected BMDCs in the presence of IL-2. These data suggest that rickettsiae can target DCs to stimulate a protective type 1 response in resistant hosts but suppressive adaptive immunity in susceptible hosts.
Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A
Streptococcus
in the Oropharynx
Authors: Shelburne Samuel A. , Okorafor Nnaja , Sitkiewicz Izabela , Sumby Paul , Keith David , Patel Payal , Austin Celest , Graviss Edward A. , Musser James M.
Published: April 2007

Group A
Streptococcus
(GAS) genes that encode proteins putatively involved in polysaccharide utilization show growth phase-dependent expression in human saliva. We sought to determine whether the putative polysaccharide transcriptional regulator MalR influences the expression of such genes and whether MalR helps GAS infect the oropharynx. Analysis of 32 strains of 17 distinct M protein serotypes revealed that MalR is highly conserved across GAS strains.
malR
transcripts were detectable in patients with GAS pharyngitis, and the levels increased significantly during growth in human saliva compared to the levels during growth in glucose-containing or nutrient-rich media. To determine if MalR influenced the expression of polysaccharide utilization genes, we compared the transcript levels of eight genes encoding putative polysaccharide utilization proteins in the parental serotype M1 strain MGAS5005 and its Δ
malR
isogenic mutant derivative. The transcript levels of all eight genes were significantly increased in the Δ
malR
strain compared to the parental strain, especially during growth in human saliva. Following experimental infection, the Δ
malR
strain persistently colonized the oropharynx in significantly fewer mice than the parental strain colonized, and the numbers of Δ
malR
strain CFU recovered were significantly lower than the numbers of the parental strain CFU recovered. These data led us to conclude that MalR influences the expression of genes putatively involved in polysaccharide utilization and that MalR contributes to the persistence of GAS in the oropharynx.
Differential Innate Immune Cell Activation and Proinflammatory Response inAnaplasma phagocytophilumInfection
Authors: Choi Kyoung-Seong , Webb Tonya , Oelke Mathias , Scorpio Diana G. , Dumler J. Stephen
Published: April 2007

Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacteriumAnaplasma phagocytophilum. The critical role of gamma interferon (IFN-γ) for induction of severe inflammatory histopathology, even in the absence of a significant bacterial load, was previously demonstrated in a murine model of HGA. We hypothesized that NK, NKT, and possibly CD8+cytotoxic T cells participate in the development of histopathologic lesions withA. phagocytophiluminfection. Mice were mock infected or infected with low- or high-passageA. phagocytophilumand assayed for hepatic histopathology and splenocyte immunophenotype during the first 21 days after infection. Compared to high-passageA. phagocytophilum-infected mice, low-passageA. phagocytophilum-infected mice had more severe hepatic lesions and increased apoptosis. The hepatic histopathology severity in low-passageA. phagocytophilum-infected mice peaked on day 2 at the time of peak plasma IFN-γ levels and gradually decreased through day 21. Low-passageA. phagocytophilum-infected mice also showed significantly increased levels of lymphocyte NK1.1/FasL expression on days 4 to 7 corresponding to early, severe hepatic inflammation, whereas the levels of NKT cells were substantially lower on day 4, suggesting that there was NKT cell involvement. This result supports the concept that NK1.1+cells, including NK and NKT cells, are major components in the early pathogenesis ofA. phagocytophiluminfection.
CD14 Mediates Cross Talk between Mononuclear Cells and Fibroblasts for Upregulation of Matrix Metalloproteinase 9 byBorrelia burgdorferi
Authors: Zhao Zhihui , Fleming Rhonda , McCloud Bilaal , Klempner Mark S.
Published: April 2007

Lyme disease is an infection caused by a tick-borne spirochete,Borrelia burgdorferi.Matrix metalloproteinase 9 (MMP-9) was selectively upregulated in the erythema migrans skin lesions of patients with acute Lyme disease. In this study, the mechanism of upregulation of MMP-9 was investigated in vitro and in vivo. The concentrations of MMP-9 and soluble CD14 were markedly elevated in serum from patients with acute Lyme disease and were also upregulated in U937 cells byB. burgdorferiin a time- and concentration-dependent manner. MMP-9 mRNA was expressed at baseline in fibroblasts in the presence or absence ofB. burgdorferi. However, when fibroblasts were incubated with supernatants from U937 cells withB. burgdorferior recombinant CD14, the expression of MMP-9 was significantly increased. This effect was completely abolished by the anti-CD14 antibody. These data suggest that the upregulation of MMP-9 byB. burgdorferiinvolves the CD14 pathway in infiltrating inflammatory cells. Fibroblasts could be recruited to amplify local production of MMP-9 by acquiring CD14 from macrophages.
Interleukin-23 (IL-23)-IL-17 Cytokine Axis in Murine
Pneumocystis carinii
Infection
Authors: Rudner Xiaowen L. , Happel Kyle I. , Young Erana A. , Shellito Judd E.
Published: April 2007

Host defense mechanisms against
Pneumocystis carinii
are not fully understood. Previous work in the murine model has shown that host defense against infection is critically dependent upon host CD4
+
T cells. The recently described Th17 immune response is predominantly a function of effector CD4
+
T cells stimulated by interleukin-23 (IL-23), but whether these cells are required for defense against
P. carinii
infection is unknown. We tested the hypothesis that
P. carinii
stimulates the early release of IL-23, leading to increases in IL-17 production and lung effector CD4
+
T-cell population that mediate clearance of infection. In vitro, stimulation of alveolar macrophages with
P. carinii
induced IL-23, and IL-23p19 mRNA was expressed in lungs of mice infected with this pathogen. To address the role of IL-23 in resistance to
P. carinii
, IL-23p19−/− and wild-type control C57BL/6 mice were infected and their fungal burdens and cytokine/chemokine responses were compared. IL-23p19−/− mice displayed transient but impaired clearance of infection, which was most apparent 2 weeks after inoculation. In confirmatory studies, the administration of either anti-IL-23p19 or anti-IL-17 neutralizing antibody to wild-type mice infected with
P. carinii
also caused increases in fungal burdens. IL-17 and the lymphocyte chemokines IP-10, MIG, MIP-1α, MIP-1β, and RANTES were decreased in the lungs of infected IL-23p19−/− mice in comparison to their levels in the lungs of wild-type mice. In IL-23p19−/− mice infected with
P. carinii
, there were fewer effector CD4
+
T cells in the lung tissue. Collectively, these studies indicate that the IL-23-IL-17 axis participates in host defense against
P. carinii
.
Involvement of Caspase-9 in the Inhibition of Necrosis of RAW 264 Cells Infected withMycobacterium tuberculosis
Authors: Uchiyama Ryosuke , Kawamura Ikuo , Fujimura Takao , Kawanishi Michiko , Tsuchiya Kohsuke , Tominaga Takanari , Kaku Taijin , Fukasawa Yutaka , Sakai Shunsuke , Nomura Takamasa , Mitsuyama Masao
Published: April 2007

In order to know how caspases contribute to the intracellular fate ofMycobacterium tuberculosisand host cell death in the infected macrophages, we examined the effect of benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethane (z-VAD-fmk), a broad-spectrum caspase inhibitor, on the growth ofM. tuberculosisH37Rv in RAW 264 cells. In the cells treated with z-VAD-fmk, activation of caspase-8, caspase-3/7, and caspase-9 was clearly suppressed, and DNA fragmentation of the infected cells was also reduced. Under this experimental condition, it was found that the treatment markedly inhibited bacterial growth inside macrophages. The infected cells appeared to undergo cell death of the necrosis type in the presence of z-VAD-fmk. We further found that z-VAD-fmk treatment resulted in the generation of intracellular reactive oxygen species (ROS) in the infected cells. By addition of a scavenger of ROS, the host cell necrosis was inhibited and the intracellular growth of H37Rv was significantly restored. Among inhibitors specific for each caspase, only the caspase-9-specific inhibitor enhanced the generation of ROS and induced necrosis of the infected cells. Furthermore, we found that severe necrosis was induced by infection with H37Rv but not H37Ra in the presence of z-VAD-fmk. Caspase-9 activation was also detected in H37Rv-infected cells, but H37Ra never induced such caspase-9 activation. These results indicated that caspase-9, which was activated by infection with virulentM. tuberculosis, contributed to the inhibition of necrosis of the infected host cells, presumably through suppression of intracellular ROS generation.
Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by
Streptococcus pneumoniae
ClpL
Authors: Tu Le Nhat , Jeong Hye-Yoon , Kwon Hyog-Young , Ogunniyi Abiodun D. , Paton James C. , Pyo Suhk-Neung , Rhee Dong-Kwon
Published: April 2007

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of
Streptococcus pneumoniae
was assessed. A
clpL
mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-α) from macrophages infected with the
clpL
mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW 264.7 cells decreased TNF-α secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator jasplakinolide reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of
S. pneumoniae
to host cells and induces secretion of TNF-α via a mechanism dependent upon actin polymerization during the initial infection stage.
Mast-cell sarcoma of the tibia
Authors: Brčić Luka , Batelja Vuletić Lovorka , Stepan Jasminka , Bonevski Aleksandra , Jakovljević Gordana , Gašparov Slavko , Marjanović Ksenija , Seiwerth Sven
Published: April 2007

The mast-cell sarcoma of a bone is described here for the first time. The tumour presented in a 4-year-old boy, with pain, oedema and deformation of his right lower leg. Radiological findings revealed a destructive tumourous mass. Histopathological examination showed the tumour to be composed of large, atypical cells, with hyperchromatic oval and polygonal nuclei. The cytoplasm around them was eosinophilic with many basophilic and toluidine-blue-positive granules. These atypical mast cells were positive for chloroacetate esterase, c-kit, tryptase and negative for myeloperoxidase. The primary disease quickly progressed to mast-cell leukaemia, and despite intensive chemotherapy the patient died 18 months after first symptoms.
THE JOINT PREDICTIVE-POSTERIOR METHOD IN THE BAYESIAN ANALYSIS OF STRESS-STRENGTH RELIABILITY
Authors: PHAM-GIA T. , TURKKAN N.
Published: April 2007

The joint predictive-posterior approach to the study of the reliability of an engineering system, under a stress-strength model, is presented in this article. This new combined approach is original, is supported by charts and graphs and can be quite useful since it allows the realistic forecasting of system reliability, with known credibility levels, ahead of real experimentation and testing results. In this article, it is concretely illustrated by several engineering applications related to a highway bridge study and a quality control problem.
SKEW NORMAL DISTRIBUTION AND THE DESIGN OF CONTROL CHARTS FOR AVERAGES
Authors: TSAI TZONG-RU
Published: April 2007

The paper develops two new control charts and process capability ratios based on the skew normal distribution to monitor the process average and evaluate the process capability of non-normal data. Both control charts reduce to Shewhart-type control charts when the underlying distribution of quality characteristic is symmetric. A simulation study is conducted to compare the performances of the proposed control charts with those of existing control charts. Simulation results indicate that considerable improvement over those of existing control charts can be achieved when the proposed control charts are used to monitor the process average of non-normal data. Two examples are presented for illustration.
Synergism between psychosocial and metabolic stressors: impact on reproductive function in cynomolgus monkeys
Authors: Williams Nancy I. , Berga Sarah L. , Cameron Judy L.
Published: April 2007

The role of energy imbalance versus psychosocial stress in the pathogenesis of female reproductive dysfunction characterized by anovulation and amenorrhea remains controversial. In women, functional hypothalamic amenorrhea can develop in the absence of significant weight loss, excessive exercise, or profound psychosocial disruption. We posited, therefore, that commonplace, seemingly minor stressors that alone would have minimal impact upon reproductive function might interact synergistically such that combinations of stressors would cause a greater impairment of the reproductive axis than any single stressor alone. We then developed a monkey model to test this hypothesis. Adult female cynomolgus monkeys with normal menstrual cycles were randomized into three experimental groups and studied over four menstrual cycles. The groups were: low-level psychosocial stress (i.e., moving to a new housing environment; Move, n = 8), moderate energy imbalance (Exercise + Diet, n = 9); and all stressors in combination (Move + Exercise + Diet, n = 10). Food intake, body weight, menstrual cyclicity, and reproductive hormones were assessed for two control menstrual cycles followed by two experimental cycles during which the monkeys experienced the stressors. Abnormal cycles were considered to be abnormally long or anovulatory cycles. Few abnormal cycles occurred in the Move group (1 of 8 monkeys) and in the Exercise + Diet group (1 of 9 monkeys). In contrast, 7 of 10 monkeys in the Move + Exercise + Diet group displayed at least one abnormal cycle (χ2 = 9.61, P = 0.008). These findings suggest that infertility due to hypothalamic hypogonadism can result from the combination of commonplace, seemingly minor stressors that often escape clinical attention.
Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke
Authors: Tzoulaki Ioanna , Murray Gordon D. , Lee Amanda J. , Rumley Ann , Lowe Gordon D.O. , Fowkes F. Gerald R.
Published: April 2007

Background—

The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability.

Methods and Results—

We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein(a) (all
P
<0.01), as well as von Willebrand factor and plasma viscosity (both
P
<0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein(a)] provided some added discrimination.

Conclusions—

Several “novel” risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.
Mutation of the Circadian Clock Gene
Per2
Alters Vascular Endothelial Function
Authors: Viswambharan Hema , Carvas João M. , Antic Vladan , Marecic Ana , Jud Corinne , Zaugg Christian E. , Ming Xiu-Fen , Montani Jean-Pierre , Albrecht Urs , Yang Zhihong
Published: April 2007

Background—

The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene
Period2
(
Per2
) in endothelial function in a mouse model.

Methods and Results—

Compared with the wild-type littermates, mice with
Per2
mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers. During transition from the inactive to active phase, this response was further increased in the wild-type mice but further decreased in the
Per2
mutants. The endothelial dysfunction in the
Per2
mutants was also observed with ionomycin, which was improved by the cyclooxygenase inhibitor indomethacin. No changes in the expression of endothelial acetylcholine-M
3
receptor or endothelial nitric oxide synthase protein but increased cyclooxygenase-1 (not cyclooxygenase-2) protein levels were observed in the aortas of the
Per2
mutants. Compared with
Per2
mutants, a greater endothelium-dependent relaxation to ATP was observed in the wild-type mice, which was reduced by indomethacin. In quiescent aortic rings, ATP caused greater endothelium-dependent contractions in the
Per2
mutants than in the wild-type mice, contractions that were abolished by indomethacin. The endothelial dysfunction in the
Per2
mutant mice is not associated with hypertension or dyslipidemia.

Conclusions—

Mutation in the
Per2
gene in mice is associated with aortic endothelial dysfunction involving decreased production of NO and vasodilatory prostaglandin(s) and increased release of cyclooxygenase-1–derived vasoconstrictor(s). The results suggest an important role of the
Per2
gene in maintenance of normal cardiovascular functions.
Association of Ambulatory Blood Pressure With Ischemic Brain Injury
Authors: Schwartz Gary L. , Bailey Kent R. , Mosley Thomas , Knopman David S. , Jack Clifford R. , Canzanello Vincent J. , Turner Stephen T.
Published: April 2007

Cerebral white matter hyperintensities on brain MRI (leukoaraiosis) are associated with increased risk of stroke and dementia. To assess the relationships of blood pressure level and circadian pattern with leukoaraiosis, we obtained 24-hour ambulatory blood pressure recordings and brain magnetic resonance images in 343 white and 267 black adults who were members of sibships that had ≥2 siblings with essential hypertension. In multiple linear regression models, factors associated with greater leukoaraiosis in both racial groups included age (
P
≤0.002), homocysteine levels (
P
≤0.006), and brain volume (
P
≤0.008). In blacks, ambulatory blood pressure measures associated with greater leukoaraiosis were higher awake, asleep, and 24-hour systolic and diastolic levels (
P
≤0.009 for each). In addition, there was a trend for smaller nocturnal declines in systolic and diastolic levels (ie, nondipping patterns) to be associated with greater leukoaraiosis, and all of these associations, except nondipping of diastolic level, remained or became significant after controlling for office blood pressure (
P
<0.05 for each). In whites, among ambulatory blood pressure measures, only higher asleep diastolic levels trended toward association with greater leukoaraiosis. However, similar to findings in blacks, nondipping of systolic and diastolic ambulatory blood pressure levels were each associated with greater leukoaraiosis (
P
≤0.008), and all of these associations remained or became significant after controlling for office blood pressure (
P
≤0.009 for each). Higher ambulatory blood pressure levels and a nondipping circadian pattern contribute to greater leukoaraiosis volume after controlling for office blood pressure.
Regulation of Scavenger Receptor Class BI Gene Expression by Angiotensin II in Vascular Endothelial Cells
Authors: Yu Xiao , Murao Koji , Imachi Hitomi , Cao Wen-Ming , Li Junhua , Matsumoto Kensuke , Nishiuchi Takamasa , Ahmed Rania A.M. , Wong Norman C.W. , Kosaka Hiroaki , Unterman Terry G. , Ishida Toshihiko
Published: April 2007

High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. In this process, a scavenger receptor of the B class (SR-BI)/human homologue of SR-BI, CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from high-density lipoprotein. In endothelial cells, high-density lipoprotein activates endothelial NO synthase via hSR-BI/CLA-1. Angiotensin II (Ang II) is a powerful accelerator of atherosclerosis and modulates the expression of endothelial NO synthase. In the present study, we have examined the role of Ang II on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells. Our results showed that endogenous expression of hSR-BI/CLA-1 was suppressed by exposure to Ang II in human umbilical vein endothelial cells. Administration of the Ang II type-1 receptor blocker olmesartan inhibited Ang II–induced hSR-BI/CLA-1 protein repression. In Ang II–treated cells, high-density lipoprotein had no effect on endothelial NO synthase activation. Ang II decreased transcriptional activity of the hSR-BI/CLA-1 promoter. The inhibitory effect of Ang II on hSR-BI/CLA-1 promoter activity was abrogated by wortmannin and LY294002, specific inhibitors of phosphatidylinositol 3-kinase. Exposure of human umbilical vein endothelial cells to Ang II elicited a rapid phosphorylation of Akt and FoxO1, a known target of Akt signaling. Constitutively active Akt inhibits the activity of the hSR-BI/CLA-1 promoter, and a dominant-negative mutant of Akt or mutagenesis of a FoxO1 response element in the hSR-BI/CLA-1 abolished the ability of Ang II to suppress promoter activity. Together, these results indicate that the phosphatidylinositol 3-kinase/Akt/FoxO1 pathway participates in Ang II suppression of hSR-BI/CLA-1 expression and suggests that the endothelial receptor for hSR-BI/CLA-1 is downregulated by the renin–angiotensin system.
Left Ventricular Hypertrophy, Subclinical Atherosclerosis, and Inflammation
Authors: Mehta Sameer K. , Rame J. Eduardo , Khera Amit , Murphy Sabina A. , Canham Russell M. , Peshock Ronald M. , de Lemos James A. , Drazner Mark H.
Published: April 2007

To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (
P
<0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (
P
<0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (
P
=0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction.
The 'Law' of Uneven and Combined Development: Some Underdeveloped Thoughts
Authors: van der Linden Marcel
Published: April 2007

This paper presents a critical reconstruction of the main Marxist debates about the idea of 'leaps forward' in historical development. There have been two important approaches: the so-called 'law of uneven and combined development', as developed by Leon Trotsky, George Novack and Ernest Mandel, and Jan Romein's 'handicap of a head start'. Although Romein's approach is Stalinist in origin, elements of it are compatible with Trotsky's interpretation. But, even an expanded version of the 'law' of uneven and combined development lacks predictive value, although one can say with certainty in hindsight whether a combined development has taken place. It is argued that the 'law' is, in fact, an underspecified social mechanism and that its explanatory power can be increased by identifying a number of recurrent patterns.
Genetic Testing of Language Replacement Hypothesis in Southwest Asia
Authors: Yepiskoposian Levon , Khudoyan Armine , Harutyunian Ashot
Published: April 2007

The regions of the Caucasus, Anatolia, and the Near East represent an extremely important area with respect to ancient population migration and expansion, and the spread of the Caucasian, Indo-European, Afro-Asiatic, and Altaic languages. We examined genetic variation within and between 12 ethno-territorial populations belonging to four major language families by using six microsatellites, or short tandem repeats (STR) and 12 Unique Event Polymorphism (UEP) loci mapped to the non-recombining portion of the human Y-chromosome. The applied set of markers did not unconditionally support the language replacement hypothesis for the populations under consideration. Moreover, regarding the South Caucasus and Anatolia, our results showed greater genetic distances between the populations from different language families, and close genetic affinity for the populations from the same language group—in this case, for the Turkophone ethnic units. The results point to the importance of appropriate Y-chromosome sampling procedures in geographically structured populations and to the necessity of using a relevant set of markers that provides best discrimination of populations with different genetic histories.
A Comparative Overview of the Iranian Constitutions of 1906-07 and 1979
Authors: Borbor Dariush
Published: April 2007

The history and the essential and important articles of the constitutional laws of Iran and its immediate neighbours are elucidated and compared. The article includes an analytical comparison of the 1906-07 and 1979 Constitutions of Iran. A brief analytical synoptic overview of world constitutions is also presented in order to obtain a balanced view of the process of constitutionalism and popular suffrage for men and women.In 1979, the Islamic Republic of Iran became the first country in the world to include a declaration for the preservation of the environment in its Constitution.Having compared the 1906-7 Constitution of Iran with a good number of others, it is very evident that the transformation of an autocratic monarchy into a constitutional one was in itself a great leap forward, at a time, when most of the world still lived under dictatorship.In Iran, a number of civil institutions have played their role for a whole century thanks to the 1906-07 Constitution, though far from perfect, nevertheless more or less accepted and functioning. These include a hundred years of direct parliamentary elections, and several years of presidential, municipal and other popular suffrage.The propagation of the 1906-07 Constitutional Movement of Iran has been paramount; it had greatly influenced the awakening of many other peoples of the neighbouring and regional countries. The 1908 re-institution of parliament in the Ottoman Empire, the 1911 Chinese Revolution, and the 1917 Revolution in Tzarist Russia were undoubtedly influenced by the Constitutional Movement of Iran.
Kurdish Lō-Lō
Authors: Asatrian Garnik
Published: April 2007

This paper is an attempt to trace the origin of an interesting Kurdish lexeme with a high occurrence frequency, which is usually perceived by the neighbouring Armenians as sort of a shibboleth for characterising the Kurds. The author rejects the possible connections of this lexeme with the Oriental Caucasian *läg-"man, slave".
On the History of Slave-Trade in Dagestan
Authors: Inozemtseva Elena
Published: April 2007

Slave-trade was one of the main factors in the system of complicated and contradictory interactions between the peoples of the North Caucasus, Transcaucasia, and Russia. Everlasting inter-ethnic clashes and wars, political instability, great demand and high prices for 'human commodities' strongly promoted the growth of this business in Dagestan and in the North Caucasus in general. The feudal lords used to organise "commercial" campaigns, aimed at capturing people and getting ransom. For centuries, this cruel industry had remained one of the dominating elements in the economy of this multi-ethnic region. The paper, based mainly on the archive documents, offers a short history of slave-trade in Dagestan up to its final abolishment in the 60-s of the 19th century.
Sāhib-dīvān Šams ad-dīn Muhammad Juvaninī and Armenia
Authors: Margarian Hayrapet
Published: April 2007

Following the Seljuk invasion of the 11th century, the Armenians and Iranians found themselves under one rule, and the ancient historical and cultural ties between these two neighbouring nations became once again close and versatile. The similarity of their historical destinies appears to be more evident in the 13th-14th centuries, when Armenia and Iran were incorporated in the Mongol Empire.Among the Sāhīb Dīvāns, the highest ranking officials in the hierarchical system of the Īl-khānid state, a special place belongs to Šams ad-dīn Muhammad Juvainī, famous for his civilised personality and attainments. The present article tries to elucidate those details of the biography of Javainī, which concern Armenia and Armenian-Iranian relations of his time. Along with the Armenian and Persian sources, the author has made extensive use of the data obtained from the Georgian chronicles, which considerably improve the picture of the historical reality.
Global Market Integration and Central Political Control: Foreign Trade and Intergovernmental Relations in China
Authors: Yumin Sheng
Published: April 2007

Prevailing economic theories predict that world market integration unleashes centrifugal forces from within and undermines domestic central political authority. Reversing the conventional bottom-up, demand-side approach, this article highlights the incentives of national-level political actors. It suggests that when institutionally empowered vis-à-vis the subnational units, the center will seek to enhance political control over regions thriving in the global market to extract revenues, remedy interregional disparity, and maintain central rule. Through analyzing pooled cross-sectional, time-series data for Chinese provinces during 1978 to 2002, it shows that the Chinese political center has manipulated its personnel monopoly power within the ruling Communist Party to exert a tighter grip over provincial party secretaries, the top officials in the provinces more exposed to the international market. Furthermore, provinces overseen by more controlled party secretaries actually received less favorable terms during fiscal contracting, implying their greater revenue submission to the center.
Late Industrialization, the State, and Social Changes
Authors: Yong Chool Ha
Published: April 2007

Although much has been written about the economic success of South Korea and other newly industrializing countries social changes in late industrializing countries are a significantly underexplored terrain of research. Focusing on the Korean case, this article analyzes how the state affected social changes in the course of industrialization. Contrary to conventional sociological findings, the author contends that industrialization in Korea brought about neofamilism, which is the unintended reinforcement of blood, school, and regional ties. The historical legacy of colonialism, the top leadership's perception of lateness and urgency in industrialization and economic modernization, and patterns of recruitment in government and industry were identified as factors that caused the emergence of neofamilism in South Korea. The article also proposes the need for more extensive comparative studies to explore the socioinstitutional implications of state-led industrialization.
The Limits of Economic Globalization
Authors: Reuveny Rafael , Thompson William R.
Published: April 2007

Economic globalization has loomed, at least for some, as the world system's next crisis carrier. Globalization is said to accelerate economic growth rates, compel closer economic interactions throughout the globe, and trample on the distinctiveness of local cultures and sovereignty. While we accept the existence of economic globalization, our question in this article is whether it, or at least one important dimension of it, is truly a `global' process. A number of cleavages that have characterized the global North and South in the past appear to be growing more acute. Globalization, predicated on a motor of global economic growth, should be expected to be less than universal if the pulsations and effects of global economic growth are less than universal across the global South and North. That being the case, our theory anticipates that one aspect of economic globalization, conceptualized here as economic openness to exports, and measured by the ratio of export value to economic output, will be more discernible in the global North, than in the global South. Moreover, trade globalization in the North should be positively affected by a rise in world economic growth and systemic leadership, whereas trade globalization in the South should be driven largely by Southern autonomous inertia and periodic economic crises. The empirical results largely support our theoretical expectations.
Are there reasons to be worried about the 'caretelization' of residential care?
Authors: Scourfield Peter
Published: April 2007

Successive governments have encouraged both the marketization and the privatization of the residential and nursing care sector. This paper describes how the large corporate providers continue to increase their share of the market through a continual process of mergers, takeovers and acquisitions. Market analysis suggests that this trend is set to continue. The name given to this phenomenon in this paper is `caretelization'. The process of caretelization is examined in the context of New Labour's public sector modernization agenda. The paper raises questions of whether continued caretelization is more or less likely to help New Labour achieve certain aims of modernization. For example, New Labour often talks of `putting people themselves in the driving seat of the public services'. It is argued that, with caretelization, not only is public accountability diminished, but key principles such as consumer choice and user involvement are likely to be compromised by allowing ownership of residential and nursing care to be dictated by market forces. Such developments raise questions about both New Labour's desire and its capability to manage the forces of neo-liberalism.
Letting them get away with it: Fathers, domestic violence and child welfare
Authors: Featherstone Brid , Peckover Sue
Published: April 2007

Recent developments at policy, legislative and practice levels have led to the mainstreaming of domestic violence as a child welfare issue. However, research evidence would suggest that familiar and well established tensions in service provision to women and children continue to be recycled. Moreover, there remains a central dichotomy in relation to men. Constructed as perpetrators or offenders, their identities as fathers remain invisible with serious consequences for the development of policies and practices which engage with them as `domestically violent fathers'. The discursive removal of violent men from the category of father or indeed parent needs addressing in order to support women and children, but also to offer possibilities for men to develop non-violent parenting and partnering relationship patterns.
Some critical comments on Law and Mooney (2006)
Authors: Bechhofer Frank , Mccrone David
Published: April 2007

In an article in this journal in 2006, Law and Mooney hold up our book, Living in Scotland: Social and Economic Change since 1980, written with Lindsay Paterson, as a prime example of what they regard as a theoretically ill-informed account of the social structure of Scotland. In reaching their conclusions they make use of highly selective quotations, inaccurate statements and unacceptable inferences from what we say to why we say it. Our purpose in this brief note is to set the record straight and defend ourselves against what we see as a perverse use of Living in Scotland to support their ideological position by damning our book with faint praise, employing selective quotation and misinterpreting what we say.
Participation, power, conflict and change: Theorizing dynamics of service user participation in the social care system of England and Wales
Authors: Carr Sarah
Published: April 2007

Drawing on the findings of a major review on service user participation in the social care system of England and Wales, this paper explores some of the challenging dynamics that are emerging as service users begin to take up strategic power in social care organizations. Analysis of the current situation suggests that such participation is challenging the very fabric of the institutions in which it is taking place, exposing problems with the political, strategic and structural elements of established non-user organizations. On many levels traditional power relations are being unsettled. The conceptual clash between citizenship and consumerism is being exposed as participation becomes more widespread and sites of resistance are revealed. The associated issues of power, conflict and democracy are discussed with reference to the work of the political philosopher Chantal Mouffe.
Job Satisfaction of Nursing Home Administrators and Turnover
Authors: Castle Nicholas G. , Engberg John , Anderson Ruth A.
Published: April 2007

We know little about factors associated with job satisfaction and dissatisfaction for nursing home workers. In this investigation, the authors use data from a large sample of nursing home administrators (NHAs) to examine: (1) their levels of job satisfaction, (2) whether job satisfaction is associated with intent to leave, (3) whether job satisfaction is associated with turnover after 1 year, and (4) whether job satisfaction after 1 year varies for NHAs who left based on where they subsequently worked. Overall, NHAs were more satisfied with the job satisfaction subscales of: rewards, work skills, and workload but were less satisfied with work demands and coworkers. NHAs appeared particularly sensitive to work skills, with this area of job satisfaction being associated with intent to turnover and actual turnover. In general, the authors found a stronger association with job satisfaction and actual turnover than with intent to turnover.
Financial Protection Afforded by Employer-Sponsored Health Insurance
Authors: McDevitt Roland , Gabel Jon , Gandolfo Laura , Lore Ryan , Pickreign Jeremy
Published: April 2007

This article provides the first national estimates of actuarial values and out-of-pocket spending from the era of nonrestrictive managed care that began in the late 1990s. Employer plans paid about 84 percent of total medical expense for those with employer-sponsored coverage in 2004, about 1 percent less than in 2000, and high users faced potential out of pocket spending in the thousands of dollars when they received a portion of their care out of network. Since 2004, more employers have offered plans with higher deductibles coupled with employer-funded personal accounts. These arrangements can result in low out of pocket costs for many employees, but high users will face substantially higher costs. Many employers adopting high-deductible plans are not contributing to personal accounts. Those who are concerned about higher out-of-pockets might consider income-related cost sharing, educational efforts to communicate the savings that can result from using in-network providers, and continued availability of managed care options that limit out-of-pocket spending.